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JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 4,

APRIL 2017

Dr K K Aggarwal

Dr R N Tandon

Dr Dilip Kumar Dutta

Dr Kakali Sen

National President IMA

Honorary Secretary General, IMA

Honorary Editor, JIMA

Honorary Secretary, JIMA

CONTENTS Editorial : u Role of Obstetrician to Prevent Cerebral Palsy — Dilip Kumar Dutta ..............................................5 Original Articles : u CT based morphometric analysis of cervical pedicles in Indian population : Is transpedicular screw fixation feasible? — Apoorva R Patwardhan, Pradip S Nemade, Sunil K Bhosale, S K Srivastava ...........................................................................8 u Human chorionic gonadotropin levels as a biochemical marker in pregnancy induced hypertension— Laxmi Narayana S, Md Imam Ghori, Venkat Ramana Y.............................................12 Observational Studies : u A study of the morbidity pattern of communicable and non-communicable diseases amongst patients attending the OPD at urban health training centre, Era’s Lucknow Medical College and Hospital (ELMC&H), Lucknow — Abhishek Arun, Daya Prakash, J P Srivastava, Pratibha Gupta, Zeeshan Haider Zaidi ......................................................................16 u A study on species prevalence of enterococci in clinical isolates and their antimicrobial resistance in central Rajasthan, India — Geeta Parihar, Surbhi Mathur ............................................21 Case Reports : u Amlodipine — induced gingival overgrowth : a case report — Pradip Kumar Chowdhury, Subhadeep Gupta, Manidipa Majumdar, Apurba Kumar Mukherjee, Jyotirmay Pal.........................25 u Anaesthetic management of cystic hygroma in neonate — Sushma Ladi, Pallavi Singh, Sarita Swami, Jyotsana Bhosale, Shubhada Aphale ....................................................26 u Primary insular carcinoid tumour of ovary : a rare case report — Jayashree G Pawar, Nischita Budihal, Ranjana R, Chatura K R ....................................................28 u Malignant melanoma of the eyelid : a rare entity — Chongtham Sarda Devi, Lukram Ajit Singh, Gautam Mukhopadhyay.......................................................................................30 u Pulmonary actinomycosis with bronchiectasis — Ajithkumar C S......................................................31 u Bilateral hyperdense thalami in GM1 Gangliosidosis : a case report — Ahmed Rizwan Karim, Rakesh Kumar, Punita Kumari ..................................................................35 Wcomments / Feedback 3


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JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 4,

APRIL 2017

Editorial

JOURNAL OF THE INDIAN MEDICAL ASSOCIATION Founder Hony Editor Founder Hony Business Manager Ex-officio Members

: : :

Hony Editor Hony Secretary Hony Associate Editors

: : :

Assistant Secretary

:

Sir Nilratan Sircar Dr Aghore Nath Ghosh Dr Santosh Kumar Mandal Hony. Joint Secretary, IMA (Hqs), Kolkata Dr Santanu Sen Hony Jt Finance Secretary, IMA (Hqs), Kolkata Dr Dilip Kumar Dutta Dr Kakali Sen Dr Amitabha Bhattacharya Dr Dipanjan Bandyopadhyay Dr Gopal Das

Honorary Secretary General Dr R N Tandon

IMA CGP (Chennai) Dean of Studies Dr V C Shanmuganandan (Karnataka) Honorary Secretary Dr R Gunasekaran (Tamil Nadu)

IMA AMS (Hyderabad) Chairman Dr Joseph Mani (Kerala) Honorary Secretary National President-Elect (2017-2018) Dr Ravi S Wankhedkar (Maharashtra) Dr Sadanand Rao Vulese (Telangana)

Immediate Past National President Dr S S Agarwal (Rajasthan)

National Vice-Presidents Dr Roy Abhram Kallivayalil (Kerala) Dr K Prakasam (Tamil Nadu) Dr Mahendra Choudhary (Gujarat) Dr Parmanand Prasad Pal (Bihar)

IMA AKN Sinha Institute (Patna) Director Dr Sarbari Dutta (Bengal) Honorary Executive Secretary Dr Raman Kumar Verma (Bihar)

Honorary Finance Secretary Dr V K Monga (Delhi)

JIMA (Calcutta) Honorary Editor Dr Dilip Kumar Dutta (Bengal) Honorary Secretary Dr Kakali Sen (Bengal)

Honorary Joint Secretaries Dr Vinod Khetarpal (Delhi) Dr Anil Goyal (Delhi) Dr Ashwini Kumar Dalmiya (Delhi) Dr Santosh Kumar Mandal (Bengal) Dr B B Gupta (Delhi) Honorary Assistant Secretaries Dr Dinesh Sahai (Delhi) Dr Amrit Pal Singh (Delhi) Honorary Joint Finance Secretaries Dr Manjul Mehta (Delhi) Dr Santanu Sen (Bengal)

Your Health (Calcutta) Honorary Editor Dr Ashok Kumar Chatterjee (Bengal) Honorary Secretary Dr Meenakshi Gangopadhyay (Bengal) IMA N.S.S.S. (Ahmedabad) Chairman Dr Kirti M Patel (Gujarat) Honorary Secretary Dr Yogendra S Modi (Gujarat)

IMA N.P.P.Scheme (Thiruvananthapuram) Chairman Dr Krishna M Parate (Maharashtra) Honorary Secretary Dr Jayakrishnan A V (Kerala) Apka Swasthya (Varanasi) Honorary Editor Dr Vivek Kumar (Uttar Pradesh) Honorary Secretary Dr Sanjay Kumar Rai (Uttar Pradesh) IMA Hospital Board of India Chairman Dr R V Asokan (Kerala) Honorary Secretary Dr Jayesh M Lele (Maharashtra) IMA National Health Scheme Chairman Dr Ashok SAdhao (Maharashtra) Honorary Secretary Dr Alex Franklin (Kerala) IMA National Pension Scheme Chairman Dr Sudipto Roy (Bengal) Honorary Secretary Dr K V Devadas (Kerala)

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MD, PhD, FRCOG (Hon), FICOG, FIAMS, FICMCH, MAMS, DACOG (USA), DPS (Germany) Chairman, Indian College of Obstetrics & Gynecology (2015) Dean, Indian Academyt of Obstetrics & Gynecology (IAOG) 2017 Vice Chairman, ISAR Bengal 2015-2017 National Editor of 'Jogi Journal' Director, GICE, Kalyani, Nadia, WB Author of 36 books (Obstetrics and Gynaecology) Honorary Editor, Journal of the Indian Medical Association (JIMA)

Dr Dilip Kumar Dutta

Role of Obstetrician to Prevent Cerebral Palsy

OFFICE BEARERS OF IMA (HQs) National President Dr K K Aggarwal

JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 4,

C

erebral palsy is considered a neurological disorder caused by a non progressive brain injury or malformation or dysfunction or non-function that occurs while the child’s brain is under development before, during and after birth.

Incidence : One million affected every year in India, around 7,64,000 in USA. It is one of the financial tool both for the family and society. National Institute of Health (USA) yearly funding for cerebral palsy total 29 million dollar. Historical Review: Dr. William John Little (1810), (1843),(1861)-first person to study the spastic baby. Dr. George Fridrich Little (1836) focused disorder of child hood. Dr. Sir William (1889) used the term cerebral palsy. Dr. Symonda Fraud (1897), highlighted the oxygenation at birth lead to cerebral palsy. Harry J Winthropes, Havay, Jnugs (1910-1950) NIMH (1949) centre for disease control & prevention first USA Multi state study on prevalence of cerebral palsy. How it affect the brain : Damage to cerebellum, upper part of the brain before, during or within the 5 years of birth can cause cerebral palsy causing defect in vision, hearing, communication & learning. 1980’s research showed that 1 in 10 cases of cerebral palsy occurs due to Oxygen deprivation during birth, maximum damage occurs 6 week of pregnancy. Types of cerebral palsy: 4 types –(a) spastic, (b) athetoid-dyskinatic, (c) Ataxic & (d) Hypotonic. Cerebral palsy may be (i) congenital (unknown) (ii) acquired (stroke) accidental & shaken baby syndrome (iii) genetics. Pregnancy & Cerebral Palsy : Three possible reasons (a) preventricular Leukemalacia (PL) (b) Abnormal development of the brain (ADB) (c) Intracranial Haemorrhage (IH) (a) PKL – A kind of damage that affects the brain’s white matter due to lack of oxygen supply in the womb caused by Rubella or German Measles, low blood pressure, preterm labor, SFD or illegal drugs. (b) ADB — During the first 6 months of pregnancy damage stem from mutation in the genes responsible for brain development caused by toxo plasmosis (a parasitic infection), herpies and herpies like virus and head trauma. (c) IH — Bleeding inside the brain happens when as fetus experience a stroke .Factors can cause stroke in


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JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 4,

a fetus during pregnancy are follows:(1) Before delivery : (a) blood clot in the placenta that blocks the flow to blood of the foetus (b) Partial detachment of the placenta (c) clotting disorder in the fetus (d) interruption in the arterial blood to the fetal brain (e) untreated PET, inflammation of the placenta, PID, emergency LUCS, prolonged 2nd stage, vacuum extraction, fetal or neonatal heart anomalies, umbilical cord abnormality. Other possible causes-multiple birth, consumption of alcohol, toxic substance, breech delivery may cause cerebral palsy. (2) After Birth : Meningitis, head injury, drowning accident or poisoning. OBSTETRICIAN ROLE TO PREVENT CEREBRAL PALSY : (A) PRE PREGNANCY – prevention of TORCH infection, UTI & reproductive tract infection, immunization against virus or others if any. (B) DURING PREGNANCY- prevention of UTI, RTI & chorio amnionities . (C) monitoring of placental maturity, its function or any detachment from uterine wall by USG and blood profile. (D) Outmost care to be taken to prevent premature labor /SFD. (E) RH incompatibility/thrombophilias/severe jaundice can be monitored properly during pregnancy. (F) balance or adequate supply of oxygenation to the fetal brain has to be maintained during labor or delivery (lucs). (G) Atleast half hours or one hour oxygentation to newborn baby (natural baby) and more to be given to premature and SFD body.

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Monitoring of blood supply and development of the brain : (A) uterine (B) umbilical (C) Cerebral by serial ultrasonography (droppler) (D) Development of brain specially cerebellum alongwith others (USG). ROLE OF CERTAIN DRUG : (i) prophylactic antibiotics can be given to a woman who has the history of repeated pelvic infection. (ii) Magnasium Sulphate, neuroprotective, is often used during the preterm birth, and SFD baby but there is currently insufficient evidence to assess the efficacy & safety of Magnesium Sulphate. Recent evidence showed that, Magsulph is used also in term fetus. Author is advocating the use of Magsulph in case of PET (3 dose) at 28, 30 and 32 weeks of pregnancy. (iii) Melatonin has found to be neuroprotective, small hormone from pineal gland is an antioxidant that protect cells from the damage caused by free radical & interacts with the immune system (Immune system may affect due to infection). CONCLUSION : For last 30 years author had the vast experience to deal with high risk pregnant mother & advocated above mentioned protocol. Till date no Cerebral Palsy has encountered by the author. But further Study is required regarding the monitoring, implementation of different drugs and its safety to new born baby alongwith others measures to prevent cerebral palsy. Hope in future proper ant, intra and postnatal care - is not only prevent brain damage to the foetus (cerebral palsy) but also prevent financial tool both for the family and society too.

Disclaimer The information and opinions presented in the Journal reflect the views of the authors and not of the Journal or its Editorial Board or the Publisher. Publication does not constitute endorsement by the journal. JIMA assumes no responsibility for the authenticity or reliability of any product, equipment, gadget or any claim by medical establishments/institutions/manufacturers or any training programme in the form of advertisements appearing in JIMA and also does not endorse or give any guarantee to such products or training programme or promote any such thing or claims made so after. — Hony Editor


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eter of the cervical pedicle using CT imaging. MATERIALS AND METHODS

Original Article CT based morphometric analysis of cervical pedicles in Indian population : Is transpedicular screw fixation feasible? 1

2

3

Apoorva R Patwardhan , Pradip S Nemade , Sunil K Bhosale , S K Srivastava

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This study involved evaluation of pedicle diameters of cervical spine using computed tomography imaging of 27 patients presenting in our institution between October 2010 and December 2010 with injuries other than cervical spine injuries. The patients chosen for this study were between 18-45 years of both genders. Pre study radiographic evaluation was done to rule out congenital malformation, previous signs of trauma and any signs of neoplastic or infective changes in the cervical spine. Most studies have shown the saggital diameter of the cervical pedicles to be larger than the transverse diameter in all the vertebrae . Hence in this study we have focussed only on the transverse diameter of the cervical pedicles. The CT cuts were taken at 2.5 mm interval. The transverse diameter was measured from the CT images using measurement tools of the workstation (Siemens 3D Virtuoso Software, Siemens Medical Systems, Inc ST: Illinois). The transverse pedicle diameter was defined as the outermost diameter of the pedicle, taken perpendicular to the axis of the pedicle at the narrowest point and measured in millimeters ±0.1 mm (Fig 1 & 2). The method of measurement was adapted from technique reported by Jones et al . The levels measured were C2-C7 bilaterally in 27 subjects. The statistical analysis was performed using SPSS software (version 16.0; SPSS, Inc, Chicago, IL). 1,8

The cervical pedicle diameter in Asian population is smaller compared to western population. The authors have studied the transverse cervical pedicle diameter of C2-C7 vertebrae in Indian population using computed tomography (CT) imaging. To study the average transverse diameter of cervical pedicles in Indian population, and to evaluate the feasibility of transpedicular screw fixation in these patients. Cervical transpedicular screw fixation has better pullout strength compared to lateral mass fixation. It is probably going to be the gold standard procedure for cervical spine fixation. However, its use in the Asian population can be limited as the transverse diameter of Asian population may not be adequate to accommodate the 3.5 mm pedicular screw. Any breech of pedicle may lead to neurovascular damage in the patient due to the proximity of the spinal cord medially and vertebral artery laterally. Measurements of cervical pedicles in 27 subjects were performed on the CT workstation from the CT images taken at 2.5 mm interval. The transverse pedicle diameter was defined as the outermost diameter of the pedicle, taken perpendicular to the axis of the pedicle at the narrowest point and measured in millimeters ±0.1 mm. The mean transverse diameter in Indian population ranges from 4.6 to 6.1 mm. If the minimum transverse pedicle diameter required is 5.0 mm for transpedicular screw fixation; 2.1% to 55.7% pedicles in male population and 5.5% to 74.3% of pedicles in the female population cannot undergo fixation with 3.5 mm screw. The transverse pedicle diameter of cervical pedicle in Indian population is smaller compared to western population. Although transpedicular screw fixation has stronger pullout strength compared to other methods of fixation, its use must be considered carefully and individually. Preoperative CT evaluation is a must before transpedicular fixation in cervical spine, especially in Indian female population. [J Indian Med Assoc 2017; 115: 8-11]

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ontemporary spinal reconstruction surgery can employ a wide variety of surgical implants to impart immediate segmental stability. The major aspects of the treatment of cervical spine instability include neural decompression, spinal realignment, rigid fixation, solid fusion and early rehabilitation. The insertion of such instrumentation must respect the anatomic limits of the region. Transpedicular screw fixation provides the greatest stability for stabilizing the cervical spine. It is becoming a standard way to stabilise the spine in scoliosis surgery, degenerative conditions, trauma treatment, tuberculous spondylitis and tumour reconstruction. The results of comparative biomechanical study provided evidence of the greater pullout

strength of cervical pedicle screws compared to lateral mass screws . Screw placement, however, can cause injuries to adjacent vital structures such as spinal cord medially and vertebral artery laterally. Studies performed upon Singaporean Chinese and Malaysian population have showed the cervical pedicle dimension to be smaller compared to the western counterparts . Thus the exact diameter of the pedicles of Indian population must be determined before any transpedicular screw fixation can be performed and accepted as a standard procedure in this population. The morphology of the cervical spine pedicles has been studied extensively by both using cadavers and computerised tomography (CT) films . Measurement of cervical pedicles using CT with 2.5 mm slices is reasonably accurate . In this study we particularly focussed on the feasibility of transpedicular screw fixation in the cervical spine in the Indian population by measuring the transverse diam1

2,3

4-6

Department of Orthopaedics, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai 400012 1 MS (Ortho), (Student), Resident 2 MS (Ortho), DNB (Ortho), Assistant Professor 3 MS (Ortho), D Ortho, Assistant Professor 4 MS (Ortho), Professor

