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A young male patient had palpitations after consumption of few high caffeinated energy drinks which he took after his office hours to relieve fatigue. He immediately seeked medical help. Electrocardiogram showed multiple runs of non-sustained ventricular tachycardia and ventricular bigeminy and trigeminy. Echocardiography was normal. The patient was admitted to intensive care unit and treated with anti-arrhythmic drugs to which the arrhythmias responded and subsided. Cardiac magnetic resonance imaging of heart did not reveal any structural heart abnormality and treadmill stress test was negative ruling out significant coronary artery disease. High caffeinated energy drinks can produce serious ventricular arrhythmias if taken beyond safe doses. These ventricular arrhythmias are known to be causative factor for sudden cardiac arrest and therefore a caution & regulation is needed in widespread unrestricted used of these drinks., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

Background: Cardiac injury is associated with high mortality in patients with COVID-19 infection. Electrocardiographic changes can give clues to the underlying cardiovascular abnormalities. Raised inflammatory markers like raised interleukin-6 (IL-6) are associated with arrhythmia, heart failure, and coronary artery disease. However, past studies have not highlighted the electrocardiographic abnormalities in patients with COVID-19 infection with raised IL- 6 levels. This study compared the electrocardiogram (ECG) changes in COVID-19 patients with high and normal IL-6 levels., Methods: A retrospective analysis of ECG of 306 patients with COVID-19 infection was done, out of which 250 patients had normal IL- 6 levels, whereas 56 patients had raised IL-6 levels. IL-6 levels were measured in all the patients. Detailed clinicodemographic profile of all the serial COVID-19 patients admitted with moderate to severe COVID-19 pneumonia was noted from the hospital record section. Electrocardiographic findings and biochemical parameters of all the patients were noted., Results: Out of 56 patients with raised IL-6 levels, 41 (73.2%) patients had ECG abnormalities compared to 177 (70.8%) patients with normal IL-6 levels. This difference was not statistically significant. However, ECG abnormality such as sinus tachycardia was significantly more common in patients with raised IL-6 levels than those with normal levels. Among patients with raised IL-6 levels who were discharged, 5 (16.6%) had sinus tachycardia, 2 (6.6%) had ST/T wave changes as compared to 15 (57.6%), and 10 (38.4%) who had tachycardia and ST/T wave change respectably succumbed to death. This difference was statistically significant., Conclusions: Sinus tachycardia followed by atrial fibrillation and right bundle branch block are common ECG changes in patients with COVID-19 infection with raised IL-6. The possible association of cardiac injury in patients with COVID-19 infection with coexisting raised IL-6 levels should be explored further., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Purpose: Adrenocortical carcinoma (ACC) is a rare primary malignancy of the adrenal gland. The present study was aimed to compare the performance of fluoro-2-deoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) compared to contrast-enhanced computed tomography (CECT) in diagnosis and management of ACC., Materials and Methods: A retrospective analysis of the PET-CT studies from January 2010 to October 2020 was performed. Patients with adrenal lesions suspicious of ACC and diagnosed cases of ACC who underwent PET-CT for staging, restaging, and surveillance were reanalyzed. The PET-CT parameters were compared with the clinical, biochemical, histopathological, and CECT parameters., Results: The study included 96 scans performed in 77 patients (36 males, aged 40.4 ± 17.9 years). Of these, 55 scans were performed to diagnose and stage suspected ACC (30 of them diagnosed as ACC), 31 for restaging, and 10 scans for surveillance of ACC. PET/CT revealed metastases from an extra-adrenal primary in 5/55 patients. FDG-PET-CT had a sensitivity and specificity of 100% and 70% to diagnose ACC. Standardized uptake value-peak more than 5.4 had a sensitivity of 90.9% and specificity of 91.7% for differentiating ACC from non-ACC lesions, while tumor-to-liver ratio peak (TLRpeak) of 3.3 was most specific. PET-CT changed the staging in 23.3% of the patients with an accuracy of 100%. PET-CT changed the management plan in 25.8% of the patients during restaging with a sensitivity and specificity of 95.6% and 100%, respectively. For surveillance, CECT was as sensitive as PET-CT; however, PET-CT was more specific (100% vs. 97.9%)., Conclusion: FDG-PET-CT performs better than CECT in the diagnosis, staging, restaging, and surveillance of ACC., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Nuclear Medicine.)

