Real Time-PCR HBV-DNA Analysis: Significance and First Experience in Armed Forces

Background

HBV DNA quantitation is used extensively world wide for the diagnosis and monitoring of treatment of Hepatitis B virus (HBV) infection. However, it has still to be popular in India. The aim of this study was to quantitate HBV – DNA by Real time – PCR method in Hepatitis B and in immuno-compromised patients, to compare the results with HBeAg detection and to monitor the response to therapy of chronic Hepatitis B patients to antivirals.

Methods

Ninety one serum samples of Hepatitis group of patients (all HBsAg positive), 41 samples from immuno-compromised patients (all HBsAg negative) and 49 patients of Chronic Hepatitis B group (all HBsAg positive) were the subjects of this first ever study in Armed Forces. Twenty serum samples from healthy volunteers and non-hepatitis B patients served as negative controls. The amplification detection was carried out in a Rotor-Gene 2000-sequence detector

Results

Amongst Hepatitis B group, 33% (30/91) of the samples were positive for HBV-DNA and 26% (24/91) of samples were positive for HBeAg. In the immuno-compromised group of patients 14.6% (6/11) of samples were positive for HIV-DNA and 9.7% (4/41) were positive for HBeAg. Of the Chronic Hepatitis B patients on treatment, all (100%) were positive by HBV-DNA, whereas 29/49 (59.2%) were positive by HBeAg before treatment. After treatment with antivirals, 06/49 (12.2%) were positive by both tests and 11/49 (22.5%) were positive only by HBV-DNA. 32/49 (65.3%) patients became negative serologically after therapy.

Conclusion

HBeAg status did not necessarily reflect HBV-DNA level in the serum, as 10/91 (11%) in the Hepatitis B group, 2/41 (4.9%) in the immuno compromised group and 20/49 (40.8%) patients in the Chronic Hepatitis B group were positive for HBV-DNA but negative for HBeAg. HBV-DNA was not found to be positive amongst any of the negative controls. Real time – PCR is a sensitive and reproducible assay for HBV-DNA quantitation and may be started in Armed Forces referral centers in the near future.Key Words: Real time – PCR, Chronic Hepatitis B, HBV – DNA, Antivirals     

Correlation between clinical diagnosis and arthroscopic findings of the shoulder

Objective: To assess the accuracy of clinical examination by non-specialist orthopaedic surgeons of patients presenting to a diagnostic and treatment centre (DTC) for arthroscopic shoulder surgery. Methods: A retrospective review of notes of 130 consecutive shoulder arthroscopies performed at a DTC over a 10 month period. Preoperative clinical diagnosis was compared with operative arthroscopic findings. Additional information from preoperative imaging was compared with clinical examination and arthroscopic findings. Preoperative clinical examinations and consent were undertaken by clinical fellows, (SpR level) and non-upper limb consultant orthopaedic surgeons. Consultants specialising in upper limb surgery performed the operations. Results: Six main groups were identified on the basis of clinical examination: impingement 76 cases (58%), instability 22 cases (17%), frozen shoulder 11 cases (8%), rotator cuff tear four cases (3%), non-specific pain eight cases (6%), and normal clinical examination nine cases (7%). Impingement and instability diagnosed clinically strongly correlated with the arthroscopic findings. Clinical diagnosis of frozen shoulder and rotator cuff tears had a weaker correlation with the arthroscopic findings. Of the nine cases of normal clinical examination, abnormality was found at arthroscopy in all cases. Conclusion: There have been very few studies comparing clinical examination of the shoulder with arthroscopic findings. This study emphasises the importance of good clinical examination skills in diagnosing common shoulder abnormalities. The addition of imaging, particularly ultrasound and magnetic resonance imaging further increases the likelihood of an accurate diagnosis. Shoulder examination should be taught with as much emphasis at both undergraduate and postgraduate level as other orthopaedic clinical examinations.     

Shaken baby syndrome masquerading as apparent life threatening event

Disseminated cryptococcosis is a rare and often fatal disease in children. The majority of cases usually occur in individuals with defective cell-mediated immunity, most commonly due to HIV infection. The authors here in report an 8-year-old girl from Nepal who presented with fever, cough, headache, lymphadenopathy, hepatosplenomegaly and cutaneous lesions. Lymph node biopsy revealed multiple granulomas composed of histiocytes and epitheliold cells along with numerous yeast forms of cryptococcus. Cultures of CSF, sputum and urine yielded cryptococcus neoformans. Surprisingly,the immune function in terms of T-cell number, CD4 : CD8 ratio, serum immunoglobulins and HIV serology was normal. After the diagnosis of disseminated cryptococcosis was established, the patient was treated with 5-fluorocytosine (100 mg/kg/day) for initial two weeks and amphotericin B (1 mg/kg/day) for 13 weeks. Patient responded well to the treatment with disappearance of presenting symptoms, cutaneous lesions, and lymphadenopathy, though she still had hepatosplenomegaly, which also decreased. Unfortunately, she developed loss of vision in 10th week of therapy. The patient was discharged on oral fluconazole (6 mg/kg/day) and no recurrence was found during the follow-up period of more than 9 months. This is the first case of disseminated cryptococcosis with no detectable immune deficit, from India.     

