Bangladesh Medical Research Council Bulletin (Vol 46, No 01 2020)

Table of Contents


Editorial

VIEW 01-03
COMMENT

COVID – 19 is now a pandemic, as WHO director General Tedros Adhanom Ghebreyesus declared during a media briefing on Wednesday, 11 March.

Bangladesh situation as on 27 March, total affected 44 out of which died 5. Some of them have returned from abroad and others had come in contact with those coming from abroad. So community spread has already been started. 1st three cases detected on 8 March. 1st death declared on 18th March.

VIEW 04
Research Papers

Abstract

Background: In order to achieve the Sustainable Development Goal (SDG) 3 target of reduction in under-five mortality below 25 per thousand live birth by the year of 2030, major reductions are going to be required in neonatal mortality. Congenital anomalies have become the fourth cause of neonatal deaths and most of these are curable. The largest public hospital of the country is serving the poor and lower middle class people where surgery and medical facilities are mostly free of cost.

Methods: This was a retrospective study done over a period of 17 years from July 2001 to June 2018 and carried out in the Department of Pediatric Surgery. A total of 2492 neonates were admitted during this period and it was the 16.16% of total number of 15414 pediatric surgical admission upto12 years of age. Data was collected from hospital records and analyzed retrospectively.

Results: Out of these 2492 neonates, 1932 (77.53%) were admitted for Neonatal Intestinal Obstruction (NIO) and Intestinal atresia 246 (09.87%), Omphalocele 163 (06.54%), Meconium ileus 154 (06.18%), Volvulous neonatoram 125 (05.02%), Septicemia 114 (04.57%), Posterior Urethral Valve 78 (03.13%), Gastroschisis 75 (03.01%), Abscess 57 (02.29%), Congenital Diaphragmatic Hernia 54 (02.17%), Ectopia Vesicae 50 (02.01%), Infantile pyloric stenosis 42 (01.68%), Tracheo-oesophageal fistula 24 (0.96%), Prune belly syndrome 8 (0.32%), Neonatal injury 5 (0.20%), Conjoint twin 4 (0.16%). The most common cause of NIO was anorectal malformation (ARM) 806 (32.34%). Among them 516 (64.02%) patients had high variety and 290 (35.98%) patients had low variety ARM. Next was Hirschsprungs disease and 487 (19.54%) neonates presented with this. One hundred and forteen (4.57%) patients presented with septicemia and 246 (9.87%) presented with intestinal atresia, 154 (6.18%) neonates had meconium ileus and 125 (5.02%) patients presented with volvulus neonatorum. Total 1791 (71.86%) patients were managed surgically. Most of the surgerical procedures were pelvic colostomy 541 (21.71%), transverse colostomy and biopsies 376 (15.09%), resection and anastomosis 261(10.47%), anoplasty 239 (9.59%), primary repair 135(5.42%) and ileostomy 104(4.17%). Out of 2492 patients, 351 died, so mortality was 14.09%, before surgery 12.12% and after surgery was 14.85%.

Conclusion: Pediatric surgeons by their skill and teamwork greatly improved the neonatal surgical service and contributing significantly in reducing infant mortality rate to achieve SDG 3. But to improve further, neonatal intensive care unit (NICU) and other support systems are essential as well as support from UNICEF and World Health Organization (WHO) to include pediatric surgery and surgeons in their activities especially in developing countries. Due to socio-political and economic reasons of the developing countries the roll of pediatric surgeons are multidimensional.

Key words: Neonatal surgery, neonatal intestinal obstruction Anorectal malformation, Hirschsprungs disease

VIEW 05-11

Abstract

Background: Juvenile Idiopathic Arthritis (JIA) is the most common chronic rheumatic disease of childhood and a leading cause of short and long-term disability. Abnormal level of serum homocysteine (Hcy) may be found in Juvenile idiopathic arthritis (JIA) patients. Some studies were done on serum homocyestine levels in children with JIA which showed conflicting results. So far, no study regarding the Hcy level in JIA patients was done in Bangladesh.

Objectives: To assess the homocysteine level in children with different subtypes of JIA.

Materials and methods: It was a cross sectional and case control study. Fifty newly diagnosed cases of JIA attending the Pediatric Rheumatology clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from January 2016 to March 2017 were included. Fifty age and sex matched controls were selected. Serum homocysteine levels were measured in cases and controls.