Background: Cardiovascular involvement is a significant cause of death in COVID pneumonia. Early electrocardiographic changes may predict cardiovascular involvement and predict mortality in COVID pneumonia patients., Methods: A total of 250 consecutive patients with COVID-19 pneumonia admitted to the emergency were studied for electrocardiographic abnormalities and their relation to mortality., Results: Most patients required supplemental oxygen to maintain optimal saturation. A total of 72% showed ECG abnormalities, and the overall cohort had a mortality of 50%. New-onset atrial fibrillation, left bundle branch block or right bundle branch pattern, and ventricular premature complexes were associated with high mortality. Sinus tachycardia and atrial fibrillation were the most common arrhythmia and were significantly associated with mortality., Conclusions: New-onset atrial fibrillation, intraventricular conduction defects, and sinus tachycardia are associated with increased mortality in COVID pneumonia patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Objective: The use of hydroxychloroquine (HCQ) for COVID-19 treatment and prophylaxis raised issues concerning its cardiac safety owing to the possibility of QT prolongation and arrhythmias. There was no study on long-term electrocardiographic telemetry monitoring of patients taking HCQ. We planned a continuous electrocardiographic Holter telemetry of these patients for 7 days., Material and Methods: Health care workers taking HCQ as pre exposure prophylaxis and patients on HCQ were monitored using seven day Holter electrocardiographic telemetry with continuous beat to beat analysis. Telemetry can instantly convey any arrhythmic event or significant QT prolongation to the medical faculty., Results: Twenty-five participants with a mean age of 42.4 ± 14.1 years were included in the study; 40% were females. Twenty percent of participants needed to stop HCQ. Four patients developed QT prolongation >500 ms and needed to stop HCQ, one patient had accelerated idioventricular rhythm and stopped treatment, and one had short episodes of atrial fibrillation. No malignant arrhythmia or ventricular arrhythmia, or torsade de pointis were noted. No episode of significant conduction disturbance and arrhythmic death was noted. Baseline mean QTc was 423.96 ± 32.18 ms, mean QTc corrected at 24 h was 438.93 ± 37.95, mean QTc was 451.879 ± 37.99 at 48 h, and change in baseline mean QTc to max QTc was 30.74 ± 21.75 ms at 48 h. All those who developed QTc prolongation >500 ms were greater than 50 years of age., Conclusion: Ambulatory telemetry ECG monitoring detects early QT prolongation, and stopping drugs prevents malignant arrhythmias. HCQ seems to have less risk of QT prolongation in young, healthy individuals., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Background: Endothelial dysfunction, inflammation, and hypercoagulability are hallmarks of severe COVID-19 related disease. Endothelial function can be measured non-invasively by flow-mediated dilatation in the brachial artery. We planned a study to measure it as a marker of the severity of COVID-19 disease., Objective: To evaluate the association of clinically recognizable endothelial dysfunction in COVID-19 disease and its usefulness as a marker of severe COVID-19-related disease., Methods: 20 COVID-19 patients being admitted to our unit were analyzed for endothelial dysfunction and correlated with disease severity as per computed tomography (CT) chest score. Patients with diabetes, atherosclerotic coronary artery disease, dyslipidemia, chronic renal disease, and infections other than COVID-19 were excluded. Endothelial dysfunction was measured by flow-mediated dilatation in the brachial artery., Results: The mean age was 46.4 ± 16.5 years; 70% were males. The mean CT severity score was 22 ± 8; 60% required supplemental oxygen and steroids. The incidence of endothelial dysfunction was more in patients with a computed tomography severity score of >19.5 or oxygen saturation of <93% at room air as compared to mild cases ( P = 0.003). Endothelial dysfunction was more evident >7 days after onset of disease as compared to early (<7 days) disease ( P = 0.016). There was negative correlation between % flow-mediated dilatation in brachial artery and severity of lung involvement and prolonged symptomatic phase., Conclusions: Endothelial dysfunction as measured by impaired brachial artery flow mediated dilatation correlates with disease severity., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Background: Coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China in December 2019. It is caused by SARS-CoV-2, a beta coronavirus. In this study, we assessed the association of biomarkers such as neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lymphocyte monocyte ratio (LMR) with the severity of COVID-19 in patients., Methods: This retrospective observational study was carried out at a tertiary care hospital of the sub-Himalayan region of Uttarakhand over a period of six months from May to October 2020. A total of 350 patients with confirmed RT-PCR COVID-19 infection were included in the study. Detailed clinical, demographic and biochemical data of each patient was obtained from the hospital record section after permission from the Institute Ethical Committee. NLR, PLR and LMR ratios were calculated and compared with the outcomes in each patient. The patients were subdivided into two sub-groups: those with saturation less than 94% and those with saturation more than 94%. The patients were categorised as mild (with SpO 2 of > 94%) and moderate-severe (with SpO 2 of ≤94%) based on oxygen saturation., Results: A total of 350 patients with Covid-19 pneumonia were enrolled in the study. The mean age of the patients with oxygen saturation of ≤94% was 54.91 ± 13.29 years, which was comparable to the other group. Absolute neutrophil count (ANC) and NLR were significantly higher in patients with a saturation of < 94%. However, LMR and PLR were significantly lower in the group with saturation of <94%. Thus, a significant association was found between haematological inflammatory ratios and the severity of COVID-19 infection., Conclusion: NLR, LMR and PLR ratios can be utilised as point of care markers to assess severity in patients with COVID-19 pneumonia., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Family Medicine and Primary Care.)