Maternal estimates of mental age in developmental assessment

Objective: To examine the accuracy and clinical utility of maternal estimates of mental age in young children referred for developmental assessment.Methods : Mothers of 100 children aged 16 to 60 months referred for developmental evaluation to psychology services of Department of Pediatrics of a tertiary care teaching hospital were asked to estimate the mental age of their child. Maternal estimates were converted to intelligence quotient (IQ) and were compared to results from developmental tests of cognitive and adaptive behavior functioning which were administered to all children.Results : Maternal estimate IQ was highly correlated with IQ calculated from Developmental Profile II (r=.83, p<.001) and social quotient (SQ) calculated from Vineland Social Maturity Scale (r=.81, p<.001). Maternal estimate IQ was 82% sensitive to cognitive delay and 81% specific in identifying children likely to have normal development. Twenty seven percent of the maternal estimates were within ±5 IQ points of actual IQ. Mothers were more likely to overestimate their child’s functioning. Maternal IQ (Mean=62.1, S.D. =25.8) was significantly higher (t=2.93, p<.004) than the actual IQ (Mean=57.9, S.D.=21.9). Step-wise multiple regression analysis revealed that the child’s IQ and SQ explained 10% of the variance (F=6.40, p<.001) in maternal accuracy. The lower the SQ and IQ of the child, more accurate the estimates.Conclusion : Maternal estimates of mental age provide an accurate measure of developmental functioning in young children and may be used as a screening technique to identify a subset of children who need more detailed evaluation.     

Shaken baby syndrome masquerading as apparent life threatening event

A variety of diseases and disorders can present as an acute life-threatening event among which shaken baby syndrome has been recently recognized. A high index of suspicion along with an ophthalmologic evaluation and cranial imaging helps to identify this form of child abuse, which needs multidisciplinary management.     

Treatment of bipolar depression: focus on pharmacologic therapies

Recent studies have highlighted significant limitations in our capacity to effectively treat bipolar depression. This article reviews the present status of treatments for this condition, highlighting emerging new pharmacotherapies such as lamotrigine, olanzapine and quetiapine, while also addressing modern psychologic interventions such as cognitive behavioral therapy and psychoeducation. The role of older treatments such as lithium and the antidepressants is also discussed, particularly as a recent meta-analysis has thrown into question current heightened concern over antidepressant-induced mania. The advent of new pharmacologic and psychologic treatments provides optimism for improved outcomes for this highly disabling condition.     

When euthymia is just not good enough: the neuropsychology of bipolar disorder

Bipolar disorder (BD) is a debilitating psychiatric illness that is uniquely characterized by switching between psychopathologically contrasting phases of mania and depression, often with intervening periods of euthymia. However, these periods of apparent clinical recovery (euthymia) are marked by subtle social, occupational, and cognitive impairments, profiled by recent neuropsychological investigations. Determining the cognitive changes across these three phases may help differentiate the disruptions that are mood state-dependent from those associated with underlying pathology. This article therefore critically reviews the reported neuropsychological impairments in BD and the methodological limitations facing such research. Integration of the available evidence, principally from the field of neuropsychology, when synthesized, implicates the prefrontal cortex in the etiopathogenesis of BD and posits cortical-subcortical-limbic disruption in recovered euthymic patients that manifests as cognitive dysfunction.     

Evaluation of quality of life in indian children with bronchial asthma using a disease-specific and locally appropriate questionnaire

AIM: To evaluate quality of life (QOL) in Indian children with bronchial asthma. METHODS: A disease-specific, locally appropriate QOL questionnaire was administered in asthmatic children and compared with FEV1, FVC, PEFR and asthma symptom score, on three occasions. RESULTS: QOL score had strong negative correlation with symptom score and weaker positive correlation with pulmonary function tests. CONCLUSION: Disease-specific QOL score correlates inversely with symptom score in children with bronchial asthma.     

Warfarin and celecoxib interaction in the setting of cytochrome P450 (CYP2C9) polymorphism with bleeding complication

Drug metabolism may be perturbed by genetically determined differences in the metabolic activity of cytochrome P450 enzymes. The authors encountered extensive bleeding in a patient receiving warfarin for anticoagulation after the introduction of celecoxib, an anti-inflammatory drug. As the CYP2C9 enzyme metabolises these drugs, it was determined whether variant alleles were responsible for altering warfarin handling. Genetic analysis established that the patient was a compound heterozygote with CYP2C9*2 and *3 variant alleles, which exhibit lower drug metabolising capacity and enhance susceptibility to drug toxicity.