Oradea Medical Journal

Oradea Medical Journal

CONTENT ................. p.3............ THE LASER IN UROLOGY.

Hofstetter Alfons

ORADEA MEDICAL JOURNAL published by

CENTER FOR HIGH PERFORMANCE MEDICAL RESEARCH

UNIVERSITY OF ORADEA ................. p.8............ AUTONOMIC NEUROPATHY IN TYPE 1

DIABETES: PREVALENCE, SEVERITY,

CORRELATIONS WITH: AGE, GENDER,

DISEASE DURATION, SYSTOLIC BLOOD

PRESSURE, BODY MASS AND GLYCEMIC

CONTROL.

Comanescu Alexandra Diana

P-ta 1 Decembrie 10, room 129, Oradea, 410073, Bihor County, RO Mobile. +40.720.565585 ; Phone/ Fax. +40.359.439092 editor@ccmip.ro / www.ccmip.ro

EDITORIAL BOARD Editor-in -Chief

Gheorghe BUMBU, MD, PhD

Editors

................. p.10.......... NICOTINE REPLACEMENT THERAPY.

Casian Sanda, Lajosi P., Ratiu C.,

Stefanescu Teodora

................. p.12.......... NEW INSTRUMENTS TO MEASURE QUALITY

OF LIFE IN HIP OSTEOARTHRITIS.

Cseppento Carmen ................. p.16.......... CLINICAL-ETIOLOGICAL AND

EPIDEMIOLOGICAL CORRELATIONS IN

ACUTE VIRAL LARYNGITIS IN INFANTS

AND TODDLERS (3-36 MONTHS).

Marusca Patricia Ramona, Spineanu R.,

Burta Olivia Ligia, Micle Otilia, Reikli S.

................. p.20.......... ORTHODONTIC TREATMENT BETWEEN

ABANDONMENT AND SUCCESS.

Vaida Ligia, Berechet Diana ................. p.22.......... THE CARBONIC ANHYDRASE I ACTIVITY

IN HUMAN ERYTHTROCYTES IS AN

INDICATOR FOR BLOOD PRESSURE VALUES.

Iacobescu Alina, Uniţa L., Puşcaş I., Popescu M.,

Magheru Sorina, Maghiar F.

................. p.24.......... THE GASTRIC ULCER PRODUCED BY

INDOMETHACIN ASSOCIATED WITH

HISTAMINE MAY BE CAUSED BY CARBONIC

ANHYDRASE II ACTIVITY IN GASTRIC

MUCOSA.

Uniţa L., Iacobescu Alina, Puşcaş I., Straciuc O.,

Rahota Daniela, Uivarosan Diana, Lerintiu Antonia

................. p.26.......... PREVENTION AND MANAGEMENT OF

INFECTIONS AFTER SPLENECTOMY.

Alin BĂLAJ, MD Mihail-Claudius BERECHET, MD Radu IOVAN, MD Patricia MARUSCA, MD

Iova Camelia

Senior Editors Alfons HOFSTETTER, MD, PhD, Dr.h.c.mult. (D) George Nicu IONESCU, MD, PhD (RO - Or) Ioanel SINESCU, MD, PhD, Corresp. member of Ro. Acad. (RO - B)

Local Consulting Editors (RO - Or)

Petru ARMEAN, MD, PhD Marius BEMBEA, MD, PhD Florin BODOG, MD, PhD Hadrian BORCEA, MD Ciprian BRISC, MD, PhD Simona BUNGĂU, PhD Ovidiu BURTĂ, MD, PhD Olivia BURTĂ, MD, PhD Gheorghe CARP, MD, PhD Gavril CORNUŢIU, MD, PhD Mihaela COROI, MD, PhD Doru CRĂIUŢ, MD, PhD Luiza DEMIAN, MD, PhD Sonia DRĂGHICI, MD, PhD Teodor JURCUŢ, PhD Liviu LAZĂR, MD, PhD

Adrian MAGHIAR, MD, PhD Teodor Traian MAGHIAR, MD, PhD Ioan MATEUŢĂ, MD, PhD Emil MĂRGINEANU, MD, PhD Gheorghe MERMEZE, PhD Otilia MICLE, MD, PhD Petru MIHANCEA, MD, PhD Dumitru MOHAN, MD, PhD Gabriela MUŢIU, MD, PhD Horea OLAH, MD, PhD Amorin POPA, MD, PhD Mircea POPESCU, MD, PhD Ladislau RITLI, MD, PhD Constantin ROMANUL, MD, PhD Oreste STRACIUC, MD, PhD

National Consulting Editors (RO) Monica ACALOVSCHI, MD, PhD (RO - Cj) Radu BADEA, MD, PhD (RO - Cj) Alexandru BUCUR, MD, PhD (RO - B) Cristina CIJEVSCHI-PRELIPCEAN, MD, PhD, (RO - Is) Mircea DICULESCU, MD, PhD, (RO - B) Dan DUMITRAŞCU, MD, PhD (RO - Cj) Adrian GOLDIŞ, MD, PhD (RO - Tm)

Mircea PETRU, MD, PhD (RO - Cj) Marius RAICA, MD, PhD (RO - Tm) Ion ROGOVEANU, MD, PhD, (RO - Cr) Adrian SĂFTOIU, MD, PhD, (RO - Cr) Zeno SPÂRCHEZ, MD, PhD, (RO - Cj) Ioan SPOREA, MD, PhD (RO - Tm) Mircea SUCIU, DMD, PhD, (RO - Tm)

International Consulting Editors

Holger BLENK, MD, PhD (D) Christiane BRUNS, MD, PD, PhD (D) Lucas GREINER, MD, PhD (D) Erich KELLER, MD, PhD (D) Bernd KLEINE-GUNK, MD, PhD (D) Astrid KRÜCKHANS, MD, PhD (D) Robert OELLINGER, MD, PhD (D)

Gorrieri OLIVIERO, MD, PhD (IT) Klaus PLOGMEIER, MD, PhD (D) Diego RIVA, MD, PhD (IT) Hannes SCHEDEL, MD, PhD (D) Bernd SCHMITZ-DRÄGER, MD, PhD (D) Stefan SCHNEIDER, MD, PhD (D) Claus SCHULTE-UEBBING, MD, PhD (D)

Oradea Medical Journal ................. p.30.......... BLOOD SERUM C-TELOPEPTID OF TYPE I

COLLAGEN IN PATIENTS WITH

OSTEOPOROSIS AND HIP OSTEOARTHRITIS.

Pascalau Nicoleta, Mihailov Mariana, Lazar L.,

Cioara Felicia, Farcas Daniela

................. p.32.......... CELL ADHESION MOLECULES INVOLVED

IN BREAST CANCER.

Zaha Dana Carmen, Codreanu Ioana Coralia,

Lazăr Elena

................. p.36.......... WILSON`S DISEASE ONSET WITH

PYRAMIDAL SIGNS

Sabău Monica, Adela Maria,

Comanescu Alexandra Diana, Iova Andrada Claudia

1 / volume 1, no. 2 / November 2009

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Copyright © 2009 Oradea Medical Journal. All rights reserved.

I.S.S.N. 2066 - 7183 The Journal is peer reviewed.

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Oradea Medical Journal

2 / volume 1, no. 1 / November 2009

Oradea Medical Journal

LETTER FROM THE EDITOR THE LASER IN UROLOGY

Prof. Alfons Hofstetter, MD, PhD, Dr.h.c.mult. (D) Senior Editor Direktor der Urologischen Klinik und Poliklinik der Ludwig-Maximilians Universität München Großhadern / Innenstadt

3 / volume 1, no. 2 / November 2009

Our 30 year experience of research and development for the use of lasers in medicine have led to novel procedures in tumor diagnosis and therapy and stone destruction, so that the laser nowadays in certain indications in urology is not only an alternative but also the way of choice.

In cases of severe inflammations (e. g. interstitial cystitis, bilharziosis) the laser coagulation seems to be very helpful.

In the meantime the ILC has been proved as an excellent methode for prostatectomy in adenomas till to 60 cm3, avoiding fluid uptake and severe bleeding.

In case of prostate cancer or other tumors and metastases the effectiveness of interstitial laser application, possibly combined with a parenterally or orally applicated photosensitizers, must be checked.

The experiences with athermic, pulsed micro beam lasers on in vitro fertilisation or in gentechniques are very promising.

Oradea Medical Journal

INTRODUCTION

Laser is an acronym for a physical principle and means: Light Amplification by stimulated Emission of Radiation.

This principle offers a lot of tissue/light effects caused by the parameters: power density/time and the special qualities of the laser light (12, 18, 28, 31, 51, 65).

Nowadays for diagnosis and therapy following lasers are used in urology: Krypton- and Dye-lasers as well as the Neodymium-YAG- (Nd:YAG-), Holmium-YAG (Ho:YAG-), Diode-, Argonand the CO2-lasers (28).

LASER EFFECTS LOW POWER DENSITY

WITH

Photodynamic Methods

The Dye-lasers are used since an few years for the treatment of epithelial early stage carcinomas. In this case there´s utilized the principle of tumor destruction via photosensibilisation in which laserlight of low power density produces oxygen- and hydroxyl-radicals in the tumor cell via photosensitizer as well as it causes changes of the vascular endothelium (4, 5, 7, 10, 32, 33, 36, 38, 64). The interstitial destruction of prostate cancer by PDT is under test, just as small lokalized kidney tumors and penile cancer till to T2.

For tumor-diagnosis the Krypton-laser- or UV-lights induced fluorescence gives new starting points (1, 37, 67, 68).

Till now this procedure hasn´t been of wide clinical use, because the patients suffered in the most cases from a longer photosensibilisation of the skin and the mucous membranes after application of Hematoporphyrine Derivates.

Novel drugs like 5-Aminolevulinic Acid (ALA) avoids with its local applicability such side effects.

The ALA-induced photodynamic diagnosis is a useful supplementing for the endoscopical destruction of bladder cancers by Nd:YAG- or Diode-lasers because in this manner the tumor not visible to the naked eye can be destroyed also.

Above that the laser induced fluorescence permits the early recognition of Cis and urothelial dysplasias.

Interesting, but unclear are the biostimulating effects of lasers due to wound healing and pain suppressing.

We have been able to prove, that the cell growing can be influenced by laser light (59).

Hyperthermy

The transformation of laserlight into heat in tissue is used for coagulation, vaporisation and cutting.

The strong light absorption of the CO2-laser leads to an excellent incision effect with a low edema reaction.

The light of the Argon Ion-laser

is mainly absorbed in the tissue by hemoglobin and pigment colourings and therefore suitable for the destruction of highly vascularized tumors of malformations.

For achieving greater volume effects, e. g. on tumors, bilharzial lesions and interstitial cystitis, the Nd:YAG-laser must be used (18, 28).

The homogeneous deep tissue necroses and the closing of blood- and lymphatic vessels produced by Nd:YAGand Diode-lasers predestine these lasers for tumor destruction.

The use of Nd:YAG-laser for the treatment of urethra strictures (52, 60) shows promising results, although this method hasn´t been accepted generally.

Further lasers, for example the Excimerand Holmium-YAG-laser must be examined if they are suitable as endoscopical cutting vv. vaporisation tools.

a: Lasercoagulation of tumors of the bladder and the upper urinary tract

- Urinary Bladder

Since the first bladder tumor coagulation with the Nd:YAG-laser in 1976 patients with bladder cancers have been irradiated in more and more centers (2, 15, 16, 17, 19, 20, 23, 29, 30, 41, 42, 48, 54).

The published results up to now show a local relapse rate after laser coagulation between 1% and 5 %. In comparison to the rate after transurethral resection (TUR) you can find relapse rates between 40 % and 60 % (33, 34, 35, 45). Apart from avoiding of tumor spreading the touchless technique of laser coagulation permits a tumor destruction under excellent visual conditions, because bleedings hardly occure during the operation. In bladder cancers one has to use an irradiation power between 30 and 40 Watt.

Procedure and Control:

First as a rule, the basic of the tumor has to be irradiated circularely in a distance of 1 to 2 mm of the laser probe to the tumor, afterwards the exophytic part of the tumor is irradiated line-by-line till to whitish discolouration. Tumors with a greater exophytic part can be electroresected deep into the bladder wall after irradiation of the tumorbase. Afterwards the edges and the basic must be irradiated again. The coagulated tumor masses can be identified histologically without problems.

Biopsies from the edges and the base of tumor also permit a clear tumor grading and staging after laser coagulation.

In case of multiple tumors on the bladder rear wall we carry out the laser irraditation controlled by pelviscopy to avoid a perforation of the intestine.

Within the framework of the quarterly and half-yearly controls biopsies from the former tumor area are taken centrally and from the edges and above that from fluorescent areas after instilla-

tion of aminolevulinic acid (ALA). With our present photodynamic diagnosis the former used, so called quadrant biopsy, isn´t necessary any more.

Clinical observations have shown that the laser therapy in bladder cancers is superior to the TUR with regard to the relapse rate as well as the burden of the patient. It is to expect that the effectiveness will be reinforced by combination of photodynamic diagnosis and Nd:YAG- or Diode-laser coagulation.

We have been able to prove that there´s no functional disorder of the urinary storage or the micturition also after extensive coagulation of greater bladder wall areas (49). Even in transmural necroses there´s restoring of the tissue almost with minimal scaring without loss of flexibility and stability, but with regeneration of the musculature of the bladder. Till now we couldn´t notice a perforation of the bladder wall in serveral thousand operations, however in 0,6 ‰ a secondary perforation of the intestine loops. This is the reason why we carry out the endoscopical laser application in pretreated bladders (TUR) or after open operations in the small pelvis only controlled by pelviscopy. Independent of that, each patient should be observed for 12 to 24 hours after extensive lasering of bladder tumors to recognize a bowel perforation in time.

- Upper Urinary Tract (21, 40, 47, 58)

By development of modern ureterorenoscopes the total upper urinary tract can be inspected. With biopsy forceps tissue from suspect areas can be removed and identified histologically.

The laser coagulation is real an alternative to ureteronephrectomy in case of small tumors in the upper urinary tract, especially in low differentiated tumors or in patients who refuse an conventional operation.

Obligatory indications are: Single kidneys attacked by tumors, tumor growth and insufficiency of the kidneys, bilateral tumor attack and superficial tumors of the ureter.

The Nd:YAG- or Diode-laser system, tested in the urinary bladder, is an obvious possibility to destroy tumors in the upper urinary tract with adapted laser parameters (not more than 20 Watt).

The coagulation in the upper urinary tract can be carried out endoscopically, percutaneously or transurethrally.

- Kidney Pelvis

In extensive tumor spreading of the kidney pelvis the exposure of the kidney is indicated for the tumor destroying under microsurgery conditions. The thermical laser necroses reach to a depth till to 8-10 mm by a laser power of 30 to 40 Watt.

For postoperative metaphylaxis can be used BCG or cytostatics. For a controlling 4 / volume 1, no. 1 / November 2009

Oradea Medical Journal

there is inserted a 18 to 20 French nephrostomy catheter which should be left in its place for 5 to 6 months. A treatment result controlling is possible via this channel or transureterally.

- Ureter

For treatment of ureter carcinomas the ureteroscopical proceeding offers at first. The irradiation in the ureter is carried out tangentially with a power between 15 and 20 Watts. Postoperatively there will be inserted a 7 to 10 FrenchDouble-J-catheter, which should be left for 3 to 4 weeks in the case of extensive irradiation. That´s necessary because immediately after coagulation there´s a temporary disorder of peristalsis of the ureter caused by an edema. Nevertheless the coagulated tissue can be repaired nearly without scares.

Disadvantage of the maintenance of the organs by laser therapy in the upper urinary tract is the necessity of closemeshed controlls every three months by ureteroscopy and test biopsies or the performance of an irrigation cytology for a year and more. After a year the control intervals can be prolonged to 6 months if a relapse hasn´t arised. As a complication of endoureteral laser irradiation we found in circular coagulation including the periureteral tissue a scarred stricture of the ureter, which could be removed by an internal ureterotomy as a rule.

Whereas the urothelial tumors of the bladder can be reached well with the Nd:YAG- or Diode-laser the carcinoma in situ (Cis) have caused problems in the past because they couldn´t be seen by naked eyes. In the meantime this problem has been solved by photodynamic diagnosis. At the moment we use an Argon Ion pumped Dye-laser with a wavelength of 635 nm for the photodynamic therapy and for diagnosis a Krypton Ion-laser with a wavelength of 406,7 nm or UV light.

b: Microsurgery

The microsurgical use of the laser in urology is still in the stage of an experiment. Apart from the restoration of vascular- and nerve anastomoses above all there´s tried to join the severed ductus deferentes by CO2- or Nd:YAG lasers (11).

c: Bilharzial lesions

The worm eggs in the bladder wall and the bilharzial lesions in the bladder mucosa can be destroyed by Nd:YAGor Diode-laser irradiation excellently. The results on more than thousand patients of the Assuit University Hospital / Egypt are considerable (9, 13, 28, 50).

d: Interstitial cystitis

In cases of interstitial cystitis Neodym:YAG- or Diode laser irradiation shows good results (28, 62).

5 / volume 1, no. 2 / November 2009

e: Neodym:YAG- / Holmium: YAG- Diode lasers in the Benign Prostatic Hyperplasia (BPH)

BPH can be treated by side fireing, contact and non contact methods as by interstitial laser coagulation (ILC).

Side fire chapneld the adenoma only, ILC makes deep homogeneous necroses followed by an excavation looks like TUR-P.

The interstitial laser coagulation, which was developed by us with the Nd:YAG-laser for destruction of hyperplastic and carcinomatous changed prostate tissue, could revolutionize the prostate surgery if long-time results confirm our present results (26, 27, 43, 44).

f: ILC in Prostate Cancer

In the carcinoma of the prostate we use this procedure if the resection of the prostate isn´t possible or there is a relapse after radical prostatectomy in combination with androgen deprivation. In case of metastases and in tumor seeding in other organs the ILC could also be important if metastases cann´t be removed or if the function of the tumor attacked organs have to be maintained (3, 6, 28).

Nowadays we are checking the combination of interstitial light application and photosensitizing in prostate cancer, as mentioned above.

g: Laser coagulation of tumors in the external genitalia (8, 61)

Because of the excellent volume effect the Nd:YAG- and Diode-lasers are also suitable as coagulation tool for the treatment of tumors in the external genitalia. The advantages of laser therapy are sure in comparison with other methods of treatment, above all in the treatment of Condylomata acuminata and in hemangiomas.

The most frequent indication for laser coagulation in the external genitalia are the Condylomata acuminata. This venerally caused wart formation must be consequently treated because of the danger of infection and the risk of malignant transformation. As a rule the laser coagulation takes place after circumcision and putting on a 4 % acetic acid on the suspicious area in local anesthesia. After the irradiation an urethrocystoscopy is carried out to examine the intraurethral spreading of the condylomas. Especially flat or very small condylomas are visible after marking with acetic acid.

For treatment of hemangiomas in the area of the external genitalia the Nd:YAG- or Diode-laser is very helpful.

During the coagulation a superficial water-cooling is necessary for a good depth effect. With this therapy good cosmetic results can be reached and problems in micturition and cohabitation can be observed only in a few cases. Because of the radicality and the homogeneity of the tissue coagulation the relapse rate is low compared with other methods.

Also in the penile carcinomas (14, 53, 55, 56) till to a stage of T2 the Nd:YAG-laser therapy has proved excellently effective. In principle patients with carcinomas of the penis are circumcised.

The laser irradiation is carried out in the lack of blood and with taking out of tissue sample. The local tumor irradiation follows a bilateral inguinal lymphadenectomy. Similar to the treatment of tumors of the urinary tract after an healing time of about 6 to 8 weeks a biopsy is made from the former tumor bed. Our experiences and literature report by the Nd:YAG laser can be achieved better results than by the nowadays practised method of partial amputation of the penis.

LASER INDUCED SHOCK WAVE LITHOTRIPY (22, 24, 25, 46, 57)

Problems with the endoscopical used energy transformer for lithotripsy of urinary calculi and the power of pulsed laser light has led to the development of laser induced shockwave lithotripsy. In a pulse period between 10 ns and 2 us and pulse energies of about 50 to 150 mJ directly in front of the calculus there are reached high electrical fields producing a plasma. The induced shockwaves with a pressure rate of several 100 bar cause a local fragmentation of stone material. These conditions are carried out for example by a Q-switched Nd:YAG-, Diode- and Alexandrite laser with a 600 µm transmission system.