Context: Primary Amenorrhea is worrisome for the adolescent as well as their guardian. It is essential to be able to identify the underlying pathology and initiate appropriate management strategies, well in time., Aims: To study the clinical features, with an aim to identify discriminatory clinical features to indicate a most probable diagnosis., Design: A prospective, observational study., Setting: The Gynecologic Endocrinology Clinic of Department of Obstetrics and Gynecology and Endocrinology Outpatient Department of a tertiary centre in North India., Methodology: In total 328 women with primary amenorrhea, registered during a duration of 10 years (January 2008 to December 2017), were enrolled for the study and a proforma was filled with their medical details., Results: It was observed that patients with normal stature and underdeveloped breasts were likely to be hypogonadotropic hypogonadism, whereas those with short stature and underdeveloped breasts were more likely to be gonadal failure with underlying chromosomal abnormality. The three most common causes of primary amenorrhea in the index population were hypogonadotropic hypogonadism (117/328 = 35.1%), gonadal dysgenesis (99/328 = 30.2%) and mullerian agenesis (53/328 = 16.2%)., Conclusion: Age, height, and Tanner staging at presentation can provide a clue toward diagnosis, even before confirmatory tests are available. One of the largest studies reported on primary amenorrhea, we found hypogonadotropic hypogonadism to be the commonest cause, in contrast to previous studies., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Family Medicine and Primary Care.)

Background & Objectives: The frequency and predictors of pancreatitis in primary hyperparathyroidism (PHPT) are not well understood. The objective of the present study was to evaluate the frequency of pancreatitis in patients with PHPT and its association with clinical and biochemical parameters of the disease., Methods: In this retrospective study all consecutive patients with PHPT registered in the PHPT registry (www.indianphptregistry.com) from the year 2004 to 2013 were included. The clinical, biochemical and radiological parameters related to pancreatitis were evaluated in histologically proven PHPT patients., Results: A total of 218 patients (63 men; mean age: 40.6±14.4 yr) underwent surgery for PHPT during the study. Pancreatitis occurred in 35 [16%, 18 acute and 17 chronic pancreatitis (CP)] patients and male:female ratio was 1:0.94. Skeletal manifestations were seen less frequently in PHPT with pancreatitis as compared to that of PHPT without pancreatitis. PHPT with pancreatitis had significantly higher serum calcium (12.4±2.0 vs. 11.7±1.5 mg/dl, P <0.05) in comparison to PHPT without pancreatitis. PHPT with acute pancreatitis (AP) had higher serum calcium (P <0.05) and parathyroid hormone (PTH) (P <0.05) levels than PHPT with CP. Curative parathyroidectomy improved the symptoms associated with pancreatitis as there was no recurrence in AP group, whereas recurrence was observed only in about 10 per cent patients of the CP group., Interpretation & Conclusions: Pancreatitis was observed in 16 per cent of PHPT patients with male predominance in the study population. No recurrence of AP was observed after curative surgery. It may be proposed that serum amylase with calcium and PTH should be measured in all patients of PHPT with pain abdomen to rule out pancreatitis., Competing Interests: None

Background & Objectives: Accurate histopathological subtyping of non-small cell lung carcinoma (NSCLC) is essential for targeted therapeutic agents. Immunohistochemistry (IHC) is helpful in identification of different tumour subtypes. In this study two marker approaches, one each for glandular and squamous cell differentiation was applied to maximize the proportion of accurately subtyped NSCLC not otherwise specified (NOS) tumours on small biopsy samples., Methods: Two hundred and sixty three consecutive lung biopsies of primary lung carcinoma were prospectively studied. These were subtyped first morphologically and then by IHC for p40 and thyroid transcription factor-1 (TTF-1). The diagnosis of NSCLC-NOS before and after addition of IHC was evaluated. Results were correlated and validated with morphologically proven cases and matched surgical specimens., Results: Based on morphology, only 140 of the 263 (53.2%) cases of NSCLC were characterized, whereas 123 (46.7%) were classified as NSCLC-NOS type. With addition of IHC (p40 and TTF-1), the latter category reduced to 14.4 per cent and a sum of 225 (85.5%) cases were accurately subtyped into squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma. p40 showed 100 per cent sensitivity and specificity for squamous differentiation whereas TTF-1 showed sensitivity of 85.3 per cent and specificity of 98.1 per cent. Ninety per cent correlation of morphologic subtypes was achieved with matched resected specimens., Interpretation & Conclusions: Our results showed that an approach of using only a two-antibody panel (p40 and TTF-1) might help in reduction of diagnostic category of NSCLC-NOS significantly and contribute in saving tissue for future molecular testing.