Results: Among JIA patients, 36% had high serum homocysteine (Hcy) level whereas 100% of controls had normal level. Mean hcy level was significantly (p<0.05) higher among cases than controls. Significantly higher number and level of hyperhomocysteinemia was found among JIA patients having duration of illness more than 1 year than duration less than 1 year. Mean homocysteine level of polyarticular RF positive cases was found as 14.38±3.79 µmol/L and that of SJIA was found as 13.0±4.66μmol/L. When compared with homocysteine levels of control group these two groups had significantly higher homocysteine level.

Conclusion: More than one third of JIA patients had hyperhomocysteinemia. Mean hcy level of JIA cases was significantly higher than that of controls. Significant association of hyperhomocysteinemia was present with duration of illness and certain types of JIA.

Key words: Juvenile Idiopathic Arthritis, Serum homocysteine levels, Hyperhomocysteinemia, Polyarticular RF

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Abstract

Background: Rhabdomyosarcoma (RMS) is a malignant tumor of mesenchymal origin, is the most common form of pediatric soft tissue sarcoma. It is the third most common solid tumor comprising 4.5% of all childhood cancer with an annual incidence of 4.5 cases per 1 million children. There is no statistical data on RMS in Bangladesh because no study has done in Bangladesh.

Objective: To evaluate the clinical characteristics and treatment outcome of children with rhabdomyosarcoma among a series of 39 children at BSMMU Hospital with emphasis on age, gender, clinical presentation, site, histological subtype, TNM stage, treatment modalities and survival.

Method: A retrospective study carried out analyzing the medical records of 39 patients with rhabdomyosarcoma from the BSMMU tumor registry. Medical records of children with rhabdomyosarcoma were reviewed over a period of 6 years from June 2011 to May 2017. All patients received chemotherapy, for a duration ranging 32–54 weeks according to low, Intermediate and high risk group with VCR, Actinomycin D, Cyclophosphamide, Ifosfamide and Etoposide. Relapsed patients from Low risk group received VAC, intermediate and high risk group received 5 doses of ICE every 28 days (Ifosfamide, Carboplatine and Etoposid). Most patients received multimodality therapy (chemotherapy, surgery, radiotherapy).

Results: There were males 56% and females 44%. M: F ratio 1.2:1. The age at diagnosis ranged from 7 days to 13 years. More than half of cases presented with a mass at varying sites The predominant complaint 12% was pain. The primary site of disease was the head and neck in 46% followed by pelvis 40%. Pathologically most frequent histological subtype was in 46% embryonal rhabdomyosarcoma followed by alveolar rhabdomyosarcoma 23%, botryoid type 5%, spindle cell type 5% and unspecified 21%. At the time of diagnosis 64% of patients were TNM stage 3 next frequency was stage IV 23%. The survival rate from diagnosis to subsequent demise was poor – between 13 days and 3.5 years. The overall 5-year survival rate was 41% which is may be due to advanced stage of disease.

Conclusion: The majority of presentations were in the advanced stages of disease but sensitive to multimodality therapy. Poor survival rate is correlated with the advanced stage of the disease. The clinical characteristics of rhabdomyosarcoma at BSMMU Hospital are similar to worldwide countries but treatment outcome not like developed country. Further multicentre studies are needed to report our experiences with rhabdomyosarcoma.

Keywords: Rhabdomyosarcoma, Treatment outcome, Botryoid type, Ifosfamide

VIEW 17-21

Abstract

Background: To investigate the spread of specific genotypes in a defined geographical area and to determine any relationship of these genotypes with drug resistance the most essential method is molecular typing. It allows a rapid and precise species differentiation.

Objectives: This study is intended to observe the genotypes of XDR Mycobacterium tuberculosis by determining 24 loci MIRU-VNTR analysis.

Methods: To gain an insight about molecular typing of MTB and drug resistance-associated mutations in XDR-TB isolates a total of 98 Multi drug resistant Tuberculosis (MDR-TB) isolates collected through Xpert MTB/RIF assay. They were subjected to 2nd line (Fluoroquinolones, kanamycin, capreomycin and amikacin) drug susceptibility testing through Line Probe Assay (LPA) in a view to detect extensively drug resistant tuberculosis (XDR-TB). Genotyping was done for XDR-TB isolates using 24 loci Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) using the online tool at http://www.MIRU-VNTRplus.org.. Out of 98 MDR-TB isolates 11(11.23%) XDR-TB isolates were typed and analysed.