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Fig 1 — Schematic diagram showing transverse pedicle diameter (PA - Pedicular axis, TD - Transverse diameter of pedicle)

1

RESULTS

A total of 27 subjects were analysed for their cervical pedicles in this study. They were between 18 to 39 years of age. A total of 14 (51.8 %) subjects were males, with an average age of 29.3 years and 13 (48.2 %) were females with an average age of 29.1 years. C2-C7 pedicles were measured bilaterally in each of the subjects with the total number of pedicles measured being 324. The analyses of male and female subjects were performed separately. The results are summarised in Tables 1 and 2. The mean transverse diameters of the cervical pedicle of C2, C3, C4, C5, C6 and C7 in males were 5.3, 5.3, 5.3, 5.6, 5.6 and 6.1 mm respectively. The diameter of the pedicles ranged between 5.3 to 6.1 mm. (Table 1)(Fig 3) The mean transverse diameters of the cervical pedicle of C2, C3, C4, C5, C6 and C7 in females were 5.1, 4.6, 4.7, 4.7, 5.3 and 5.6 mm respectively. The diameter of the pedicles ranged between 4.6 to 5.6 mm(Table 2)(Fig 3). There was no significant difference in transverse diameter between right and left pedicle in both male and female subjects (p>0.05). DISCUSSION

Pedicle screw fixation has become an established technique for the lumbar and thoracic regions. The

Fi 2 — CT image showing transverse cervical diameter (PA - Pedicular axis, TD - Transverse diameter of pedicle)

cervical spinal pedicles are very strong structural elements of the vertebrae. The transpedicular screw fixation gives best stability of all the fixation devices in the circumferential discoligamentous cervical injury model . In addition, pedicle screw fixation may obviate the need for anterior surgery in some patients with metastatic vertebral tumour, who might otherwise require combined anterior and posterior surgery. Heightened concern exists for the consequences of technical errors in this region due to the proximity of the vertebral arteries and neural elements. Neurological and 9


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Table 1 — Transverse diameter of the cervical pedicles based on CT measurement of male subjects (n=14) Males

Pedicle Diameter range (mm)

Cervical level

Right

Left

4.0-6.2 3.4-6.8 4.1-6.4 4.5-6.4 4.2-6.4 5.5-6.9

5.3 5.3 5.3 5.6 5.6 6.1

Mean (mm) Diameter

JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 4,

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pedicle screw is initiated. Data extracted from studies on non Asians should be used with caution because they might not be applicable for Indian population. Measurements of transverse pedicle diameter in the cervical spine showed a characteristic trend which has been reported earlier by other investigators . The C7 has the widest diameter of all cervical pedicles measured in both male and female subjects. A study by Ludwig et al demonstrated that if the pedicle diameter was greater than 5.0 mm, 79% of pedicle screws were in, 19% had non critical breeches and only 2% had critical breeches . Thus, if the 3.5 mm pedicular screw is to be inserted into the cervical pedicle, the minimum transverse diameter desired is 5.0 mm, to allow at least 0.75 mm bony bridge medially and laterally to avoid injury to adjacent vital structure. As per Table 3, between 5.5% and 74.3% of pedicles in our male population and as per Table 4, 2.1% and 55.7% pedicles in our female population were smaller than 5.0 mm. Thus our data showed that higher number of pedicles in our female population cannot be fixed using 3.5 mm pedicular screws compared to our male population because of smaller transverse diameter. Lateral mass fixation is another option available for cervical instrumentation. However lateral mass screws have less pullout strength compared to transpedicular screw fixation . As an option 2.7 mm screws can be devised for the Indian population giving a wider safety margin. Biomechanical studies have to be conducted upon the prospective use of these 2.7 mm screws comparing them with 3.5 mm lateral mass fixation. Pedicle diameter was also smaller in females compared to males at all cervical levels especially at C5 and C7 levels. Hence, transpedicular screw fixation is more risky in the Indian female population. Based on these findings, pre operative CT evaluation is mandatory especially in Indian female patients before any transpedicular screw fixation is considered in them. Wider database cutting across the geographical barriers is required in order to corroborate these findings. 2,8

C2 C3 C4 C5 C6 C7

4.1-6.5 3.8-6.3 4.1-6.1 4.2-6.2 4.3-6.3 5.2-7.8

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Fig 3 — The mean diameter of the cervical pedicles in male and female patient

vascular complications due to misplaced pedicle screw can result in profound and permanent physical impairment to patients undergoing spinal fusion and instrumentation. Morphological studies of the cervical spine have been reported as a way to evaluate the feasibility and safety of the technique. Studies conducted upon the western population have showed the diameter of the cervical spine to be adequate for screw fixation . Various studies have shown a difference between the size of lumbar and thoracic pedicles in Western and Asian population . Since the transverse diameter measurement is critical before screw insertion, a study of pedicles in local population is imperative before any attempt for cervical fixation using a 4-6

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Table 2 — Transverse diameter of the cervical pedicles based on CT measurement of female subjects (n=13) Females

Pedicle diameter range (mm) Right

C2 C3 C4 C5 C6 C7

4.2-6.4 4.2-5.8 3.6-6.4 3.4-6.7 3.8-6.6 3.9-6.9 4.4-6.1 4.3-6.6 3.9-7.1 4.0-6.9 4.8-7.4 4.5-7.2

Left 5.1 4.6 4.7 4.7 5.3 5.6

Mean (mm)

CONCLUSION

The transverse pedicle diameter of cervical pedicle in Indian population is smaller compared to western population. Although transpedicular screw fixation has stronger pullout strength compared to other methods of fixation, its use must be considered carefully and individually. Preoperative CT evaluation is a must before transpedicular fixation, especially in Indian female population. KEY POINTS

• Mean transverse diameter of cervical pedicles in Indian population ranges from 4.6 to 6.1 mm. • Transpedicular cervical screw fixation is not feasible in as high as 55.7% (males) and 74.3% (females) of our population. • Pre operative CT evaluation is mandatory before transpedicular cervical fixation is attempted, especially in female population. REFERENCES 1 Jones EL, Heller JG, Silcox H — Cervical pedicle screws versus lateral mass screws. Anatomic feasibility and biomechanical comparison. Spine 1997; 22: 977-82. 2 Tan SH, Teo EC, Chua HC — Quantitative threedimensional anatomy of cervical, thoracic and lumbar vertebrae of Chinese Singaporeans. Eur SpineJ 2004; 13: 137-46. 3 Yusof MI, Ming LK, Abdullah MS, Yusof AH — Computerized tomographic measurement of the cervical pedicles diameter in a Malaysian population and the feasibility for

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transpedicular fixation. Spine 2006; 31: E221-4. 4 Bozbuga M, Ozturk A, Ari Z — A morphometric evaluation of subaxial cervical vertebrae for surgical application of transpedicular screw fixation. Spine 2004; 29: 1876-80. 5 Kothe R, Ruther W, Schneider E — Biomechanical analysis of transpedicular screw fixation in the subaxial cervical spine. Spine 2004; 29: 1869-75. 6 Sakamoto T, Neo M, Nakamura T — Transpedicular screw placement evaluated by axial computed tomography of the cervical pedicle. Spine 2004; 29: 2510-4. 7 Kim HS, Heller JG, Hudgins PA — The accuracy of computed tomography in assessing cervical pedicle screw placement. Spine 2003; 28: 2441-6. 8 Panjabi MM, Duranceau J, Goel V — Cervical human vertebrae: Quantitative three-dimensional anatomy of the middle and lower regions. Spine 1991; 16: 861-9. 9 Ludwig SC, Kowalski JM, Edwards CC 2nd — Cervical pedicle screws: comparative accuracy of two insertion techniques. Spine 2000; 25: 2675-81. 10 Hou S, Hu R, Shi Y — Pedicle morphology of the lower thoracic and lumbar spine in a Chinese population. Spine 1993; 18: 1850-5. 11 Kim NH, Lee HM, Chung IH — Morphometric study of the pedicles of thoracic and lumbar vertebrae in Koreans. Spine 1994; 19: 1390-3.

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Table 3 — Percentage of Cervical pedicles at different levels smaller than 5.0 mm in diameter measured in male subjects (n=14) Males

Right (%) < 5 mm

C2 C3 C4 C5 C6 C7

21.4 22.6 33.6 35.6 55.7 53.8 20.8 22.6 7.2 8.6 2.1 0

Left (%) < 5 mm

Table 4 — Percentage of Cervical pedicles at different levels smaller than 5.0 mm in diameter measured in female subjects (n=13) Females C2 C3 C4 C5 C6 C7

Right (%) < 5 mm

Left (%) < 5 mm

30.2 70.2 60.3 45.3 38.9 7.3

28.3 74.3 64.8 43.6 41.3 5.5

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JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 4,

estimated both in normotensive pregnant women and PIH women. The study was aimed at the estimation of levels of maternal serum b -hCG which included 18 normotensive women (control group) and 36 PIH women (Experimental group). Experimental group was further divided into group-1, group-2 and group-3 based on the degree of diastolic blood pressure of 90-95, 96-100 and >100 mmHg respectively.

Original Article Human chorionic gonadotropin levels as a biochemical marker in pregnancy induced hypertension 1

2

Laxmi Narayana S , Md Imam Ghori , Venkat Ramana Y

3

MATERIALS AND METHODS

Pregnancy Induced Hypertension and its sequel are severe complications of pregnancy. The prognostic significance of high levels of serum human Chorionic Gonadotropin (b -hCG) in early pregnancy for subsequent obstetric and perinatal risks is still poorly documented. The primary aim of the present study was to investigate whether an isolated second trimester free b -hCG level in pregnancies could serve as a predictor of various pregnancy complications or adverse pregnancy outcome. The present results showed that the serum b -hCG levels were progressively increasing and were found to be significantly different between 3 groups of Pregnancy Induced Hypertension (PIH) in accordance with progressive increase of diastolic Blood Pressure. It is evident from the present study that the serum b hCG levels were significantly higher and significantly correlated with increased risk of PIH in women with increased b -hCG levels in the hypertensive group as compared to those in the normotensive group; which indicates the strong correlation between higher serum b -hCG levels and development of PIH later on during pregnancy. Hence, the b -hCG levels can be considered as good predictor of PIH in early gestational age. It can be concluded that the maternal serum b -hCG levels can act as potential markers for early detection of PIH, thereby helping in initiating early treatment to minimize and/or avoid the complications of PIH. [J Indian Med Assoc 2017; 115: 12-5]

Key words : Pregnancy induced hypertension (PIH), free b-hCG, predictor, potential markers.

S

ince years, there has been a search for an early predictor of Pregnancy Induced Hypertension (PIH), so that special care can be given to these patients . Pregnancy Induced Hypertension (PIH) in particular, Pre-eclampsia/Eclampsia remain important causes of maternal mortality and morbidity worldwide . A number of clinical studies have supported the possible association of unexplained elevated maternal serum (MS) human Chorionic Gonadotropin (hCG) in the second trimester with later pregnancy disorders. Pregnancy Induced Hypertension, Gestational Hypertension or Transient Hypertension of pregnancy are terms used to describe new hypertension which appears after mid-term (20 weeks) and resolves within 10 days postpartum without other symptoms of pre-eclampsia in a previously normotensive woman. In pregnancy, the placenta forms especially large quantities of human Chorionic Gonadotropin which is essential to a normal pregnancy and more so in Pregnancy Induced Hypertension. Elevated serum b -hCG in the sec 1

2

Department of Biochemistry, Gandhi Medical College, Secunderabad 500009 1 MD, Assistant Professor 2 MD, Retired Professor 3 MSc PhD, Dy Director, National Institute of Nutrition, Tarnaka, Hyderabad 500007

ond trimester has repeatedly been shown to be significantly associated with later PIH. The patients with abnormal b -hCG levels and in very few reports, the free âsubunit (free b -hCG) were reported as possible predictors of Pre-eclampsia , Pregnancy Induced Hypertension , spontaneous miscarriage, low birth weight, preterm delivery and Intra Uterine Growth Retardation (IUGR) . Pregnancy Induced Hypertension and its sequel are severe complications of pregnancy. The prognostic significance of abnormal free b -hCG serum levels in early pregnancy for subsequent obstetric and perinatal risks is still poorly documented. Therefore, the estimation of serum b -hCG may be helpful in the early detection of PIH later in the same pregnancy, in turn helps in early treatment by preventing complications of PIH. Hence, this will bring down the maternal and foetal morbidity and mortality. Therefore, the present study was conducted to understand and investigate further the association of selected physical and biochemical parameters among pregnant women with PIH subjects (Experimental group) and without hypertension (Normotensive / Control group). To achieve this, biochemical parameters like maternal serum b -hCG, and the physical parameters like Gestational age, Systolic and Diastolic blood pressures of the subjects were 3,4,5

3,6,8

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Standard Deviation values and One Way Analysis of Variance (One Way ANOVA) to decipher the intra and inter group variations of the study subjects from both control and experimental groups. In addition, the correlation coefficients were also used for all the groups studied to understand the extent of relationships between the important variables pertaining to physical and biochemical parameters like gestational age, systole, diastole and serum b -hCG. P<0.05 and P<0.01 were considered statistically significant. Results : The descriptive statistics (Mean and SD) for gestational age, systole, diastole, serum b - hCG of control (n=18) and experimental (n=36) group are presented in Table 1. Considering the blood pressure of control group, the mean systole and diastole was observed to be 121.67±7.46 and 76.7±5.86 respectively. Whereas, mean values of experimental PIH group were observed to be 143.9±3.26 and 96.9±4.21 respectively. Hence, the control group can be considered as normotensive. On the other hand, mean value of the biochemical parameter serum b-hCG was recorded to be 440.94±27.28 in the control group, while 509.83±18.43 in the experimental PIH group. The correlation coefficient pertaining to physical and biochemical parameter of the control group and experimental group are presented in Table 2. Systole significantly correlated with diastole and serum b-hCG (P<0.01) in the control group. Whereas, significantly correlated with gestational age, diastole and the biochemical parameter serum b -hCG (P < 0.01) in the PIH group. On the other hand, diastole was observed to be significantly correlated with systole and b -hCG (P<0.01) in the control group; whereas, significantly correlated with gestation age, systole and the biochemical parameter serum b -hCG (P<0.01) in the PIH group. Further, it was observed that hCG was significantly correlated with systole and diastole (P< 0.01) in the control group. Whereas, significantly correlated with the biochemical parameter studied (P<0.01) in the experimental PIH group.