Background & Objectives: Studies have shown that immunohistochemical (IHC) staining using epidermal growth factor receptor (EGFR) mutation specific antibodies, is an easy and cost-effective, screening method compared with molecular techniques. The purpose of present study was to assess the percentage positivity of IHC using EGFR mutation specific antibodies in lung biopsy samples from patients with primary lung adenocarcinoma (ADC)., Methods: Two hundred and six biopsies of primary lung ADC were subjected to EGFR mutation specific antibodies against del E746-A750 and L858R. Detection of EGFR mutation done by high resolution melting analysis (HRM) was used as gold standard. A concordance was established between molecular and IHC results. Frequency of IHC positivity was assessed., Results: Of the 206 patients, 129 were male and 77 were female patients, with a mean age of 54.1 yr. Fifty five (26.6%) patients (36 men; 19 women) showed positivity for IHC of del E746-A750 (33) and L858R (22). HRM results were available in 14 patients which showed EGFR mutations in correspondence with del E746-750 or L858R in 64.2 per cent cases. Positive cases on HRM were further confirmed by DNA sequencing and fragment analysis. Three patients showed exon[20] variation. Two cases were negative for mutation. The genotype of del E746-750 mutation was more common than L858R. A concordance was established between molecular mutation and IHC in 85.7 per cent cases., Interpretation & Conclusions: In this preliminary study from India mutation specific IHC was used for assessment of mutation status of EGFR. Although the number tested was small, a good concordance was observed between molecular EGFR mutation and IHC expression. IHC methodology is a potentially useful tool to guide clinicians for personalized treatment in lung ADC, especially where facilities for molecular analysis are not readily available and for use in small biopsies where material is scant for molecular tests.

Background: Endobronchial involvement is frequently absent in many patients with bronchogenic carcinoma. Malignant involvement may be confined to lymph nodes/peribronchial locations only or may be present along with endobronchial lesions. Transbronchial needle aspiration (TBNA) is a flexible bronchoscopic technique which can be employed to obtain tissue samples from mediastinal lymph nodes or peribronchial locations. Although a safe and cost effective bronchoscopic modality, it is frequently underutilized owing to concerns regarding its diagnostic utility and safety. Herein, we describe our experience over 1 year on the diagnostic utility of TBNA without rapid on-site evaluation (ROSE) in patients with suspected diagnosis of lung cancer., Materials and Methods: We retrospectively reviewed the cases in which conventional TBNA-without ROSE was performed for suspected lung cancer, between January 2012 and December 2012. Each lymph node station from which aspiration was performed was sampled thrice and smears were prepared on slides which were later examined by a cytopathologist., Results: Twenty-six cases were retrieved in which conventional TBNA without ROSE for suspected lung cancer with mediastinal involvement was performed during the study period. Adequate lymph node sampling could be achieved in 57.7% cases. Conventional TBNA was diagnostic in 11 out of the 26 (42.3%) patients. The diagnostic yield improved to 73.3% in patients in whom an adequate lymph nodal sample could be obtained. TBNA was the sole diagnostic sample in six (54.5%) patients. Alternative diagnoses (sarcoidosis and tuberculosis) were obtained in two patients., Conclusion: Conventional TBNA without ROSE is a safe and efficacious flexible bronchoscopic procedure which should be performed routinely from bronchoscopically accessible locations in patients with a suspected diagnosis of lung cancer.

Background & Objectives: Studies conducted to assess the prevalence of cardiovascular (CV) risk factors among different regions of the country show variation in risk factors in different age groups and urban and rural population. We undertook this study to determine the prevalence of cardiovascular risk factors among urban adults in a north Indian city., Methods: In a cross-sectional survey, 2227 subjects aged ≥ 20 yr were studied from April 2008 to June 2009 in Urban Chandigarh, a north Indian city. Demographic history, anthropometry and blood pressure were assessed. Fasting, and 2 h capillary plasma glucose after 75 g glucose load, HDL-C and triglycerides were estimated., Results: The most prevalent cardiovascular risk factors in the age group of 20-29 yr was sedentary lifestyle (63%), while from fourth decade and onwards, it was overweight/obesity (59-85%). The second most common prevalent cardiovascular risk factor in the age group of 20-29 yr was overweight/obesity, in 30-49 yr sedentary lifestyle, in 50-69 yr hypertension and in subjects ≥70 yr, it was hypertriglyceridaemia. The prevalence of overweight/obesity, hypertension, dysglycaemia and smoking was almost double in subjects in the fourth decade of life, as compared to those in the third decade of life. The prevalence of CV risk factors significantly increased with age irrespective of gender and prevalence of low HDL-C was significantly more common in women as compared to men., Interpretation & Conclusions: Sedentary lifestyle, obesity and low HDL-C are the most prevalent CV risk factors in subjects in the third and fourth decade of life in this north Indian population and clustering of these cardiovascular risk factors increases with advancing age. Strategies need to be formulated to target this population to prevent the epidemic of cardiovascular disease.