Results: 24 Loci MIRU-VNTR genotyping involving similarity searching and phylogenetic tree analysis revealed that six (54.55%) XDR-TB isolates belonged to Beijing strain, Other MTB strain also detected were Delhi/CAS two(18.18%), Haarlem two(18.18%) and New-1, one (9.10%) in number. Minimum spanning tree analysis showed two strain of Beijing family form a clonal complex. Beijing strains were more common among younger age group and within urban population. Beijing strains were also predominant in treatment failure patient. Only one new case of XDR-TB belongs to Delhi/CAS family. Second line Mycobacterial drug resistance (MTBDRsl) detected by LPA showed the most prevalent mutations involved in Fluoroquinolones drug resistance (FQ) was Asp94Gly in gyrA gene (54.55%) in quinolone resistance determining region (QRDR) and for Injectable 2nd line Drug resistance (ISL) was A1401G, C1402T in 16S rrs gene (100%).. All XDR-TB isolates showed resistance to Levofloxacin in 2nd line LPA but Moxifloxacin showed low level resistance to some cases.

Conclusion: Molecular typing of XDR- TB isolates and pattern of drug resistance associated mutations in XDR-TB isolates in Bangladesh have not been reported previously. The result of this study highlights the need to reinforce the TB policy in Bangladesh with regard to control the spread and transmission as well as detection and treatment strategies regarding XDR-TB.

Keywords: MTB strains, XDR-TB, MIRU-VNTR Typing, Line Probe Assay

VIEW 22-28

Abstract

Background: Thyroid dysfunction, a common endocrine disorder that increasing day by day. Hypothyroidism occasionally occurs in diabetic patients especially those with poor glycemic control.

Objectives: The objective of the study was aimed to observe the effect of glycemic control on thyroid hormones level in type 2 diabetic patients & to determine selected socio-demographic characteristics of the respondents.

Methods: This was a case control comparative study carried out in the Department of Physiology, Sir Salimullah Medical College (SSMC), Dhaka from July 2016 to June 2017. Total sixty (60) subjects of both male and female age ranged from 40 to 60 years were included in this study. Among them thirty (30) were type 2 diabetic patients (both uncontrolled and controlled) and another thirty (30) were included for comparison as control & they were matched by age, sex, & Body Mass Index (BMI). Both case & control group were selected purposively based on selection criteria volunatrily. Serum TSH, FT4 and FT3 levels were measured by chemiluminescent micro particle immunoassay (CMIA) method. Fasting blood glucose level was estimated by glucose oxidase (GOD) method and blood HbA1c level was estimated by ion exchange high performance liquid chromatography (HPLC) method. The statistical analysis was done by ANOVA test, Bonferroni test and Pearson's correlation coefficient test. Data quality control was done by using a checklist.

Results: In this study, mean serum TSH level was significantly higher in uncontrolled diabetic patients than that of controlled diabetic patients. Serum FT4 level was significantly lower in uncontrolled diabetic patients in comparison to that of controlled diabetic patients. Besides these, serum TSH level was positively correlated (r = +0.575), serum FT4 and FT3 levels were negatively correlated (r=-0.588, r =-0.527) with HbA1c level in uncontrolled diabetic patients and all these relationships were statistically significant p≤0.05 respectively.

Conclusion: The present study revealed that hypothyroidism occurs in type 2 diabetic patients which were found only in uncontrolled diabetic patients due to their poor glycemic control.

Keywords: Thyroid stimulating hormone, free thyroxine , free triiodothyronine , Type 2 Diabetes Mellitus

VIEW 29-34

Abstract

Background: Brucellosis is an important re-emerging zoonosis which remains an uncontrolled public health problem worldwide because of serious diminution of man power, animals and essential foodstuffs. Transmission to human can occurs through contact with infected animals or animal products. It is a poorly recognized health problem in our country though there is persistence of large reservoirs of the organism among livestock such as sheep, goat and cows creating fertile field for unabated transmission. But data on it’s transmission potential and prevalence in our country specially in Sylhet region remained scarce. In the absence of supportive epidemiological information Physicians on most of the cases have to depend on their clinical judgement to suggest relevant tests.

Objective: The present study was conducted to compare the sero-prevalence of human brucellosis among high risk and normal individuals.

Materials and Methods: This cross-sectional, comparative study was conducted amongst a total of randomly selected 90 participants including 65 high risk individuals during the period of July 2016-June 2017. Brucella IgM and IgG antibody in the serum were determine by Enzyme Linked Immunosorbent Assay (ELISA) technique.

Results: Among the 65 participants of the high risk group, Brucella IgM and IgG seropositivity were found in 6 (9.2%) and 32(49.2%) cases respectively. On the other hand, no IgM seropositivity, but 10 (40.0%) IgG seropositivity cases were found in normal group. No significant difference (p>0.05) was found between the groups. Of the 23 high risk individuals of the 18-30 years age group, the highest IgGseropositivity was found in 60.9% cases. Considering occupations, the highest 11 (61.1%) Brucella IgG seropositivity was found among the 18 dairy farm workers (p>0.05). Participants with 0-5 years duration of job had highest seropositivity 7 (70%) among high risk group and 3 (50%) among normal group. The maximum IgG seropositivity was found in participants with education up to higher secondary level. No significant association was identified between seropositivity and duration of occupation, education (p>0.05).