The study was carried out in the Department of Biochemistry, Gandhi Medical College, Secunderabad, A.P. The cases for the present study were selected from the antenatal outpatient department, Gandhi Hospital, Secunderabad, according to specific criteria like women with age group between 18-24 years, primigravide with known last menstrual period and gestational age between 20-30 weeks. If menstrual history and examination findings were not correlating, ultrasonography was done to find out the exact period of gestation. Those with known hypertension, diabetes mellitus, multiple pregnancy and ultrasound proven congenital malformations in the foetus were excluded. All 54 women included in the present study were subjected to a detailed history taking, systematic examination, obstetric examination and routine antenatal investigations. Among 54 women, 36 were Pregnancy Induced Hypertensive (BP >140/90 mmHg) who were considered as experimental group and remaining 18 were normotensive (BP <140/90 mmHg) taken as controls. The experimental group was further categorized into three groups, having 12 women in each group, based on the degree of hypertension. The Group-1 was having diastolic blood pressure of 90 to 95 mmHg, the Group-2 with diastolic blood pressure of 96 to 100 mmHg and the Group-3 having diastolic blood pressure more than 100 mmHg. Collection of Samples : Under strict aseptic conditions, 3 ml of venous whole blood sample was collected from each subject in a plain, dry and properly labelled bottle. Precautions were taken to prevent haemolysis. Samples were brought to Clinical Biochemistry Laboratory, Gandhi Hospital and centrifuged after Table 1 — Descriptive statistics of individual clinical data of control group (n=18) and experimental group (n=36) clotting and retraction at room temperature. Clear serum was Parameter Control group Experimental group Mean ± STD collected and subsequently Mean ± STD analysed for the biochemical Group-I Group-II Group-III Total (n=12) (n=12) (n=12) (n=36) parameter serum â -human Chorionic Gonadotropin by Gest age (weeks) 26.89 ± 4.1 23.0 ± 1.60 27.3 ± 0.98 31.2 ± 1.03 27.17 ± 3.59 following the ELISA technique. Diastole (mmHg) 76.67 ± 5.8 92.3 ± 1.67 96.7 ± 0.98 101.8 ± 1.80 96.9 ± 4.21 Systole (mmHg) 121.67 ± 7.5 142.0 ± 2.09 142.7 ± 2.15 147.2 ± 2.76 143.9 ± 3.26 Statistical Analysis : hCG (mIU/ml) 440.94 ± 27.3 487.3 ± 12.34 516.4 ± 4.46 525.8 ± 5.26 509.8 ± 18.43 The data was subjected to Gest Age - Gestational age; hCG - serum b-hCG. descriptive statistical analysis to find out Means and


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In the present study, it was observed that the biochemical parameter serum b -hCG significantly increased in Parameter Control group (n=18) Experimental group (n=36) experimental group compared to control group subjects . reported that G age Systole Diastole hCG G age Systole Diastole hCG the increased risk of development of PIH is associated with increased levels G.age 1.000 0.551** 0.849** 0.909** 1.000 0.738** 0.961** 0.942** Systole 1.000 0.942** 0.930** 1.000 0.770** 0.669** of serum b -hCG in second trimester. Diastole 1.000 0.965** 1.000 0.910** The present results showed that the hCG 1.000 1.000 serum b -hCG levels were G Age - Gestational age, hCG - serum b-hCG, *Correlation is significant at (P < 0.05), progressively increasing and were **Correlation is significant at (P < 0.01), NS = Not significant. found to be significantly different between 3 groups of PIH in accordance with progressive increase The data presented in Table 3 shows One Way Analysis of diastolic Blood Pressure. of Variance of physical and biochemical parameters in the Elevated serum b -hCG in second trimester has experimental group was observed that all the parameters repeatedly been shown to be significantly associated with (systole, diastole, serum b -hCG) were found to be PIH . It has been reported that women with markedly significantly different between the three groups of PIH elevated maternal serum b -hCG levels has significantly (P<0.001). increased risks of having spontaneous miscarriage, Multiple comparisons of different parameters studied preterm delivery and IUGR . in the experimental group showed significant differences in the mean difference of the parameter like serum b -hCG Table 4 — Multiple comparisons of different parameters studied in (in group 1 & 2; group 1 & 3 (P<0.001) and group 2 & 3 experimental group (P<0.05), diastole (P<0.001), gestational age (P<0.001) in Dependent variable Groups Mean STD Error Sig all the three groups. Considering the mean difference difference among the three groups of PIH with regard to systole, highly significant difference was observed between the Gestational age (weeks) 1&2 -4.33* 0.504 0 1&3 -8.17* 0 groups 1 & 3 and 2 & 3 (P<0.001). However, no significant 2&3 -3.83* 0 difference was observed in groups 1 & 2 (Table 4). The data of comparisons between control and total Diastole (mmHg) 1&2 -4.33* 0.624 0 experimental group of PIH women (Table 5) showed a 1&3 -9.50* 0 2&3 -5.17* 0 significant increase in mean systole (P<0.01), diastole (P<0.05), serum b -hCG levels (P<0.05) in experimental Systole (mmHg) 1&2 NS 0.960 NS group when compared with the control group. 1&3 -5.17* 0 Statistical analysis on comparison between controls 2&3 -4.50* 0 and individual group of PIH women (groups 1 to 3 of hCG (mIU/ml) 1&2 -29.092* 3.333 0 experimental subjects) showed a significant increase in 1&3 -38.558* 0 mean values of systole, diastole and serum b-hCG levels 2&3 -9.467* 0.008 (P<0.001) in all the three groups of PIH when compared to control group (Table 6). Table 2 — Correlation coefficients of physical and biochemical parameters in control group (n=18) and experimental group (n=36)

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Table 5 — Comparison between controls versus PIH subjects

DISCUSSION

The primary aim of the present study was to investigate whether an isolated second trimester free b-hCG (>2.0 Multiple levels of Median MoM) serum levels in pregnancies could serve as a predictor of various pregnancy complications or adverse pregnancy outcome.

Parameters Diastole Systole hCG

F

Sig

T

df

Sig (2-tailed)

4.195 19.749 5.963

0.046 0.000 0.018

14.599 15.329 10.982

52 52 52

0 0 0

Table 6 — Comparison between controls and Group I, Group II and Group III of PIH subjects Table 3 — One way ANOVA of physical and biochemical parameters in experimental group (n=36) Parameter Gest. age (Weeks) Diastole (mmHg) Systole (mmHg) hCG (mIU/ml)

Sum of squares

Df

Mean square

F

Sig

400.667 542.889 189.556 9690.752

2 2 2 2

200.333 271.444 94.778 4845.376

131.344 116.333 17.154 72678

0 0 0 0

Parameters

Diastole Systole hCG

Group I

Group II

Group III

F

Sig (2-tailed)

F

Sig (2-tailed)

F

Sig (2-tailed)

17.381 14.446 10.001

0 0 0

23.593 13.834 24.275

0 0 0

16.042 11.618 22.325

0 0 0

The estimation of serum b -hCG levels may be helpful in both early detection of PIH and to prevent further associated complications . This will perhaps bring down the maternal and foetal morbidity and mortality. Reported from their study that all those who developed PIH had higher levels of serum b -hCG confirmed 100% correlation between high serum b -hCG levels and development of PIH which in turn significantly increased risks of having poor/adverse pregnancy outcomes (Spontaneous miscarriage, Intra Uterine Growth Retardation (IUGR) and Preterm delivery), where the magnitude of risk correlates with the levels of b -hCG. The present study results indicate that b -hCG determination may have value in the prediction of Preeclampsia / PIH. Reports provide some evidence that the b -hCG is elevated not only in established PIH but perhaps even before the clinical signs of the disease appears. It is evident from the present study that the serum bhCG levels were significantly higher (487 to 510 mIU/ml) and significantly correlated with increased risk of PIH in women with increased b -hCG levels in the hypertensive group as compared to those in the normotensive group; which indicates the strong correlation between higher serum b -hCG levels and development of PIH later on during pregnancy. The present study results showed significant positive correlation of serum b -hCG levels with gestational age, systolic and diastolic blood pressure. This observation was in tune with the studies reported by and hence, the serum b -hCG levels can be considered as good predictor of PIH in early gestational age. On the other hand , have also reported that there is a positive relationship between the PIH and increased bhCG levels with increased risk of most pregnancy complications and outcome. It seems reasonable to presume from the results of the present experimental study that the increased synthesis and secretion of free b -hCG is associated with immunosuppressive activity of hCG which helps to initiate early treatment so as to minimize and/or avoid adverse effects of PIH. 12

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population to understand the detailed mechanisms/interactions between the biochemical molecule and development of PIH.

REFERENCES 1 Jaiswar, SP, Nisha RM — Maternal Serum Human Chorionic Gonadotropin as a predictor for Pregnancy Induced Hypertension. J Obstet Gynecol Ind 2003; 53: 5435. 2 Chamberlain, G, Phillips E, Howlett B, Masters K — British births 1970, Obstretic care, 7. Heinemann, London 1978; 2: 80-100. 3 Wenstrom KD, Owen J, Boots LR, Du Bard MB — Elevated second-trimester human chorionic gonadotropin levels in association with poor pregnancy outcome. Am J Obstet Gynecol 1994; 171: 1038-41. 4 Benn PA, Horne D, Briganti S, Rodis JF, Clive JM — Elevated second-trimester maternal serum hCG alone or in combination with elevated alpha-fetoprotein. Obstet 13,14 Gynecol 1996; 87: 217-22. 5 Fejgin MD, Kedar I, Amiel A, Ben-Tovim T, Chen R, Petel Y, et al — Elevated hCG as an isolated finding during the second trimester biochemical screen: Genetic, ultrasonic, and perinatal significance. Prenat Diagn 1997; 17: 1027-31. 6 Gonen R, Perez R, David M, Dar H, Merksamer R, Sharf M — The association between unexplained second-trimester maternal serum hCG elevation and pregnancy complications. Obstet Gynecol 1992; 80: 83-5. 7 Palacio M, Jaumiaux E, Kingdom I, Sheldrake A, Rodeck CH — Perinatal outcome in pregnancies with a positive serum screening for Down's syndrome due to elevated levels of free beta subunit of hCG. Ultrasound Obstet Gynecol 1999; 13: 58-62. 8 Lieppman RE, Wiliams MA, Cheng EY, Resta R, Zingheim R, Hickok DE, et al — An association between elevated levels of human chorionic gonadotropin in the midtrimester 1,12 and adverse outcome. Am J Obstet Gynaecol 1993; 168: 1852-6. 9 Sorensen TK, Williams MA, Zingheim RW, Clement SJ, Hickok DE — Elevated second-trimester human chorionic 11,15 gonadotropin and subsequent pregency-induced hypertension. Am J Obstet Gynecol 1993; 169: 834-8. 10 Walton DL, Norem, CT, Schen EJ, Ray CT, Colby CJ — Second Trimester Serum Chorionic Gonadotropin concentrations and complications and outcome of pregnancy. N Engl J Med 1999; 341: 2033-8. 11 Nathalie L, David C, John K, Tianhua — Associaiton between second trimester isolated high maternal serum human chorionic gonadotropin levels and obstretic complications in singleton and twin pregnancies. Am J Obstet Gynaecol 2003; 188: 1354-9. 12 Yaron Y, Cherry M, Kramer RL, O'Brien JE, Hallak M, Johnson MP, Evans MI — Second-trimester maternal serum CONCLUSION marker screening: maternal serum alpha-fetoprotein, betaIt can be concluded that the maternal serum b -hCG human chorionic gonadotropin, estriol, and their various levels can act as potential markers for early detection of combinations as predictors of pregnancy outcome. Am J PIH, thereby helping in initiating early treatment to Obstet Gynecol 1999; 181: 968-74. 13 Crosignani PG, Trojsi L, Attanasio AEM, Lombroso Finzi GC minimize and or avoid the complications of PIH. — Value of hCG and hCS measurement in clinical practice. Thus, all the patients with a high levels of serum free b Obstet Gynaecol 1974; 44: 673-81. hCG in second trimester should be informed about the 14 Said ME, Campbell DM, Azzam ME — Beta-human possible association between the biochemical findings Chorionic Gonadotropin levels before and after the development of preeclamsia. Br J Obstet Gynaecol 1984; 9: and subsequent PIH (Pre-eclampsia). Furthermore, with 772-5. more extensive investigations and better knowledge of the 15 Sujata Chandra S, Heather Scott, Linda Dodds, Carolyn different risk factors, we can intervene on time with Watts, Claire Blight, Michiel Van Den Hof — Unexplained appropriate Obstetric management and possible elevated maternal serum alpha-fetoprotein and/or human chorionic gonadotropin and the risk of adverse outcomes. therapeutic interventions for these pregnancies. American Journal of Obstetrics and Gynecology 2003; 189: It is also opined further studies are needed on larger 775-81. 1,11


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Observational Study A study of the morbidity pattern of communicable and non-communicable diseases amongst patients attending the OPD at urban health training centre, Era’s Lucknow Medical College and Hospital (ELMC&H), Lucknow 1

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Abhishek Arun , Daya Prakash , J P Srivastava , Pratibha Gupta , Zeeshan Haider Zaidi

Health which is multidimensional in nature and difficult to measure, often captured through a range of indicators like mortality and morbidity. The data on morbidity is easy to collect but difficult to measure without subjective bias. A bulk of the research has been done for standardization of definitions of morbidity at National and local levels by various researchers. This study attempts to find out the pattern of morbidities of the people along with their age, sex and in different seasons of the year, amongst the patients attending to the OPD at Urban Health and Training Centre (UHTC), Era’s Lucknow Medical College and Hospital, (ELMC&H). Data for 06 months (April 2012 to September 2012) was obtained from routine consultation and recorded on a pre designed morbidity sheets from out patient attendance of our Urban Health and Training Centre (UHTC), under the department of Community Medicine, ELMC&H, Lucknow. Only new patients were taken into account. A total of 17,890 individuals (3399 males, 14,491 females) gave their consent and participated in the study. The case rate was reported higher for the age group (31-40 years). The percentage of female OPD consultations (11,273 ie. 63%) was more than that of males (6617 ie, 37%). Respiratory & GIT diseases still contributed the major proportion of morbidities in both sexes. In the non-communicable disease group, hypertension (43%) was the major disease burden followed by anaemia (20.8%) and asthma (11.7%). [J Indian Med Assoc 2017; 115: 16-20]

Key words : Morbidity pattern, Communicable diseases, Non-communicable diseases.

N

on-communicable diseases are increasing world wide due to rapidly changing life style. Earlier burden of communicable diseases was much higher than non-communicable diseases. Changing scenario of disease burden in a community can best be studied on the basis of hospital data due to lack of reliable community-based data and some to some other difficulties experienced from the community. In the year 2001, chronic diseases contributed approximately 46% of the global burden of diseases . This shift in the pattern of disease from communicable to non-communicable is occurring at a faster rate in developing countries than it did in the industrialized regions of the world half a century ago . Projections nevertheless indicate that communicable diseases will still occupy a critically important position up to 20203. Sometimes chronic diseases are con1

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Department of Community Medicine, Era’s Lucknow Medical College and Hospital, Lucknow 226003 1 MBBS, MD, Resident 2 MBBS, MD, Associate Professor 3 MBBS, MD, Professor and Head 4 PhD, Assistant Professor (Statistics)

sidered communicable at the risk factor level. Modern dietary patterns and physical activity patterns are risk behaviors that travel across countries and are transferable from one population to another like an infectious disease, affecting disease pattern globally . The rapidity of the changes in developing countries is such that a double burden of disease may often co-exist which strains the existing resource poor health delivery system. Changing disease pattern and treatment seeking behavior of patients demand restructuring / remodeling of existing health care system also. There seems to be an urgent need of effective utilization of specific clinics established in tertiary health care institutions. Geographical variation of diseases must be taken as an opportunity to carry out continuous surveillance of different diseases in hospitals so that reliable and updated data are timely available for health administrators to plan, implement and evaluate disease control and prevention programme strategies . Present study aims at studying morbidity pattern of communicable and non-communicable diseases amongst pa4

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tients attending to the OPD of Urban health and training centre (UHTC) at Era’s Lucknow medical college and hospital, Lucknow, reflecting the disease burden in the community. Aims and objectives : (1) To study morbidity pattern of diseases at Urban Health and Training Centre (UHTC), of Era’s Lucknow Medical College and Hospital, (ELMC&H). (2) To observe the sex and age wise distribution of morbidities among the studied subjects. MATERIALS AND METHODS The study was undertaken by the department of Community Medicine, Eras Lucknow medical college and hospital (ELMC&H), Lucknow. The Urban Health Training Center (UHTC), Nakkhas, Lucknow supervises 20 mohallas covering around 24,500 population in the area. In the present study, the morbidity pattern was seen through Out Patients Department (OPD) approach in a span of 06 months at OPD of UHTC. The analysis was done on the basis of new patients only; if the same patient came for consultation for more than one time for a particular illness then he/she may be considered once. As per the norms laid down at UHTC, OPD services are run on every working day at Nakkhas. All the diagnosed diseases were classified in to broad categories on the basis of physiological systems and a separate head was given for generalized pain, weakness, fever, and headache. Morbidity pattern was analyzed from the OPD attendance register from April 2012 to September 2012. Type of study : This was a cross sectional study carried out for a period of 06 months amongst patients who attended the OPD at Urban Health Training Centre of the Department of Community Medicine, Era’s Lucknow Medical College and Hospital, Lucknow, India. Duration of the study : This study was conducted between April 2012 and September 2012. A total of 17,890 individuals (3399 males, 14,491 females) gave their consent and participated in the study. A structured, pretested schedule was used to collect the data with regards to the socio-demographic characteristics (age, gender, religion) and the morbidity pattern. Inclusion criteria : All the adults who were aged 18 years and above, who attended the OPD at Urban Health Training Centre of the Department of Community Medicine, Era’s Lucknow Medical College and Hospital, Lucknow, India. Exclusion criteria : All the participants who were aged less than 18 years of age were excluded from the study. The patients who were non cooperative and those who refused to provide the necessary information were also excluded. The patients/subjects were assured of the confidential-

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ity of the data and their informed consent was obtained. A pretested performa was employed to record the necessary information such as socio demographic factors, occupational history, past and present medical history, findings of clinical examination and investigations performed among the workers. Standard clinical methods and investigations were used for the diagnoses of diseases, and opinion of the specialists from the Eras Lucknow medical college and hospital (ELMC&H), Lucknow, was obtained to confirm them. International Classification of Diseases version 10 (ICD 10) was used to perform the final diagnoses, eg, Chronic bronchitis (ICD No. J44) was defined as the presence of a chronic productive cough in a patient on most of the days for three months and persistent chronic productive cough in a patient in for two successive years; and patients in whom other causes of chronic cough have been excluded (other causes of chronic cough were excluded by sputum microscopy and chest X-ray). To detect anemia in all the subjects, the hemoglobin level (g/dl) was estimated using Sahli's Hemoglobinometer. The subjects in whom the hemoglobin values were lower than that prescribed by the WHO norms were diagnosed with anemia (males <13 g/dl and females <12 g/dl). Other diagnostic tests applied were Complete Blood count, Urine routine analysis and microscopic examination, HbsAg, HIV-ELISA, WIDAL test, Fasting and Post parendial blood sugar, Paps smear, VDRL etc. Injuries that had occurred in the past six months were included in the study. Test for the statistical significance was applied by using x test for analyzing the difference between the two proportions (P<0.05 was considered significant). 2

RESULTS

Table 1 shows distribution of study subjects/patients according to age, sex and predominant pattern of disease. A majority of subjects belong to the age group 31-40 years. The percentage of females (63%) outnumbered males (37%). Non-communicable disease (63.1%) were more common than the communicable disease (36.9%). Most Common URTI/ARI (44%) with second most common Pulmonary Tuberculosis (24%) (for difference z=25, p<0.0001) Table 2 Shows morbidity pattern of communicable diseases in OPD (Out Patient Department) of UHTC and also by gender. Acute respiratory infection (ARI) was the most common (44%) reported communicable disease followed by pulmonary tuberculosis (24%) and STD (15.1%). All there communicable diseases were mostly managed at OPD only. Females dominated males in the reported morbidity spectrum of all communicable diseases. There were 4325 (65.3%) females among all reported cases. Diseases patterns among males and females were also found significantly different (P<0.01).