Lipoid pneumonia is an unusual and uncommon form of pneumonia caused by aspiration of fatty substances. Hydrocarbon pneumonitis following aspiration of diesel is a form of exogenous lipoid pneumonia wherein, aspirated diesel reaches the alveoli rapidly without evoking any significant cough, but initiates an intense inflammatory reaction in the pulmonary parenchyma. This is a rarely described clinical scenario, although the practice of diesel siphonage from automobiles is a common practice in developing countries. We herein describe a 40-year-old male patient, in whom the diagnosis of lipoid pneumonia was delayed for a long duration and highlight the importance of taking a detailed occupational exposure history in patients with non-resolving pneumonia to rule out the underlying possibility of this rare clinical entity.

Background & Objectives: Hyperthyroidism is associated with increased food intake, energy expenditure and altered body composition. This study was aimed to evaluate the role of adipocytokines in weight homeostasis in patients with hyperthyroidism., Methods: Patients (n=27, 11men) with hyperthyroidism (20 Graves' disease, 7 toxic multinodular goiter) with mean age of 31.3±4.2 yr and 28 healthy age and body mass index (BMI) matched controls were studied. They underwent assessment of lean body mass (LBM) and total body fat (TBF) by dual energy X-ray absorptiometer (DXA) and blood sample was taken in the fasting state for measurement of leptin, adiponectin, ghrelin, insulin, glucose and lipids. Patients were re-evaluated after 3 months of treatment as by that time all of them achieved euthyroid state with carbimazole therapy., Results: The LBM was higher (P<0.001) in healthy controls as compared to hyperthyroid patients even after adjustment for body weight (BW), whereas total body fat was comparable between the two groups. Serum leptin levels were higher in patients with hyperthyroidism than controls (22.3±3.7 and 4.1±0.34 ng/ml, P<0.001), whereas adiponectin levels were comparable. Plasma acylated ghrelin was higher in patients than in controls (209.8±13.3 vs 106.2±8.2 pg/ml, P<0.05). Achievement of euthyroidism was associated with significant weight gain (P<0.001) and significant increase in lean body mass (P<0.001). The total body fat also increased but insignificantly from 18.4±1.8 to 19.9±1.8 kg. There was significant decrease (P<0.05) in serum leptin and acylated ghrelin but adiponectin levels remained unaltered after treatment. Serum leptin positively correlated with TBF and this correlation persisted even after adjustment for BW, BMI, gender and age (r=0.62, P=0.001). However, serum leptin and acylated ghrelin did not correlate with the presence or absence of hyperphagia., Interpretation & Conclusion: Patients with hyperthyroidism predominantly had decreased lean body mass which increased after achievement of euthyroidism with carbimazole. The hyperphagia and the alterations in weight homeostasis associated with hyperthyroidism were independent of circulating leptin and ghrelin levels.

Background & Objectives: Conventionally, biphasic human insulin (30/70, BHI) is used twice daily for the management of patients with diabetes. However, this regimen is suboptimal to control post-lunch and/or pre-dinner hyperglycaemia in some patients. This study was undertaken to compare the efficacy and safety of thrice-daily biphasic human insulin (30/70, BHI) versus basal detemir and bolus aspart (BB) in patients with poorly controlled type 2 diabetes mellitus (T2DM)., Methods: In this open labelled randomized pilot study, 50 patients with uncontrolled T2DM on twice-daily BHI and insulin sensitizers were randomized either to BHI thrice-daily or BB regimen. HbA1c, six point plasma glucose profile, increment in insulin dose, weight gain, hypoglycaemic episodes and cost were compared between the two treatment groups at the end of 12 wk., Results: Mean HbA l c (± SD) decreased from 9.0 ± 0.9 per cent at randomization to 7.9 ± 0.8 per cent in BHI (P<0.001) and from 9.4 ± 1.3 to 8.2 ± 1.0 per cent in BB regimen (P<0.001) after 12 wk of treatment. The mean (± SEM) weight gain in patients in the BHI regimen was 1.5 ± 0.33 kg compared to 1.4 ± 0.34 kg in the BB regimen. Insulin dose increment at 12 wk was significantly more in the BB regimen 0.46 ± 0.32 U/kg/day compared to 0.15 ± 0.21 U/kg/day in the BHI regimen (P<0.001). The incidence of major as well as minor hypoglycaemic episodes was not different in both the regimen. The BB regimen was more expensive than the BHI regimen (P<0.001)., Interpretation & Conclusions: The thrice daily biphasic human insulin regimen is non-inferior to the basal bolus insulin analogue regimen in terms efficacy and safety in patients with poorly controlled T2DM. However, these data require further substantiation in large long term prospective studies.