For induction of optical breakdown using Nd:YAG laser either the fibre end must be spherical sharpened or the shock wave will be reached with an optomechanical coupler. The fibre is very flexible and has a maximal diameter of 1,9 mm inclusively irrigation system. The effect is stone selective and even after a longer application on the tissue only modest bleeding into the mucous membrane can be observed.

With the Alexandrite-laser a good stone destruction is possible too, so far as it isn´t about very bright struvit stones. A problem of the Alexandrite laser is the fact that at energies above 50 mJ the fibre end begins to splinter.

Besides that the flashlamp pumped Dye-laser (66) is also suited for the fragmentation of stones. The transmission system consists of a 200 µm fibre. The induced shock wave is reached by absorption processes in the stone material without special focusing systems or opticomechanical couplers. This system shows though a lower stone selectivity and after application on the surrounding tissues (e.g. ureter wall) bleedings could be observed till to the muscular layers. This unfavourable side effects can extensivly be avoided by a feedback steering system developed by us. A spectrum analysis of the stone material can be carried out simultaneously from the plasma shining.

Oradea Medical Journal

In our experience the DYE-laser with automatic stone idenification has proved under clinical conditions so that we only use this tool (63). The main indications are obstructing calculi in the middle or the lower third of ureter. The effectivity is above 95 %. In the meantime we have also developed a special catheter for the laser lithotripsy in the ureter that makes possible a stone destruction without endoscopy.

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Lipson RL, Baldes EJ (1960): The photodynamic properties of a particular hemato-porphyrin derivate.

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40.

Malloy TR (1985): Laser treatment of ureter and upper collecting system. In: Lasers in urologic surgery.

Smith JA (ed.). Year Book Medical, Chicago

41.

Malloy T (1986): Neodymium-YAG laser in transitional cell cancer of the bladder with emphasis on outpatient potential. Eur. Urol. 12 (Suppl 1): 25

42.

Meier U, Hofstetter A, Pflüger H (1985): Effects of intravesical instillation of mitomycin after endoscopic treatment with TUR or laser of recurrence rate of bladder tumors. XXth Congr. Int. Soc. Urol., Vienna

43.

Müller-Lisse UG, Heuck AF, Thoma M, Muschter R, Schneede P, Weninger E, Faber S, Hofstetter A, Reiser MF (1998): Predictability of the size of laser-induced lesions in T1-weighted MR images obtained during interstitial laserinduced thermotherapy of benign prostatic hyperplasia. JMRI, 8:31-38 6 / volume 1, no. 1 / November 2009

Oradea Medical Journal

44.

Muschter R, Hofstetter A (1995): In: Laser in der Urologie: Prostata, Hofstetter A (Hrsg.), Springer Berlin, Heidelberg, New York, London, Paris, Tokyo, Hongkong, Barcelona, Budapest

45.

Page BH, Levison UB, Corwen MP (1978): The site of reccurence of non-infiltrating bladder tumors. Br. J. Urol. 50:237

46.

Pensel J, Frank F, Rothenberger KH, Hofstetter A, Unsöld E (1981): Destruction of urinary calculi by Neodym:YAG laser irridation. In: Laser surgery, Kaplan J (ed.) IV. Int. Symp. Las. Surg., Acad. Press Tokyo, Jerusalem

47.

Pensel J, Schmeller N, Unsöld T, Kriegmair M, Hofstetter A (1985): Percutaneous Ureter Occlusion with Neodym:YAG Lasers. Laser 85 Opto Elektronik, München

48.

Pensel J (1986): Dosimetry of the Neodymiun-YAG-Laser in urological applications. Eur. Urol. 12, (Suppl.

1): 17

49.

Pensel J, Sommer K, Thomas S, Lieck P, Baretton G (1988): Functional and histolo-gical restitution in the urinary tract after Neodym:YAG laser coagulation. LISAM 8:371

50.

Pensel J, Dann Th, Hofstetter A (1986): Schistosomiasis as a cause of paineful urogenital syndrome. Int. Congr. Infections and Parasitic Disease, München

51.

Pensel J, Hofstetter A, Frank F, Keiditsch E, Rothenberger KH (1981): Temporal and Spatial Temperature Profile of the Bladder Serosa in Intravesical Neodymium-YAG-Laser Irradiation.

Eur. Urol. 7:298

52.

Rothauge CF (1980): Urethroscopic recanalization of urethra stenosis using argon laser. Urology 16:158

53.

Rothenberger KH, Hof-

stetter A, Pensel J, Keiditsch E (1982): Neodym:YAG-Laser-Behandlung maligner Tumoren des Penis. Fortschr. Med. 100:1806

54.

Schilling A, Böwering R, Keiditsch E (1986): Use of Neodym:YAG Laser in the treat-ment of ureteral tumors and urethral condylomata acuminata.

Eur. Urol. 12 (Suppl. 1), 30

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Rothenberger KH (1986): Value of the Neodym:YAG laser in the therapy of penile carcinoma. Eur. Urol. 12 (Suppl. 1): 34

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Rothenberger KH, Hofstetter A (1995): In: Laser in der Urologie. Peniskarzinom, Hofstetter A (Hrsg.)

Springer Berlin, Heidelberg, New York, London, Paris, Tokyo, Hongkong, Barcelona, Budapest

57.

Schmeller N, Hofstetter A, Pensel J, Frank F, Wondrazek F (1987): Der gepulste Neodym-YAG-Laser zur laserinduzierten Stoßwellen-Lithotripsie (LISL). In: Ziegler. Stoßwellen-Lithotripsie bei Harn- und Gallensteinen.

Springer, Berlin

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Schmeller N, Hofstetter A (1989): Laser treatment of ureteral toumors. J. Urol. 141:840

59.

Schneede P, Jelkmann W, Schramm V, Fricke H, Steinmetz M, Hofstetter A (1988): Effects of the HeliumNeon Laser on Rat Kidney Epithelial Cells in Culture. Lasers in Medical Science, 3:249

60.

Schneede P, Klammert R (1995): Lasereinsatz bei Harnröhrenstrikturen. In: Laser in der Urologie, Hofstetter A (Hrsg.), Springer Berlin, Heidelberg, New York, London, Paris, Tokyo, Hongkong, Barcelona, Budapest

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Schneede P, Hofstetter A (1995): In: Laser in der Urologie. Äußeres Genitale, Hofstetter A (Hrsg.), Springer

Berlin, Heidelberg, New York, London, Paris, Tokyo, Hongkong, Barcelona, Budapest

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Shanberg AM, Baghdassarian R, Tansey LA (1983): Treatment of interstitial cystitis with the Neodym:YAG laser. J. Urol. 184:885

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Thomas S, Pensel J, Engelhardt R, Meyer W, Hofstetter A (1988): The pulsed dye laser versus the Q.switched Neodym:YAG laser in laserinduced shockwave lithotripsy. LISAM 8:363

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Waidelich R, Hofstetter A, Stepp H, Baumgarnter R, Weninger E, Kriegmair M (1993): Early clinical experience with 5-Aminolevulinic acid for the photodynamic therapy of upper urothelial tumos. The Journal of Urology, 159:401404

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Waidelich W (1995): Laserphysik. In: Laser in der Urologie.

Hofstetter A (Hrsg.), Springer Berlin, Heidelberg, New York, London, Paris, Tokyo, Hongkong, Barcelona, Budapest

66.

Watson GM und Wickham JFA (1986): Initial Experience with a Pulsed Dye Laser for Ureteric Calculi.

Lancet 1:1357

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Zaak D, Stepp H, Baumgartner R, Waidelich R, Knüchel R, Kriegmair M, Hofstetter A (1998): Photodynamische Diagnostik und Therapie des Urothelkarzinoms der Harnblase. In: Aktuelle Onkologie, 100, 80-84: L. Schmid; W. Wilmanns (Hrsg.) Zuckschwerdt München, Bern, Wien, New York

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Zaak D, Wagner S, Stepp H, Baumgartner R, Kriegmair M, Hofstetter A, Knüchel R (1998): Fluoreszenzquantifizierung bei der 5-Aminolävulinsäure induzierten Fluoreszenzendoskopie des oberflächlichen Harnblasenkarzinoms. Akt Urol. 29:39

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AUTONOMIC NEUROPATHY IN TYPE 1 DIABETES: PREVALENCE, SEVERITY, CORRELATIONS WITH: AGE, GENDER, DISEASE DURATION, SYSTOLIC BLOOD PRESSURE, BODY MASS AND GLYCEMIC CONTROL Comanescu Alexandra Diana University of Oradea, Faculty of Medicine and Pharmacy

ABSTRACT

Objective: To asses the prevalence, the severity and to identify the factors involved in cardiovascular autonomic neuropathy in type 1 diabetes.

Patient and Methods: 48 type 1 diabetic patients and 100-nondiabetic healthy people as controls were submitted to five cardiovascular tests of heart rate and blood pressure variability.

Cardiovascular autonomic neuropathy was defined as at least 2 abnormal cardiovascular responses.

Results: The overall prevalence of autonomic impairment was 45.83%. Cardiovascular autonomic neuropathy correlated with: disease duration (p=0.001), body mass (p=0.001), HbA1C (p=0.0007). It did not correlate with gender (p=0.506), age (p=0.876), and systolic blood pressure (p=0.295).

Conclusions: Autonomic impairment in its sub clinical phase is a frequent finding in type 1 diabetes. Cardiovascular autonomic neuropathy correlates well with: disease duration, body mass and HbA1C, and not with age and with systolic blood pressure.

Key words: diabetic autonomic neuropathy, cardiovascular autonomic neuropathy, autonomic function tests

INTRODUCTION

Diabetic cardiovascular autonomic neuropathy is one of the most important form of diabetic neuropathies, as long as the mortality of patients with CAN is 5 fold greater than in patients without CAN [1].

Diagnosis of CAN in its subclinical phase is based on autonomic reflexes testing.

Presence of CAN could be determined right from onset in young patients diagnosed with type 1 diabetes [2].

The prevalence of CAN has a wide range of values, different authors reporting values between 1% and 90%! [3]. This large variability is due to differences in: selection criteria, algorithms of definition of CAN according to number of abnormal tests, different normative values [4] and to confounding variables like .age, gender, height, diabetes duration, diabetes type, glycemic control.

Nonetheless, large population studies still report different values of CAN prevalence: 25,3%, [4], 16,6% [5], 16,7% [6], 66% [7], 50% [8], 54% [9], 34% [10], 30% [11], 63% [12].

OBJECTIVE

To asses the prevalence, the severity and to identify the factors involved in cardiovascular autonomic neuropathy in type 1 diabetes

PATIENTS AND METHOD

48 type 1 diabetic patients (19–69 years old) with and without clinical signs or symptoms of autonomic dysfunction and 100 healthy control subjects were submitted to five cardiovascular reflex tests:

1. heart rate variation during deep breathing

2. heart rate variation during stand-up,

3. heart rate variation during Valsalva manoeuvre

4. systolic blood pressure variation during stand-up

5. diastolic blood pressure variation during handgrip

Exclusion criteria: end-organ failure and nondiabetic causes of autonomic dysfunction

Cardiovascular autonomic neuropathy was defined as at least 2 abnormal cardiovascular responses. Each test was given a conventional value: a normal result =”0”; a borderline result = ”0.5”; an abnormal result = ”1”. According to the total vegetative score, the patients were grouped in the following severity stages: absent (score=0-0.5); possible (score=1–1.5); definite (score=2–4); severe (score=4.5–5).

Study type: clinical study (analytical, case-control, retrospective)

while the proportion between patients with and without CAN is rather equal in the group of 5–10 years duration, and CAN becomes predominant in the group of more than 10 years duration.

Fig. 1. Prevalence of CAN in type 1 diabetes.

RESULTS

Overall prevalence of CAN in type 1 diabetes was high, as it is shown in Fig. 1.

The distribution of patients in severity groups shows the preponderance of early and definite forms, as it is shown in Fig. 2.

There was not any correlation between CAN (vegetative score) and age (p=0.876), but there was a correlation with disease duration (p<0.001) Fig. 3.

CAN is predominantly absent in the group of less than 5 years duration,

Fig. 2. Severity stages according to the vegetative score.

There was no correlation between CAN and gender, CAN was more prevalent in both sex groups, as it is shown in Fig. 4!

There was a linear significant correlation (p=0.001) between CAN and body mass, as it is shown in Fig. 5a! and 8 / volume 1, no. 1 / November 2009

Oradea Medical Journal

Fig. 5b!

Fig. 6. Distribution of CAN according to systolic blood pressure.

Fig. 3. Distribution of CAN according to diabetes duration.

Fig. 7. Correlation between CAN and HbA1C. Fig. 4. CAN did not correlate with gender.

DISCUSSIONS

CONCLUSION

Our prevalence is less than that reported in the large populational study of Dyck (prevalence of CAN = 66% in type 1 diabetes) [7].

We reported similar factors of correlation for diabetes duration, body mass index, HbA1C [13, 14, 15, 16], but did not find the correlation with hypertension.

Fig. 5a. Distribution CAN according to different body mass groups.

CAN in its subclinical phase is a frequent finding in an unselected population of type 1 diabetes. Early and definite forms are most frequent. It correlates well with disease duration, with body mass and with HbA1C. We did not find any correlation with age, gender, and systolic blood pressure.

Fig. 5b. Linear correlation between CAN and body mass index.

A correlation between CAN and systolic blood pressure was not found (p=0.551), as it is shown in Fig. 6!

There was a strong significant correlation betweeen definite CAN and HbA1C>8%, (p<0.0001), as it is shown in Fig. 7!

9 / volume 1, no. 2 / November 2009

REFERENCES

1.

Ziegler D. Cardiovascular autonomic neuropathy: clinical manifestations and measurement. Diabetes Reviews, 1999; 7: 300-315

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Boysen A, Lewin MA, Hecker W, Leichter HE, Uhlemann F. Autonomic function testing in children and adolescents with diabetes mellitus. Pediatr Diabetes; 8 (5): 261-4, 2007

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Vinik AI, Maser R, Mitchell BD, Freeman R: Diabetic Autonomic Neuropathy, technical review. Diabetes Care, 2003, 26: 1553-1576

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Ziegler D, Gries FA, Spuler M, Lessmann F. Diabetic Cardiovascular Autonomic Neuropathy Muticenter Study Group: The epidemiology of diabetic neuropathy. J Diabet Complications 1992; 6: 49-57

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O’Brien IA, O’Hare JP, Lewin IG, Corral RJ: the prevalence of autonomic neuropathy in insulin dependent diabetes: a controlled study based on heart rate variability. Q J Med, 1986; 61: 957-967

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Neil HA, Thompson AV, John S, et al. Diabetic autonomic neuropathy: the prevalence of impaired heart rate variability in a geographically defined population. Diabet Med 1989; 6: 20-24

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Dyck PJ, Kratz KM, Karnes JL, Litchy WJ, Klein R, Pach JM, WilsonDM, O’Brien PC, Melton LJ III. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology 1993, 43: 817-824

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Verrotti A, Chiarelli F, Blasetti A, Morgese G: Autonomic neuropathy in diabetic children. J Paediatr Child Health, 1995: 31: 545-548

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Ewing DJ, Campbell IW, Clark BF: Assesment of cardiovascular efects in diabetic autonomic neuropathy and prognostic implications. Ann Intern Med, 1980; 92: 308-311

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Maser RE, Steenkiste AR, Dorman JS, et al. Epidemiological correlates of diabetic neuropathy. Report from Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes 1989; 38: 1456.

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Dyck PJ, Kratz KM, Karnes JL, Litchy WJ, Klein R, Pach JM, WilsonDM, O’Brien PC, Melton LJ III. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology 1993, 43: 817-824

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Valensi P, Huard JP, Giroux C, Attali JR: factors involved in cardiac autonomic neuropathy in diabeteic patients. J Diabet Complications, 1997; 11: 180-7

13.

Latini A, Martin LS, Limiti G, et al: Autonomic neuropathy in a diabetic population. Validity of cardiovascular tests and correlations with the complications. Recenti Prog Med, 2000; 91: 562-6

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Tesfaye S, Stevens LK, Stephenson JM, et al. Prevalence of diabetic peripheral neuropathy and its relation to glycaemic control and potential risk factors: the EURODIAB IDDM Complications Study. Diabetologia, 1996: 39: 13771384

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Tesfaye S, Chaturvedi N, Simon M, Eaton DM, et al. Vascular Risk factors and Diabetic Neuropathy: the EURODIAB Complications Study Group; N Engl J Med, 2005: 352: 341-50

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Witte DR, Tesfaye S, Chaturvedi N, Eaton SE, Kempler P, Fuller JH. Risk factors for cardiac autonomic neuropathy in type 1 diabetus mellitus.

Diabetologia, 2005; 48: 164-171.

Oradea Medical Journal

NICOTINE REPLACEMENT THERAPY Casian Sanda, Lajosi P. 1, Ratiu C. 2, Stefanescu Teodora

3

1 Conferenţiar universitar, Catedra de Medicină Dentară II,Universitatea Oradea 2 Sef de lucrări,Catedra de Medicină Dentară I,Universitatea Oradea 3 Preparator,Catedra de Medicină Dentară II,Universitatea Oradea

ABSTRACT The aim of nicotine replacement therapy is temporarily to replace much of the nicotine from cigarettes, to reduce motivation to smoke and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence.

The most used nicotine replacement therapies, the recommended dose, side effects, time of treatment and efficacy are reviewed further.

Key words: nicotine withdrawal, smoking, nicotine replacement therapies .

INTRODUCTION

Quitting smoking means after all stopping nicotine delivery. As nicotine is responsible of dependence, this will start a lot of symptoms like depression, anxiety, increased appetite, decrease of cardiac rhythm, decrease of attention, sleep disturbance, lightheadedness, poor concentration, craving for nicotine, irritability or aggressiveness, restlessness. The aim of nicotine replacement therapy is temporarily to replace much of the nicotine from cigarettes, to reduce motivation to smoke and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence.

All of the commercially available forms of nicotine replacement therapy (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) can help people who make a quit attempt to increase their chances of successfully stopping smoking. Nicotine replacement therapies increase the rate of quitting by 50-70%, regardless of setting. The most effective quitting rates are when helped by other forms of support.

The most used nicotine replacement therapies, the recommended dose, side effects, time of treatment and efficacity are reviewed further.

DISCUSSIONS

Nicotine gums(Nicorette®, Nicorette®DS) They are approved from 1984 and have the strength of 2 mg or 4 mg nicotine fixed on a resin base. It is recommended that normally 9 to 12 pieces of gum should be chewed daily, but the maximum can be 20 to 30 pieces.

Chewing such a gum 30 minutes, the nicotine content is slowly released and absorbed through oral mucosa.

The absorption of nicotine from gum is much slower than from cigarettes.

The rate of nicotine release is dependent on the speed of chewing. Rapid chewing may result in the swallowing of nicotineloaded saliva and can result in gastrointestinal side effects and headaches. The

patients should be thought to chew slowly and to stop one minute when a peppery taste appears in the mouth and to restart chewing only when the gum is tasteless. A low pH suppresses the buccal absorption of nicotine. Patients should be counseled to avoid carbonated drinks, coffee, beer, wine, or any other acidic drinks for 15 minutes before and during gum chewing, especially if they previously associated such activities with smoking a cigarette.

Other side effects are hyper salivation, pain in chewing muscles, irritability, poor sleep, nausea both because the chewing is too fast and the nicotine is absorbed in higher concentrations, or because of the symptoms of withdrawal.

The time recommended for treatment is between 3 and 6 months.

The best results are obtained when associated with other methods of quitting like counseling and non –nicotine preparations. ,

Nicotine Patches(Nicotrol®, Habitrol®, Nicoderm®, Nicorette®, Nicotinell®, Nico-Stop®)

Transdermal nicotine delivery systems were approved by the US Food and Drug Administration (FDA) in 1991 as an adjunct to physician support for smoking cessation. In recent years, patches of various designs and differing pharmacokinetic actions have become available .The low-dose patches are designed to produce blood nicotine levels that are lower than those resulting from smoking. The rate of nicotine absorption is maximal between 6 and 12 hours after application, with an absolute bio-availability of about 82%. Blood nicotine levels peak after 16 to 24 hours and then decline. The plasmatic nicotine concentration with nicotine patches range from 10 to 20 ng\ml, depending on the patch concentration. The skin may serve as a reservoir for nicotine, because about 10% of transdermal nicotine is systemically absorbed after the patch is removed.