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JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 4, Table 1 — Distribution of patients according to age and gender Age and Gender

Total number

Age in years : 18-30 1789 31-40 6798 41-50 5367 51-60 2156 >60 1780 Total 17890 Gender : Male 6,617 Female 11,273 Total 17,890 Pattern of disease : Communicable disease 6619 Non-communicable disease11271 Total 17890

Percentage % 10.0% 37.9% 30.0% 12.0% 9.9% 100%

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categories were also found to differ significantly (P<0.01). Females were found to be comparatively more sufferers of anaemia (95%), hypertension (59%), Diabetes mellitus (54%), asthma (53%) and arthritis (64%). Rest of the reported non-communicable diseases were found to be comparatively more prevalent among males than that of females. DISCUSSION

In this study, we explored spectrum of communicable 37% and non-communicable diseases in the OPD of UHTC. 63% Burden of non-communicable diseases came out to be 100% much higher (63.1%) as compared to communicable 36.9% diseases (36.9%) in the studied health facility. Among 63.1% communicable diseases, ARI (44%) was the most common 100% disease reported followed by pulmonary tuberculosis (24%) and STD/RTI (15.1%). In the non-communicable disease group, Hypertension (43%) was the major disease burden followed by Anaemia (20.8%) and Asthma (11.7%). Higher proportion of ARI cases in OPD than that in IPD contradicts observation in an earlier study . Possibility of misdiagnosis for diseases like ARI in the OPD set up cannot be ruled out for this finding. Considerable respiratory diseases like ARI, pneumonia and pulmonary tuberculosis were treated in the OPD of UHTC. Most patients visiting the Out Patient Department have already been to many practitioners before landing in the studied health facility and might very well be suffering from Fig 1 — Showing morbidity pattern according to age infections with resistant bacteria. Also, among adults complications can develop despite clinical improvement Most Common Hypertension (43%) with second most requiring indoor care. common Anemia (20.8%) (for difference z=39.97, Hypertension being the commonest nonp<0.0001) communicable morbidity corresponds with the findings of Table 3 Shows morbidity pattern of nonothers . The female preponderance of this disorder is as per communicable diseases for OPD at UHTC and also for expectations. After 45 years systolic blood pressure males and females. In the non-communicable disease increases more in females than in males . In OPD patients group, hypertension (43%) was the major disease burden of UHTC, female population predominate among elderly followed by anaemia (20.8%) and asthma (11.7%). A large percentage of non- communicable cases were and approaching for treatment here. This fact can explain m a n a g e d i n O P D . O b s e r v e d d i s t r i b u t i o n s the female predominance in hypertension. In most regions, of males and females in different morbidity hypertension accounts for 10% of adult hospital morbidity . In Chennai reported prevalence of hypertension was Table 2 — Morbidity pattern of communicable disease 8.3% among males and 8.2% among Disease OPD Male Female z-value p-value ICD-10 code females. Crude Prevalence of hypertension in the age group 20 URTI/ARI* 2912(44%) 960(33%) 1951(67%) 19.5 <0.0001 J00 Pulmonary tuberculosis 1589(24%) 826(52%) 763(48%) 1.582 0.114 A15.0 years and above was reported to be Pneumonia 198(3.0%) 121(61%) 78(39%) 3.207 0.001 J17 21.1% with the age standardized Acute diarrhea 530(8%) 149(28%) 381(72%) 11.208 <0.0001 R19.7 Hepatitis 175(2.6%) 77(44%) 98(56%) 1.599 0.11 B15.9 prevalence of 17% . Prevalence of Typhoid/Enteric fever 125(1.8%) 42(34%) 83(66%) 3.882 0.0001 A01.09 hypertension even in rural areas of RTI/STD** 992(15.1%) 89(9%) 903(91%) 45.22 <0.0001 A64 Kerala is as high as 12.5% to 17.9% Others 98(1.5%) 30(31%) 68(69%) 4.164 <0.0001 Overall 6619(100%) 2294(34.7%) 4325(65.3%) 26.23 <0.0001 in spite of the fact that this state is considered a model for betterment of *URTI - Upper Respiratory Tract Infection. ARI - Acute Respiratory Infection. health situation in India. In some **RTI/STD – Reproductive Tract Infection/Sexually Transmitted Diseases 6

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Diabetes prevalence ranged from 8.4% among normotensives to 25.6% amongst hypertensives in a study conducted in South India . This fact indicates the role of hypertension as an important component of studying morbidity spectrum for health planning in India. In India approximately 1 million patients of cancer develop annually. To reinforce the population-based registry, Fig 2 — Showing the distribution pattern of communicable diseases hospital-based cancer registry data play amongst patients attending OPD at UHTC (ELMC&H) important roles and they provide Table 3 — Morbidity pattern of non communicable disease valuable information for planning effective strategies for cancer control . Disease OPD Male Female z-value p-value ICD-10 code Anaemia was more prevalent than Hypertension 4959(43.0%) 2034(41%) 2925(59%) 12.86 <0.0001 I10 Asthma and Diabetes. In Asian Diabetes mellitus 789(7%) 363(46%) 426(54%) 2.25 0.02 E14 population, IHD was present in 9.4% of Asthma 1318(11.7%) 619(47%) 699(53%) 2.21 0.03 J45 normotensives and 17.1% IHD* 1014(9.1%) 690(68%) 324(32%) 12.32 <0.0001 I20.8 Bronchitis 146(1.3%) 85(58%) 61(42%) 2.01 0.04 J41 hypertensives giving 3.3% prevalence CVA**/ hemiparesis 563(5.1%) 343(61%) 220(39%) 5.31 <0.0001 G81 in combined population . This finding Anemia 2254(20.8%) 113(5%) 2141(95%) 97.87 <0.0001 D50 is in agreement with our study results of Arthritis 124(1.2%) 45(36%) 79(64%) 3.17 0.001 M15.4 14.6% prevalence. Prevalence of CHD Others 104(0.9%) 31(30%) 73(70%) 4.51 <0.0001 was reported to be 4.5% in Jaipur . The Overall 11,271(100%) 4323 6948 25.42 <0.0001 variations in prevalence of IHD at *IHD – Ischemic Heart Disease. **CVA – Cerebral-Vascular Accident different places suggest the need of conducting more studies on regional developing countries especially those with a high basis. Patients were found not to be approaching at proper prevalence of diabetes almost 100 percent of persons with OPD resulting in wastage of clinical expertise. Expert diabetes fall into its type-2 category . Type-2 Diabetes clinicians were not adopting proper inter departmental affects approximately 8% of adults in United States . referral system, perhaps due to avoiding denial from services and managing patients to the extant possible at their own level. Although there were no serious ethical concern associated with the adoption of referral system. Also, patients were approaching tertiary care hospital for some common ailments also which can easily be managed at primary and secondary care health facilities. Even after approaching they were not seeking treatment at proper OPD. This may be due to lack of proper awareness and guidance at the time of registration. Limitations of study : The study has several limitations Fig 3 — Showing the distribution pattern of non-communicable in terms of duration and 16

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diseases amongst patients attending OPD at UHTC (ELMC&H)


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crease in disease burden from communicable to noncommunicable diseases cannot be commented on the basis of this study as only 06 months data were analyzed. Also, the study reports diseases covered under IDSP (Integrated Disease Surveillance Project) only and some other diseases remain unreported. The study does not explore causes of the observed patterns also. Future scope of the study : The study has several implications for health care policy and practice. Observed patterns of communicable and non-communicable diseases among different sub group may be extrapolated at community levels and may be helpful for health planners to frame policies capable to facing future challenges. Observed distribution in OPD and IPD may guide health managers in strengthening and remodeling health care facilities in health institutions for attaining better satisfaction levels for both patients as well as health care providers. Further multi-centric long-term studies with wider coverage are desirable for studying disease trends suggesting better planning strategies. REFERENCES 1 The world health report 2002 : reducing risks, promoting healthy life. Geneva, World Health Organization, 2002. 2 Popkin BM — The shift in stages of the nutritional transition in the developing world differs from past experiences! Public Health Nutrition 2002, 5: 205-14. 3 Murray CJL, Lopez AD, eds — The global burden of diseases: a comprehensive assessment of mortality and diability from diseases, injuries, and risk factors in 1990 and projected to 2020. Cambridge, Harvard School of Public Health on behalf of the World Health Organization and the World Bank, 1996 (Global Burden of Disease and Injury Series, Vol.1. 4 Choi BCK, Bonita R, McQueen DV — The need for global risk factor surveillance. Journal of Epidemiology and Community Health 2001; 55: 370. 5 Sharma MK, Kumar D — Health Care Utilization Pattern For Communicable And Non-Communicable Diseases In A Tertiary Care Health Facility In Chandigarh, India. The Internet Journal of Health 2008; 7:. 6 Grahan SM — Respiratory problems in the tropics. In Gordon C. Cook and Alimuddin Zumla. Manson's tropical diseases 21st Ed. ELST with Saunders 2003, London NW- 1 7BY:149.

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7 Leser CF, Samuel I, Miller S — In: Harrisoris Principles of Internal Medicine 16th Ed 2005, pp 899, Mc Graw Hill Companies Inc. USA. 8 Ashavadi TF, Todur, Dherai AJ — Health Status of Indian Population-Current Scenario. J Asso Phys India 2004; 52: 363-9. 9 Swales JD — Essential hypertension. In: DJ Weatherall, JGG Ledingham and DA Warrell. Oxford Textbook of Medicine. III Ed Vol. 2 Seetien 11-17:2528. 10 Sharma MK, Swami HM, Gulati R, Bhatia V, Kumar D —Lifestyle Morbidity Profile of Geriatric Population in Urban Area of Chandigarh. Journal of the Indian Academy of Geriatrics 2005; 3: 122-5. 11 Mbanya JC, Guickshank JK, Beevers DB — Hypertension in tropics. In Gordon C Cook and Alimuddin Zumla. Manson's tropical diseases 21st Ed. ELST with Saunders 2003, London NW-1 7BY. 12 Shanthirani CS, Pradeepa R, Deepa R, Premalata G, Saroja R, Mohan V — Prevalence and risk factors of hypertension in a selected South Indian Population - The Chennai Urban Population Study. J Assoc. Physicians India 2003; 51: 20-7. 13 Anand MP — Epidemiology of hypertension. In: GS Sainani API Text Book of Medicine. 6th Ed, Mumbai, 1999: 401. 14 Hetzel BS, Zommet P, Seeman E — Endocrine and metabolic disorders. In. Detels R, Mceven J, Beag R, Tanaka H. Oxford textbook of Public Health 4th Ed. Oxford University Press, New York 2002: 1291. 15 Diabetes prevention programe Research Group. Reduction in the incidence of Type - 2 diabetes with life style intervention or metformin. N Engl J Med 2002; 346: 393-403. 16 Snehalatha C, Chandraru AR, Kapoor A, Vijay V — Age specific prevalence and risk association for impaired Glucose Tolerance in Urban Southern Indian Population. J Assoc Physicians India 2003; 51: 766-70. 17 Desai PB — Cancer control efforts in the Indian Subcontinent. Japanese Journal of Cinicl Oncology 2002; 32: 513-6. 18 Singh RB, Sud IL, Singh VP — Hypertension and Stroke in Asia: Prevention, control and strategies in developing countries for prevention. J Hum Hypertens 2000; 14: 749-63. 19 Gupta R, Gupta S, Gupta VP, Prakash H — The Prevalence and determinants of hypertension in the urban population of Jaipur in Western India. J Hypertens 1995; 13: 193-200.

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Observational Study A study on species prevalence of enterococci in clinical isolates and their antimicrobial resistance in central Rajasthan, India 1

2

Geeta Parihar , Surbhi Mathur

A total of One hundred and twenty five isolates of Enterococci were investigated for antimicrobial resistance and species distribution. Antimicrobial susceptibility to ten antimicrobial agents was performed by disk diffusion technique as recommended by Clinical and laboratory standard Institute(CLSI). Screening for vancomycin resistance was done by the vancomycin screen agar method and minimum inhibitory concentration (MIC) of vancomycin was determined for vancomycin resistant strains by microbroth dilution method. Enterococcus faecalis was found to be the predominant species 63.2 (79/125) followed by E faecium 34.4% (43/125). The remaining species 2.40% (3/125) were identified as E hirae 1.6% (2/125 ) and E durans 0.80% (1/125). The isolates were resistant to penicillin (53.6%) ampicillin (40%), high level gentamicin (53.6%), Erythromycin (98.40%) Quinupristin/ Dalfopristin (55.2%) Ciprofloxacin (76%), Tetracycline (20%) and teicoplanin (1.60%). None of the isolates were resistant to linezolid. Vancomycin resistance was found in 2 (1.60%) isolates. E faecium was more resistant to penicillin, ampicillin and high level genetamicin than E faecalis. Forty four ( 35.2%) strains showed multidrug resistance (MDR). Our study showed low prevalence of vancomycin resistance. However, there is a need to carry out regular surveillance of endemic prevalence and susceptibility patterns of Enterococci to prevent the spread of antimicrobial resistance in India. [J Indian Med Assoc 2017; 115: 21-4]

Key words : Vancomycin resistant enterococci (VRE), High level gentamicin resistance (HLGR), Minimum inhibitory concentration (MIC), Multidrug resistant (MDR), Clinical and laboratory standard Institute (CLSI).

E

nterococci are members of the normal flora in the gut of humans and animals but have emerged as important nosocomial pathogens in India as well as throughout the world. They have been associated with infections of the urinary tract, post surgical wounds, septicaemia, endocarditis and Meningitis (Cetinkay et al, 2000. Jones et al, 1997l; huycke et al, 1998). E-faecalis is the most frequent, enterococcal species isolated from human clinical specimens followed by E faecium (Buschetman et al, 1993, facklam et al 1989; Gordon et al, 1992; Mondino et al, 2003). The intrinsic and acquired antimicrobial resistance to a wide range of antibiotics is an important feature in the emergence of Enterococci as a cause of nosocomial infection (Hunt CP, 1998). Enterococci acquire resistance to several available antimicrobial agents by either Department of Microbiology, Jawaharlal Nehru Medical College, Ajmer 305001 1 MBBS, MD (Microbiol), Professor 2 MBBS, DIHBT, MD (Microbiol), Senior Demonstrator of Microbiology

mutation or by receiving the foreign resistance determinants through plasmids and transposons ( Murray, 1990). A combination of Penicillin and gentamicin had been the main stay of treatment of entrococcal infections till now but with the emergence of high level resistance to aminoglycosides and ampicillin in the last two decades, (Herman and Gerding, 1991; Grayson et al, 1991) vancomycin is the only alternative available. The widespread use of glycopeptides in hospitals has led to the emergence of VRE which is a major concern for health care professionals. Infection by VRE was first reported in France and UK and since then it has been documented from many countries world wide. There is a paucity of information on species prevalence and anti microbial resistance in Enterococci from India. The present study was undertaken to investigate species distribution and antimicrobial susceptibility of clinical isolates of Enterococci recovered at JLN Medical College and AG of Hospitals, Ajmer (Central Rajasthan, India) during March to September, 2009.