Conclusions: Based on the study findings, it may be concluded that the extent of human brucellosis should not be ignored, and measures like awareness building, vaccination, transboundary screening needed to prevent and control the disease in animals and limit human transmission. Further study involving larger sample size and geographical areas are thus recommended.

Keyword: Brucellosis, Brucella IgM, Brucella IgG, Seroprevalence, Zoonosis, ELISA.

VIEW 35-40

Abstract

Background:Shiga toxin (Stx) producing Escherichia coli (STEC) colonize human intestinal tract and their infections have asymptomatic clinical manifestations which cause local and systemic pathological changes.

Objective:This study intended to establish the role of Shiga toxin (Stx2d) in developing clinical manifestations in STEC infections using experimental models.

Methods:A total 300 stool samples were screened from hospitalized diarrheal patients enrolled in 2% surveillance system at International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). The stx gene profile including their variants were identified by PCR. stx2d gene positive STEC PT187 was selected for toxin(s) preparation.Toxin was prepared by centrifugation of culture supernatant. Enterotoxic and paralytic-lethal activities were tested in rabbit ileal loops and mice, respectively. Histopathological study of the rabbit ileal loop segments and different tissues of mice was performed by paraffin embedded method and stained by H & E staining. Cytotoxic effect was performed on HeLa cells.

Results:Nine STEC strains were identified for stx2 gene positive. Among them STEC PT187 was found stx2d gene positive strain and selected for toxic activities. Toxin(s) responsible for causing accumulation of fluid in rabbit ileal loops and its segments showed inflammation and enterocyte necrosis. In mouse model, toxin(s) was found to cause hind limbs paralysis and death. Brain, spinal cord and kidney tissue of mice showed histopathological changes. Toxin(s) also showed positive cytotoxic activity in HeLa cell.

Conclusion:In this report, we demonstrate that Stx2d producing E. coli exhibit not only enterotoxic activity, but also cause impaired neurological functions and cytotoxic effect.

Key words:Stx2d, STEC, Cytotoxic effect, Neurotoxic effect.

VIEW 41-47

1Department of Obs & Gynae, Central Regional Referral Hospital, Bhutan; 2Department of Obs & Gynae, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh; 3Ibrahim Medical College and BIRDEM Hospital, Dhaka, Bangladesh; 4Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Abstract

Background: Cervical cancer is the most frequent cancer in women worldwide. It is a preventable and curable disease with proper screening. After primary screening Colposcopy is a valuable tool in the detection and treatment of precancerous cervical lesions. Histopathology is the gold standard method of diagnosis of Precancerous lesions.

Objective: The objective of this study was to evaluate the performance of colposcopy in the diagnosis and to make correlation between colposcopic & histopathological findings in precancerous cervical neoplasia (CIN).

Methods: It was a cross sectional study, conducted at the Colposcopy Clinic, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. Study was done for a period of one year from January, 2016 to December, 2016. Sixty two married women having following complaints: positive visual inspection of cervix (VIA + ve) with 3-5% Acetic acid, postcoital bleeding, postmenopausal bleeding, and intermenstrual bleeding were recruited for the study. Written informed consent was obtained from the participants. The questionnaire was pretested, corrected and finalized. The data collection was done using the interviewer administered questionnaire. Colposcopic examination of cervix was done in 62 participants. Colposcopy guided punch biopsy/Loop electrosurgical excision procedure (LEEP) from acetowhite area was taken in cases of VIA +ve women and random four quadrants (1, 5, 7 & 11 O’ clock position) cervical biopsy in cases of VIA – ve women having other indications. Histopathological examinations of specimens were done in the Department of Pathology, BSMMU. Descriptive analysis, chi-square test (χ2) and Fisher’s exact test were performed. P value<0.05 was taken as statistically significant.