A review of the findings of double-blind studies concluded that prescription nicotine patches are an effective aid to tobacco dependence treatment; however, since

success rates varied greatly across studies, it was concluded that the results may be influenced by the nature and intensity of adjuvant smoking cessation counseling.

An analysis of over-the-counter products showed that their use resulted in greater cessation rates by a factor of up to 2.8 compared with placebo and proved as effective as when given on prescription. Higherdose nicotine (44 mg/d) can achieve blood concentrations similar to those resulting from smoking. Patches are designed for 16- or 24-hour wear. No significant difference was found in cessation rates or withdrawal symptoms between the 16- and 24- hour types, and both proved effective, more than doubling 6-month cessation rates. The treatment is recommended for 6 till 18 weeks. The patches should be bonded on dry skin, without lesions or hair and they may have 10, 20 or 30 cm square and concentrations of 7, 14, 21mg of nicotine (Nicotinell®), 5, 10, 15 mg nicotine (Nicorette®) or 15, 30 mg nicotine (Nico Stop®).

They can be maintained on the skin the whole day (those for 16 hours) or also during the night (those for 24 hours).The most frequently reported side effects with all 24-hour patches, but not with 16-hour patches, are local skin irritation and contact sensitization. These events may be reduced by applying the patch to a different site each day. Use of 24-hour patches may also result in sleep disturbance, an effect that appears to be dose-dependent. For patients experiencing sleep disturbances, a 16-hour patch may prove more acceptable.

Alternatively, the 24-hour patch should be removed before bedtime. Patients who continue to smoke while using nicotine patches should be warned that they may experience nausea, abdominal pain, diarrhea, vomiting, dizziness, profuse perspiring, flushing, hearing and vision disturbances, confusion, weakness, palpitations, altered respiration, and hypotension; these are signs and symptoms of nicotine toxicity. These events may be confused with nicotine withdrawal . The use of nicotine patches should not be started around the time of an acute myocardial infarction or in patients undergoing coronary artery 10 / volume 1, no. 1 / November 2009

Oradea Medical Journal

surgical procedures [4].

Nicotine Nasal Spray (Nicotrol® NS)

Nicotine nasal spray is approved for clinical use as an aid to smoking cessation and for the relief of nicotine withdrawal symptoms. One dose consists of 2 squirts (1 in each nostril), each squirt delivering 0.5 mg nicotine. The nicotine nasal spray can replace about 50% of the blood nicotine concentrations that occur with smoking. Smokers normally use 1–2 doses per hour, but this may be increased to 40 doses per day for 3 months. Peak concentrations of nicotine in the blood occur 5–10 minutes after use thus, delivery is faster than with gum or an inhaler, but slower than with cigarettes. The plasmatic nicotine concentration ranges from 5 to 15 ng\ ml, depending on the frequency of doses token. The nasal spray can be used in association with nicotine patches to achieve increased efficacy. Originally, it was thought that the dependence potential of nasal spray would be high because of the rapid nicotine absorption and the need for frequent administration. Studies have shown that this is not the case and have found no evidence of abuse liability. Cessation rates at 6 months of between 25% and 35% have been reported. Local irritation of the nose and throat are the most common side effects. Incidences of moderate to-severe irritation usually disappear or become mild within a few days of starting use. Other events include watery eyes, runny nose, coughing, and sneezing. Long-term nasal complications have not been reported. The recommended time for use is 3 months, with 20-30 doses per day. Although the nicotine blood level is quickly obtained, quicker than from gums or lozenges, this effect does not last in time. As a result, the spray can not offer a constant release of the nicotine as other forms of nicotine replacement therapy do [4].

tine replacement therapies, the nicotine inhaler results in cessation rates that are double then those achieved with placebo.

If used concurrently with nicotine patches, high cessation rates may be achieved.

Some patients experience local irritation, such as a burning sensation in the throat, as well as sneezing, dizziness, vomiting, paleness, cold sweat, coughing, and hiccups. These side effects may compromise compliance with heavy use and reduce the efficacy of an inhaler [5].

Nicotine Inhaler (Nicotrol® Inhaler)

The nicotine inhaler became available by prescription in 1998 and was developed to mimic the hand-to-mouth ritual. It looks very much like a cigarette and comprises a nicotine cartridge attached to a plastic mouthpiece. Users may need to inhale vigorously and frequently to achieve a 30% replacement of blood nicotine levels; each deep puff delivers 13 micrograms of nicotine. Unlike cigarettes, the inhaler delivers more nicotine by the buccal (36%) than pulmonary (4%) route, with absorption being temperature-dependent and with poor bioavailability below 10°C. The plasmatic nicotine concentrations range from 5 to 15 ng\ml, the same as for low level cigarette smokers. Successful use of inhalers depends on the number of doses taken; typically 6–16 cartridges per day are required to be successful in preventing smoking.

As is common with other nico-

In conclusion, all of the available nicotine replacement therapies have proven some efficacy. They are more effective when associated with non nicotine therapies like bupropion, rimonabant or varenicline and psychological guidance. Still

11 / volume 1, no. 2 / November 2009

Nicotine Lozenges/Sublingual tablets (Commit®lozenges)

Nicotine lozenges may be suitable for a patient who prefers oral nicotine replacement therapy but is intolerant of gum because of hyper salivation or gastric symptoms. The nicotine lozenge was approved by the FDA in 2002. In a placebocontrolled clinical trial, lozenges containing 2 and 4 mg nicotine fixed on alpha cyclodextrine were shown to be effective, with side effects similar to those of nicotine gum. The nicotine lozenge is placed under the tongue, where it melts slowly in approximate 30 minutes, and this is the way nicotine is released into the oral cavity. The recommended dose is 10-12 lozenges, and this means approximate one per hour. It shows to be the most successful at patients that smoke 10-15 cigarettes a day. Like the other nicotine replacement therapies, the time recommended for treatment lies between 3 and 6 months. Side effects are gastric pains, irritability, nausea, headaches, basically the same as for gums but with less intensity and fewer cases.

The plasmatic concentration is the same as for gums, if taken one lozenge per hour.

It is not recommended to use lozenges and acid medication or food, because the acid pHs decrease the absorption through oral mucosa [6].

CONCLUSION

the high rate of failures during the quitting attempts require for more efficient ways of withdrawal.

REFERENCES

1.

Le Houezec J. Role of nicotine pharmacokinetics in nicotine addiction and nicotine replacement therapy: a review. Int J Tuberc Lung Dis. 2003 Sep;7(9):811-9

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Molyneux A. - Nicotine replacement therapy,BMJ,21 Feb 2004, 454-456

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Coleman T - Cessation interventions in routine health care,BMJ,13 March 2004,631-633

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Trofor A, Radu-Loghin C, – Fumatul de la obicei la boală, Editura Tehnopress, Iaşi,2004

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Schneider NG, Olmstead RE, Franzon MA, Lunell E. The nicotine inhaler: clinical pharmacokinetics and comparison with other nicotine treatments.

Clin Pharmacokinet. 2001;40(9):661-84.

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Wang D, Connock M, Barton P, Fry-Smith A, Aveyard P, Moore D. ‘Cut down to quit’ with nicotine replacement therapies in smoking cessation: a systematic review of effectiveness and economic analysis. Health Technol Assess.

2008 Feb;12(2):iii-iv, ix-xi, 1-135

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Bush TM, McAfee T, Deprey M, Mahoney L, Fellows JL, McClure J, Cushing C, The impact of a free nicotine patch starter kit on quit rates in a state quit line.Nicotine Tob Res. 2008 Sep;10(9):1511-6

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Roth MT, Westman EC - Asthma exacerbation after nasal nicotine spray administration for smoking cessation, Pharmacotherapy,22(6),2002, 79-82

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Dempsey DA, Benowitz NL - Risks and benefits of nicotine to aid smoking cessation in pregnancy. Drug Safety 2001;24:277-322

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Lancaster T, Stead LF - Self help interventions for smoking cessation, Cochrane Database Syst Rev 2003,(2):CD001118

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Molander L, Lunnell E – Pharmacokinetic investigation of a nicotin sublingual tablet, Eur J Clin Pharmacol, 2001:56;813-9

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Oradea Medical Journal

NEW INSTRUMENTS TO MEASURE QUALITY OF LIFE IN HIP OSTEOARTHRITIS Cseppento Carmen University of Oradea, Faculty of Medicine and Pharmacy “Avram Iancu” Oradea Emergency Clinical Hospital

ABSTRACT

Osteoarthritis (OA) is a major public health problem and the leading cause of disability in developement countries, particulary in the elderly. The prevalence of symptomatic OA has be assessed at 12% in the US population of persons ages 25-75 yers.

Osteoartrithis is caractersed by progressiv degradesion and loss of articular cartilage accompanied by subcondral boneremodeling, osteophyte formation and synovial inflammation. The clinical manifestations are a garadual developement of joint pain, sweling, instability, stiffnes and loss motion. The main objectives in the management of OA to reduce symptoms, minimise functional disability and limit the progression of structural change. Pain is usually evaluated using VAS score and WOMAC algofunctional index.

Conclusion: Quality of life was associated with pain, functional limitations, and depressed mood. It is important to identify the problems when caring for older adults, and special attention should be given to individuals with osteoarthritis because of their higher degree of pain and functional limitations.

OA has a significant impact on quality of life, only partly ameliorated by arthroplasty, as assessed by the SF-36 and WOMAC .

Keywords: Quality of life, Osteoarthritis, health status instruments , disability and health.

INTRODUCTION

DISCUSSIONS

Optimal prevention and therapy management depends upon the quality of health assessment in the field of increasingly frequent degenerative health disorders. Quality of life has increased in importance as a result of World Health Organizations’ new concept of health and disease. This review addresses strategies and measurement in the quality of life assessment in osteoarthritis over the past 15 years..

Osteoarthritis (OA) of the hip is a major cause of functional disability and reduced quality of life. Management options aim to reduce pain and improve or maintain physical functioning. Current evidence indicates that therapeutic exercise has a beneficial but short-term effect on pain and disability, with poor long-term benefit. The optimal content, duration and type of exercise is yet to be ascertained.

Usually OA affects elderly people, and is one of the main causes of physical disability. In OA patients, Health Related Quality of Life (HRQoL) and activities of daily living are negatively affected. Significant work disability, reduced ability to deal with household duties and sleep disorders are reported in patients with symptoms of OA flare-ups, together with dysfunctions in the areas of ambulation, body-care and movement (in terms of perceived health status), and emotional behaviour (in terms of perceived psychological functioning) (1,2,4-8).As a chronic condition, the impact of OA has been studied mainly focusing on its consequences on health status.

Similarly, treatment efficacy is assessed within the context of health status and/ or symptomatology in many clinical trials [6,7,9-12]. However, health status and symptomatology can be considered only

two components of HRQoL [13] and little is known about the impact of OA and its treatments on patient’s subjective perspective, in spite of increasing attention on this topic [14-19].In literature, HRQoL refers to patients appraisals of their current levels of functioning and satisfaction, compared to what they perceive to be ideal [20].

HRQoL assessment allows a subject to express his or her ability to perform daily activities across many domains which include physical, social and cognitive functioning, role activities and emotional wellbeing. Besides, “...how a subject feels about the performace of each of those activities may be assessed separately by measuring satisfaction for each domain.” [21]. The subjective implications of HRQoL, within the context of patient centred medicine, have been already stressed by suggestions from recent reliable scientific literature [15,17-24].Pain and physical limitations constitute difficulties patients have to deal with and require long term pharmacological treatment and physical therapies.

Visual Analogue ScaleThe VAS is perhaps the most widely used instrument for the measurement of pain intensity. The classic version of the VAS was administered: 10 centimeter line, horizontal. “It is a simple, robust, sensitive, and reproducible instrument that enables a patient to express the severity of his pain in such a way that it can be given a numerical value.” [26] Its psychometric properties and its utility in clinical trials have been confirmed [2,8,31,32]. VAS on Present Pain ranged from “no pain” to “the worst pain possible”; VAS on Pain Relief ranged from “no pain relief” to “the maximum pain relief”. Scores ranged from 0 to 100.

SF-36.The SF-36 is a well known self-administered and generic health status measure which encompasses 8 domains related to daily life activities: physi-

cal functioning, role limitations due to physical problems, role limitations due to emotional problems, vitality, bodily pain, social functioning, mental health and general health perception [33-35]. Each domain scores from 0 (lowest level of functioning) to 100 (highest level of functioning). The instrument has been extensively validated within the Medical Outcome Study [33] and in other settings [34].A 36-item shortform (SF-36) was constructed to survey health status in the Medical Outcomes Study. The SF-36 was designed for use in clinical practice and research, health policy evaluations, and general population surveys. The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. The survey was constructed for self-administration by persons 14 years of age and older, and for administration by a trained interviewer in person or by telephone. The history of the development of the SF-36, the origin of specific items, and the logic underlying their selection are summarized. The content and features of the SF-36 are compared with the 20-item Medical Outcomes Study short-form Satisfaction Profile. The SAT-P is a self-administered, generic questionnaire which provides a satisfaction profile in daily life and can be considered as an indicator of subjective QoL.

TheQAKHQOL.The OAKHQOL is a self-administered questionnaire comprising 40 items divided into five dimen12 / volume 1, no. 1 / November 2009

Oradea Medical Journal

sions—physical activity, mental health, pain, social support and social activities—and three additional independent items [14]. Oral responses were elicited from patients and health professionals in five different ways [15]. For all methods, the sole instruction given to interviewees was to report the impact of OA on their (or their patients) HRQoL, the difficulties they encountered because of OA and during which circumstances they had difficulties in daily life. No HRQoL definition or specific question relating to the ICF components was used prior to or during the interviews. Content analysis of the taperecorded transcripts elucidated different facets of the functionalist approach to QoL and of the needs-based model and confirmed that patients expressed the impact of disease in terms of the needs they were unable to meet. During the item-selection step that combined psychometric properties and content assessment, the WHO definition of health and QoL was used and selection was based on item relevance to this concept. The process generated 80 items, of which 43 were retained after content and psychometric analysis [14]. The raw scores of the OAKHQOL are the mean of observed items of each dimension and are calculated only if at least half of the items within the considered dimension are answered. The normalized scores vary from 0 (worst) to 100 (best possible HRQoL).

The International Classification Of Functioning, Disability and Health.The ICF is a general health status framework that comprehensively represents the experience of patients. The ICF framework contains four components that interact: body functions and body structures, activities and participation, environmental factors and personal factors. In the model, problems in functioning are a consequence of the interaction of a health condition and environmental and personal factors. The four components of ICF include categories that represent the units of the ICF classification. Within the hierarchical code system of the classification, the categories are designated by a letter: (b) body functions, (s) body structures, (d) activities and participation or (e) environmental factors, followed by a numerical code. The numerical code begins with the chapter number (one digit), followed by the second level (two digits) and the third and fourth levels (one digit each) of definition [2, 16].

The ICF model defines three main health outcomes: impairment assessed by body functions and body structures categories, activity limitations and participation restrictions. The ICF allows for considering two different perspectives (subject and external observer perspective), whereas the HRQoL reflects subject perspective. Actually, all the ICF components can reflect subject perception: satisfaction with health condition, body functions and structures, activities and participation, and environmental factors. In this way, ICF and QoL 13 / volume 1, no. 2 / November 2009

are closely connected.

ICF core set for OATo facilitate the application of the ICF, experts have developed specific comprehensive ICF core sets [3] for reporting functioning and health, defined as ‘what to measure for assessment of functioning’ for a specific disease. ICF core sets are lists of ICF categories that include as few categories as possible to be practical, but as many as necessary to be sufficiently comprehensive to describe the typical spectrum of problems in functioning of patients with a specific condition. The OA core set, recently developed, contains 55 categories [4].

Linking the items of the OAKHQOL to the ICF.Each item of the OAKHQOL was linked to ICF categories according to published linking rules [17, 18]. Health professionals trained in the ICF are advised to identify all meaningful concepts within each item of the health status measure under consideration according to these linking rules. Each meaningful concept is linked to the most precise ICF category. If a single item encompasses different concepts, the information in each concept should be linked. If a concept is not explicitly named in the corresponding ICF category, the lower level of the ICF classification is linked. If the information provided by the meaningful concept is not sufficient to determine its precise category, the concept is assigned ‘not definable’ (nd). A concept can be coded as ‘personal factors’ (pf). If a concept is not covered by the ICF classification, it is assigned ‘not covered’ (nc). Two rheumatologists (J.P. and A.-C.R.) independently linked the OAKHQOL concepts to the ICF. The degree of agreement between the two investigators was assessed by analysis of the proportion of agreement in ICF second-level categories. Disagreements were discussed and a consensus was obtained.

Other health status measures.

We compared the OAKHQOL to the five most frequently used instruments in OA. Among the generic HRQoL instruments, the MOS-SF36 is available in many languages [19, 20]. It contains 36 items in eight dimensions: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health [19, 21]. The WOMAC is a three-dimensional index with five items related to pain, 17 to physical function and three to stiffness [5]. The Lequesne index is also a function scale comprising 10 items assessing pain intensity, walking ability and physical function [13]. The short form of the Arthritis Impact Measurement Scales (AIMS2-SF) [22–25] measures five domains of health: physical function divided into upper and lower body limitations, social function, symptoms and affect. The HAQ is a questionnaire measuring the ability to perform daily life activities: dressing, arising, eating, walking, hygiene, reaching, gripping and other activities [26, 27].

CONCLUSIONS

Comparison of OAKHQOL and health status instruments using the OA core set

To focus the analysis on ICF categories especially pertinent to OA, we compared the OAKHQOL with the other health status instruments in terms of the OA core set instead of the whole ICF classification. The WOMAC, Lequesne index, AIMS2-SF, HAQ and MOS-SF36 have already been linked to the ICF [1, 17] and we used the published results for comparison with the OAKHQOL. However, several discrepancies were found in the reported articles, and some of the linkage rules have recently been updated [18]. After we checked the above-sited published results, we made a few modifications to the published linking results. As an example, in the WOMAC index, we linked the item ‘light domestic duties’ to the category ‘doing housework’ rather than to the category ‘domestic life unspecified’.Since the categories of the OA core set were at the second level, we moved all third- and fourth-level ICF categories that were linked to the different instruments, to the second level. For each instrument, we analysed the number of categories linked, the mean number of concepts per item and the mean number of concepts per OA core set category. For the Lequesne index and the HAQ, several queries about aids or devices (e.g. use of a cane) are not considered to be items but, rather, serve to weight the scores. However, the queries were considered as items in terms of estimating the mean number of concepts per item.

REFERENCES

1.

Cieza A, Stucki G. Content comparison of health-related quality of life (HRQOL) instruments based on the International Classification of Functioning, Disability And Health (ICF). Qual Life Res (2005) 14:1225–37.

2.

World Health Organization. International Classification of Functioning, Disability And Health: ICF. (2002) (4 January 2008, date last accessed).

3.

Cieza A, Ewert T, Ustun TB, et al. Development of ICF core sets for patients with chronic conditions. J Rehabil Med (2004) 44((Suppl)):9–11.

4.

Dreinhofer K, Stucki G, Ewert T, et al. ICF Core Sets for osteoarthritis. J Rehabil Med (2004) 44((Suppl)):75–80.

5.

Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol (1988) 15:1833–40.

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Pouchot J, Coste J, Guillemin F. Impact of osteoarthritis on quality of life. In: Osteoarthritis, clinical and experimental aspects—Reginster JY, Pelletier JP, Martel-Pelletier J, Henrotin Y, eds.

Oradea Medical Journal

(1999) Berlin: Springer. 331–55.

7.

Ethgen O, Bruyere O, Richy F, Dardennes C, Reginster JY. Health-related quality of life in total hip and total knee arthroplasty. A qualitative and systematic review of the literature. J Bone Joint Surg Am (2004) 86:963–74

8.

Fitzgerald JD, Orav EJ, Lee TH, et al. Patient quality of life during the 12 months following joint replacement surgery. Arthritis Rheum (2004) 51:100–9

9.

Hawker G, Melfi C, Paul J, Green R, Bombardier C. Comparison of a generic (SF-36) and a disease specific (WOMAC) (Western Ontario and McMaster Universities Osteoarthritis Index) instrument in the measurement of outcomes after knee replacement surgery.