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Table 1 — Distribution and species identities of Enterococci from various

Patient’s Specimens and bacterial strains clinical samples During the study period a total of one hundred and No (%) of isolates Total twenty five enterococcal isolates were recovered Specimen Type from various clinical samples (pus, blood, would, E faecalis E faecium E hirae E durans swab, sputum, urine, etc) Department of 43 (54.43) 33 (41.77) 2 (2.53) 1 (1.26) 79 (63.20) Microbiology of JLN Medical College, and AG of Urine Pus and Hospitals, Ajmer. wound swabs 16 (94.11) 1 (5.88) 0 0 17 (13.60) The genus Enterococcus was indentified by the Blood 18 (69.23) 8 (30.76) 0 0 26 (20.80) following physiological land biochemical Specimens from lower respiratory characteristics, Gram reaction, catalase reaction, tract 2 (66.66) 1 (5.88) 0 0 3 (2.40) hydrolysis of l-Pyrrolidonyl-b napthylamide (PYR Body fluids 0 0 0 0 0 test), growth on bile esculin agar and 6.5% sodium CSF 0 0 0 0 0 79 (63.2) 43 (34.4) 2 (1.60) 1 (0.80) 125 (100) chloride media. For species identification of the Total isolates sugar fermentation, pigmentation, motility, Arginine hydrolysis and pyruvate utilization were spectively. High level gentamicin resistance (HIGR) was done. detected in 67 (53.6%) of the isolates. Resistance to Susceptibility Testing Antimicrobial susceptibility testing of the Enterococci Penicillin, ampicillin and high level gentamicin among was performed by the Disk diffusion method as E.faecium isolates was higher than E faecalis isolates. Out recommended by the clinical and laboratory standard of 67 HLGR strains, 74.62% and 64.17% were found to be Institute, 2009 (CLSI). The antimicrobial disks used were resistant to penicillin and ampicillin, respectively. The pencillin (IOU), ampicillin (10m g), Erythromycin (15m g) HLGR strains were mostly isolated from blood (61.53%) Quinupristin/dalfopristin (15m g), ciprofloxacin (5m g), followed by Urine (53.16% Almost all of the Enterococcal Tetracycline (30m g) Linezolid (30mg), vancomycin isolates were resistant to Erythromycin (98.40%) followed by ciprofloxacin (76%). Least resistance was seen for (30m g) and teicoplanin (30m g). High level aminoglycoside resistance (HLAR) was tetracycline (20%) and none of the isolates were resistant determined using gentamicin (120mg) disc. In this study, to linezolid. Only two isolates were found to be VRE of which one multiple drug resistance was defined as resistance to three or more antibiotics (Hujer et al, 2005) and the Screening was E faecium from blood & other was E.faecalis from for vancomycin resistance was done by vancomycin urine. The resistance pattern of VRE strains are shown in screen agar method using (6gmg /ml) vancomycin Table 3. The VRE strains showed high degree of resistance according to CLSI, recommendations. Minimum to most of the antibiotics tested but all VRE strains were inhibitory concentrations (MICs) of vancomycin were susceptible to linezolid. determined for VRE strains by microbroth dilution method. Control strains included E faecalis, ATCC 29212 Table 2 — Anti microbial Resistance pattern of Enterococcus (vancomycin susceptible) and fully characterized VRE species tested by Kirby Bauer disc diffusion method strain ( recovered from AIIMS, New Delhi), respectively. OBSERVATIONS

Species Distribution The distribution of isolates & their species among all the clinical specimens is given in Table 1. Of all the 125 isolates, 79 (63.20%) strains were isolated from urine; 17(13.60%) from pus and wound swabs; 26 (20.80%) from blood and 3(2.40%) from secretions of lower respiratory tract. E faecalis (63.2%) was the most common species isolated from the clinical samples followed by E faecium (34.4%). The other Enterococcus species (2.4%) comprise of E hirae (1.6%) and E durans (0.8%). Antimicrobial Resistance Antimicrobial resistance pattern of all the isolates are shown in Table2. Sixty Seven (53.6%) and 50(40%) of the isolates were resistant to penicillin and ampicillin, re-

Anti Microbial agents

No (%) of resistant strains

Total (n=125)

E faecalis E faecium Other (n= 79) (n = 43) enterococci (n = 3) Penicillin – G Ampicillin Gentamicin (HLGR) Erythromycin Vancomycin Teicoplanin Quinupristin / Dalfopristin Linezolid Ciprofloxacin Tetracycline

25 (31.64) 4 (95.34) 1 (33.33) 67 (53.6) 18 (22.78) 37 (86.04) 1 (33.33) 56 (44.8) 35 (44.30) 31 (72.89) 1 (33.33) 67 (53.6) 77 (97.46) 43 (100) 3 (100) 123 (98.40) 1 (1.26) 1 (2.32) 0 2 (1.60) 1 (1.26) 1 (2.32) 0 2 (1.60) 65 (82.27) 1 (2.32) 3 (100) 69 (55.2) 0 0 0 0 57 (72.15) 35 (81.39) 3 (100) 95 (76.00) 23 (29.11) 1 (2.32) 1 (33.33) 25 (20%)

HLGR = High Level Gentamicin resistance Include E – hirae (2) and E – Durans (1)

Table 3 — Species specific antibiotic resistance pattern of VRE isolates Antimicrobial agents

No (%) of VRE strains E faecalis (n=1)

Penicillin-G Ampicillin Teracycline Teicoplanin Linezolid Quinu pristin/ Dalfopristin Erthromycin Gentamiun (HLGR) Ciprofloxacin

Total (n=2)

E faecium Other (n=1) enterococci (n=0)

1(100) 1(100) 1(100) 1(100) 0

1(100) 1(100) 0 1(100) 0

0 0 0 0 0

2(100) 2(100) 1(50) 2(100) 0

1(100) 1(100) 1(100) 1(100)

1(100) 1(100) 1(100) 1(100)

0 0 0 0

2(100) 2(100) 2(100) 2(100)

Forty four (35.2%) resistance.

strains showed multi drug

DISCUSSION

The most frequent source of Enterococcal isolations in this study was urine (6.04%), which is consistent with the previous reports from India (MG Karmarkar et al. 2004; Mathur P et al, 2003). The majority of the clinical isolates were E faecalis (63.20%), followed by E faecium (34.4%), while other Enterococcus species accounted for 2.40% of isolates comparable to the distribution of species reported in earlier studies (Kacmaz & Aksoy, 2005). However, unlike those studies, our proportion of E faecium strains was higher than those reported previously. The prevalence of E faecium. in our study (34.4%) was comparable to the prevalence of E faecium reported in a study from Mumbai (80%) (Karmarkar et al, 2004). This finding is of clinical importance since E faecium is often more resistant than E faecalis, thus limiting the therapeutic options. Our study reveals that the prevalence of unusual species of Enterococci was 2.40% (Including 1.6% E hirae and 0.80% E durans) which was in accordance with previous studies (Perlada et al, 1997). Penicillin or ampicillin along with gentamicin is the drug of choice for treatment of Enterococcal infections. Therefore, resistance of Enterococci against these antibiotics has important clinical implications. Overall, in the present study, entercoccal species were resistant to penicillin and ampicillin, 53.6% and 40% respectively. Seventeen (13.6%) isolates were resistant to penicillin but susceptible to ampicillin similar to the data obtained in the earlier study (Miskeen and Deodhar, 2002). In this study, E faecium had higher frequency of resistance to penicillin (97.67%) and ampicillin (93.02%) than E faecalis (31.64%, 12.65%, respectively). Our results are consistent with other studies conducted elsewhere in India and abroad (Srifuengfung et al, 2004, Binay Thapa et al,

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2007, Mathur P et al, 2003). In our study, E faecalis accounted 44.30% whereas E faecalis revealed 72.0% resistance to high level gentamicin. This was lower than one study reported from India where 100% and 85.7% for E faecalis and E faecalis respectively were reported (Karmakar et al, 2004) but much lower than that obtained in another study from Delhi (Mathur P et al, 2003) in which they reported only 26% E faecalis strains to be HLGR. Our result is also contrary to the one reported in Turkey (Kacmaz & Aksoy, 2005), where E.faecalis accounted 16% resistance and E-faecium accounted 88%. Moreover, 64.17% of the total high level gentamicin resistant strains showed resistance to both penicillin and ampicillin signifying poor efficacy of combination therapy at least in this hospital, and this is a serious concern in the treatment of Enterococcal infections. Tetracycline resistance was found only 20% and none of the isolate was resistant to linezolid suggesting their possible role in VRE infection, 98.4% strains in this study were resistant to Erythromycin. which is in accordance to that observed in study conducted in New Delhi. (Mathur P, 2003). Thus, it can be said that Erythromycin is ineffective against Enterococci. In our study, only two (1.6%) strains were resistant to vancomycin and this was similar to previous studies (Kacmaz and Aksoy, 2005, Udo et al, 2003; Mathur P et al, 2003) but, contrary to the situation in most hospitals in the USA (Jones et al, 1997; Perlada et al, 1997) and Europe (Nelson et al, 2000, Schouten et al, 2000) where high prevalence of vancomycin resistance is common. One of the VRE strains in our study was isolated from blood and another from urine. All these VRE strains were also resistant to teicoplanin, high level gentamicin, penicillin and ampicillin. This implies that the combination therapy of high level gentamicin a and b lactam agents remain ineffective against these VRE infections in our clinical settings. But, the low prevalence of VRE in our study indicates that vancomycin retains its therapeutic efficacy against the majority of Enterococci in this hospital. Qunupristin/dalfopristin is almost ineffective to Efaecalis. (Maschieto et al, 2004). In our study, 82.27% of E-faecalis and 2.32% of E-faecalis strains showed resistance to this agent. This result was in concordance with the one reported from Korea (Oh et al, 2005). Our result indicates that these drugs alone do not assure their efficacy against entrococcal infections in this hospital, where most of enterococcal isolates were E-faecalis. All isolates tested were susceptible to linezolid. No, Indian study other than our is yet available reporting antibiotic resistance pattern to this agent. Binary Thapa et al, 2007 from Thailand found 8% of Enterococci to be resistant to linezolid. 35.2% enterococcal strains were resistant to three drugs plus high level gentamicin (120mg) and hence were labelled multidrug resistant


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(MDR). E-faecium was more resistant to commonly used antibiotics than other enterococcal species. Overall, this study revealed E-faecium as the most common species among the clinical isolates of Enterococci in JLN hospital, Ajmer. E.Faecium was isolated considerably in higher percentage than other studies Linezolid was found to be the most effective amongst the drugs tested followed by vancomycin and tetracycline. This study also showed low prevalence of vancomycin resistant enterococci but high prevalence of MDR strains and HLGR strains. Therefore, there is a need for development of Effective Strategies to address the problem of multi-drug resistance Speciation of Enterococcus needs to be carried out in clinical diagnostic microbiology lab in this hospitals in order to determine species specific drug resistance profile as that would be helpful in formulating local guideline for early treatment of enterococcal infections. It is also equally essential to conduct periodical surveillance of Enterococci to monitor changes in the antimicriobial resistance patterns and to prevent spread of resistant isolates. ACKNOWLEDGEMENT

I wish to give special thanks to Dr. Arti Kapil, Professor and Dr Benu Dhawan, Associate professor, Department of Micribiology, AIIMS New Delhi, for their gracious gift of enterococcal isolates which were used as standard in this investigation. REFERENCES 1 Cetinkaya Y, Falk P, Mayhall CG — Vancomycin-resistant enterococci. Clin Microbiol Rev 2000; 13: 686-707. 2 Jones RN, Marshaull SA, P faller MA, Wilke WW, Hollis RJ, Eruwin ME, Edmond MB, Wenzel RP — Nosocomial entero coccal blood stream infections in the SCOPE programme antimicrobial resistance, species occurence, molecular testing results and laboratory testing. accuracy. SCOPE Hospital Study Group Diagn, Microbiol Infect Dis 1997; 29: 95-102. 3 Huycke MM, Sahm DE, Gilmore MS — Multiple drug resistant enterococci: the nature of the problem and an agenda for the future. Emerg Infect Dis 1998; 4: 239-49. 4 Buschelman BJ, Bale BJ, Jones RN — Species identification and determination of high-level aminoglycoside resistance among enterococci. Comparison study of sterile body fluid isolates, 1985-1991. Diagn. Microbiol Infect Dist 1993; 16: 119-22. 5 Facklam RR, Collins MD — Identification of Enterococcus species isolated from human infections by a conventional test scheme. J Clin Microbiol 1989; 27: 731-4. 6 Gordon S, Swenson JM, Hill BC, Pigott NE, Facklam RR, Cooksey RC, et al — Antimicrobial susceptibility patterns of common and unusual species of enterococci causing infections in the United States. Enterococcal Study Group. J Clin Microbiol 1992; 30: 2373-8. 7 Mondino SSB, Castro ACD, Mondino PJJ, Carvalho MGS, Silva KMF, Teixeira LM — Phenotypic and genotypic. characterization of clinical and intestinal enterococci isolated from impatients and outpatients in two Brazilian hospitals-Microb. Drug Resist 2003; 9: 167-74.

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8 Hunt CP — The emergence of enterococci as a cause of nosocomial infection. Br J Biomed Sci 1998; 55: 149-56. 9 Murray BE — The life and times of the Enterococcus. Clin Microbiol Rev 1990; 3: 46-65. 10 Herman DJ, Gerding DN — Screening and treatment of infections caused by resistant enterococci-Antimicrob Agents Chemother 1991; 35. 11 Grayson ML, Elio poulos GM, Wennersten CB, Ruoff KL, De Girolami PC, Ferraro MJ, et al — Increasing resistance to beta lactam antibiotics among clinical isolates of Enter coccus faecium: a 22 year review at one institution. Anti microb Agents Chemother 1991; 35: 2180-4. 12 Clinical and laboratory standard Institute — Performance standards for Antimicrobial Disk Susceptibility test, Mo2 AIO 2009; 29. 13 Clinical and laboratory standard institute — Methods for Dilution Antimicrobial susceptibility tests for bacteria that grow aerobically M07-A8 2009; 29. 14 Hujer, Hujer KM, Hulten AM, Bajaksouzian EA, Adams S, Denskey JM, et al — Analysis of antibiotic resistance genes in multidrug resistant Acinetobacter sp. isolates from military and civilian patients treated at the Walter Reed Army Medical Center. Antimicrobial agents and Chemotherapy 2005; 50: 4114-23. 15 Karmkarkar MG, Gershom ES, Mehta PR — Enterococcal infections with special reference to phenotypic characterization and drug resistance. Indian J Med Res 2004; 119: 22-5. 16 Mathur P, kapil A, Chandra R Sharma P, Das B — Antimicrobial resistance in Enterococcus faecalis at a tertiary care centre of northern India. Indian J Med Res 2003; 118: 25-8. 17 Kacmaz B, Aksoy A — Antimicrobial resistance of entercocci in Turkey. Int J Antimicrob Agents 2005; 25: 535-8. 18 Perlada DE, Smulian AG, Cushion MT — Molecular Epidemiology and antibiotic susceptibility of enterococci in cincinnati Ohio : a prospective city wide survey. J clin microbiol 1997; 35: 2342-7. 19 Miskeen PA, Deodhar L — Antimicrobial susceptibility Pattern of Entercoccus species from urinary tract infections. J Assoc Physicians India 2002; 50: 378-81. 20 Srifuengfung S, Techachaiwiwat W, Sanpanya S, Dhiraputra C — The antibiotic susceptibility of Enterococcus species in Siriraj Hospital during 1994 and 2001. J Infect Dis Antimicrob Agents 2004; 2: 47-52. 21 Jhapa Binary, Unchalee Tatta wasort Anong lak Manjai Chantazg suk.: Antimicrobial Resistance and species prevalence of enter coccal isolates in Srinagarind hospital. North Eastern Thailand KKU Res J (GS) 2007; 7. 22 Nelson RR, Mc Gregor KF, Brown AR, Amyes SG, Young H — Isolation and characterization of glycopeptide resistant enterococci from hospitalized patients over a 30 month period. J Clin Microbiol Tun 2000; 38: 2112-6. 23 Schouten MM, Hoogkamp- Korstanje JA, Meis JF, Voss A — Prevalence of Vancomycin-resistant Enterococci in Europe. Eur J Clin microbiol Infect Dis 2000; 19: 816-22. 24 Maschieto A, Martinez R, Palazzo IC, Danni Al — Antimicrobial resistance of Enterococcus Sp. Isolated from the intestinal tract of patients from a Uni. Hospital in Brazil. Mem Inst Oswaldo Cruz 2004; 99: 763-7. 25 Oh WS, Ko KS, Song JH, Lee MY, Park S, Peck KR, et al — High rate of resistance to Quinupristin Dalfopristin in E Faecium. Clinical isolates from Korea. Antimicrobial Agents and Chemotherapy 2005; 49: 5176-8.