Background & Objectives: Angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have been used to normalize the blood pressure and the dipping pattern in patients with type 1 diabetes mellitus (T1DM) and nephropathy. However, there are no data on the effect of the dual blockade on the dipping pattern in these subjects. We therefore, carried out this study to evaluate the effect of administrating an ACEI followed by ARB in the optimum doses in T1DM patients with nephropathy on 24 h blood pressure (BP) profile and nocturnal dipping pattern., Methods: An open label interventional pilot study was done during a one year period involving 30 consecutive patients who were treated with telmisartan 80 mg (0800-1000 h) for eight weeks followed by addition of ramipril 10 mg (1200-1400 h) for the next eight weeks. Ambulatory BP, dipping pattern and albumin excretion rate were studied after each phase. Twenty patients were hypertensive and 10 patients had macro- and 20 patients had microalbuminuria., Results: Telmisartan produced a fall in the clinic BP by 4/1.3 mm Hg (P<0.05 and P<0.362, respectively), 2/1.9 mm Hg in the mean 24 h BP, 1.4/1.1 mm Hg in the day BP and 3.7/3 mm Hg in the trough BP. Addition of ramipril to telmisartan produced a further reduction of 6.3/5.9 mm Hg in the clinic BP (P<0.001 for both), 4.3/4.2 mm Hg in the mean 24 h BP (P<0.01 and P<0.0001, respectively), 5.8/3.9 mm Hg in the day BP (P<0.01 for both), 4.2/2.5 mm Hg in the trough BP, with a reduction of clinic SBP and DBP of 10.3/7.2 mm Hg from the baseline. Telmisartan restored normal systolic dipping pattern in 33.3 per cent of the nondippers (P<0.01) but addition of ramipril was not complimentary. Hyperkalamia (>5.5 mmol/l) was observed only in 2 patients towards the end of the study., Interpretation & Conclusions: The dual blockade with telmisartan and ramipril had complimentary effect on lowering of the BP, however, similar beneficial effect on the nocturnal dipping was not observed. Further studies with large number of subjects with longer duration of follow-up are required to validate these observations.

Background & Objectives: Hyperprolactinaemia affects testicular functions by influencing hypothalamo-pituitary-testicular (HPT) axis at various levels. Available literature on the level of defect, time course of improvement of gonadal functions and its relation with decline in prolactin levels is scanty. We carried out this study to evaluate the HPT axis in patients with macroprolactinomas, before and six months after cabergoline therapy., Methods: Fifteen men with macroprolactinomas underwent gonadotropin and testosterone response to their respective stimuli before and after six months of cabergoline therapy., Results: Serum prolactin levels decreased after six months of therapy. Pretreatment, mean lutenizing and follicle stimulating hormones (LH and FSH) levels were 2.0 ± 0.4 and 1.4 ± 0.2 IU/l, respectively. However, LH and FSH responses to GnRH were preserved in majority of the patients and LH peaked to 12.1 ± 2.3 IU/l (P<0.01), while FSH to 2.9 ± 0.4 IU/l suggesting the influence of hyperprolactinaemia at the level of hypothalamus with preserved gonadotrope reserve. After cabergoline therapy, there was an increase in basal as well as stimulated LH and FSH levels, though these were not statistically significant when compared to respective pretherapy levels. Basal testosterone (T) levels significantly improved after therapy, but peak T response to hCG was similar at both pre- and post treatment. A significant correlation was observed between peak LH and peak T at baseline (r=0.53, P<0.01) and it further strengthened after therapy (r=0.70, P<0.01). After cabergoline therapy, there was significant improvement in seminal volume, sperm count and motility and sperm count correlated with peak FSH response (r=0.53, P<0.05)., Interpretation & Conclusions: Hyperprolactinaemia affects testicular functions probably by influencing at the level of hypothalamus resulting in subnormal basal secretion of gonadotropins required for optimal testicular functions.