J Rheumatol (1995) 22:1193–6

10.

Nilsdotter AK, Petersson IF, Roos EM, Lohmander LS. Predictors of patient relevant outcome after total hip replacement for osteoarthritis: a prospective study. Ann Rheum Dis (2003) 62:923–30.

11.

Sharma L, Sinacore J, Daugherty C, et al. Prognostic factors for functional outcome of total knee replacement: a prospective study. J Gerontol A Biol Sci Med Sci (1996) 51:152–7.

12.

Fortin PR, Penrod JR, Clarke AE, et al. Timing of total joint replacement affects clinical outcomes among

patients with osteoarthritis of the hip or knee. Arthritis Rheum (2002) 46:3327–30.

13.

Lequesne MG, Mery C, Samson M, Gerard P. Indexes of severity for osteoarthritis of the hip and knee. Validation – value in comparison with other assessment tests. Scand J Rheumatol Suppl (1987) 65:85–9

14.

Rat AC, Coste J, Pouchot J, et al. OAKHQOL: a new instrument to measure quality of life in knee and hip osteoarthritis. J Clin Epidemiol (2005) 58:47–55

15.

Rat AC, Pouchot J, Guillemin F, et al. Content of quality-of-life instruments is affected by item-generation methods. Int J Qual Health Care (2007) 19:390–8

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Organisation Mondiale de la Santé. Classification Internationale du Fonctionnement, du Handicap et de la Santé: CIF (2001) Genève: OMS.

17.

Cieza A, Brockow T, Ewert T, et al. Linking health-status measurements to the International Classification of Functioning, Disability and Health.

J Rehabil Med (2002) 34:205–10

18.

Cieza A, Geyh S, Chatterji S, et al. ICF linking rules: an update based on lessons learned. J Rehabil Med (2005) 37:212–8

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Leplege A, Ecosse E, Verdier A, Perneger TV. The French SF-36

Health Survey: translation, cultural adaptation and preliminary psychometric evaluation. J Clin Epidemiol (1998) 51:1013–23.

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McHorney CA, Ware JE Jr, Raczek AE. The MOS 36-Item shortform health survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs.

Med Care (1993) 31:247–63.

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Ware JE Jr, Gandek B. Overview of the SF-36 Health Survey and the International Quality of Life Assessment (IQOLA) project. J Clin Epidemiol (1998) 51:903–12.

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Meenan RF, Mason JH, Anderson JJ, Guccione AA, Kazis LE. AIMS2. The content and properties of a revised and expanded arthritis impact measurement scales health status questionnaire. Arthritis Rheum (1992) 35:1–10

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Ren XS, Kazis L, Meenan RF. Short-form arthritis impact measurement scales 2: tests of reliability and validity among patients with osteoarthritis. Arthritis Care Res (1999) 12:163–71

24.

Pouchot J, Guillemin F, Coste J, Bregeon C, Sany J. Validity, reliability, and sensitivity to change of a French version of the arthritis impact measurement scales 2 (AIMS2) in patients with rheumatoid arthritis treated with methotrexate. J Rheumatol (1996) 23:52–60.

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15 / volume 1, no. 2 / November 2009

Oradea Medical Journal

CLINICAL-ETIOLOGICAL AND EPIDEMIOLOGICAL CORRELATIONS IN ACUTE VIRAL LARYNGITIS IN INFANTS AND TODDLERS (3-36 MONTHS) Marusca Patricia Ramona 1, Spineanu R. 2, Burta Olivia Ligia 1, Micle Otilia 1, Reikli S. 1 1 The Department of Microbiology – Histology (The Faculty of Medicine and Pharmacy of Oradea) 2 The Municipal Clinical Hospital „Gavril Curteanu” Oradea

ABSTRACT

Introduction.The subglottic obstructive acute laryngitis has an almost exclusively viral etiology.

Objective:the detection of the viruses responsible of the subglottic obstructive acute laryngitis in children and the establishment of clinical-etiological and epidemiological correlations.

Material and method. There have been investigated 88 children, between 3-36 months, during two consecutive seasons (2004-2005and2005-2006), pursuing the identification of 8 viruses: influenza A and B, parainfluenza 1,2,3, adenovirus, measles and respiratory syncytial virus.

Results.The etiology has been identified for 79,54% of the cases, most frequent being the parainfluenza 3 (27,14%) and measles (21,42%) viruses, and the less detectable influenza A (5,71%) and B (4,28%) viruses. There have been observed differences between the age groups, the patients’ provenience environment and regarding the distribution between genders. The measles and parainfluenza 3 viruses have determined the most severe forms of disease.

Conclusions.Assessing viral etiology of laryngitis allows us to conclude specific peculiarities between etiological, clinical and demographic spread.

Key words: subglottic laryngitis, viral etiology

INTRODUCTION

OBJECTIVE

ODS

MATERIAL

The subglottic obstructive acute laryngitis of the infant and small child has an almost exclusively viral aetiology. They represent a consistent segment of the respiratory pathology of the referential children and are responsible for a large number of hospitalizations [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15].

Our objective is to identify with accuracy the viral etiology of the laryngitis and to explore the possibility of outlining clinical-etiological and epidemiological correlations.

AND

METH-

The study has been performed upon 73 children hospitalized in the Children’s Clinical Hospital “Gavril Curteanu” Oradea, for a clinical picture of subglottic obstructive acute laryngitis, and upon 15 patients infected with measles, complicated with laryngitis, hospitalized in the Clinical Hospital of Infectious Diseases Oradea.

The inclusion criteria have been:

- age: 3 – 36 months;

- children without malformative pathology of laryngotracheobronchitis sphere;

- children, hospitalized or home observed for a 14 days period after release, for a correct evaluation of the studied material, respectively the monitorization of the IgM antibody titre in dynamics.

The exclusion criteria have been: - the existence of malfor-

mative syndromes of laryngotracheobronchitis sphere;

- other forms of obstructive laryngitis (spastic laryngitis, epiglottitis);

- children which, after release, could not be monitorized for reevaluation up to a total of 14 days.

The design of the research: The selected patients have been clinically examined in the first day of hospitalization, establishing the diagnosis of subglottic obstructive acute laryngitis and including them in a certain severity score.

Therefore, there have been described 3 stages of severity [16]:

- light, score 1: the child has a good general condition, accepts the food, has no stridor in repose and no retraction;

- medium, score 2 – 7: the stridor is present and in repose, the retraction is moderate, tachypnea, tachycardia, maintains interest for people and the surrounding environment. If a child with medium obstruction becomes agitated or tired, it is a sign of progression to the severe form;

- severe, score > 7: stridor and ample retraction, also present in repose, cyanosis, tachycardia, convulsion or obnubilation, loss of interest for the people around, can not feed or hydrate, presents tiredness, exhaustion. The respiratory distress can be less pronounced than in the medium form due to exhaustion.

The children have been monitorized under the clinical evolution report and the response to treatment, also noting the length of hospitalization. If the hospitalization period has been shorter than 14 days, those children were monitorized

ambulatory and were recalled on the 14th day at the ambulatory service of the hospital, for the second sampling of blood.

The samples taken from the same patient (in day 1 and 14) have been analyzed concomitantly, to confirm the etiology.

The tests for the virus diagnosis have been performed for the following etiological agents: the respiratory syncytial virus, the adenovirus, the influenza A virus, the influenza B virus, the parainfluenza 1 virus, the parainfluenza 2 virus, the parainfluenza 3 virus, the measles virus.

For identification there has been used the ELISA technique (enzyme-linked immunosorbent assay).

For statistics data there has been used the EPIINFO aplication, 6.0 version, a program of The Center of Disease Control and Prevention – Atlanta, with the Student method (test t) and χ2.

RESULTS

Of the total number of 88 children which were paraclinically analysed, the aetiology could be determined for 70 patients (79,54%), as it results from fig. 1.

Fig. 1. Distribution of cases according to the identified or unidentified aetiology.

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From the total 70 cases with established etiology, there has been determined a predominance of the parainfluenza 3 virus, which was detected at 19 people (27,14%), followed by the measles virus, which caused 15 cases within the two seasons (21,43%). This aspect is presented in table no. I.

The distribution on groups of age was the following: 8 cases (11,43%) have had ages between 3-12 months, 39 cases (55,71%) between 13-24 months and 23 cases (32,86%) between 25-36 months (fig.

3).

4).

Fig. 4. Correlation between the patientsâ&#x20AC;&#x2122; gender and the identified etiology.

Table I. Assignment of the cases according to the identified aetiology.

The lowest incidence have had the infections caused by the influenza B virus: 3 patients (4,29% of the cases with stated aetiology) and the influenza A virus: 4 patients (5,71% of the cases with identified aetiology), in all, during the two seasons.

In our study group, the aetiology has been stated in 31 cases in the urban environment (44,29%) and 39 cases in the rural environment (55,71%), the rural/urban report being of 1,3:1.

Regarding the relation etiological agent- origin environment of the patient, the situation can be evaluated based on table no. II, resulting a significant difference between the urban and the rural (p<0,001).

Therefore, the VRS prevalence, the parainfluenza 1 and 2 viruses, is 2-2,9 times bigger in the urban area, and the prevalence of the influenza A and B viruses, the parainfluenza 3 and measles viruses is significantly bigger in the rural environment.

Fig. 3. Distribution of the cases according to age.

Fig. 5 shows that the most frequent forms of disease have been those with medium severity (60,00%) and severe (30,00%).

Table III. Correlation between the age of the patients and the identified etiology.

Referring to the groups of age, we have observed that: the age group 3-12 months presents risk of acute laryngitis with VRS (RR=2,44) and adenovirus (RR=1,94), the age group 13-24 months having laryngitis with measles virus (RR=3,18) and the age group 25-36 months having acute laryngitis with parainfluenza 1 and 2 virus (RR=2,04). We can not state that one of the age groups presents a higher risk of acute laryngitis with parainfluenza 3 virus.

In table IV is presented the distribution of the studied cases, making the correlation between the patientsâ&#x20AC;&#x2122; gender and etiological agent of the laryngitis. One may observe that more male patients have been hospitalized, that is 41 (58,57%), compared to only 29 female (41,42%).

Fig. 5. Distribution of the cases according to the severity score.

One of the very important aspects of this study has been represented by the highlight of the correlation between the severity score and the etiological agent of the disease. Table V shows that for the parainfluenza 3 virus and the measles virus have been encountered more severe forms of disease (52,63%, respectively 73,33%).

Table II. Distribution of the cases according to the etiological agent and environment.

Table V. Correlation between the severity score and the identified etiology.

Table IV. Correlation between the patientsâ&#x20AC;&#x2122; gender and the stated aetiology.

Fig. 2. Distribution of the cases according to the etiological agent and environment.

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We note that the VRS prelevance, of the influenza A and B viruses is significantly bigger with girls (1,4 -2,8 times bigger, p=0,044, 0<0,001), and of the parainfluenza 1 virus with boys (p=0,021) (fig.

There is a very tight correlation between the severity score and the number of days of hospitalization (see table VI). Therefore, the patients with subglottic obstructive acute laryngitis given by the infection with the parainfluenza 3 and measles viruses, which determined the severe forms of disease, have needed a significantly longer period of hospitalization

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(p<0,01).

Table VI. Correlation between the stated etiology and the number of hospitalization days.

From the analysis of the average number of hospitalization days, are to be noticed 4 groups: the first one includes VRS and adenovirus, the second the parainfluenza 1 and 2 viruses, the third one the influenza A and B viruses, and the forth one the parainfluenza 3 and measles viruses. Within the groups there is no significant difference regarding the average number of hospitalization days, while between the four groups there are significant differences (p=0,042 between groups 1 and 2, p=0,037, between the groups 2 and 3, p=0,024 between the groups 3 and 4 and p<0,01 between the groups 3 and 4) (fig. 6).

Fig. 6. The average value of the hospitalization days according to the etiological agent.

DISCUSSION

Because the incidence of the subglottic acute laryngitis is conditioned mainly by the season, the viral aetiology has been investigated only in the interspace 1st of October- 30 of April (autumnwinter- early spring) [7,15].

The aetiology identified for 79,54% of the cases, presents a structure that is only partially similar with the one presented in other published studies.

Still, we note that the high frequency of the infection with measles virus explains through the fact that, in February 2005, in Bihor County started a measles epidemic. According to the data published by the Public Health Authority of Bihor, the epidemics developed along the entire year, the descendent evolution taking place only in 2006, after the intervention in the foyers represented by the less accessible communities, with infant population that was not registered in the family doc-

tors’ lists and that was not vaccinated.

The predominance of the parainfluenza 3 virus represents an ascertainment applicable to other referential works [3,7].

The study performed by us indicated a predominance of the cases with origins in the rural environment, where certain conditions (agglomeration, housing, general and medical care) have made infants and children more vulnerable in front of the referential viral infections.

The ascertainment is correlated with the fact that the biggest number of unvaccinated children that were infected with measles was in the rural environment. It has been observed the predominance of the measles, influenza B and parainfluenza 3 type viruses, in the rural environment, compared to the urban environment. We found no observations in the professional literature that would study the two origin environments in comparison, our work being a premiere in this respect.

As other authors did, we signalized a maximum of incidence in the second year of life and an obvious predominance in the male gender [7, 15, 16].

We observed a predominance of the parainfluenza 3 and measles viruses for the age groups 19-24 months and 1318 months. Also, there has been registered a significantly bigger prevalence of the respiratory syncytial virus and of the influenza A and B viruses in the female gender, and of the parainfluenza 1 virus in the male gender.

The most severe forms of subglottic laryngitis have been determined by the parainfluenza 3 virus and especially by the measles virus. The ascertainment is inconsistent with one of the reports, where the most severe forms have been given by the influenza A virus [15].

The longest hospitalization was registered with the cases of laryngitis having as etiology the parainfluenza 3 and measles viruses that also generated the most alarming forms of disease.

CONCLUSIONS

1.

The viral aetiology has been analysed for 88 children with ages between 3-36 months, with subglottic obstructive acute laryngitis during 2 seasons (2004-2005 and 2005-2006), with the purpose to identify 8 serological confirmed viruses.

2.

The aetiology could be established for 70 cases (79,54%), most detected being the parainfluenza 3 (19 cases, 27, 14%) and measles (15 cases, 21,43%) viruses, and less identified were the influenza B and A viruses (3 cases, 4,29%, respectively 4 cases, 5,71%).

3.

The most severe forms, that implied the biggest number of hospitalization days, have been determined by the parainfluenza 3 and measles viruses.

REFERENCES

1.

American Academy of Pediatrics, “Adenovirus Infections“ in : Pickering LK, ed. RedBook: 2003 Report of the Committee on Infections Diseases.

26th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2003, p. 190-192;

2.

American Academy of Pediatrics, “Influenza“ in : Pickering LK, ed. RedBook: 2003 Report of the Committee on Infections Diseases. 26th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2003, p. 82-391;

3.

American Academy of Pediatrics, “Parainfluenza Viral Infections“ in : Pickering LK, ed. RedBook: 2003 Report of the Committee on Infections Diseases. 26th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2003, p.

454-455;

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American Academy of Pediatrics, “Respiratory Syncytial Virus“ in : Pickering LK, ed. RedBook: 2003 Report of the Committee on Infections Diseases. 26th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2003, p.

523-529;

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Cherry JD, „Adenoviruses” in McMillan JA, Feigin RD, DeAngelis C, Jones MD (Ed), Oski’s Pediatrics, Lippincott Williams and Wilkins, Philadelphia, 2006, p. 1210 - 1213

6.

Cherry JD, „Influenza Viruses” in McMillan JA, Feigin RD, DeAngelis C, Jones MD, (Ed), Oski’s Pediatrics, Lippincott Williams and Wilkins, Philadelphia, 2006, p. 1213 - 1216

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Hall CB, „Parainfluenza Viruses” in McMillan JA, Feigin RD, DeAngelis C, Jones MD, (Ed), Oski’s Pediatrics, Lippincott Williams and Wilkins, Philadelphia, 2006, p. 1216

8.

Hall CB, „Respiratory Syncyitial Viruses” in McMillan JA, Feigin RD, DeAngelis C, Jones MD, (Eds.), Oski’s Pediatrics, Lippincott Williams and Wilkins, Philadelphia, 2006, p. 1225-1230

9.

Cazacu AC, Demmler GJ, “Measles” in McMillan JA, Feigin RD, DeAngelis C, Jones MD. (Ed), Oski’s Pediatrics, Lippincott Williams and Wilkins, Philadelphia, 2006, p. 1275 - 1279

10.

Mason WH, “Measles” in Kliegman RM, Behrman RE, Jenson HB, Stanton BF, (Ed), Nelson Textbook of Pediatrics, Saunders, Philadelphia, 2007, p.1331 – 1337

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Wright P, “Influenza Viruses” in Kliegman RM, Behrman RE, Jenson HB, Stanton BF, (Ed), Nelson Textbook of Pediatrics, Saunders, Philadelphia, 2007, p.1384 – 1387

12.

Wright P, “Parainfluenza Viruses” in Kliegman RM, Behrman RE, Jenson HB, Stanton BF, (Ed), Nelson Textbook of Pediatrics, Saunders, Philadelphia, 2007, p.1387 – 1388

13.

MacIntosh K, “Respiratory Syncyitial Viruses” in Kliegman RM, Behrman RE, Jenson HB, Stanton BF, (Ed), 18 / volume 1, no. 1 / November 2009

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Nelson Textbook of Pediatrics, Saunders, Philadelphia, 2007, p.1388 - 1391

14.

MacIntosh K, “Adenoviruses” in Kliegman RM, Behrman RE, Jenson HB, Stanton BF, (Ed), Nelson Textbook of Pediatrics, Saunders, Philadelphia, 2007, p.1393 - 1395

15.

Roosvelt GE, “Croup,

Epiglottitis, Laryngitis, Bacterial Tracheitis” in Kliegman RM, Behrman RE, Jenson HB, Stanton BF, (Ed), Nelson Textbook of Pediatrics, Saunders, Philadelphia, 2007, p.1762 - 1766

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Nanulescu MV, Man S, Predescu D, Iordachescu M, “Infectiile respiratorii acute la copil – Ghid de diag-

nostic si tratament“, Tipografia Universitatii de Medicina si Farmacie “Iuliu Hatieganu” Cluj-Napoca, 2005, p. 21 – 33

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Wald RE, „Croup” in McMillan JA, Feigin RD, DeAngelis C, Jones MD (Eds.), Oski’s Pediatrics, Lippincott Williams and Wilkins, Philadelphia, 2006, p. 1505-1508.

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Oradea Medical Journal

ORTHODONTIC TREATMENT BETWEEN ABANDONMENT AND SUCCESS Vaida Ligia 1, Berechet Diana

2

1. University of Oradea, Faculty of Medicine and Pharmacy 2. Private Practice

ABSTRACT

Introduction. The research studies the main factors that lead to the appearance of total or partial abandonment in orthodontic treatment, along with the importance and value of these factors in determining the abandonment, taking into consideration the necessary period of time.

Material and method. The sample of subjects is composed by 289 patients that requested orthodontic treatment during 2002-2005, the age average = 12.31, the standard deviation = 2.99, the gender ratio: 41.46% boys and 58.54% girls, where 185 patients had removable orthodontic appliances and 104 had fixed orthodontic appliances. The analysis of the abandonment was made according to the step of the treatment, external and internal factors, and type of the orthodontic appliance – removable or fixed.

Results. From 185 (63.13%) patients with removable orthodontic appliances 63 (34.16%) represented total abandonment and 14 (8.69%) represented partial abandonment.

From 104 (36.87%) patients with fixed orthodontic appliances, 13 (12.76%) represented partial abandonment (there where not included the non-compliant patients), only 3 (3.19%) cases represented total abandonment (2 for obvious reasons – establishing in another country).

Conclusions. The identification of the factors involved in the appearance of abandonment and taking measures to increase the patients’ adherence to the orthodontic treatment should lead to favourable results in decreasing the abandonment rate.

Key words: removable and fixed orthodontic appliances, partial abandonment, total abandonment

INTRODUCTION

The orthodontic treatment takes a long time, which comes against patient’s motivation to gain a clinical amelioration as quick as possible.