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Case Report Amlodipine — induced gingival overgrowth : a case report Pradip Kumar Chowdhury1, Subhadeep Gupta2, Manidipa Majumdar2, Apurba Kumar Mukherjee3, Jyotirmay Pal4 Amloidipine (a 3rd generation CCB) is a well known antihypertensive used as a first line drug for the treatment of hypertension.Calcium channel blocker particularly nifedipine can cause gingival overgrowth and it is well known to all physicians. Nifedipine have an additive effect when used together with cyclosporine in transplant recipient patients with hypertension. Other causes of gingival overgrowth are gingivitis, use of phenytoin, cyclosporine, as well as vitamin C deficiency, pregnancy, leukemia and sarcoidosis. Amloidipine is not well known offending agent for gingival overgrowth. The knowledge of this case report can help the physicians to reach a correct diagnosis as well as proper management of the patients with gingival overgrowth. [J Indian Med Assoc 2017; 115: 25 & 27]

Key words : Pulmonary actinomycosis, bronchiectasis, lobectomy.

A

mloidipine (a 3rd generation CCB) is a well-known antihypertensive used as a first line drug for the treatment of hypertension.Calcium channel blocker particularly nifedipine can cause gingival overgrowth and have an additive effect in this regard when used together with cyclosporine in transplant recipient patients with hypertension. Amloidipine is not well known offending agent for gingival overgrowth. But the knowledge of this case report can help the physicians to reach a correct diagnosis as well as proper management of the patients with gingival overgrowth. CASE REPORT

A 60 years female came to OPD for follow up of Hypertension. She was hypertensive for 10 years and on amlodipine 10 mg P/O/day for last 2 years. On examination her BP was control and blood sugar was normal but she complained for increasing gum swelling for last 6 months. There was no history of any other prescription drugs use during this time. Examination of the oral cavity revealed diffuse gingival swelling of both the upper and lower gums (Fig 1 & Fig 2). Swelling was painless, and there was no sign of inflammation or ulceration. Her oral hygiene was normal. Systemic examination was normal and laboratory tests appropriate to exclude other possible differential diagnosis were also normal. After excluding other potential causes, we considered the diagnosis of amlodipineinduced gingival overgrowth. DISCUSSION

Calcium channel blocker particularly nifedipine can cause gingival overgrowth in as high as 20% patients . Nifedipinehave 1

Department of General Medicine, R G Kar Medical College & Hospital, Kolkata 700004 1 MBBS, MD, RMO cum Clinical Tutor 2 MBBS, Junior Resident 3 MBBS, MD, Professor and Head 4 MBBS, MD, Professor

an additive effect when used together with cyclosporine in transplant recipient patients with hypertension .Amloid ipine (a 3rd generation CCB) is not well k n o w n o ff e n d i n g agent for gingival Fig 1 — Showing gingival swelling in overgrowth but there are upper gum few case reports. In one series prevalence up to 3% reported. Though there is no sexual predilection for drug-induced gingival overgrowth but males were three times more developed gingival overgrowth with CCB Fig 2 — Showing diffuse gingival than females revealed swelling in lower gum in one study. Other causes of gingival overgrowth are gingivitis, use of phenytoin, cyclosporine, as well as vitamin C deficiency, pregnancy, leukemia and sarcoidosis. The reason for this adverse event is not absolutely known, but mechanisms involving inflammatory and non-inflammatory pathways have been suggested. Calcium channel blockers alter membrane permeability to calcium; as a result collagenases production is reduced or inhibited. Thus, increased fibroblastic proliferation and collagen synthesis occurs. Individual sensitivity to a drug’s metabolic pathway might be a trigger and possibly there is genetic predisposition . 2,3

[4]

4,5,6

(Continued on page 27)


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management of a difficult paediatric airway . Since our patient had extension into the mouth but not obliterating laryngoscopic view we could do a successful laryngoscopy. Epiglottis was deviated to the right side by mass but external manipulation allowed successful intubation. Kim et al reported endobronchial dislodgement of the tube which led to desaturation requiring discontinuation of surgery and reintubation . To avoid such mishap, we chose to manually hold the tube at the tip despite of fixing it with elastic adhesive tape. This prevented accidental migration and extubation. Considering the difficult airway and postoperative airway edema we kept the baby on elective ventilation. Baby was extubated on 3rd postoperative day. 7

Anaesthetic management of cystic hygroma in neonate Sushma Ladi1, Pallavi Singh2, Sarita Swami3, Jyotsana Bhosale4, Shubhada Aphale5

8

15 day old neonate presented with cystic hygroma on left side with difficulty in breathing planned for excision. Anaesthetic implication in this case were maintaining airway patency, difficult intubation, risk of perioperative dislodgement of tube and judgment of proper time for extubation. Baby was intubated with inhalational induction. Endotracheal tube was held after fixing it to avoid accidental extubation. Neonate was ventilated because of airway difficulties.

CONCLUSION

[J Indian Med Assoc 2017; 115: 26-7]

Management of neonate with huge cystic hygroma requires adequate preparation and vigilance not only for securing the airway but also for intraoperative management of tube avoiding accidental extubation and determining the appropriate time for extubation.

Fig 2 — Manual holding of tube

was electively ventilated in the neonatal intensive care unit. The baby was ventilated for three days and then weaned off.

Key words : Cystic hygroma, difficult airway, neonatal anaesthesia, neonatal intensive care unit.

DISCUSSION

T

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he incidence of cystic hygroma is approximately 1:6000 live births . 70-80 % of cystic hygromas occurs in the neck, usually in the posterior cervical triangle . The remainder 20-30% occurs in axilla, superior mediastinum, chest wall, mesentery, retroperitoneal region, pelvis and lower limbs . Cystic hygroma is known to present at birth in about 50% of the affected newborns and 90% present by the age of 2 years. Anaesthetic concerns include difficulty in visualizing the airway, extrinsic and intrinsic pressure obstructing airway and bleeding. We are reporting an airway crisis in a paediatric patient admitted with severe respiratory distress due to huge cystic hygroma arising from the neck and extending into the base of the tongue, pharyngeal space, and mediastinum. In addition to involving the laryngeal inlet it also caused deviation and minimal compression at the trachea. 1

2

3

CASE REPORT

A 15 day old, 3 kg male baby was planned for surgical removal of cystic hygroma on left side of the neck. Caesarean section was performed at 37 weeks and baby was shifted to neonatal intensive care unit for respiratory distress and kept on CPAP (continuous positive airway pressure). Baby was off CPAP on 5th day of life. USG neck showed cystic hygroma of 16x8x12 cm with multiple septations on left side of the neck, left lobe of thyroid displaced inferiorly, mass displacing trachea towards right side with minimal compression. Computerized tomography (neck) showed cystic hygroma with mediastinal extension. The mass extended to right submandibular space and floor of mouth. An IV line was secured in the operation room. Difficult airway cart, tracheotomy set and fiberoptic bronchoscope 3.5mm were kept ready. Pulse oximeter, non invasive blood pressure, electrocardiogram, and temperature probe were attached. Inj. glycopyrrolate 0.01mg iv given. Department of Anaesthesiology, Bharati Vidyapeeth University Medical College, Pune 411043 1 MD, Professor 2 Senior Resident 3 MD, Professor 4 MD, Lecturer 5 MD, Professor and Head

Patient was induced with sevoflurane 3% and 100% oxygen. Inj fentanyl 1 mcg and Inj Ketamine 3 mg were given. Mask ventilation was difficult but was facilitated by lifting the mass. After adequate mask ventilation and achieving adequate depth, direct laryngoscopy was done with Macintosch 0 no blade which revealed deviated epiglottis. By holding the mass from outside and keeping the neonate in lateral position (Fig1) intubation was done with a 3mm uncuffed portex endotracheal tube. Placement was confirmed by ventilation and end tidal carbon dioxide tracing. The endotracheal tube was fixed at 9cm following which Inj vecuronium o.o8 mg/kg was given. The tube was manually held at the angle of the mouth throughout the surgery to avoid any mishap (Fig 2). Patient was maintained on controlled ventilation with N O in O (50:50), sevoflurane (1-2%), vecuronium and 6mcg of fentanyl. Ringer’s lactate 165 ml and 40 ml packed RBCs were administered IV. The total blood loss was 40 mL The patient maintained saturation of 98-100% and was hemodynamically stable. Urine output was 60 ml. Dexamethasone (0.6mg) and hydrocortisone (6mg) was given to prevent edema. The patient 2

2

We report an unusual case of neonatal cystic hygroma of neck and mediastinum. Neonates owing to their high O consumption, lesser muscle composition and thoracic cage structure are at high risk of desaturation in case of prolonged laryngoscopy. Even in expert hands successful intubation occurs in 60% cases. Huge lump in neck deviation of the trachea makes the situation challenging Different options are available for intubation. Though fiberoptic (FOB) is an ideal technique, paediatric bronchoscopic intubation needs experience, skill, expert assistant, and proper size fiberoptic scope. Smooth inhalational induction, deep plane of anaesthesia and maintenance of spontaneous ventilation are also needed. Paediatric FOB have a minimal external diameter of 2.2-5.5 mm, we had 3.5mm FOB over which a 4mm ETT could be negotiated . This child needed a 3 mm tube. Due to indistinguishable landmarks, tracheostomy is impossible. Inhalational anaesthesia remains the preferred technique for 2

[4]

5,6

REFERENCES

1 Dahnert W — Radiology review manual. 2nd edition. Arizona: Williams & Wilkins; 1993. 2 Song TB, Kim CH, Kim SM, Kim YH, Byun JS, Kim EK — Fetal axillary cystic hygroma detected by prenatal ultrasonography: a case report. J Korean Med Sci 2002; 17: 400-2. 3 Manikoth P, Mangalore GP, Megha V — Axillary Cystic Hygroma. J Postgrad Med 2004, 50: 215-6. 4 Sharma S — Aminuldin AG Cystic Hygroma: Anaesthetic considerations and review. Singapur Med J 1994; 35: 52931. 5 Bryan Y, Chwals W, Ovassapian A — Sedation and Fiberoptic intubation of a neonate with a cystic hygroma. Acta Anaestesiol Scand 2005; 49: 123-3. 6 Stiles CM — A flexible fiberoptic bronchoscope for endotrachealintubation of infants. Anaest Analg 1974; 53: 1017-9. 7 Al Salem AM — Lymphagiomas in infancy and childhood.Saudi Med J 2004; 25: 466-9. 8 Kim H, Kim HS, Oh JT, Lee JR — Anaesthetic managemrnt for neonate with giant cystic hygroma involved upper airway: A case report. Korean J Anaesthesiol 2011; 60: 201-13.

(Continued from page 25)

CONCLUSION

Amlodipine is a common drug used for Hypertension. So every physician should be aware of this entity because untreated gingival overgrowth can cause ulceration, bleeding, pain, teeth displacement and periodontal infection.The knowledge of this case report can help the physicians to reach a correct diagnosis as well as proper management of the patients with gingival overgrowth.

3

4 5

REFERENCES

1 Nery EB, Edson RG, Lee KK, Pruthi VK, Watson J — Prevalence of nifedipine-induced gingival hyperplasia. J Periodontol 1995; 66: 572-8. 2 Tavassoli S, Yamalik N, Caglayan F, Caglayan G, Eratalay K Fig 1 — Pre-op airway maintenance

6

— The clinical effects of nifedipine on periodontal status. J Periodontol 1998; 69: 108-2. Bahamondes C, Godoy J — Cyclosporine-induced gingival hyperplasia: report of one case. Rev Med Chil 2007; 135: 370-4. Jorgensen MG — Prevalence of amlodipine-related gingival hyperplasia. J Periodontol 1997; 68: 676-8. Ellis JS, Seymour RA, Steele JG, Robertson P, Butler TJ, Thomason JM — Prevalence of gingival overgrowth induced by calcium channel blockers: a community based study. J Periodontol 1999; 70: 63-7. Prisant LM, Herman W — Calcium channel blocker induced gingival over-growth. J ClinHypertens (Greenwich) 2002; 4: 310-1.


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Case Report Primary insular carcinoid tumour of ovary : a rare case report Jayashree G Pawar1, Nischita Budihal2, Ranjana R3, Chatura K R1 Ovarian carcinoids are the second most frequent monodermal teratomas. They represent less than 1% of ovarian teratomas. Ovarian primary carcinoid tumors can pose a significant diagnostic challenge in its separation from metastatic carcinoids from the gastrointestinal tract. Yet, their clinical management and prognosis are drastically different. We report a 12cm ovarian insular carcinoid tumor in a 55 year old postmenopausal woman who had no evidence of extraovarian tumour which on histological examination revealed features of insular carcinoid. Clinicopathologic features of unilaterality and early stage favor a primary ovarian neoplasm.

Fig 1 – Solid unilateral tumor with nodular surface with cut section of the tumor mass showing brown to yellow (tan) to pale grey areas

[J Indian Med Assoc 2017; 115: 28-9]

Key words : Ovarian tumors, insular, neuroendocrine,teratoma.

O

varian carcinoids are the second most frequent monodermal teratoma . Primary ovarian carcinoid tumors are so very rare, accounting for only 0.3% to 1% of all carcinoid tumours . Furthermore, because these tumors account for <0.1% of all ovarian neoplasms, they may not be suspected by the gynecologic surgeon and remain undiagnosed until the time of surgery . These tumors contain extensive components of well differentiated neuroendocrine cells and most subtypes resemble carcinoids of gastrointestinal tract . Primary carcinoids are subdivided into four categories : (1) insular, (2) trabecular, (3) strumal, and (4) mucinous. Insular carcinoid tumour is the most common followed by trabecular and mucinous types. It usually arises in association with gastrointestinal or respiratory epithelium present in a mature cystic teratoma . Gross Features : The carcinoid may vary in size from microscopic to 20 cm in greatest dimension and is solid and homogeneous . Cut surface is firm, homogenous and tan to yellow . Primary ovarian carcinoids practically always are unilateral . Microscopic Features : Primary ovarian insular carcinoid usually shows the typical appearance associated with midgut carcinoids .The tumour is composed of collections of small acini and solid nests of uniform polygonal cells with ample amounts of cytoplasm and round or oval, centrally located hyperchromatic nuclei . Mitotic activity is low . The cytoplasm is basophilic or amphophilic and may contain red, brown, or orange argentaffin or argyrophil granules, which are demonstrated in the majority of cases of primary ovarian carcinoids . Immunohistochemical Features : Demonstration of immunohistochemical expression of chromogranin and synaptophysin further supports the diagnosis and has become the method of choice to confirm the diagnosis . 1

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Department of Pathology, Jagadguru Jayadeva Murugarajendra Medical College, Karnataka 577004 1 MD (Pathol), Professor 2 Postgraduate student 3 MBBS, (DCP), Postgraduate student

Differential Diagnosis : Primary insular carcinoid of the ovary must be differentiated from metastatic insular carcinoid of the ovary, which is usually of gastrointestinal origin. Metastatic carcinoid nearly always affects both ovaries, unlike primary ovarian carcinoid, which is unilateral. Macroscopically, the metastatic carcinoid is composed of tumour nodules, whereas primary ovarian carcinoid forms a single homogeneous mass. Presence of other teratomatous elements associated with an ovarian carcinoid confirms that it is primary . 6

CASE REPORT

A 55 year old postmenopausal woman presented with mass per abdomen since 1½years, gradually increasing in size associated with pain in abdomen. Abdominal palpation revealed a mass in left hypogastric region extending up to midhypogastrium. USG was reported as sub serosal fibroid. On laparotomy, a left sided irregular solid mass m/s 12x12 cm was present. Uterus was 10 week size with a small fibroid at the posterior pole. No secondary deposits seen within the omentum . Panhysterectomy specimen sent for histopathological analysis showed bosselated uterus and eroded cervix. On cut section uterus, intramural fibroid was present (Fig 1). Right adnexa unremarkable. Left fallopian tube was stretched and adhered on to the tumor mass. Left ovary measured 12x12x7 cm, nodular surface, hard in consistency, dilated blood vessels seen. On cut section ovary, solid grey yellow areas seen. No areas of hemorrhage / necrosis. On microscopy, left ovarian mass showed tumor tissue .Tumor cells were arranged in round, oval and angular islands with some peripheral pallisading. Also seen were some acini diffusely distributed with eosinophilic secretion within the lumen (Fig 2). The tumor cells were remarkably uniform, round to polygonal with abundant basophlic to amphophilic cytoplasm and rounded central nuclei with stippled chromatin, at places nuclei were hyperchromatic. Tumor nests separated by fibromatoid stroma (Fig 3). Occasional mitotic activity seen. Focally trabecular areas seen.