Result: The mean age of the study population was 36.8±11.9 years ranging from 20 to72 years. Out of 62 participants, 40.3% (n=25) had VIA positive, 41.9% (n=26) had postcoital bleeding among which 24 was VIA positive and 2 was VIA negative, 8.1% (n=5) had intermenstrual bleeding with positive VIA and 9.7% (n=6) post-menopausal bleeding among which 4 was VIA positive and 2 was VIA negative. Among total 62 participants Sensitivity of colposcopy to diagnose histopathologically confirmed CIN I was 82.6%, CIN II was 25% and CIN III was also 25%. The specificity to diagnose CIN I was 42.4%, CIN II was 91.4% and CIN III was 93.1%. PPV of colposcopy to diagnose histologically confirmed CIN I was 55.8%, CIN II was 16.7% and CIN III was 20%. The NPV to diagnose CIN I was 73.7%, CIN II was 94.6% and CIN III was 94.7%. The colposcopic accuracy to diagnose CIN I was 61.3%, CIN II was 87.1% and CIN III was 90.3%.There was statistically significant (P value <0.05) correlation for colposcopic diagnosis of histopathologically confirmed CIN I,CIN II and III.

Conclusion: The accuracy of colposcopy to diagnose histopathologically confirmed precancerous cervical lesions was quite high. Patients presenting with postcoital bleeding and postmenopausal bleeding should have colposcopy and biopsies even if the screening test result normal. Moreover colposcopy has high sensitivity, so we can easily adopt the see and treat method to reduce the dropout.

Keywords:VIA, Postcoital bleeding, Intermenstrual bleeding, Postmenopausal bleeding

VIEW 48-54

Abstract

Background: Anaemia is very common in hypothyroid patient. The results of the type of anaemia in hypothyroid patient studied outside may not be similar on Bangladeshi population. So far, there is no such study regarding the types of anaemia in hypothyroid patients in Bangladesh.

Objective: The study was aimed to find out types of anemia with hypothyroid and its possible aetiological factors.

Methods: This was a cross sectional study in patients with hypothyroidism who was attending in the thyroid and endocrine clinic of Bangabandhu Sheikh Mujib Medical University, Dhaka, over a period of one year. All newly diagnosed cases were selected considering inclusion and exclusion criteria. A structured questionnaire was used for data collection.

Results: Fifty newly detected hypothyroid patients were studied. Among the study population, 52.0 % was between 05 to 35 years and another 48.0% were in 36 to 65 years. 76.0% were female. Bradycardia was found in 20.0% cases. Puffiness of face, peripheral oedema and cold intolerance were found in 78.0%, 68.0% and 82.0 cases respectively. Hoarseness of voice, delayed relaxation of tendon reflexes and paraesthesia were found in about 80.0% cases. Myxoedema and vitiligo were found in 54.0% and 6.0% cases. FT4 level was reduced in 100% cases (Normal range of FT4-9.14-23.81 pmol/L). The mean of FT4 was 5.10 pmol/L. On the other hand TSH level increased in all cases (Normal range of TSH-0.47-5.0l mIU/L). The mean of TSH was 109.88 mIU/L. 50 cases were positive anti TG-Ab and also anti PO¬-Ab was positive in 50 cases. Hemoglobin concentration was reduced in 70% cases. The mean of hemoglobin concentration was 10.67 gm/dl. In this present study, association of serum anti TG Ab and anti PO Ab of the patients with hypothyroidism and their corresponding hemoglobin concentration were found significant (P<0.05) but on the other hand there was no association between serum FT4 of the patients with hypothyroidism and their corresponding hemoglobin concentration (P> 0.05). Normocytic normochromic anaemia were found in 64% cases, and Microcytic hypochromic anaemia in 32.0% and Macrocytic anaemia in 04% of the cases. Iron deficiency was found in 90% and chronic blood loss in 44.0% of the cases.

Conclusion: Anaemia is frequently found in hypothyroid patients. Therefore, hypothyroidism should be excluded in anaemia of nonspecific origin.

Key words: Hypothyroidism, Anaemia., Mmyxoedema, Vitiligo

VIEW 55-60
Case Report

Background: Brain abscess is a neurosurgical emergency. It has to be evacuated without any delay. Though these patientsmay have congenital heart diseases with ASD and VSD, presence of situs inversus and dextrocardia are relatively uncommon in neurosurgical practice.

Objective: The aim was to present the case with multiple episode of convulsions and gradual deterioration of consciousness without history of fever.

Methods: The case was carefully evaluated with taking history and examining the patient. Diagnosis was confirmed with a MRI of the brain. It had shown a large ring enhancing lesion in the left temporal lobe which was diagnosed as brain abscess.

Results: He underwent left temporal craniotomy and the abscess was totally removed along with the capsule. He made an uneventful recovery.

Conclusion: Dextrocardia and cardiac congenital anomalies are serious conditions especially when they are accompanied with brain abscess. But prompt surgery and careful intraoperative and post operative care can help the patient to recover early without any adverse event.

Key words: Brain abscess, Dextrocardia, Situs inversus, Craniotomy.

VIEW 61-63
Letter to the Editor
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