Thus, after the first signs of dental-maxillary anomaly amelioration on one arch (especially the superior one) some patients are satisfied and they reject the rest of the steps of the treatment. Sometimes patients refuse to wear their retainer after the apparent amelioration and their motivation to comply with the orthodontic treatment disappears.

Patients may adjust differently to the functional and social discomfort determined by the orthodontic treatment, according to several researches5; there may appear various complains, such as: talking difficulties, swallowing problems, oral tension and soreness, unpleasant sensitivity, negative tension on the oral tissues, lack of confidence when socializing. These complaints are much more significant during the first days of the treatment and fade to disappear after the fifth day. According to patient’s attitude toward the treatment, the intensity of these problems vary: a strong motivated patient will hold up to any discomfort while those insufficiently motivated will dissent a lot each treatment phase. The patients from the last category will easily abandon the treatment, due to the somatic effect that comes about.

The somatic effect represents a nonverbal kind of communication of the psycho-social distress, a type of adjustment to life’s attempts and anguish. The somatic effect may express a physiological hyperactivity, a symptom of depression or anxiety, or an unaware psychological ac-

tivity, or a well-learned social behaviour, for example: a child may copy the symptoms from his or her family, particularly in brothers or sisters when their behaviour draws attention to themselves or they may even run away from their responsibilities2. In orthodontic patients’ case the somatic effect appears as complaint like: “the orthodontic appliance causes me soreness in gums, toothaches, headaches and soreness while eating”, without any biological reason. These types of somatic effects may be prevented by warning the patient’s parents or relatives that in case a possible discomfort persists more than five days, an appointment should be set immediately.

Another reason for abandonment is residence changing. Relocating to another country leads to losing contact with the current practitioner and not referring to another one in order to continue the treatment.

Patients living in other towns or villages that don’t have an orthodontist belong to a special category. Patients come to appointment in long periods of time with unfavourable consequences.

The analysis of abandonment was taken according to the type of the orthodontic appliance – removable or fixed. The reject risk gets higher with removable appliances, depending on patients’ consciousness.

We consider total abandonment when patients with removable appliances fail to come to their appointments for more than 12 months.

In patients with fixed appliances, total abandonment appears when they miss their appointments for more than 12 months or when they request the removal of the appliance before the final stage of

the treatment.

Partial abandonment appears when the period between appointments is 3 to 12 months; we consider non-compliant patients the ones who disregard the schedule of their appointments.

This article analyses the main factors involved in the appearance of total or partial abandonment during orthodontic treatment, as well as the ratio of this factors in abandonment rate.

MATERIAL AND METHOD

The sample of subjects is composed by 289 patients who requested orthodontic treatment during 2002-2005, aged 7 to 18, age average = 12, 31, standard deviation = 2,99, gender report: 41,46% boys and 58,54% girls (fig.1); 185 patients had removable orthodontic appliances and 104 had fixed orthodontic appliances.

Fig. 1. Allocation of orthodontic patients according to gender.

In patients with removable appliances the analysis of total abandonment factors was completed according to each treatment stage:

- after the first week (just after the appliance was fixed)

- after the first signs of amelioration

- after the dental-maxillary anomaly improvement on one of the 20 / volume 1, no. 1 / November 2009

Oradea Medical Journal

arches

- at the end of the active treatment stage (not wearing the retainer) The main factors we have taken into consideration for being responsible for the partial abandonment in every patient’s case are:

- external factors: illnesses, transportation difficulties, after-school activities, psycho-social medium (family and peers’ support)

- internal factors: amelioration of aesthetics, intrinsic or extrinsic motivation to follow the orthodontic treatment, amelioration of self-esteem level

Total abandonment in patients with fixed appliances may appear when the patient requests the continuation of the treatment with another orthodontist which involves the abandonment of the orthodontist and not of the treatment; total abandonment may also appear due to objective reasons such as: moving to another part of the country where it is impossible to follow the treatment and therefore the patient demands the removal of the appliance before the final stage. Another factor involved in total abandonment is patient’s desire to remove the appliance at the first signs of amelioration before the final stage against the orthodontist’s advice regarding secondary effects that may appear if the treatment does not follow the entire stages.

RESULTS

From 289 orthodontic patients, 185 (63.13%) had removable appliances and 104 (36.87%) had fixed appliances. (fig.2)

Fig. 2. Allocation of orthodontic patients according to the type of the orthodontic appliance.

From 185 patients with removable appliances 63 patients (34.16%) represent total abandonment and 14 (8.69%) represent partial abandonment.(fig.3).

Fig. 3. Patients with removable appliances allocation according to abandonment type.

Regarding total abandonment according to the stages of the treatment, there were 10 patients that abandoned the treatment after the first week, 37 patients after the first signs of dental-maxillary 21 / volume 1, no. 2 / November 2009

anomaly amelioration, 6 patients after the amelioration on one of the arches and 10 patients that disregarded the retainer step at the end of the active treatment stage.

From 104 patients with fixed appliances, 13 cases (12.76%) represented partial abandonment (non-compliant patients were not included), only 3 cases (3.19%) represented total abandonment (2 for objective reasons – establishment in another country) (fig. 4).

Fig. 4. Patients with fixed appliances allocation according to the abandonment type.

DISCUSSION

CONCLUSIONS

The discontinuance of the treatment may have negative impact on the dental-maxillary system (periodontal, temporomandibular joint, malocclusion), especially in cases that required radical measures like extraction to allow the alignment of teeth on the arches.

It is necessary to warn patients before the beginning of the treatment that it takes a long time and it is mandatory to follow up all the stages in order to obtain a favourable and stable outcome.

There are researches6 demonstrating that the failure ratio (unfulfillment of all the objectives of the treatment) in compliant patients was 10.3% and in noncompliant ones was 21.4%.

Authors like Richardson A. and Trenouth M.J. & Hough highlight the major factor involved in abandoning patient’s is forgetting about his or her appointment; this sort of situation requires a mean of reminding or sensitizing the patient4.

In a randomized study3 that had 2500 orthodontic patients, the authors appeal to 3 different means of announcing the time of the next appointment: a phone call, a message on their machine or a post card. Using one of these 3 ways of noticing the patients did decrease the rate of missing the appointments, but none of these means was more efficient than the other one3.

Annemieke Bos at. Al1 in a similar research use 301 orthodontic patients divided into 3 lots, using emails for the 1st lot, phone calls for the 2nd lot and text messages for the 3rd one; there also was a control lot that did not beneficiated of any means of announcement. The results of the study showed that there wasn’t a statistically significant difference neither between the four lots of subjects nor between genders. The study also revealed patients’ favourite way of notice: the email.

Abandonment must be regarded as a failure of doctor-patient relation and

it is necessary to fully identify the main factors involved in its appearance, because in most cases patient’s feedback is nonexistent. Taking measures to increase patients’ adherence to the orthodontic treatment should lead to favourable results in decreasing the abandonment rate.

REFERENCES

1.

Bos A, Hoogstraten J, Failed appointments in an orthodontic clinic, American Journal of Orthodontics and Dentofacial Orthopedics, 2005; 3: 3557 2.

Miu N, Stiinţele comportamentului, Editura Medicală Universitară Iuliu Haţieganu”, Cluj-Napoca, 2004, p.129.

3.

Reekie D, Devlin H, Preventing failed appointments in general dental practice: a comparison of reminder methods, Br. Dent. J., 1998; 185: 472-4.

4.

Richardson A, Failed appointments in an academic orthodontic clinic, Br. Dent. J., 1998; 184: 612-520 .

5.

Sergl HG, Klages U, Trenouth MJ, Hough A, Reasons for broken and cancelled appointments in a British orthodontic clinic, J Clin Orthod., 1991; 15: 115-20.

6.

Zentner A, Functional and Social Discomfort During Orthodontic Treatment – Effects on Compliance and Prediction of Pacients’ Adaptation by Personality Variables, European Journal of Orthodontics, 22, 2000.

Oradea Medical Journal

THE CARBONIC ANHYDRASE I ACTIVITY IN HUMAN ERYTHTROCYTES IS AN INDICATOR FOR BLOOD PRESSURE VALUES Iacobescu Alina, Uniţa L., Puşcaş I., Popescu M., Magheru Sorina, Maghiar F University of Oradea, Faculty of Medicine and Pharmacy

ABSTRACT

Aim of the study: We know that carbonic anhydrase activators (CA) increase the arterial tension and his inhibitors decrease the arterial tension. Starting from this we have studied a possible correlation between arterial tension values and carbonic anhydrase activity.

Methods: We have made the measurements in vivo and ex vivo. We have included 3 groups, 200 patients each: group A, healthy volunteers, group B, patients with high blood pressure and group C with systolic blood pressure under 110 mmHg and diastolic blood pressure under 70 mmHg. We have measured the activity of CA in erythrocytes.

Results: In group A activity of CA was: 1.08 UE, of CA I 0.212 UE and CA II 0.866 UE. In group B: CA activity 1.88UE, CA I 0.601 UE and CA II 1.281 UE. In group C the activity of CA has been: 0.748 UE, CA I 0.077UE and CA II 0.671UE. In ex vivo CA activity has been increased in group A by betaadrenergic agonists. In group B the activity of CA has been less then 50% of that of group A; and in group C was 25% more than in group A. In group A, as in the group B the activity of CA from human erythrocytes was decreased betaadrenergic antagonists. In group C the activity of CA was not significantly changed by these substances.

Conclusions: CA is implicated in modulating vascular tonus by adrenergic agonists and antagonists. CA I activity is increased on patients with high arterial tension and decreased at patients with low arterial tension. There is a good correlation between CA I activity and arterial tension and the activity of CA I reflect the changes in vascular tonus. This correlation suggests a strong implication of CA in arterial tension changes and pathogenesis of high arterial tension.

Key words: carbonic anhydrase, arterial tension, erythrocytes, adrenergic agonists

INTRODUCTION

It has been proved that alpha and beta antagonists are strong activators of the carbonic anhydrase (CA), and their antagonists are CA inhibitors, antagonising the activating effects of the antagonists on the CA. (1, 2) Starting from the premise that the CA I activators increase the blood pressure value (BP), and the isoenzyme inhibitors lower it (3,4), we have studied the existence of a possible correlation between the BP values and the CA I activity. In this view, we have performed a study on a relatively high number of patients with high blood pressure, and on volunteers with lower than normal blood pressure values and on volunteers with normal blood pressure values.

MATERIAL AND METHOD

The research has been performed in vivo and in ex vivo. We included 3 batches of patients, as follows: batch A, 200 healthy volunteers, with systolic and diastolic normal BP values; batch B, 200 patients in our evidence for at least 5 years for moderate or severe arterial hypertension, that is with systolic BP values between 160 and 200 mmHg and diastolic BP values between 100 and 120 mmHg, in our evidence for at least 5 years. These patients have been incompliant when administering the hypertensive medication, they have been prescribed a new hypertensive treatment, but before starting the treatment again, they have been drawn blood for this study, with their consent. In batch C, were included 200 patients with sys-

tolic BP values below 110 mmHg BP and diastolic BP values below 70 mmHg. To al these patients we have determined the AT values in standard conditions and the CA activity in erythrocytes.

The differentiation of the CA I activity form the CA II has been made through the nicotinate method described

by Puşcaş et al.(4) In ex vivo, for each blood test, in order to determinate the CA I activity, we have also associated adrenergic beta agents: adrenaline, noradrenalin, isoprenaline as well as adrenergic beta antagonists: atenolol, propranolol and timolol, in 10-6 M concentrations.

The CA activity was determined through the stopped flow method. (1) The CA activity is measured in UE where 1 U.E represents the quantity of enzyme doubling the hydration or dehydration of CO2 reaction speed.

The study was conducted according to the statement for human rights: “World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects”, JAMA 2000, Dec 20, 284 (23):3043-5.

RESULTS

At the patients in batch B, the CA I activity values are 3 times higher than at those in the following batch, and at those with low BP values are 3 times lower compared to the values in the following batch. For the CA II activity, this is not that well-marked; the values in batch C being at the level of 75% of the activity of the following batch, and in the batch with the hypertensive patients the values are 50%

higher than in the following batch, as is illustrated in image 1.

Fig. 1. Values of the CA activity in erythrocytes for the healthy, hypertensive and hypotensive volunteers batches.

The results obtained at batch A, with normal BP values, show that the CA I activity represents a percentage of 21% of the CA activity, which is of 1.08 UE/ml.

The CA I activity at the hypertensive patients is of 0.6, that is 3 times the value of the following batch. It can be noticed also an increase of the CA I total activity in erythrocytes up to 1.88 UE/ml, 1.7 times higher than the value in the following batch. The increase of the CA activity at the patients in batch B has been predominantly produced by the increase of the CA I activity.

In batch C, with low BP values, the CA I activity is 0.07, 3 times lower than the average value in the following batch and 8 times lower than the CA I activity in the hypertensive patients batch. The total CA activity at the volunteers in this batch is of 0.75, being 1.44 times lower than in the following batch and 2.5 times lower than in the hypertensive patients batch.

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Oradea Medical Journal

The lowering of the CA activity has been produced in this case by the low CA I activity at the patients with low BP.

In ex vivo the CA activity in erythrocytes increases in the following batch, with 50% in the presence of adrenaline, with 40% in the presence of noradrenalin and with 23% in the presence of isoprenaline. In batch B, the increase of the CA activity in erythrocytes is slightly less of the half of the activity of the following batch and in the hypotensive patients batch the increase of the CA activity is with approximately 25% higher than in the following batch, in the presence of the same substances, as is illustrated in image 2.

Fig. 2 . AC activating erythrocytes through the alpha and beta adrenergic agonists.

The CA activity in erythrocytes lowers with 34% in the presence of propanolol, with 24% in the presence of timolol and with 26% in the presence of atenolol.

In the presence of the same betablockers, the CA I activity in the hypertensive patientsâ&#x20AC;&#x2122; erythrocytes lowers with 42% in the presence of propanolol, 31% in the presence of timolol and 34% in the presence of atenolol, and at the patients with low AT values the CA activity lowers much less significantly, in the presence of the same substances, as is illustrated in image number 3.

Fig. 3. CA inhibition in erythrocytes through alpha and beta adrenergic antagonists.

DISCUSSIONS

In the batch of the arterial hypertension patients, the substances having a vasodilator effect, the anti-adrenergics, lower the CA I activity with more than 3 times stronger than in the loer than normal blood pressure batch. These data prove the existence of some endogenous activators of the catecholamine type, which maintain the CA I activity of the high blood pressure patients at maximum values, in contrast with the healthy volunteers.

Based on the same principle, due to the insignificant reduction of the CA I activity by the anti-adrenergics to the volunteers 23 / volume 1, no. 2 / November 2009

with low BP values, we can assume that there are substances maintaining the CA I activity at low values, slightly sensitive to the additional effect of the betablockers.

The results prove that the CA I activity is significantly modified in the batch of the hypertensive patients and of the volunteers with low BP values, in comparison with the witness batch, being higher at the hypertensive patients and lower at those with low arterial tension values. Due to the fact that our data show that the CA I activity faithfully correlates with the BP values, we appreciate that the activity of this isoenzyme faithfully reflects the changes of the vascular tonus. The existence of the correlation between the CA I activity and the AT values suggests the implication of the CA in the arterial tension changes and the hypertension pathogenesis, as well as the implication of the enzyme inhibitors or activators in the hypertension or arterial hypotension therapy.

CONCLUSIONS

1.

CA is involved in modulating the vascular tonus regulated by the adrenergic agonists and antagonists.

2.

The CA I activity is higher at the hypertensive patients and lower at those with low blood pressure values.

3.

CA I faithfully correlates with the BP values, this isoenzymeâ&#x20AC;&#x2122;s activity faithfully reflects the changes of

the vascular tonus.

4.

The existence of the correlation between the CA I activity and the BP values suggests the implication of the CA in the arterial tension changes and the hypertension pathogenesis.

REFERENCES

1.

Puscas I & Supuran CT (1995). Carbonic anhydrase, a modulator of the physiological and pathological processes in the organism: The theory of pH. The 4th International Conference on the Carbonic Anhydrases. Oxford, England, July 26-30, 1995, 172-9

2.

Puscas I, Pasca R, Lazoc L & Kun C (1994). Effects of alpha- and beta-adrenergic agonists and antagonists on carbonic anhydrase. In: Puscas I (Editor), Carbonic Anhydrase and Modulation of Physiologic and Pathologic Processes in the Organism. Helicon Publisher House, Timisoara, Romania, 260-268.

3.

Puscas I, Coltau M, Baican M, Domuta G & Hecht A (1999). Vasodilatory effect of diuretics is dependent on inhibition of vascular smooth muscle carbonic anhydrase by a direct mechanism of action. Drugs under Experimental and Clinical Research, XXV:271-279.

4.

Puscas I, Coltau M & Domuta G (1999). Rapid method for differentiation of carbonic anhydrase I from carbonic anhydrase II activity. Analytical Letters, 32: 915-924.

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THE GASTRIC ULCER PRODUCED BY INDOMETHACIN ASSOCIATED WITH HISTAMINE MAY BE CAUSED BY CARBONIC ANHYDRASE II ACTIVITY IN GASTRIC MUCOSA Uniţa L., Iacobescu Alina, Puşcaş I., Straciuc O., Rahota Daniela, Uivarosan Diana, Lerintiu Antonia University of Oradea, Faculty of Medicine and Pharmacy

ABSTRACT

Aim of study is to follow the effect of histamine and indomethacin and of histamine – calcium - indomethacin association by in vivo and in vitro studies and to find a reasonable explication for the gastric ulcer produced by association of indomethacin and histamine.

Methods: in vitro we have followed the effect of indomethacin alone, histamine alone and the triple association histamine - indomethacin - calcium on carbonic anhydrase I (CA I) and CA II. In vivo we have monitored 24 healthy volunteers which we have divided in 2 groups, 12 volunteers each: group 1 has received systemic indomethacin 5mg/kg/24h, and group 2 has received the same dose of indomethacin associated with histamine one single dose 0.04 mg/kg. We have determined the activity of CA from erythrocytes and gastric mucosa before and after treatment. Activity of CA has been determined by stopped flow method.

Results: In vitro: indomethacin activates CA and CA II after a dose – effect curve. The maximum effect has been obtained at 10-3 M concentrations. The association of indomethacin and histamine amplify the activator effect of those on CA II but doesn’t change the effect of indomethacin on CA I. In vivo, in group 1, indomethacin increases the CA activity in erythrocytes by 93% and in gastric mucosa by 61%. In group 2 the indomethacin histamines association increase the CA activity in erythrocytes by 196% and in gastric mucosa by 140%.

Conclusions: Indomethacin has and activator effect on CA I and CA II. The association of indomethacin and histamine double or triple the activator effect of the last on CA II but doesn’t change its effect on CA I. The gastric ulcer produced by association of indomethacin and histamine may be produced by strong activation of CA II which leads to low pH, inhibition of cyclooxygenase and low prostaglandins production. Our results lead to conclusion that CA may be a modulator of secretors processes and vascular circulation in gastric mucosa and may be implied in ulcerogenesis.

Key words: carbonic anhydrase, gastric ulcer, indomethacin, histamine.

INTRODUCTION

The research performed in the USA shows that, in the present, 4 million Americans suffer from chronic peptic ulcer disease [1] out of which at least 20% are produced by non-steroidal anti-inflammatory drugs (AINS) [2]. The same study shows that AINS are associated with a five times increase of the risk of chronic gastric ulceration. The risk of gastric ulcer complications is 3 times increased by the use of non-steroidal drugs. On the world level, more than 30 million patients use daily anti-inflammatory drugs.

Previous research shows that the intravenous infusion of AINS or the histamine association when administering intravenous AINS to cats augments the gastric ulceration. It has been proved also that the ulcer incidence and severity has increased together with the increase of the AINS dosage, as well as the duration of its administration. [4,5] The ulcerogenic action of AINS on the stomach is amplified by the exposure of the gastric mucosa to acid solutions. The amplification of the gastric mucosa lesions produced by this association is tightly connected to the prostaglandin synthesis.

Therefore, the simple instillation of acid solution in the stomach, without AINS, significantly reduces the PGE2 production. [6] The mechanism of ulcer produced

by AINS, as well as that of their associa-

tion with histamine and with acid solutions administered per os is not completely elucidated.

The aim of this paper is to follow the histamine and indomethacin effect on the carbonic anhydrase (CA), as well as of the association of indomethacin with histamine through in vitro and in vivo studies; possible explanations regarding the increased ulcerogenic effect produced by: the association of histamine to indomethacin, the intra-gastric acid instillation with or without indomethacin association.