Background & Objectives: Despite years of salt iodization, goitre continues to be a major public health problem worldwide. We examined the prevalence of goitre in the post-iodization phase and the relationship of goitre with micronutrient status and thyroid autoimmunity in school children of Chandigarh, north India., Methods: Two phase study; in the first phase, 2148 children of 6 to 16 yr were screened for goitre by two independent observers as per the WHO grading system. In the second phase, a case-control study, 191 children with goitre and 165 children without goitre were compared with respect to urinary iodine, iodine content of salt, serum levels of T3, T4, TSH, anti-TPO (thyroid peroxidase) antibody, haemoglobin, ferritin and selenium., Results: Prevalence of goitre in the studied subjects was 15.1 per cent (13.9% in 6 to 12 yr and 17.7% in 13 to 16 yr age group, P = 0.03). Median urinary iodine excretion in both the groups was sufficient and comparable (137 and 130 μg/l). 3.2 per cent children with goitre and 2.4 per cent without goitre had hypothyroidism (subclinical and clinical) and only one child with goitre had subclinical hyperthyroidism. Nine (4.9%) children in the goitre group and 3 (1.9%) in control group had anti-TPO antibody positivity. The median serum selenium levels were not different in both the groups (181.9 and 193.5 μg/l). Seventy one (37.4%) of the goitrous children had anaemia (haemoglobin <12 g/dl) as compared to 41 (24.8%) of the control group (P < 0.01). More number of goitrous children (39, 20.6%) were depleted of tissue iron stores (serum ferritin <12 μg/l) as compared to controls (11, 6.4%; P < 0.001). Serum ferritin level negatively correlated with the presence of goitre (r = -0.22, P = 0.008) and had an OR of 2.8 (CI 1.20-6.37, P = 0.017)., Interpretation & Conclusions: There was a high prevalence of goitre in young children despite iodine repletion and low thyroid autoimmunity. The concurrent iron deficiency correlated with the presence of goiter. However, the cause and effect relationship between iron deficiency state and goitre requires further elucidation.

Acute erythroid leukemia in children is very rare. Here is a case of erythroleukemia in a child of age 1.5 years, which was diagnosed on peripheral smear, bone marrow examination, cytochemistry but was confirmed on immunophenotyping. CD45 versus side scatter demonstrated blast population (29%) expressing CD45 of variable intensity (dim to negative). The myeloid nature of blast population showed bright expression of cytoplasmic myeloperoxidase (MPO), heterogenous positivity of CD117 and dim expression of CD13, CD33. These blasts also showed bright positivity for CD71 which showed erythroid nature of blasts. Flow cytometry can be comprehensive enough to completely subtype cases of leukemias/myelodysplastic syndromes, polycythemia rubra vera, non-neoplastic conditions like reactive erythroid hyperplasia following immunosuppressive therapy or viral infections or nutritional deficiencies, unlyzed RBCs or thrombocytosis which may mimic acute erythroid leukemia on flow cytometry.

Background & Objectives: The efficacy of the combination of angiotensin receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors in patients of type 1 diabetes mellitus (DM) with nephropathy is debatable. The antialbuminuric efficacy of dual blockade in patients of type 1 DM with micro- or macroabuminuria were evaluated., Methods: In this open label observational study 30 patients (20 male 10 female) with type 1 DM were included who were initially treated with telmisartan 80 mg for eight weeks followed by addition of ramipril 10 mg for a further eight weeks. Albuminuria reduction was studied at the end of each phase., Results: Therapy with telmisartan for 8 wk resulted in a 39 per cent (P<0.01) reduction in albumin excretion rate (AER). Combination therapy with telmisartan and ramipril produced a further reduction in AER of 33.4 per cent (P<0.01), amounting to a total AER reduction of 59 per cent (P<0.001). Dual blockade was more effective in the group of macroalbuminuric as compared to microalbuminuric subjects (P<0.05). Telmisartan produced a significant reduction in SBP (P<0.05). The addition of ramipril produced a further reduction in BP, the total reduction being 10.3 in SBP and 7.2 mmHg in DBP (P<0.001 for both). There was an increase in mean serum potassium of 0.39 mmol/l (P<0.01) from baseline at the end of the study period and two patients had hyperkalemia>5.5 mmol/l with dual blockade., Interpretation & Conclusion: Dual blockade with ramipril enhanced the antialbuminuric efficacy of telmisartan and further reduced blood pressure. The effect of dual blockade was more pronounced in the macroalbuminuric subjects and it was well tolerated. However, careful monitoring of serum potassium is required.