Fig 2 — Showing primary insular carcinoid tumor of ovary showing typical solid and acinar pattern of midgut carcinoid H&E, 40X

Fig 3 — Showing Primary insular carcinoid tumor of ovary showing stroma is dense, fibroma like, H&E, 10X

because of the following evidences that support the diagnosis strongly: (1) It was a unilateral, large, homogenous, solitary mass (2) Not associated with teratomatous elements (3) Possibility of metastasis was excluded by extensive search for primary in other organs (4) On cut section, tumor was grayish yellow, smooth, homogenous. No areas of haemorrhage/ necrosis seen (5) Microscopy showed insular pattern of primary carcinoid of ovary which is the most common type of ovarian carcinoid tumor after trabecular carcinoid of ovary (6) In this case patient gave history of flushing, excessive sweating and intermittent diarrhea suggestive of carcinoid syndrome. REFERENCES

DISCUSSION

Carcinoid ovarian tumors seen mostly in peri/postmenopausal women and may occur in pure form or combined with other teratomatous elements . Differential diagnosis includes metastatic carcinoids, Brenner tumor, granulosa cell tumor, sertoli-leydig cell tumor which can be excluded by their characteristic features on microscopy . Stanely J Robboy describes 2 cases of insular carcinoid (1984) which arose in cystadenoma of borderline malignancy and the other in mucinous adenocarcinoma. Prior studies have shown that 5% of well differentiated carcinoids can act aggressively . Jorge Dotto, Thomas Mezetti, Pei Hui studied a case of primary carcinoid tumor of pure histological type with absence of teratomatous component (2008), confirmed that it was primary, by demonstrating its germ cell origin through DNA genotyping . A Talerman reported 3 cases of primary trabecular carcinoid of ovary (1982). In 2 cases, tumor was pure trabecular carcinoid and in third it was associated with mature cystic teratoma He also documented in his study that carcinoid tumors of ovary have low malignant potential . However, Baker PM, Oliva E, Young RH et al discussed in their report that women in stage 1 who would like to preserve their ovarian function can elect a unilateral salphingo oophorectomy with close follow up . Thus an early diagnosis of primary ovarian carcinoid can prevent secondaries in other organs and thus offer better prognosis to the patients . 6

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CONCLUSION

This case is more in favor of primary carcinoid of ovary

1 Prat J — Pathology of ovary.1st edn. Newyork: Saunders 2004: 271-4. 2 Maggard MA, O’Connell JB, Ko CY — Updated population based review of carcinoid tumours. Ann Surg 2004; 240: 117-223. 3 Somak R, Shramana M, Vijay S, Nita K — Primary carcinoid tumour of the ovary: A case report. Arch Gynecol Obstet 2008; 277: 79-82 4 Modlin IM, Shapiro MD, Kidd M — An analysis of rare carcinoid tumours: Clarifying these clinical conundrums. World J Surg 2005; 29: 92-101. 5 Robboy SJ, Russell P, Prat J — Ovarian Germ cell tumours. In: Robboy SJ, Mutter GL, Prat J, Bentley RC, Russell P, Anderson MC. Pathology of female reproductive tract. 2nd ed. Churchill Livingstone Elsevier 2009: 761-5. 6 Talerman A, Vang A — Germ cell tumours of the ovary. In: Kurman RJ, Elleson LH, Ronett BM. Blaustein‘s Pathology of the Female Genital Tract. 6th edn, Springer 2011: 883-5. 7 Baker PM, Oliva E — Germ cell tumours of Ovary. In : Nucci MR, Oliva E.Gynecologic Pathology. 1st edn, Churchill Livingstone Elsevier 2009: 527-30. 8 Robboy SJ — Insular carcinoid of ovary associated with malignant mucinous tumours. Cancer 1984; 54: 2273-6. 9 Dotto J, Mezzetti T, Hui P — Primary or Secondary?Genotyping Confirmation of an Ovarian Primary Carcinoid Tumor. Int J Gynecol Pathol 2008; 27: 33-6. 10 Talerman A, Evans MI — Primary trabecular carcinoid of the ovary. Cancer 1982; 50: 1403-7. 11 Baker PM, Oliva E,Young RH, Talerman A, Scully RE — Ovarian mucinous carcinoids including some with a carcinomatous component: a report of 17 cases. Am J Surg Pathol 2001; 25: 557-68.


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Case Report

Case Report

Malignant melanoma of the eyelid : a rare entity

Pulmonary actinomycosis with bronchiectasis

1

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Chongtham Sarda Devi , Lukram Ajit Singh , Gautam Mukhopadhyay

Ajithkumar C S

Malignant melanoma of the eyelid is a rare entity, which accounts for about 1% of all eye malignancies. We present a case of a 66 year old female who had a nevus on the right lower eyelid since childhood and which gradually involved the whole lower and upper right eyelid, with extension into the lateral periocular area. Metastatic workup was done and there was no evidence of metastasis. Excisional biopsy was done and histopathology confirmed a diagnosis of malignant melanoma. Malignant melanoma is an invasive proliferation of malignant melanocytes. Cutaneous malignant melanoma of the eyelid accounts for about 1% of all eyelid malignancies, excluding the conjunctival surface. Cutaneous malignant melanoma arises from the neoplastic transformation of intraepidermal melanocytes derived from the neural crest. This is a case of malignant melanoma involving both the right upper and lower eyelid and the lateral periocular area.

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1

54 year old male chronic alcoholic, diabetic patient presented with massive hemoptysis. He had cough with sputum and fever for the past one week period. Examination showed marfanoid habitus and digital clubbing. Respiratory system showed asthenic chest with findings of right lower lobe bronchiectasis. No hepatic flap was there. Chest X ray showed right lower lobe bronchiectasis with bronchopneumonia but no rib erosion or osteomyelitis were there. HRCT Thorax revealed right lower lobe bronchiectasis without rib lesions or pleural effusion. Due to massive hemoptysis and localized disease patient undergone right lower lobectomy. Lobectomy specimen on histopathology revealed actinomycosis with sulphur granules and bronchiectasis. Postoperatively patient received intravenous penicillin against complications in lung actinomycosis including bronchopleural fistula and relapse. [J Indian Med Assoc 2017; 115: 31-4]

[J Indian Med Assoc 2017; 115: 30 & 34]

Key words : Pulmonary actinomycosis, bronchiectasis, lobectomy.

Key words : Malignant melanoma eyelid.

A

66 year old woman presented with a raised lesion involving both the right upper and lower eyelid (Fig 1) and the right lateral periocular area for the past 3 years. She gave a history of a nevus in the right lower eye lid since childhood. It was painless and was progressively increasing in extent over the last 3 years. On examination, there was a lesion in the right eyelid with elevated, nodular thickening (about 6 mm thick) of both the lid margins lateral to the puncta and extended upto the upper lid crease. The lateral 2/3rd of the right lower lid and about 2.5 × 2 cm from the lateral canthus was also involved. Both the upper and lower palpebral conjunctiva were involved, sparing the bulbar conjunctiva. The lesion was nodular, painless, brown to black in colour, non- ulcerated and not associated with any discharge. The best corrected visual acuity was 6/9P, N6 in both eyes. She had bilateral nuclear sclerosis grade 1 and posterior subcapsular cataract and the posterior segment examination was normal. Examination – Systemic examination was normal with no palpable lymphadenopathy. Metastatic work up was done including (a) ultrasound (USG) neck which was normal, (b) chest X- ray showing no abnormality, (c) liver function test (LFT) within normal limits, (d) serum urea was 19 mg/dl, serum creatinine was 0.9 mg/dl, (e) whole body positron emission tomography (PET) scan showing increased FDG (fludeoxyglucose) uptake in the region of the right eyelid corresponding to the lesion clinically seen. The blood investigations were total count - 5500/mm , hemoglobin count 11.4 gm/dl, platelet count - 2.4 lakhs/mm , prothrombin time (PT) – 12.8 secs, activated partial thromboplastin time (APTT) – 29.7 secs and international normalized ratio (INR) – 1.01. A wide surgical excision of the lesion (Fig 2) with a 3 mm 3

3

Sankara Nethralya, Kolkata 700099 1 DNB (Ophthalmol), Registrar 2 DNB (Gen Surg), Senior Registrar, Ruby General Hospital, Kolkata 700107 3 MS, Consultant Oncosurgeon, Ruby General Hospital, Kolkata 700107

P

ulmonary actinomycosis is a difficult condition to di-agnose. Even among experienced physicians, sometimes despite pointers to the disease, delayed diagnosis or misdiagnosis as tuberculosis, lung abscess or lung cancer is common . An increased awareness of the infection may expedite diagnosis and prevent undesirable complications, including unwarranted surgery. A higher incidence of pulmonary actinomycosis has also been reported in patients with underlying respiratory disorders such as bronchiectasis, emphysema, chronic bronchitis and in alcoholics . The pulmonary form of actinomycosis constitutes 15% of the total burden of disease, although estimates of up to 50% have been reported . 1

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Fig 1 — Pre-operative picture of malignant melanoma of the right eyelid

margin was done under general anaesthesia. The upper and lower eyelids were compromised with only about 2 mm of upper tarsus remaining. For reconstruction of the upper lid, the nasal cartilage was taken and sutured to the remaining upper tarsus on the right eye. The skin and orbicularis oculi muscle from above the right eyelid were undermined and an advancement flap was created to cover the tarsal graft and the lateral periocular excised area. Again, for the lower lid, an advancement flap from the skin and muscle of the cheek was used for reconstruction. Postoperatively, there was no lagophthalmos or corneal exposure on closing the eye and cosmetic appearance was acceptable. Histopathology confirmed malignant melanoma with tumour infiltrating into underlying tissues and pagetoid spread to overlying skin, the Breslow’s depth was 4.2 mm. DISCUSSION

Malignant melanoma of the eyelid accounts for about 1% of all eyelid malignancies and accounts for less than 7% of head and neck region cutaneous melanomas . The incidence increases with age but remains relatively stable from the fifth to seventh decade. The upper or lower eyelid may be involved and nodular type is the most common

1,4,5,6

CASE REPORT

54 Year old male diabetic, chronic alcoholic with hepatic cirrhosis presented with massive hemoptysis . He had cough with yellowish expectoration and right sided chest pain and fever for past one week. He was on treatment for type 2 diabetes mellitus with oral hypoglycemic agents. Patient also had loss of appetite. Examination — The Patient had marfanoid habitus and he was ill nourished with finger clubbing. Tachypnoea and tachycardia was there with blood pressure of 124/76 mm Hg in right arm in supine position. Respiratory system examination revealed findings of right lower lobe bronchiectasis. Abdomen examination showed no hepatomegaly, no splenomegaly or ascites but with normal bowel sounds.

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(Continued on page 34)

1 MBBS, DNB (Respiratory Diseases), FCCP, Assistant Professor of Pulmonary Medicine, Government Medical College, Thrissur 680596

On cardiovascular system examination JVP was not found elevated; heart sounds normal and there was no murmur. Laboratory evaluation revealed hemoglobin of 11.6 gm per dL with total WBC count of 8200 cells per cmm. Differential count showed 81% polymorphs and 11% lymphocytes with ESR 72 mm in the first hour. Platelets count was 106000 per cmm. PCV was 34%. LFT showed bilirubin of 1 mg per dL, total protein 5.4 gm per dL with albumin 2.3 gm per dL and globulin 3.1 gm per dL. ALT was 49 IU/L with AST of 61 IU/L and alkaline phosphatase of 109 IU/L. Sodium was 136 mmol/L and potassium was 5.1 mmol/L. Bleeding time was 2 minutes 45 seconds with clotting time of 10 minutes. Pulmonary function test report was mild obstruction with restriction. Echocardiography revealed good LV function. Chest Xray showed (Fig 1) right lower lobe bronchiectasis. USS abdomen report was cirrhosis liver with portal hypertension and mild splenomegaly. HRCT thorax showed right lower lobe bronchiectasis with surrounding consolidation and no ymph adenopathy nor pleural effusion. HIV & HBsAg were negative. Lobectomy specimen histopathology examination showed features suggestive of pulmonary actinomycosis with sulphur granules and bronchiectasis surrounding lung showing pulmonary oedema, hemorrhage and hemosiderosis (Fig 2 & 3). Sputum AFB was negative. Sputum gram stain result was mixed pharyngeal flora. Sputum culture was sterile. Due to massive hemoptysis and localised nature of bronchiectasis thorocotomy done with right lower lobectomy. Post operatively patient received parenteral penicillin for 6 weeks followed by 6 months oral penicillin to prevent complications including


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oropharyn geal or gastrointestinal secretions into the respiratory tract . Poor oral hygiene and associated dental disease may increase the risk . Support for aspiration as a risk factor comes from reports of a higher prevalence of alcoholism in patients with the pulmonary form of the disease and from the basilar predominance of the disease radiologically . Previous presentation of pulmonary actinomycosis with prominent chest pain and cutaneous fistulas discharging sulphur granules has changed with time in line with the decrease in the disease prevalence . The commonest presentation is probably now as a shadow on a chest radiograph. Marked weight loss, malaise and high fever may be more suggestive of disseminated disease . Typical respiratory symptoms of patients with thoracic actinomycosis are cough in 84%, sputum in 74% ,chest pain in 68%, dyspnoea in 47%, haemoptysis in 31%, localised chest-wall swelling in 10%. Systemic symptoms are weight loss (53%) malaise (42%), night sweats (32%), fever (21%) . Physical signs are equally nonspecific, except in advanced, untreated disease, when sinuses and fistulae may then give the diagnosis away. The findings are occasionally those of the associated complications, such as pleural effusion or empyema. Plain chest radiograph findings in actinomycosis are nonspecific. A nonsegmental pneumonia, usually in the lower zones, tends to occur peripherally crossing fissures. The disease usually shows a peripheral and lower lobe predominance, probably reflecting the role of aspiration in its pathogenesis. The CT is probably more helpful than the plain radiograph, particularly if performed with a bone window display, which gives a better delineation of minimal bony change, such as early rib erosion and osteomyelitis. Fibreoptic bronchoscopy is usually not diagnostic in pulmonary actinomycosis unless there is clear endobronchial disease on which biopsy can be performed . Traditionally, excisional biopsy was the definitive diagnostic procedure . In general, an attempt at establishing diagnosis by percutaneous biopsy with fine needle aspiration or core biopsy is now made before “blind” thoracotomy . The rationale for the use of penicillin in actinomycosis is based more on extensive successful clinical experience over the last 50 years than on randomised control trials . The main principle of treatment is the use of high-dose intravenous penicillin for a long duration of treatment. Although treatment has to be tailored to the individual, generally 18-24 million units of penicillin per day are given for 2-6 weeks followed by oral therapy with penicillin V (or amoxicillin) for 6-12 months. In general, the thoracic form appears to require longer treatment courses compared to the other commoner forms. 8

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Fig 3 — H&E staining showing lung actinomycosis

Fig 1 — CXR PA showing right lower lobe bronchictasis

the relapse and broncho pleural fistula. Follow up period was uneventful. DISCUSSION