MATERIALS AND METHODS

In vitro: We have followed the effect on purified CA I and CA II produced by the indomethacin and histamine. Also, we have followed the effect on CA I and CA II produced by the indomethacin-histamine-calcium association. The determinations have been made for concentrations varying between l0-8M and 10-3M taking into account the dosage reaction relation.

In vivo: 24 subjects were chosen and divided into two equal groups, each group containing 12 healthy male volunteers, between 21-50 years old, weighing between 60-80 kg who received the following daily treatment for three days: group 1 received intra muscularly 5 mg/kgbody/day indomethacin; group 2 received intra muscularly 5 mg/kgbody/day indomethacin and histamine subcutaneous in a single

dosage of 0.04 mg/kg body.

We determined the CA activity in erythrocytes and the parietal cells in the gastric mucosa before and after the treatment. The CA activity was determined following the stopped-flow method [1].

CA I and CA II: Sigma (Deisenhofen, Germany); histamine: Serva Feinbiochemica (Heidelberg, Germany); indomethacin and histamine phials 1 mg: SICOMED (Bucharest, Romania).

The study was conducted according to the statement for human rights: “World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects”, JAMA 2000, Dec 20, 284 (23):3043-5.

RESULTS

In vitro: The indomethacin activates CA I and CA II following the dosagereaction relation. The maximum activator effect is obtained for concentrations of 10-3 M, the results being presented in Table 1.

The association of histamine with calcium to indomethacin amplifies their activator effect on CA II and does not modify the activator effect of indomethacin on CA I, as it can be seen in table I.

In vivo: For group 1 – the administration of indomethacin increases the CA activity in erythrocytes with 93% and in the gastric mucosa with 61% as compared to the basic values (fig. 1).

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Oradea Medical Journal

Table I. The effect on CA I and CA II of Histamine and Calcium association to Indomethacin Legend: IMG - Indomethacin; H - Histamine; Ca - Calcium

Fig. 1. The activator effect of Indomethacin on the CA in erythrocytes and gastric mucosa (Batch 1).

For group 2, the association of histamine to indomethacin increases the basic CA activity in erythrocytes with 196%, and that in the gastric mucosa with 140% (fig. 2).

Fig. 2. The activator effect of IndomethacinHistamine association on the CA in erythrocytes and gastric mucosa (Batch 2).

DISCUSSIONS

The indomethacin activates the two CA’s isoenzymes involved in the vascular processes (CA I) and in the secretor processes (CA II). The association of histamine and calcium to indomethacin in the in vitro experiments double or triple the CA II activity, unlike CA I which is not activated either by histamine or by their association. The in vivo association of histamine to indomethacin double the activator effect of it on the CA I in erythrocytes and gastric mucosa. Calcium was not administered in vivo, its endogenous presence being sufficient to amplify the activator effect of histamine and indomethacin on CA. The strong activation of CA II (an enzyme having a role in the gastric secretion), after the association of histamine to the non-steroidal inflammatory drugs, constitutes a source of increase of the acid secretion values, beyond the values obtained by their separate administration.

The indomethacin activates CA I present in the gastric mucosa capillaries with the reduction of the gastric mucosa microcirculation. The amplification of the secretor effect produced by the association of histamines through CA II, with the lowering of the gastric microcirculation produced by indomethacin (through CA I) could 25 / volume 1, no. 2 / November 2009

explain the increased ulcerogenic effect produced by this association. The strong activation of the CA produced by the association of histamine and indomethacin is followed by a lowering of Ph, favours the occupation of the active site of the cyclooxigenase by indomethacin with the inhibition of cyclooxiganase and the lowering of the prostaglandin synthesis. The intragastric acid instillation is also followed by the lowering of the PG synthesis, as it has been proved by other authors, without being able to find an explanation of this phenomenon [5]. The results of this study suggest that the intra-gastric instillation with acid lowers the cell pH in a similar manner to the CA activation. This low pH will lower the cyclooxigenase activity, having as a consequence the lowering of the PG production. The hypothesis resulted is supported also by the relation existing between the gastric acidity values and of the prostaglandin concentration [1,2].

CONCLUSIONS

1.

The indomethacin activates CA I and CA II.

2.

The association of histamine to indomethacin doubles or triples their effect on CA II but, in the same time, does not modify the CA I activity, an enzyme activated by this non-steroidal antiinflammatory drug.

3.

The increase of the ulcerogenic effect of the association of indomethacin with histamine, as well as of the intra-gastric acid instillation could be produced through the strong activation of CA II with the lowering of pH and the consecutive inhibition of the cyclooxigenase followed by the lowering of the PG synthesis.

4.

The results lead to the conclusion that CA could be a modulator pf the secretor and vascular processes in the gastric mucosa with implications in ulcer genesis.

REFERENCES

1.

Puscas I: Carbonic Anhydrase. In: New Pharmacology of Ulcer Diseases ed. Elsevier, 1987; 164-179.

2.

Puscas I: The Role of Carbonic Anhydrase in Gastric Acid Secretion Carbonic Anhydrase Activators and Inhibitiors, In: Progress in the Pathophysiol and Treatment of Gastric and Duodenal Ulcers. (I. Puşcaş, Buzas G, eds.), Romania Acad. Publishing, 1990; 43-75.

3.

Puscas I et al.: Farmacologia Clinica do Aparelho Digestive. In: Aparelho Digestivo Clinica e Chirurgia (Julio Coelho ed.), MEDSI, Rio de Janeiro, 1990; II 1371-1385.

4.

Puscas I, Buzas G, Treatment of Duodenal Ulcers with Ethoxzolamide, an Inhibitor of Gastric Mucosa Carbonic Anhydrase. Inter. J. Clin.

Pharmacol. Ther. Toxicol., 1986; 24; 2:9799.

5.

STRYER: „Biochem-

istry” 3rd Edition, Freeman, New York, 1985, 975-1004;

6.

Dohlman HG, Caron MG, Lefkowitz RJ, Biochemistry, 1987, 2660-8.

Oradea Medical Journal

PREVENTION AND MANAGEMENT OF INFECTIONS AFTER SPLENECTOMY Iova Camelia University of Oradea, Faculty of Medicine and Pharmacy

ABSTRACT Splenectomy performed at any age and for any reason, increases the risk of overwhelming infection, particularly involving encapsulated bacteria: Streptococcus pneumonia and Haemophilus influenza. Risk of infection is related to age, the underlying reason for splenectomy and the elapsed time since the procedure.

The risk is higher in children, in patients splenectomized for hematologic diseases (especially malignant) and in those who have another cause for immunosuppression, such as corticosteroids or cytotoxic drugs administration.

Preventive strategies are very important and fall into three major categories: immunoprophylaxis, antibiotic prophylaxis and education.

This article’s aim is to evaluate definition, etiology, incidence, risk factors and prophylaxis of overwhelming postsplenectomy infection.

Key words: Splenectomy, overwhelming infection, prophylaxis.

INTRODUCTION

The fact that spleen is not essential to life has been known for centuries, but it represents about a quarter of the body’s lymphoid tissue, being responsible, among other functions, for filtering encapsulated organisms from the blood.

Surgical removal of the spleen results in reduced clearance of particulate antigens, either extracellular (bacteria) or intracellular (malaria), impaired phagocytosis of unopsonized and opsonized bacteria and cells, diminished response to new antigens, particularly polysaccharides and decreased levels of tuftsin and properdin.

Therefore, splenectomy may be followed by severe systemic infection, involving the encapsulated bacteria. Overwhelming postsplenectomy infection is uncommon, but has high mortality. [1,2]

History

A correlation between sepsis and splenectomy was first made in 1891, when Bardach showed an increased index of infection in splenectomized patients. In 1919, Morris and Bullock performed experimental studies on rats, proving that splenectomy can cause a higher susceptibility to infection and asplenic patients are not capable of controlling bacterian sepsis.

[3] The first case of postsplenectomy infection was reported by O’Donnel in 1929. It was not until 1952 that attention focussed on the subject, when King and Shumacher reported five cases of severe infection in infants who had undergone splenectomy for spherocytosis, two of them being fatal.

[4]

Singer defined postsplenectomy sepsis (PSS) as septicemia, meningitis or pneumonia that is usually fulminant and occurs days to years after removal of the spleen. In 1973, he showed that the risk of PPS is much higher than it was known before. [5]

Incidence

The true incidence of severe in-

fections after splenectomy is not known, but the estimated incidence rate is 0,180,42% per year, with a lifetime risk of 5%. Bisharat et all reviewed all 78 studies published between 1966 and 1996, observing that of 19680 patients who had had a splenectomy, 3,2% developed invasive infection and the overall mortality was 1,4%.

The mean interval between splenectomy and infection was 22,6 months.

Risk of infection is related to age, the underlying reason for splenectomy and the elapsed time since the procedure.

The risk is higher in children, in patients splenectomized for hematologic diseases (especially malignant) and in those who have another cause for immunosuppression, such as corticosteroids or cytotoxic drugs. [6,7,9]

The youngest patients appear the most susceptible, especially those under two years and during the first year after splenectomy, but cases of fulminant infection have been reported more than 20 years after splenectomy. This shows that postsplenectomy patients carry a lifelong risk. In one meta-analysis, Holdsworth, Irving and Cuschieri (1991) reported that the incidence and mortality of sepsis in splenectomized adults are 0,9% and 0,8% respectively, while in children under 16 years they rise to 4,25% and 2,2% respectively. [8]

The risk of severe infection can also be stratified by underlying condition. The lowest risk is related to trauma, intermediate to spherocytosis, idiopathic thrombocytopenic purpura or portal hypertension, and highest risk in thallassaemia and Hodgkin’s disease.

An infection can occur a few days after the removal of the spleen, or various years after, but the risk of infection appears to be highest in the first 2 years after the procedure (50-70% of all cases). [1,2,9]

Epidemiology

The absence of spleen leads to deficiencies of the immune system, such as impaired phagocytosis, impaired clear-

ance of sanguine particles, especially unopsonized bacteria, reduction of serum Ig M, decreased activity of the complement by the alternative way, decreased levels of macrophage activating substances as tuftsin and properdin.

Streptococcus pneumoniae is the commonest infecting organism involved in postsplenectomy sepsis, accounting for 50-90% of isolates from blood cultures.

Haemophilus influenzae type b is the second more frequent organism in the era before the Hib conjugate vaccine, followed by Neisseria meningitidis. Capnocytophagia canimorsus is a gram negative rod and part of the normal flora of dogs and cats; this bacillus can cause fulminant sepsis (purpura fulminans) following dog or cat bites or scratches.

Salmonella species have also been associated with severe postsplenectomy infections, being a prominent pathogen in children with sickle cell anemia and splenic dysfunction .

Other pathogens in such infections include Escherichia coli and other coliforms, Pseudomonas aeruginosa, Streptococcus group B, Staphylococcus aureus. Asplenic patients appear to be more susceptible to serious infections with protozoa: Babesia microti in North America and Babesia bovis in Europe. Compared to normal individuals, asplenic patients living in malaria-endemic areas are more often parasitemic and have delayed clearance of parasites after treatment. [10,12,13]

Treatment and prophylaxis

Preventive strategies against postsplenectomy sepsis are very important and fall into three major categories: immunoprophylaxis, antibiotic prophylaxis and education.

Immunoprophylaxis

Pneumococal vaccine Because of the preeminent role of pneumococcal infection in overwhelming postsplenectomy infection, all patients undergoing this procedure should receive 26 / volume 1, no. 1 / November 2009

Oradea Medical Journal

immunization with the 23-valent capsular polysaccharide vaccine. Vaccine should be administered at least two weeks before the surgery in order to ensure an optimal antibody response. After emergency splenectomy, patients should be immunized soon after surgical recovery or at time of discharge. In case of prior immunosuppressive chemotherapy or radiotherapy, vaccination must be delayed at least six months and prophylactic antibiotics should be administered in this period.

There is no consensus on the revaccination policy in asplenic patients, but the reimmunisation of asplenic patients is currently recommended every 5-10 years.

In case of lymphoproliferative disorders or sickle cell anaemia, revaccination may be required as early as 3 years after the first dose.

Recently, a 7-valent pneumococcal protein conjugate vaccine became available. This vaccine is more immunogenic and does not require a booster dose.

Haemophilus influenzae type b immunization (Hib vaccine)

Although the efficacy of vaccination against Haemophilus influenzae type b in preventing postsplenectomy sepsis is unclear, the Hib immunization seems to be immunogenic in asplenic individuals.

Meningococcal vaccine

Meningococcal immunization is not routinely recommended for asplenic patients because of the short duration of protection and the absence of protection against the most common serogroup B, except those travelling to areas where there is an increased risk of group A infection, such as sub-Saharan regions.

Influenza vaccine

Annual administration of this vaccine is recommended because it reduces the risk of secondary infections with encapsulated bacteria.

Antibiotic prophylaxis

Antibiotic prophylaxis against pneumococcal infection in asplenic patients, especially children, in the first two years after the procedure seems to play an important role in prevention of overwhelming postsplenectomy infection.

Some guidelines advise prophylactic antibiotics for the first 3-5 years after splenectomy, but many data indicate that the risk does not decline with time. A daily dose of oral penicillin or amoxicillin is preferred.

Gaston et al reported an 84% reduction in pneumococcal bacteraemia in children with sickle cell anaemia who were administered oral penicillin prophylaxis.

Whether long term antibiotic prophylaxis in children is still necessary after the introduction of the pneumococcal vaccine has to be investigated. However, long term antibiotics can lead to selection of resistant strains.

Stand byâ&#x20AC;&#x2122; antibiotics are indicat27 / volume 1, no. 2 / November 2009

ed at the first sign of infection (increase in body temperature, malaise or shivering).

Patient education

Patient education is very important in preventing overwhelming postsplenectomy infection. Patient must be informed on the risk for serious infection, so they can search medical support at the first sign or symptom compatible with infection. Also, they must know about the increased risk for travel related infections, such as babesiosis. Several investigators encourage patients to wear a medical alert bracelet and to carry a card documenting immunization. Also patients must be advised to inform any new healthcare professionals, including dentists, of their asplenic status. [12,13,14]

Treatment of postsplenectomy sepsis

PSS is a medical emergency requiring early recognition and aggressive management. All splenectomized patients with fever of unknown origin must receive large spectrum antibiotics, in high doses, active against encapsulated bacteria. Blood cultures must be taken and a peripheral blood or buffy coat film should be examined immediately, for the presence of circulating or intraleukocytic bacteria.

Blood cultures are positive in 95% of cases of PSS, so antibiotics can be modified once the cultures are available. Intravenous immunoglobulin can also be efficient in this patients.([12,13,14]

Autotransplantation and splenic conservation

Multiple human and animal studies have established that splenic autotransplantation is a relatively safe and easily performed procedure, that results in the return of some hematologic and immunologic parameters to baseline levels. Some aspects of reticuloendothelial function are also preserved. Whether this translates into a real reduction of morbidity or mortality rates from overwhelming bacterial infection requires further investigation. [15]

REFERENCES

1.

Davies JM. The prevention and treatment of infection in patients with an absent or dysfunctional spleen.

Updated guideline. British Committee for Standards in Haematology. Br Med J 2001;312:430-4

2.

Davidson RN, Wall RA. Prevention and management of infections in patients without a spleen. Clinical Microbiology and Infection, vol 7, no 12, 2001:657-660

3.

Morris DH, Bullock FD. The importance of spleen in resistance to infection Ann Surg 1919;70:513-521

4.

King H, Schumacher HB jr. Splenic studies. Susceptibility to infection after splenectomy performed in

infancy. Ann Surg 1952;136:239-42

5.

Singer DB. Postsplenectomy sepsis. Perspective Paediatr Pathol 1973;1:285-311

6.

Diamond LK. Splenectomy in childhood and the hazard of overwhelming infection. Pediatrics 1969;43:886-9

7.

Schwarts PE, Sterioff S, Much P. Postsplenectomy sepsis and mortality in adults JAMA 1982;248:2279-83

8.

Holdsworth RJ, Irving AD, Cuschieri A. Postsplenectomy sepsis and its mortality rate: actual versus perceived risks. Br J Surg 1991;78:1031-8

9.

Lortan JE. Management of asplenic patients. Br J Haematol 1993;84:566-9 1 0.

Styrt B. Infection associated with asplenia: Risks, mechanism and prevention. Am J Med 1990;88:33-42

11.

Finch RG, Read R. Long term management after splenectomy. BMJ 1994;308:132

12.

Finch RG, Read R. Prophylaxis after splenectomy. J Antimicrob Chemother 1994;33:4-6

13.

Newland A. Preventing severe infection after splenectomy. BMJ 2005;331:417-18

14.

Mc Mullin M, Johnston G. Long term management of patients after splenectomy.BMJ 1993;307:1372-3

15.

Pisters WT, Patcher L. Autologous Splenic Transplantation for Splenic Trauma. Ann Surg 1994;219:225235.

Oradea Medical Journal

28 / volume 1, no. 1 / November 2009

Oradea Medical Journal

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Oradea Medical Journal

BLOOD SERUM C-TELOPEPTID OF TYPE I COLLAGEN IN PATIENTS WITH OSTEOPOROSIS AND HIP OSTEOARTHRITIS Pascalau Nicoleta, Mihailov Mariana, Lazar L., Cioara Felicia, Farcas Daniela University of Oradea, Faculty of Medicine and Pharmacy

ABSTRACT

One of the reasons for determining the byological markers is that they can be determined with the help of patients with high risk of rapid progression of arthritis. A number of 63 patients aged between 30 to 70 with hip ostheoarthritis and osteoporosis, outpatients and inpatients in Rehabilitation Hospital Felix Spa, were taken into consideration for this study.

Patients were divided in two groups: with rehabilitation treatment, with joint supplements (glucosamin and chondroitin) treatment, with associated treatment and with symptomatic treatment.

The results obtained after the rehabilitation and joint supplements (glucosamin and chondroitin) shows that a major influence on the two pathologycal entities had the age, the gender, the physiological status and the stage of the disease. So, the values of blood serum C-telopeptid of type I collagen (CTX-I) were bigger after the treatment in patients with an advanced stage of the disease, in women post-menopause and in men over 70 years.

This is relevant also for introduction of the bisphosphonates or teriparatide therapy associated with specific treatment for osteoarthritis.

Key words: hip osteoarthritis, osteoporosis, blood serum C-telopeptid of type I collagen, glucosamin, chondroitin, rehabilitation.

INTRODUCTION

The metabolic alteration of the components of the joint, associated with osteoarthritis, involves changes in the synthesys and degradation of matrix molecules, fact proved by detection of fragments in the sinovial fluid, blood or urine.

The markers show the intensity of the degenerative processes and are considered a mean capable to predict the progression rate of osteoarthritis. [1,2]

Considering that osteoporosis was associated to hip osteoarthritis in an important number of patients and that is the most important cause for fractures in patients over 50 years [3,4], we consider that it was necesary to analyse CTX-I. It gives us information about the evolution of the degenerative process and the bone resorbtion process.

OBJECTIVES

The purpose of the study is to observe the efficacy of the associated joint supplements (glucosamin and chondroitin) therapy and rehabilitation treatment in patients with hip osteoarthritis and osteoporosis; also to point the corelations between CTX-I and the associated treatment and also the identification of patients who need antiresorbtive therapy.

MATERIAL AND METH-

ODS

A number of 63 patients aged between 30 and 70, with hip osteoarthritis and osteoporosis, outpatients and inpatients in the Medical Rehabilitation Hospital Felix Spa, were evaluated, over a period of 3 years. The structure of the groups was the following: 20 patients had rehabilitation treatment , 12 patients had joint supplements treatment (adminis-

tered in a dosage of 1060 mg sodic sulphate of chondroitin and 1500 mg clorhidrate of glucosamin per day, four cures of 6 weeks), 21 patients followed the associated joint supplements and rehabilitation treatment, and 10 patients constituted the control group.

Inclusion criteria were:

- Hip osteoarthritis;

- Age over 30;

- The possibility of evaluation after 48 weeks.

Exclusion criteria were:

- Age under 30;

- Associated with other disabling reumatological diseases;

- Associated with disabling organic diseases;

- Presence of psyhical diseases;

- Surgical treatment of the hip osteoarthritis (OA) in the past 6 months;

- Malign obesity (IMC>35).