Background & Objectives: Since cabergoline has a long half-life and sustained occupancy of dopamine (D2) receptors in lactotrophs, its doses are slowly built up either monthly or two monthly. This possibly results in delayed normalization of serum prolactin and slow reduction in tumour size. This study was planned to assess the efficacy and safety of rapid escalation of cabergoline doses in men with macroprolactinomas., Materials: Fifteen consecutive men with macroprolactinomas underwent evaluation for anterior pituitary functions, visual fields, quality of life (QOL) score and magnetic resonance imaging (MRI), at baseline and after 6 months of cabergoline therapy. Serum prolactin and testosterone levels were assessed at monthly intervals. Cabergoline was started at a dosage of 0.5 mg twice per week and increased to 1.5 mg twice per week (3 mg ) by the third week, as 3 mg is usually considered as effective dose. Subsequent increase in doses was done as per protocol., Results: The mean age of patients at presentation was 31.7 +/- 3.3 yr and duration of symptoms was 25.0 +/- 3.6 months. Serum prolactin at baseline was 6249.3 +/- 3259.2 microg/l with a tumour volume of 28.9 +/- 8.3 cm(3). Eighty six per cent of the patients had visual field defects while 53 per cent had decreased visual acuity. The mean dose of cabergoline required was 3.2 mg/wk. Symptoms improved in majority (93%) of patients after four weeks of cabergoline therapy with a dramatic fall in serum prolactin by 99 per cent from 6249.3 +/- 3259.2 to 46.9 +/- 14.9 microg/l and it was normalized in 93 per cent of the patients by 8.2 wk. Improvement in visual field defects was noted in all but one, after one month and there was further improvement at 6 months. All patients had >25 per cent reduction in tumour size, and 73 per cent had > 50 per cent reduction after six months of cabergoline therapy. Basal circulating testosterone levels were low in 11 (73%) patients and started improving from first month of cabergoline therapy and became normal in around half of the patients after 6 months. No major side effects were observed requiring discontinuation of cabergoline therapy., Interpretation & Conclusions: Our preliminary findings show that rapid build-up of cabergoline doses increases its efficacy as well as rapidity of response in terms clinical improvement, normalization of serum prolactin and gonadal functions and reduction in tumour size, without compromising its safety in men with macroprolactinomas. Further studies with a larger sample size and control group for comparison need to be done to confirm these findings.

Background & Objective: Ectopic secretion of adrenocorticotropic hormone (ACTH) is rare, contributing to 10 per cent cases of endogenous Cushing's syndrome. We describe our experience of about two decades of patients with ectopic Cushing's syndrome (ECS) seen at a tertiary care centre from north India., Methods: Records of patients with ECS from 1985 to 2006 were retrospectively reviewed that included the presenting manifestations, clinical symptoms and signs, biochemical investigations including plasma cortisol, ACTH and high dose dexamethasone suppression test (HDDST), imaging modalities to localize the non pituitary source of ACTH production, management and follow up of these patients., Results: The study group included 12 patients (7 men) with mean (+/-SD) age at presentation 27.6 +/- 9.5 yr (range 13 to 48 yr) and the mean lag period between onset of symptoms and the diagnosis was 18.3 +/- 12.9 months with a range of 3 to 48 months. The weight loss (41.7%) followed by hyperpigmentation (25%) and infections (16.7%) were the common presenting manifestations. Cuticular atrophy (100%), hypertension (100%), bruise (92%) and proximal myopathy (83%) were the commonest signs. Plasma cortisol at 0800 h was 1267.3 +/- 483.3 nmol/l and at 2200 h was 1214.9 +/- 442.6 nmol/l indicating loss of circadian rhythm. The mean plasma ACTH was 221.1 +/- 55.9 (range 21.7 to 950 pg/ml). All but 2 patients had non-suppressibility of 0800 h plasma cortisol with HDDST. Five patients had thymic carcinoid, 3 had bronchial and one each had islet, hepatic and gut carcinoid and one had medullary thyroid carcinoma as a cause of ectopic ACTH secretion. The mean duration of follow up of these patients was 42.6 months and only two could sustain cure while remaining had either residual or recurrence., Interpretation & Conclusion: Ectopic Cushing's syndrome is a rare disease with varied manifestations and associated with increased morbidity and mortality. It presents with clinical features quite similar to classical Cushing's. Surgery with removal of primary tumour was found to be treatment of choice.

This experimental work was undertaken to study the difference in cell growth due to different attachment surface. Three types of attachment surface were studied (i) collagenized surface (ii) glass surface and (iii) plastic surface. Rat tail collagen suspension was prepared and coated on culture flasks. Human breast epithelial cells and breast carcinoma cells were cultured for three weeks. Cell counts were made before and after one, two and three weeks of culture. Out of five cases only two survived for more than a week. The best survival was observed on plastic surface. Collagenized and glass surfaces had similar results. Thus plastic surface is probably the best compared to glass and collagenized surface, possibly because the plastic surface provides better adhesion to malignant cells. It was also seen that in plastic surface the cells get lined up around a basement membrane like structure growing a resemblance to ductal structure. This is contradictory to the prevalent view that collagenized surface is best for in vitro growth and differentiation.