Actinomyces spp. are higher prokaryotic bacteria belonging to the family Actinomyceataceae. When they were first described in the early 19th Century, they were misclassified as fungi . The word “actinomycosis” was derived from the Greek terms aktino, which refers to the radiating appearance of a sulphur granule, and mykos, which labels the condition a mycotic disease. Pulmonary actinomycosis is a difficult condition to diagnose. Even among experienced physicians sometimes despite pointers to the disease delayed diagnosis or misdiagnosis as tuberculosis, lung abscess or lung cancer is common. 7

An increased awareness of the infection may expedite diagnosis and prevent undesirable complications, including unwarranted surgery, in patients under investigation for persistent pulmonary shadowing. The pulmonary form of actinomycosis constitutes 15% of the total burden of disease, although estimates of up to 50% have been reported. Pulmonary actinomycosis is having peak incidence in the 4th and 5th decades . The incidence of infection is two to four times greater in males compared with females . A higher incidence of pulmonary actinomycosis has also been reported in patients with underlying respiratory disorders, such as emphysema, chronic bronchitis and bronchiectasis, and in alcoholics. Members of the genus Actinomyces are Gram-positive, non spore-forming, predominantly anaerobic prokaryotic bacteria belonging to the family Actinomyceataceae. They are bacteria rather than fungi. Six of these are thought to be pathogenic in humans, including A israelii, A naeslundi, A odontolyticus, A viscosus, A meyeri and A gerencseriae. A israelli is the organism most commonly incriminated in human disease. Culture requires brain/heart enriched agar and the organisms grow best at a temperature of 37 C in an atmosphere of 6-10% ambient carbon dioxide. Characteristically, colonies of Actinomyces appear as “molar-tooth” or “bread-crumb” colonies in broth media after 3-7 days of incubation. Most of the literature classifies the tissue response as granulomatous or “granulomatoid-like”, although giant cells and granulomata are rarely seen . Sulphur granules are the pathological hallmark of the disease. These are round or oval basophilic masses with a radiating arrangement of eosinophilic clubs on the surface; they sometimes can be seen even with a magnifying glass. The name “sulphur granule” has its origin in the small nodules resembling elemental sulphur that were commonly used in pharmaceuticals in the 19th century . Pulmonary actinomycosis probably results from aspiration of 3,8

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Fig 2 — H&E stain of lobectomy specimen showing the ray like arrangement and sulphur granules

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Tetracyclines are the alternative especially for penicillinallergic patients. In pregnant, penicillin-sensitive patients, erythromycin is a safe alternative. Commonly used antibiotics in the treatment of actinomycosis are a) efficacious drugs like penicillin (MIC range < 0.25-0.5 mg per ml),tetracycline (doxycycline) (MIC range 0.5-0.8 mg per ml), erythromycin (MIC range <0.25-1 mg per ml clindamycin (MIC < 0.25-0.5 mg per ml) and b) drugs with probable efficacy which includes imipenem (MIC 0.125 mg per ml,ceftriaxone (MIC <0.06-2 mg per ml). Presumably, the avascularity and induration of infected areas account for the need for prolonged treatment and undoubtedly longer course minimise the risk of relapses, a clinical hallmark of the infection. Response to treatment should be monitored radiologically with plain radiographs and/or CT. Diminution in the shadowing on a chest radiograph is expected within 4 weeks. Evidence shows that this standard treatment approach applies to people who are immunocompromised forone reason or another . When surgery has been the initial treatment, even if histology suggests complete resection, it still needs to be followed by prolonged antibiotic therapy, as surgery alone is usually not curative . Inadequate antibiotic therapy postoperatively may result in complications such as bronchopleural fistulas and empyema. The prognosis of the pulmonary form of actinomycosis may be less favourable compared with the other commoner forms, such as cervicofacial and abdominal disease . This may be related to the greater incidence of disseminated disease in the thoracic form and may also be a reflection of late diagnosis in this condition. However, when the infection is recognised early and proper treatment is given, the condition has an excellent prognosis with a very low mortality. Every respiratory physician should be familiar with this important differential in any patient with long-standing pulmonary infiltrates to prevent unnecessary morbidity or even unwarranted surgery. 18

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REFERENCES 1 Russo TA — Agents of actinomycosis. In: Mandell GL, ed.Principles and Practice of Infectious Disease. 5th edn. New York, Churchill Livingstone, 1995; 2645-54. 2 Schaal KP, Lee H — Actinomycete infections in humans – a review. Gene 1992; 115: 201-11. 3 Heffner JE — Pleuropulmonary manifestations of actinomycosis and noardiosis. Semin Respir Infect 1988; 3: 352-61. 4 Holm P — Studies on the aetiology of human actinomycosisII. The “other” microbes of actinomycosis and their importance. Acta Pathol Microbiol Scand 1951; 28: 391. 5 Hachitanda Y, Nakagawara A, Ikeda K — An unusual wall tumour due to actinomycosis in a child. Paediatr Radiol 1989; 20: 96.


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6 Rose HD, Varkey B, Kutty CP — Thoracic actinomycosis caused by Actinomyces myeri. Am Rev Respir Dis 1982; 125: 251-4. 7 Rippon JW — Medical Mycology. In: Wonsiewicz MJ, ed. The Pathogenic Fungi and the Pathogenic Actinomycetes. 3rd edn. Philadelphia, WB Saunders Co, 1988; 30-52. 8 Bennhoff DF — Actinomycosis: diagnostic and therapeutic considerations and a review of 32 cases. Laryngoscope 1984; 94: 1198-217. 9 Miller M, Haddad AJ — Cervicofacial actinomycosis. Oral Surg Oral Med Oral Path Oral Radiol Endod 1998; 85: 496508. 10 Apothloz C, Regamey C — Disseminated infection due to Actinomyces myeri - case report and review. Clin Infect Dis 1995; 22: 621-5 11 Slade PR, Slesser BV, Southgate J — Thoracic actinomycosis. Thorax 1973; 28: 73-85. 12 Frank P, Strickland B — Pulmonary actinomycosis. Br J Radiol 1974; 47: 373-8. 13 de la Monte SM, Gupta PK, White CL — Systemic

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Actinomyces infection: a potential complication of intrauterine contraceptive devices. JAMA 1982; 15: 1579-80 Smego RA, Foglia G — Actinomycosis. Clin Infect Dis 1998; 26: 1255-63. Jensen BM, Kruse-Anderson S, Anderson K — Thoracic actinomycosis. Scand J Thorac Cardiovasc Surg 1989; 23:181-4. Slade PR, Slesser BV, Southgate J — Thoracic actinomycosis. Thorax 1973; 28: 73-85. Pauker SG, Kopelman RI — Clinical problem solving. A rewarding pursuit of certainty. N Engl J Med 1993; 329: 1103-7 Chaudhry SI, Greenspan JS — Actinomycosis in HIV infection:a review of a rare complication. Int J STD AIDS 2000; 11: 349-55. Harvey J, Cantrell J, Fisher A — Actinomycosis: its recognition and treatment. Ann Intern Med 1957; 46: 868-85. Berardi R — Abdominal actinomycosis. Surg Gynaecol Obstet 1979; 149: 257-66 Brown JR — Human actinomycosis. A study of 181 subjects. Human Pathol 1973; 4: 319-30.

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Case Report Bilateral hyperdense thalami in GM1 Gangliosidosis : a case report 1

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Ahmed Rizwan Karim , Rakesh Kumar , Punita Kumari

GM1 gangliosidosis is a very rare autosomal recessive genetic- metabolic disorder caused by deficiency of the lysosomal beta galactosidase. There are only very few cases reported in India of GM1 gangliosidosis. Here we present a case of GM1 gangliosidosis in a 25-days-old neonate with unique neuroimaging finding of bilateral hyperdense thalami. To our knowledge, this is the first case report of GM1 gangliosidosis in neonatal age group from India. The differential diagnosis of bilateral hyperdense thalami has been discussed in this article. [J Indian Med Assoc 2017; 115: 35-6]

Key words : GM1 gangliosidosis, bilateral hyperdense thalami.

(Continued from page 30)

Koornneef L et al . The prognosis and metastatic potential from melanoma are related to the depth of invasion, as described by Breslow with tumors less than 0.76 mm thick having 100% 5- year survival rate after complete excision and tumors more than 1.5 mm thick having <50% 5- year survival rate . Malignant melanoma involving the eyelid margin had poorer prognosis . 2

G

M1 gangliosidosis is a rare metabolic disorder caused by deficiency of the lysosomal beta galactosidase, resulting in accumulation of GM1 ganglioside and other glycoconjugates in the brain and visceral organ. There are few reports in literature, which describe the neuroradiological findings of GM1 gangliosidosis. Here we present a case of GM1 gangliosidosis in a neonate with neuroimaging finding of bilateral hyperdense thalami.

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REFERENCES

Fig 2 — Intra-operative picture after wide surgical excision of the lesion

A study by Garner A et al found that nodular lesions involving the lid margin do worse than superficial spreading lesions. The treatment of choice for cutaneous malignant melanoma of the eyelid is wide surgical excision with 1 cm of skin margins and confirmed by histopathology. In addition to a metastatic evaluation, regional lymph node dissection should be performed for tumors greater than 1.5 mm in depth and/or for tumors that show evidence of vascular or lymphatic spread . But a study by Wanebo HJ et al stated that regional lymph node dissection in cases of completely excised cutaneous melanoma of the head and neck did not result in increased survival, regardless of depth of tumor invasion . Cryotherapy may be useful in treating some conjunctival malignant melanomas, but it is not an effective treatment option for cutaneous malignant melanoma of the eyelid as was concluded by Garner A, 2

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1 Gregory JV, Richard KD, Gregg SG — Eyelid malignancies. Myron Yanoff , Jay S Duker. Ophthalmology. 2nd edn. 2004: 716-7. 2 Garner A, Koornneef L, Levene A, Collin JR — Malignant melanoma of the eyelid skin: histopathology and behavior. Br J Ophthalmol 1985; 69: 180-6. 3 McCormick SA, DeLuca RL — Tumors of melanocytic origin. In: Mannis MJ, Macsai MS, Huntley AC, eds. Eye and skin disease. Philadelphia: Lippincott-Raven; 1996: 38193. 4 Grossniclaus HE, McClean IW — Cutaneous melanoma of the eye lid-Clinicopathologic features. Ophthalmology 1991; 98: 1867-73. 5 Wanebo HJ, Cooper PH, Young DV, Harpole DH, Kaiser DL — Prognostic factors in head and neck melanoma: Effect of lesion location. Cancer 1988; 62: 831-7. 6 Breslow A — Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 1970; 172: 902-8. 7 Tahery DP, Goldberg R, Moy RL — Malignant melanoma of the eyelid: a report of eight cases and a review of the literature. J Am Acad Dermatol 1992; 27: 17-21.

CASE REPORT

A 25-days-old male baby presented with the chief complaints of refusal to feed and tightening of whole body since last 12 days. He was the first child of nonconsanguineous parents. The pregnancy had been uneventful. Baby had cried immediately after birth and was on breast feed before this illness. There was no relevant family history. Examination — On examination, his weight was 2800gm (<3rd centile) and head circumference was 35cm (3rd centile). There was brisk deep tendon reflexes, hypertonia of all four limbs and startle response to noise was present. There was no organomegaly. Investigation — Routine blood examination showed no abnormalities. USG cranium revealed bilateral hyperechoic thalami with homogenous echoes (Fig 1). Then CT scan of head was advised which showed symmetrically, homogenously bilateral hyperdense thalami (Fig 2). Fundoscopy was carried out which revealed macular cherry red spots. The skeletal survey was normal. Enzyme level estimation showed reduced level of Betagalactosidase. Thus a diagnosis of GM1 gangliosidosis was made. Management — Supportive treatment in the form of iv fluid and anti-convulsants were given. Genetic counseling of the parents was done. Department of Radiodiagnosis, Katihar Medical College, Katihar, Bihar 854109 1 MBBS, MD, Assistant Professor 2 MBBS, MD, Assistant Professor, Department of Pediatrics 3 MBBS, MD (2nd year student), Junior Resident, Department of Pediatrics

Fig 1 — USG showing bilateral hyperechoic thalami with homogenous echoes DISCUSSION

Three clinical subtypes of GM1 gangliosidosis exist. The classic infantile subtype (Type 1) is the most common and severe form with clinical features of both a neurolipidosis (ie, neurodegeneration, cherry red spots) and those of a mucopolysaccharidosis (visceromegaly, osseous dysplasia, dysmorphic facial features) . The coarse facial features, hepatosplenomegaly and dysostosis multiplex may be present or become apparent later in the first year of life. The infantile type presents between birth and 6 months of age and the affected child usually die within the first 2 years of life. Patients with the late infantile or juvenile form (Type 2) presents after 1 year of age with progressive psychomotor retardation in the absence of dysmorphism and organomegaly. Spastic, cerebellar and extrapyramidal signs dominate the neurological pictures probably as a consequence of predominant basal ganglia storage of gangliosides. Decerebrate rigidity follows, and death occurs between 3 and 10 years of life, usually precipitated by recurrent bronchopneumonia. The adult subtype (Type 3) has normal early neurologic development. It has slowly progressive coarse and predominant 1,3


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weighted MR images at a later stage . Hyperdense thalami have also been seen in GM2 gangliosidosis, another lysosomal storage disorder . The differentiation can be made on the basis of the age of the patient, systemic findings and enzymatic assays. Patients with late stage of canavan disease may manifest with hyperdense thalami and white matter necrosis, resulting in cavitation, and brain stem and cerebral atrophy, which are not seen in GM1. There is one case report of krabbe’s disease from India in which hyperdensity of thalami and also of basal ganglia and cerebellum was present . Other metabolic disorders, which show findings of hyperdense thalami, include Fabry disease, Fahr disease, Wilson disease and Leigh disease . Apart from metabolic disorders hyperdense thalami can also be seen in severe birth asphyxia, thalamic hemorrhage, thalamic calcification, primary neoplasm of thalamus (Gliomas) and infections (viral encephalitis, Creutzfeldt-Jakob disease) . In neonatal birth asphyxia, there will be increased signal intensity in the thalami and basal ganglia and absent or decreased signal intensity in the posterior limb of the internal capsule on T1-weighted images . Moreover the baby will be sick since birth. In thalamic calcification, the margins may be irregular and sonographically, there will be heterogenous echoes in thalamic calcification and thalamic hemorrhage. Thus bilateral thalamic hyperdensity has a variety of causes and the accurate diagnosis can be reached on the basis of patients’ history, imaging characteristics and presence or absence of lesions outside the thalami. 1

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Fig 2 — CT scan showing homogenously bilateral hyperdense thalami

extrapyramidal features without visceral or skeletal changes. Cherry red spots at the maculae, which are present in about half the cases of Type 1 GM1 gangliosidosis, are not seen in patients with Type 2 and Type 3 disease. Diagnosis can be confirmed by measurement of acid beta galactosidase activity in peripheral leukocytes . Detection of abnormal urinary oligosaccharides can be used as screening test. Prenatal diagnosis by measurement of enzyme activity in amniotic fluid and cultivated amniotic fluid cells is also possible. Neuroimaging findings in patients with type 1 GM1 gangliosidosis have been reported only in a few cases. In the present case, there were bilateral hyperechoic thalami on USG and hyperdense thalami on CT scan of brain. Similar neurological findings have been reported in a case of GM1 gangliosidosis from India . In one case, initial thalamic hyperdensity was found on CT scan and hypointense signal of the thalami was seen on T21,

REFERENCES

1 Kobayashi O, Takshina S — Thalamic hyperdensity on CT in infantile GM1-gangliosidosis. Brain Dev 1994; 16: 472-4. 2 Brismer J, Brismar G, Coates R — Increased density of the thalamus on CT scan in patients with GM2 gangliosidosis. AJNR Am J Neuroradiol 1990; 11: 125-30. 3 Bavisker DS, Desai DJ, Talwar I, Jaggi ST — Neuroimaging findings in GM1 gangliosidosis. Bombay Hospital Journal. 4 Grover SB, Gupta P, Jain M, Kumar A, Gulati P — Characteristic CT and MR features of Krabbe’s disease: A case report. Ind J Radiol Imag 2005; 15: 4: 503-6. 5 Smith AB, Smirniotopoulos JG, Rushing EJ, Goldotein SJ — Bilateral Thalamic Lesions. AJR 2009; 192: W53-W62. 6 Heinz ER, Provenzale JM — Imaging findings in neonatal hypoxia: A practical review. AJR 2009; 192: 41-7.

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