C-telopeptidul seric of type I of colagen (CTX-I), produced by the degrading of colagen of type I was measured through an ensymatic imunosorbant linked method „Serum CrossLaps® ELISA” (Nordic Bioscience Diagnostics A/S, Herlev, Danemarca). The method uses 2 monoclonal anticorps headed against β izomer form of the eighth sequence of aminoacids (EKAHD-βGGR) of the telopeptid of the α1 chain of the type I of colagen.(2)

The statistic analisys was done with help from the EPIINFO software, version 6.0, application from Center of Disease Control and Prevention - CDC Atlanta, adjusted to working with medical statistics.

RESULTS

The C-telopeptid in women

From the analysis of average

values of the CTX-I it results that the values are bigger in female after 48 weeks of treatment, regardless the type of treatment used. Also, it’s values are bigger in female in post-menopause than in women in premenopause.

The variation of the average values is in the normal interval, in all the groups (rehabilitation treatment, rehabilitation treatment and condroprotective treatment, condroprotective treatment, control group), regardless of the physiological status (0,025-0,573 ng/ml in premenopause and 0,104-1,008 ng/ml in postmenopause).

Tabel I. Average values of the CTX-I blood serum in women by the physiological status.

By analyzing the evolution of the CTX-I by comparing the three groups, we noticed a significant increase in group with rehabilitation and condroprotective treatment (p>0,05) and not so significant in the group with rehabilitation , and condroprotective (p<0,05).

The C-telopeptidul in men

From the average values analysis of the blood serum CTX-I in men we concluded that they are bigger after 48 weeks of treatment, regardless of the type of 30 / volume 1, no. 1 / November 2009

Oradea Medical Journal

treatment used. Also, its values grow with the age.

from type I collagen C telopeptides, Clin Chem, 44, 1998:2290-2300

3.

Christgau S., Henrotin Ye., Tanko Lb., Rovati Lc., Collette J., Bruyere O. et al., Osteoarthritis patients with high cartilage turnover show increased responsiveness to the cartilage protecting effects of glucosamine sulfate.

Clin Exp Rheum, 22, 2004:36-42

4.

Stewart A et al., Bone density and bone turnover in patients with osteoarthritis and osteoporosis, J Rheumatol 26, 1999:622â&#x20AC;&#x201C;626 Tabel V. Average values of CTX-I blood serum comparison for men-women.

Tabel II. Average values of the blood serum CTX-I in women.

The C-telopeptid comparison for men-women

The values of blood serum CTX-I are bigger in men than in women, regardless of the treatment type (p<0,001), but they do not exceed the higher limit of the normal interval.

Tabel III. Average values of blood serum CTX-I in men by age.

The variation of average values is in the normal interval, in all the three lots, regardless of age (0,016-0,584 ng/ml in ages under 50, 0,016-0,704 ng/ml in ages between 51 and 70 and 0,06-0,854 ng/ml in ages over 70).(Tabel III) Analysing the evolution of CTX-I compared in the three groups, in men, we remark insignificant increases (p>0,05) of its concentration.

Tabel IV. Average values of blood serum CTX-I in men.

31 / volume 1, no. 2 / November 2009

CONCLUSIONS

From the analysis of average values of CTX-I in women we concluded that they are bigger after 48 weeks of treatment, regardless of the treatment type. Also, its values are bigger in post-menopause women than in pre-menopause women.

The variation of average values is in the interval of normality in women, in al the three groups analyzed, regardles of the physiological status

From the analysis of average values of CTX-I in men we concluded that they are bigger after 48 weeks of treatment, regardless of the therapy type. Also, its values grow with the age.

By analyzing the evolution of CTX-I in men, comparative between the three groups, we noticed insignificant increases (p>0,05).

The values of CTX-I are higher in men than in women, regardless of the treatment type (p<0,001), but they do not grow over the higher limit of normality.

Although by the end of the treatment we noticed a significant improvement of the results, the conclusion of the study is that it is necesary to associate antiresorbtives to the specific antiosteoarthritis treatment for slowing down, the progression of the bone resorbtion, and also the bone subcondral distruction from the degenerative process.

REFERENCES

1.

Bruyere O et al., Biochemical markers of bone and cartilage remodeling in prediction of long-term progression of knee osteoarthritis., J Rheumatol 30, 2003:1043â&#x20AC;&#x201C;1050

2.

Christgau S, Rosenquist C, Alexandersen P, Bjarnson Nh, Ravn P, Fledelius C et al., Clinical evaluation of the Serum Cross Laps One Step ELISA, a new assay measuring the serum concentration of bone-derived degradation products

Oradea Medical Journal

CELL ADHESION MOLECULES INVOLVED IN BREAST CANCER Zaha Dana Carmen 1, Codreanu Ioana Coralia 2, Lazăr Elena

3

1 Preclinic I Department, Oradea University, Faculty of Medicine and Pharmacy 2 Preclinic II Department, Oradea University, Faculty of Medicine and Pharmacy 3 Histopathology Department, University of Medicine and Pharmacy “Victor Babeş“ Timişoara

ABSTRACT

Breast cancer has become one of the most intensely studied human malignancies in the genomic era.

Promising results have emerged from these studies, correlating gene expression profiles with prognosis, recurrence, metastatic potential and therapeutic response. Cell Adhesion Molecules (CAMs) are proteins located on the cell surface involved with the binding with other cells or with the extracellular matrix in the process of cell adhesion. Most of the CAMs belong to four protein families: immunoglobulin super family (IgSF CAMs), the integrins, the cadherins and the selectins.

Analysis of a tumor antigen involved in adhesion of breast cancer cells showed that there are significant differences.

Evaluation of these markers involved in cell adhesion could be a useful method for evaluating the metastasis risk in breast cancer patients.

Key words: breast cancer, the cadherins, PECAM- 1, metastasis risk.

INTRODUCTION

Breast cancer has become one of the most intensely studied human malignancies in the genomic era; several papers over the last few years have investigated various clinical and biological aspects of human breast cancer using high-throughput molecular profiling techniques. Promising results have emerged from these studies, correlating gene expression profiles with prognosis, recurrence, metastatic potential, therapeutic response, as well as biological and functional aspects of the disease.

Cell Adhesion Molecules (CAMs) are proteins located on the cell surface involved with the binding with other cells or with the extracellular matrix (ECM) in the process of cell adhesion. These proteins are typically transmembrane receptors and are composed of three domains: an intracellular domain that interacts with the cytoskeleton, a transmembrane domain and an extracellular domain that interacts either with other CAMs of the same kind (homophilic binding) or with other CAMs or the extracellular matrix (heterophilic binding). Most of the CAMs belong to four protein families: Ig (immunoglobulin) superfamily (IgSF CAMs), the integrins, the cadherins and the selectins.

Immunoglobulin superfamily CAMs (IgSF CAMs) are either homophilic or heterophilic and bind integrins or different IgSF CAMs. Here is a list of some molecules of this family:

- NCAMs -Neural Cell Adhesion Molecules

- ICAM-1-Intercellular Cell Adhesion Molecule

- VCAM-1 Vascular Cell Adhesion Molecule

- PECAM-1 Platelet-endothelial Cell Adhesion Molecule or human CD31.

- Nectins and nectin-like mol-

ecules.

The integrins are a family of heterophilic CAMs that bind IgSF CAMs or the extracellular matrix. They are heterodimers, consisting in two noncovalently-linked subunits, called alpha and beta. Twenty-four different alpha subunits that can link in many different combinations with the 9 different beta subunits are known; however not all combinations are observed. Some sources don’t consider integrins to be cell adhesion molecules.

The cadherins are a family of homophilic CAMs, Ca2+-dependent. The most important members of this family are E-cadherins (epithelial), P-cadherins (placental), and N-cadherins (neural). The selectins are a family of heterophilic CAMs that bind fucosylated carbohydrates, e.g., mucins. They are calcium-dependent. The three family members are E-selectin (endothelial), L-selectin (leukocyte), and Pselectin (platelet). The best-characterized ligand for the three selectins is P-selectin glycoprotein ligand-1 (PSGL-1), which is a mucin-type glycoprotein expressed on all white blood cells. Neutrophils and eosinophils bind to E-selectin. One of the reported ligands for E-selectin is the sialylated Lewis X Ag. Eosinophils, like neutrophils, use sialylated, protease-resistant structures to bind to E-selectin, although the eosinophil expresses much lower levels of these structures on its surface[1]. Ligands for P-selectin on eosinophils and neutrophils are similar sialylated, protease-sensitive, endo-beta-galactosidase-resistant structures, different than those reported for E-selectin, suggesting disparate roles for P-selectin and E-selectin during recruitment during inflammatory responses [2].

Analysis of a tumor antigen involved in adhesion of breast cancer cells showed that there are significant differ-

ences. Evaluation of these markers involved in cell adhesion could be a useful method for evaluating the metastasis risk in breast cancer patients.

PECAM-1 Platelet-endothelial Cell Adhesion Molecule or human CD31 CD31 functions as an adhesion receptor mo lecule, playing a key role in leukocyte trafficking across the endothelial layer [3, 4]. CD-31 is normally found on endothelial cells, platelets, macrophages and Kupffer cells, granulocytes, T/NK cells, lymphocytes, megakaryocytes, fibroblasts, osteoclasts, neutrophils. CD-31 is also expressed in certain tumors, including epithelioid hemangioendothelioma, epithelioid sarcoma-like hemangioendothelioma, other vascular tumors, histiocytic malignancies, and plasmacytomas.

A number of reports have indicated that CD31 may engage in homophilic (CD31CD31) and heterophilic (CD31-X) bindings to other cell surface or matrix proteins.

Ligand-receptor binding results in lymphocyte rolling, adhesion, and extravasation, as well as in the implementation of a signaling pathway, partly intertwined with the one controlled by integrins[5].

The proposed counterreceptors for CD31 include the integrin αvβ3, a molecule present on red blood cells an as yet unidentified ligand expressed by T cells and CD38 [6, 7, 8, 9].

Breast ductal carcinoma in situ is an intraductal proliferation of malignant epithelial cells that diffuse within the ductal system without stromal invasion. In situ growth and invasion in breast cancer are the result of a balanced equilibrium between the adhesive and migratory properties of tumor cells and the plasticity of the surrounding milieu. The malignant behavior of a tumor depends on uncontrolled growth, local invasiveness and ability to 32 / volume 1, no. 1 / November 2009

Oradea Medical Journal

metastasize. Adhesion molecules contribute to each of these features. A subset of these tumors express CD31/platelet endothelial cell adhesion molecule-1 suggests that breast cancer represents an informative model for studying the involvement of the molecule in the morphogenesis, differentiation, and diffusion of this disease.

Transfection of CD31 in MDA-MB-231 cells caused reduction in growth, loss of CD44, and acquisition of a ductal morphology. The MDA-MB-231 breast cancer cell line was obtained from a pleural effusion.The patient underwent a mastectomy and radiotherapy prior to the removal of the breast cancer specimen. In vitro, the MDA-MB-231 cell line has an invasive phenotype. It has abundant activity in both the Boyden chamber chemoinvasion and chemotaxis assay. The same effects were maintained in vivo, in which CD31+ tumors grew with in situ -like aspects, papillary differentiation, and a secretory phenotype. CD44 was down-modulated, with the CD31+ cells blocked in the G1 phase. The morphology was highly similar to what was observed in some human CD31+ ductal carcinomas in situ. MDAMB-231 mock cells grew in solid sheets, lacking stromal material, and displaying high levels of CD44 and proliferation.

CD31+ cells acquired motility characteristics in vitro assays, a finding confirmed in vivo by the diffusion of human tumor cells throughout the normal ducts residual in the murine mammary gland.

In conclusion, CD31 expression shows the undifferentiated morphology and aggressive behavior of MDA-MB-231 cells, indicating its active role in the morphogenesis of breast ductal in situ carcinomas. Recently it has reported on the expression of CD31 by a subset of ductal in situ carcinomas (DCIS) of the breast, characterized by high nuclear grade, hormone independence, and a clear propensity to invade the lobules and eventually to give rise to Pagetâ&#x20AC;&#x2122;s disease of the nipple [10]. CD31+ DCIS may or may not express CD44, an adhesion molecule involved in tumor metastatization [11], whereas CD31+ invasive carcinomas are constantly CD44+( simultaneously CD31 and CD44 ).CD31 expression seems to be a prerequisite for the acquisition of kinetic properties.

The results an other study show that CD31 inhibits migration rates in endothelial cells. The reason for this discrepancy may be related to the use of a different cellular model (endothelial versus epithelial) and it is likely referable to the complex interplay taking place between CD31 and cytoskeletal proteins. This point supports the view that CD31 acts equally efficiently as an activatory or inhibitory receptor as a function of the cell type and, likely, of the microenvironment. Further attention will be devoted to the analysis of the migratory behavior in response to selected chemoattractants, eg, epidermal growth factor to 33 / volume 1, no. 2 / November 2009

which MDA-MB-231 cells are known to respond [12]. These observations raise the possibility that CD31 plays a role in the architectural organization of breast carcinomas. According to this hypothesis, CD31 could help in establishing a polarity within mammary epithelial cells, a necessary condition for cell differentiation [13].

Evidence against this hypothesis comes from the lack of CD31 expression by nonneoplastic human breast tissue at different stages of development [14, 15]. Thus, CD31 expression in breast cancer might be the result of gene amplification, as suggested by the observation that 17q23 (the region of the chromosome where CD31 gene is localized) is frequently amplified in breast carcinomas [17].The presence of CD31 on the membrane of malignant epithelial cells could also be explained in the context of vasculogenic mimicry [18, 19].This is an appealing theory envisaging vascular cell specialization inside a single tumor. Specific tumor elements were found to form blood-filled channels and to become intensely CD31+, at least in the experimental setting of uveal melanoma [18].

Expression of Cadherin Cell Adhesion Molecules in Human Breast Cancer Tissues

Metastasis poses the most serious threat to clinicians in the management of breast cancers. The problem attains even greater dimension because of the different therapeutic modalities adopted in cases with and without nodal metastasis. The process of metastasis, either locoregionally into lymph nodes or systemically into distant organs, remains intriguing, despite various studies in this field. As an initial step in metastasis, tumor cells should detach from the primary site and enter the circulation. This is thought to be due to changes in the cellâ&#x20AC;&#x201C;cell adhesive properties.

A number of studies have found an inverse correlation between the expression of E-cadherin and the tumor stage in carcinomas of breast [20]. Graff et al. found that the reduced expression of Ecadherin is due to hypermethylation of the CpG island of the promoter region of the E-cadherin gene [21]. The expression of E-cadherin immunohistochemically investigated was localized uniformly to the cell membrane with intense staining at the intercellular junctions. A few samples showed loss of strictly membranous expression pattern but showed cytoplasmic expression. There was a significant difference in the expression of E-cadherin between those tumors with and without nodal metastases. The expression of Ecadherin was significantly downregulated in higher grade tumors.

The staining pattern of P-cadherin was almost similar to that of Ecadherin, with localization of expression to cell membrane. There was a significant down-regulation of P-cadherin in node-

positive breast cancers. Though not significantly, the expression of P-cadherin was higher in low-grade tumors in comparison to high-grade tumors. Looking at the bivariate correlations, was finding that apart from the cadherins being significantly correlated to the nodal status, E-cadherin and P-cadherin also show a significant bivariate correlation between them. An observation of interest was that the expression of E-cadherin and P-cadherin were highly correlated, which requires further evaluation for confirmation of a common regulatory pathway that could be activated in the early onset of nodal metastasis. Breast cancer cells can invade and generate metastasis via either lymphatic or blood vessels.

There are significant correlations between E-cadherin expression and clinicopathological features E-cadherin mediates tumor cell-cell adhesion. Partial or complete loss of E-cadherin expression correlates with poor prognosis in breast cancer patients. In this study [22], the expression of E-cadherin was examined in mammary ductal carcinoma in situ, invasive breast carcinomas without metastasis, invasive carcinomas with their lymph node and distant metastases and invasive carcinomas with local recurrence in breast cancer tissue. A strong expression of E-cadherin in carcinoma in situ was demonstrated.

Expression of E-cadherin was moderate in invasive carcinomas without metastases.

However, very weak expression of E-cadherin in primary carcinoma with lymph node metastases was detected. E-cadherin expression was elevated in lymph node metastases compared to the primary tumor.

Neural (N)-cadherin is a calciumdependent cell adhesion molecule that is associated with invasive tumors in breast cancer, but no association with grade or nodal status has been shown in previous studies. Using real-time polymerase chain reaction, the number of N-cadherin transcripts in normal breasts and infiltrating ductal carcinomas can be assessed. The results were then analyzed in relation to grade, nodal involvement, distant metastasis, TNM stage, Nottingham Prognostic Index, and survival over 10 years. The levels of N-cadherin transcripts (normalized to glyceraldehyde 3-phosphate dehydrogenase) in primary tumors were lower in patients with metastases, with local recurrence and those who died as a result of breast cancer. In conclusion, in ductal carcinomas, decreased levels of Ncadherin (normalized to glyceraldehyde 3-phosphate dehydrogenase) in primary tumors is correlate with local recurrence and death in long-term follow-up of patients.

CONCLUSION

Analysis of a tumor antigen involved in adhesion of breast cancer cells showed that there are significant differences of expression of these adhesion mol-

Oradea Medical Journal

ecules between primary breast cancer cells and their metastases. Analysis of odds ratio of the cadherins showed that their down-regulation can serve as predictive markers of nodal metastasis in breast cancers. Taken together, the cadherins could be better indicators of nodal metastasis.

This suggests a crucial role for the expression of cadherins in demarcating nodepositive from node-negative cases. This is very significant in patients presenting with a primary tumor and histologically undiagnosable micrometastasis. At the same time, subjecting node-negative patients with palpable nodes to higher courses of treatment can be avoided. Evaluation of these markers involved in cell adhesion could be a useful method for evaluating the metastatic risk in breast cancer patients.

REFERENCES

1.

Bochner, BS; Sterbinsky SA, Bickel CA, Werfel S, Wein M, Newman W. (Jan 15, 1994). “Differences between human eosinophils and neutrophils in the function and expression of sialic acidcontaining counterligands for E-selectin”.

J Immunol. 152 (2): 774–82. PMID 7506734

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Wein, M; Sterbinsky SA, Bickel CA, Schleimer RP, Bochner BS. (1995). “Comparison of human eosinophil and neutrophil ligands for P-selectin: ligands for P-selectin differ from those for E-selectin”. Am J Respir Cell Mol Biol. 12 (3): 315–9. PMID 7532979

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Muller WA, Weigl SA, Deng X, Phillips DM: PECAM-1 is required for transendothelial migration of leukocytes. J Exp Med 1993, 178:449-460.

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Muller WA, Randolph GJ: Migration of leukocytes across endothelium and beyond: molecules involved in the transmigration and fate of monocytes. J Leukoc Biol 1999, 66:698-704

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Lu TT, Yan LG, Madri JA: Integrin engagement mediates tyrosine dephosphorylation on platelet-endothelial cell adhesion molecule 1. Proc Natl Acad Sci USA 1996, 93:11808-11813

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Piali L, Hammel P, Uherek C, Bachmann F, Gisler RH, Dunon D, Imhof BA: CD31/PECAM-1 is a ligand for alpha v beta 3 integrin involved in adhesion of leukocytes to endothelium. J Cell Biol 1995, 130:451-460

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Buckley CD, Doyonnas R, Newton JP, Blystone SD, Brown EJ, Watt SM, Simmons DL: Identification of alpha v beta 3 as a heterotypic ligand for CD31/PECAM-1. J Cell Sci 1996, 109:437445

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Treutiger CJ, Heddini A, Fernandez V, Muller WA, Wahlgren M: PECAM-1/CD31, an endothelial receptor foAr binding Plasmodium falciparum-infected erythrocytes. Nat Med 1997, 3:14051408

9.

Prager E, Sunder-Plassmann R, Hansmann C, Koch C, Holter W, Knapp W, Stockinger H: Interaction of

CD31 with a heterophilic counterreceptor involved in downregulation of human T cell responses. J Exp Med 1996, 184:41-50.

10.

Sapino A, Bongiovanni M, Cassoni P, Righi L, Arisio R, Deaglio S, Malavasi F: Expression of CD31 by cells of extensive ductal in situ and invasive carcinomas of the breast. J Pathol 2001, 194:254261.

11.

Kremmidiotis G: CD44.

J Biol Regul Homeost Agents 1999, 13:234239 12.Price JT, Tiganis T, Agarwal A, Djakiew D, Thompson EW: Epidermal growth factor promotes MDA-MB-231 breast cancer cell migration through a phosphatidylinositol 3′-kinase and phospholipase C-dependent mechanism. Cancer Res 1999, 59:5475-5478 .

12.

Streuli CH, Schmidhauser C, Bailey N, Yurchenco P, Skubitz AP, Roskelley C, Bissell MJ: Laminin mediates tissue-specific gene expression in mammary epithelia. J Cell Biol 1995, 129:591-603 .

13.

Damjanovich L, Fulop B, Adany R, Nemes Z: Integrin expression on normal and neoplastic human breast epithelium. Acta Chir Hung 1997, 36:6971.

14.

Anbazhagan R, Bartkova J, Stamp G, Pignatelli M, Gusterson B, Bartek J: Expression of integrin subunits in the human infant breast correlates with morphogenesis and differentiation. J Pathol 1995, 176:227-232.

15.

Xie Y, Muller WA: Assignment of PECAM1 to human chromosome bands 17q22->q23 by in situ hybridization. Cytogenet Cell Genet 1996, 74:156 .

16.

Monni O, Barlund M, Mousses S, Kononen J, Sauter G, Heiskanen M, Paavola P, Avela K, Chen Y, Bittner ML, Kallioniemi A: Comprehensive copy number and gene expression profiling of the 17q23 amplicon in human breast cancer. Proc Natl Acad Sci USA 2001, 98:5711-5716 .

17.

Wong SC, Chan JK, Lee KC, Hsiao WL: Differential expression of p16/p21/p27 and cyclin D1/D3, and their relationships to cell proliferation, apoptosis, and tumour progression in invasive ductal carcinoma of the breast. J Pathol 2001, 194:35-42 .

18.

Maniotis AJ, Folberg R, Hess A, Seftor EA, Gardner LM, Pe’er J, Trent JM, Meltzer PS, Hendrix MJ: Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 1999, 155:739-752 .

19.

Oka HS, Shiozaki H, Kobayashi K, Inoue M, Tahara H, Kobayashi T, et al. Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res 1993; 53: 1696–1701.

20.

Graff JR, Herman JG, Lapidus RG, Chopra H, Xu R, Jarard DF, et al. E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. Cancer Res 1995;

55: 5195–5199.

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Jeschke U, Mylonas I, Kuhn C, Shabani N, Kunert-Keil C, Schindlbeck C, Gerber B, Friese K., Expression of E-cadherin in human ductal breast cancer carcinoma in situ, invasive carcinomas, their lymph node metastases, their distant metastases, carcinomas with recurrence and in recurrence.

34 / volume 1, no. 1 / November 2009

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WILSON`S DISEASE ONSET WITH PYRAMIDAL SIGNS Sabău Monica 1, Adela Maria 2, Comanescu Alexandra Diana 1, Iova Andrada Claudia

1

1 University of Oradea, Faculty of Medicine and Pharmacy 2 Oradea “Emanuel” Faculty

ABSTRACT

Introduction: The reported prevalence of pyramidal weakness and pyramidal signs in Wilson disease varies somewhere between” occasional” and 20% of the cases. Bat not onset with pyramidal signs was reported.

Methods: case presentation Conclusions: In spite of real progress in Wilson disease etiopathogeny, its diagnosis may be missed sometimes, as due to its polymorphic clinical picture.

Key words: Wilson disease, pyramidal signs in Wilson disease, T2 hyperintensity

INTRODUCTION

Wilson’s disease (WD) is a rare autosomal recessive disorder of copper metabolism caused by a mutation to the copper transporting-gene ATP7B. The majority of patients with WD present predominantly hepatic or neuropsychiatric symptoms. The mean age of onset of ‘neurological WD’ is in the second to third decade. Patients commonly present extrapyramidal, cerebellar and cerebral-related symptoms, in either a subacute or a chronic fashion. An acute presentation is seen in rare cases. The most common initial presentation are abnormal, posturing caused by limb dystonia interferes with writing and walking; features of Parkinsonism commonly occur in combination. A few patients present cerebellar features such as unsteadiness of gait, and incoordination of speech and limbs. Writer’s cramp and acute generalized severe dystonia known as status dystonicus are rarer presentations. Acute onset of tremor of the head, neck and limbs can also be a rare dramatic presentation. [1]

The reported prevalence of pyramidal weakness and pyramidal signs in Wilson disease varies somewhere between” occasional” and 20% of the cases.

White matter abnormalities are frequently found in imagistic studies of Wilson disease. Dentorubrothalamic, pontocerebellar and corticospinal tract abnormalities are commonly noted [2, 3] Pyramidal signs are rare too, not always present, even if MRI has evidence of cortico-spinal tract abnormalities. [3, 4, 5]

We present a case of Wilson disease with acute isolated pyramidal signs onset and unusual imagistic findings.

CASE PRESENTATION

A 42 year old woman was admitted to hospital for right hemiparesis and slurred speech which occurred the previous day. Her family history was negative.

She already was diagnosed with hypertension, but she did not take any medication.

A mild impairment of muscle strength on the right side both for arm and leg (4/5MRC), brisk reflexes and right Babinski sign were found on neurological examination. Laboratory findings, CT scan, neck vessel Doppler ultrasonography and echocardiography were normal.

The motor impairment had a regressive course in the following days. Brisk stretch reflexes and the Babinski sign were persistent on the right side, as well as a slight dysarthria. The diagnosis of lacunar infarction was made, the patient was monitored as regarding her blood pressure and an antiagregant therapy was made.

The patient presents 2 years later with progressive neck and head rotation which was treated with anti-inflammatory drugs, muscle relaxants and physical therapy Dystonic posture of the cervical region, increased muscle tone of the extrapyramidal type, brisk reflexes and Babinski sign were found on the right side. KeiserFleisher ring was found.

Liver function and ultrasonography were normal. A serum copper level of 165 µg/l and a low level of ceruloplasmin of 6 mg/dl point to the diagnosis of Wilson disease.

Urinary copper excretion was normal (38, 1µg/l). MRI disclosed a T2 hyperintensity in the posterior arm of the internal capsule (fig. 1, .2, .3)

Fig. 2

Fig. 3

The diagnosis of Wilson disease was made and D-Penicilamine was started, with good tolerability.

Fig. 1.

DISCUSSION

Dystonic movements, extra pyramidal spasticity, Keiser-Fleisher ring 36 / volume 1, no. 1 / November 2009

Oradea Medical Journal

and the low level of serum ceruloplasmin point to the diagnosis of Wilson Disease.

Differential diagnosis is made with other dystonias (Dopa-responsive dystonia, idiopathic torsion dystonia, Post-encephalitic dystonia, Dystonic cerebral palsy, Lipid storage disease, and Focal dystonias such as writer’s cramp)

The regressive pyramidal syndrome on the first admission, and dysarthria were suggesting a lacunar infarction on a hypertensive patient.

Imagistic findings were uncommon; T2 hyperintensity localized to internal capsule, but not suggesting lacunar infarct. Many studies relieved similar imagistic findings in patients with Wilson Disease. [2, 3, 4, 5].

Absence of liver disease, coexis-

tence of isolated pyramidal signs together with extrapyramidal signs from the beginning, and unspecific imagistic findings made the diagnosis difficult.

Clinical course, evidence of Keiser-Fleisher ring, increased serum copper, and decreased serum ceruloplasmin pointed to the diagnosis.

CONCLUSIONS

In spite of increasing knowledge in its pathogenesis, Wilson Disease may be under diagnosed due to the variety of its clinical pictures.

REFERENCES

1.

Shyamal K D, Kunal R Wilson’s Disease: An Update Nat Clin Pract Neurol. 2006;2(9):482-493.

2.

Nazer H, Brismar J, Alkawi MZ, Gunaserkaran TS, Jorulf KH: Magnetic Resonance Imaging of the Brain in Wilson`s Dosease, Neuroradiology 1993,35:130-133

3.

Mangahales ACA, Caranoell P, Menzes JR et all: Wilson Disease : MRI with Clinical corelation, Neuroradiolgy 1994,36:77-100

4. van Wasernaer-van Hall NH, van den Heuvel GA, Jansen HG, Hoogenrad UT, Malli PTMW: Cranial MR in Wilson Disease: Abnormal Withe Matter in Extrapiramidal and Pyramidal tracts, AJNR 1995,16:2021-2027 5.

Hefter T, Roick H, Giesen HJ et all: Motor Impairment in Wilson’s Disease; clinical impact of pyramidal Tract Involvement, Acta neurol scand, 1994, 89:421-428

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38 / volume 1, no. 1 / November 2009

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Examples of correct citations:

a. Journal article: The authors, the original title of the article, the journal with the international abbreviations, the year, the volume, the number of the journal, the first and the last pages.

Lerner DJ, Kannel WB. Patterns of coronary heart disease morbidity and mortality in the sexes. A 26-year follow up of the Framingham population. Am Heart J 1986; 111: 383–90.

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Donegan W., Spratt J. Cancer of the breast.

The 4th edition, Ed. Saunders , New York , 1995. pag 48-56

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Ledger WJ. Dystocia and prolonged labor.

In: Wilson JR, Carrington ER, editors. Volume 8: Obstetrics and Gynaecology, St Louis : Mosby; 1987:47493

or

Brooke B. The development of surgical treatment for ulcerative colitis. In Lee E., eds. Surgery of inflammatory bowel disorders, London : Churchill Livingstone; 1987:23 -32.

Personal communications and unpublished data.

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PENTRU AUTORI

Trimiterea materialelor.

Manuscrisul pe suport electronic şi listat în 2 copii va fi trimis pe adresa de mai jos însoţit de următoarele documente: scrisoarea de intenţie, declaraţia autorilor, checklist (documente disponibile pentru download la www. ccmip.ro): Revista Medicală Orădeană Gheorghe BUMBU MD, PhD, Editor-in-Chief Centrul de Cercetare in Medicină de Înaltă Performanţă (CCMIP) P-ta 1 Decembrie 10, camera 129, Oradea, 410073, Judetul Bihor, RO Mobil. +40.720.565585 ; Tel./Fax. +40.359.439092 editor@ccmip.ro / www.ccmip.ro

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Nu vor fi luate în consideraţie articolele publicate anterior în alte reviste sau în altă limbă. Dacă materialul a fost trimis spre publicare altei reviste şi nu a fost acceptat, autorul poate să trimită şi comentariile sau răspunsul comitetului de peer review.

Experimentele umane şi nonumane.

Când sunt raportate experimente umane autorii trebuie sa precizeze dacă au fost respectate standardele etice pentru experimentele umane după cum este specificat în declaraţia de la Helsinki, revizuite în 2000 (World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2000 Dec 20; 284(23):3043-5).

Pentru experimentele non-umane pe animale sau alte specii, trebuie specificat în “Material şi Metodă” că au fost respectate normele de îngrijire stabilite de către instituţia locală şi trebuie specificat tipul speciilor folosite în titlu, rezumat, material şi metodă.

Autorii

Fiecare autor trebuie să dovedească participarea sa activă în studiu. Includerea acestora se bazează numai pe contribuţia substanţială la conceptul, modelul, strângerea datelor sau analiza, prelucrarea şi interpretarea rezultatelor sau revizuirea critică. Acordul fiecăruia pentru versiunea finală trebuie trimis o dată cu manuscrisul.

Alte persoane care au contribuit la lucrare, cum sunt participanţii la studii trebuie să fie menţionate la secţiunea Mulţumiri.

Declaraţia de copyright.

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Vezi secţiunile speciale pentru Transferul drepturilor de autor, Conflictul de interes, Formularul pentru datele transmise.

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Redactarea articolelor.

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Pentru autorii români manuscrisele vor avea rezumatul în limba engleză iar pentru cei străini manuscrisele se vor trimite integral în în

limba engleză.

Articolele se trimit în format Microsoft Word 2000 sau altă versiune mai recentă, cu fonturi de cel puţin 12. Exemplarele vor fi corectate, inclusiv bibliografia şi trebuie să fie coerente ştiinţific şi lingvistic.

Paginile vor fi numerotate în colţul de sus şi dreapta în următoarea ordine: titlul, scurta prezentare, abstract, text, mulţumiri, bibliografie, legenda figurilor şi tabelele.

Autorul (ii) îşi asumă responsabilitatea că documentul electronic este complet şi corect la momentul trimiterii, după revizuire şi acceptare.

Pagina de titlu (Pagina 1)

Va conţine în următoarea secvenţă: titlul articolului, care va fi concis şi în concordanţă cu conţinutul lucrării, prenumele pentru autoare sau iniţiala prenumelui pentru autori şi numele de familie ai autorilor, fără alte prescurtări, gradul universitar, cel mai înalt titlu academic, oraşul/ele, statul/ele, provincia/ile altele decât statul în care a fost condos studiul, departamentul/ele, numele instituţiei/lor afiliate în care s-a efectuat studiul, sursa/ele finanţării, numele, adresa, nr. de fax şi e-mail-ul autorului responsabil pentru corespondenţă.

Numărul total de cuvinte al materialului fără abstract trebuie trecut în partea de jos şi în stânga a paginii de titlu.

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Pagina 2 va conţine o scurtă prezentare a materialului, cu maximum 25 cuvinte, care evidenţiază esenţialul.

- Rezumatul (Pagina 3)

Include cuvinte cheie, este precedat de titlul şi de numele autorilor. Sub rezumat sunt menţionate 3-5 cuvinte cheie sau fraze care vor fi afişate pentru indexare.

Structura rezumatului

Va avea aproximativ 10 – 15 rânduri, maximum 150 cuvinte şi va cuprinde obiectivul sau scopul studiului (motivaţie), metoda folosită (studiu clinic, experimental, metaanaliză), principalele rezultate şi principalele concluzii – semnificaţia rezultatelor. Se vor sublinia aspectele noi ale studiului.

Abrevieri

Nu sunt acceptate în titlu şi sunt de evitat în rezumat pe cât posibil. Unităţile de măsură din Sistemul Internaţional sunt recomandate. In titlu şi în rezumat nu sunt recomandate abrevieri. Numai abrevierile standard sunt permise (vezi manualul AMA pentru abrevieri). In text vor fi menţionate abrevierile între paranteze în prima apariţie.

- Textul (pagina 4).

Se recomandă pentru studii structurarea în următoarele secţiuni:

• Introducere – se arată pe scurt scopul şi raţiunea studiului. Se prezintă numai fundalul, cu un număr limitat de referinţe necesare cititorului să înţeleagă de ce a fost condus studiul. Nu trebuie să conţină date sau concluzii din studiul actual.

• Material şi metodă – se descriu pe scurt, planul, pacienţii, animalele de experienţă, materialele, metodele, criteriile de includere-exludere, explorările, procedura precum şi metoda statistică folosită. Medicamentele vor avea numai denumirea ştiinţifică sau chimică (generică).

• Rezultate – trebuie expuse rezultatele detaliate şi trebuie citate toate tabelele şi figurile în ordinea logică şi care trebuie să suplimenteze textul, nu să îl dubleze. Se subliniază numai cele mai importante observaţii şi nu comparativ cu rezultatele altora.

Aceste comparaţii se fac la secţiunea discuţii.

• Discuţii, concluzii – a nu se repeta datele prezentate la rezultate şi nici nu trebuie prezentate date noi aici. Discuţiile cuprind raportarea rezultatelor personale la datele de literatură. Vor fi subliniate aspectele noi relevate de studiu şi se vor discuta implicaţiile acestora şi limitele lucrării.

• Analiza statistică – trebuie să fie clar specificate care teste au fost folosite pentru evaluarea datelor. Când datele sunt prezentate sub forma tabelară, testul statistic trebuie să fie indicate printr-o notă de subsol pentru fiecare test în parte.

- Mulţumiri (pagina 5).

Se trec numai persoanele care au adus o contribuţie semnificativă la studiu, dacă este cazul.

- Bibliografie (pagina 6) – vezi recomandările Revistelor Biomedicale (www.icmje.

org).

Vor fi numerotate în ordinea în care apar în text, cu cifre arabe. Este obligatoriu ca toate sursele cuprinse în bibliografie să fie citate în text şi să nu apară în text trimiteri la lucrări care nu sunt menţionate în bibliografie. Titlurile periodicelor vor fi abreviate conform stilului internaţional acceptat - Index Medicus (http://www.nlm.nih.gov/tsd/ serials/terms_cond.html). Informaţiile provenite din surse nepublicate încă, dar acceptate spre publicare pot fi citate. Indicaţiile respective vor purta în bibliografie menţiunea “sub tipar” în paranteze rotunde.

Dacă lucrarea nu este acceptată încă, menţiunea va fi “observaţii nepublicate”. Nu vor fi citate decât referinţele care au fost consultate de autorii articolului.

Exemple de citare corectă:

a. Reviste: autorii, titlul original al articolului, revista cu prescurtările internaţionale, anul, volumul, numărul revistei, pagina de început şi de sfârşit.

Lerner DJ, Kannel WB. Patterns of coronary heart disease morbidity and mortality in the sexes. A 26-year follow up of the Framingham population. Am Heart J 1986; 111: 383–90.

b. Monografie: autorii, titlul original, editura, oraşul, anul, numărul paginii.

Donegan W., Spratt J. Cancer of the breast.

Ediţia a 4-a. Ed. Saunders, New York, 1995. pag 48-56

c. Capitol de tratat.

Ledger WJ. Dystocia and prolonged labor.

In: Wilson JR, Carrington ER, editors. Volume 8: Obstetrics and Gynaecology, St Louis: Mosby; 1987:47493

Sau

Brooke B. The development of surgical treatment for ulcerative colitis. In Lee E., eds. Surgery of inflammatory bowel disorders, London: Churchill Livingstone; 1987:23 -32.

Comunicări personale şi date nepublicate.

Dacă sunt esenţiale, acestea pot fi folosite între paranteze, în locul cel mai potrivit din text, nu ca referinţe numerotate. Acestea trebuie însoţite de permisiunea autorilor.

- Figurile, imaginile, tabelele (pagina 7).

Figurile sunt trimise separat, nu în cadrul documentului. In document se citează numai figurile, consecutiv, cu cifre arabe, cu un titlu şi legendă. Imaginile, tabelele şi figurile trebuie să fie în format jpeg, de minimum 300 dpi. Legenda figurilor trebuie să fie pe altă pagină separat. Figurile (desene, scheme) vor fi reprezentate grafic profesional. Fiecare fotografie va avea menţionat în subsol numărul, titlul articolului şi primul autor, iar partea superioară a figurii - indicată cu o săgeată (daca nu se poate deduce care este aceasta). Toate ilustraţiile vor fi numerotate cu cifre arabe. Autorii vor indica în text unde trebuie plasate ilustraţiile.

Legendele ilustraţiilor

Se recomandă exprimarea rezultatelor în unităţi de măsură internaţionale şi în SI. Vor fi utilizate abrevierile acceptate internaţional.

Formatul articolului.

Dimensiunea recomandată a articolelor este:

- studii clinice, terapeutica chirurgicală,

opinii/referate clinice: 7 autori ( pentru studii multicentrice 12 autori) (daca sunt mai mulţi pot fi menţionaţi la secţiunea mulţumiri), maximum 3000 de cuvinte, 25 de referinţe. Include rezumatul de max 150 cuvinte şi 3-5 cuvinte cheie pentru indexare. Se iau în calcul numărul şi dimensiunea tabelelor/imaginilor.

- prezentări de caz şi comunicările ştiinţifice şi clinice: max. 5 autori, 700 cuvinte, 3 referinţe, include abstractul de max 75 cuvinte şi 3-5 cuvinte cheie pentru indexare.

- recenziile de cărţi, referatele din reviste, informări în legătură cu activitatea societatilor de profil şi a manifestărilor ştiinţifice: 1-2 pagini.

Ordinea în care apar în revistă articolele este determinată de: data intrării în redacţie, necesităţile editoriale şi respectarea recomandărilor de mai sus. Pot surveni priorităţi pentru unele articole de actualitate, solicitate de redacţie sau de interes deosebit.

Pentru versiunea oficială integrală a recomandărilor pentru revistele biomedicale consultaţi www.icmje.org

40 / volume 1, no. 1 / November 2009