Frequency of aspirin non responsiveness in patients of ischemic heart disease.

Aspirin is widely used as an antiplatelet agent . Many patients have been noticed with recurrence of major ischemic events in- spite of antiplatelet therapy. The objective of this study was to determine frequency of aspirin non-responsiveness /resistance in patients of ischemic heart disease. Seventy one patients of IHD were selected from out-patient department of Punjab Institute of Cardiology Lahore. Whole Blood Platelet aggregation studies were performed on Diamed Impact R. Aspirin response assay was performed with DiaChidon (Arachidoinc Acid 16mmol/L). Non responders to aspirin were assessed on the basis of software generated results: Surface covered (SC) >2.5% was considered as response to aspirin and SC <2.5% was considered as no response (or resistance) to Aspirin. Chi-square test was applied to measure statistical significance. Non-response to Aspirin was observed in 11% (8 out of 71). There was significant association (p=0.045) between resistance to aspirin and Diabetes mellitus. Treatment resistance was also significantly associated with female gender (p=0.015). We concluded that non response to Aspirin is seen in significant number of patients of IHD. Diabetes mellitus and female gender are strong risk factors of developing failure to aspirin therapy.

Vitamin D deficiency associates with susceptibility to tuberculosis in Pakistan, but polymorphisms in VDR, DBP and CYP2R1 do not.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the genes encoding the vitamin D receptor (VDR) and the vitamin D binding protein (DBP) have been reported to modify the influence of vitamin D deficiency on susceptibility to active tuberculosis (TB) in the UK, but this phenomenon has not been investigated in settings with a high TB burden. SNPs in CYP2R1, which encodes a vitamin D 25-hydroxylase enzyme, are known to influence vitamin D status, but their potential role in determining susceptibility to TB has not previously been investigated in any setting. METHOD: We conducted a case-control study in 260 pulmonary TB patients and 112 controls recruited in Lahore, Pakistan. Analyses were conducted to test for main effects of vitamin D status and SNPs in VDR (rs731236, rs2228570 and rs1544410), DBP (rs7041 and rs4588) and CYP2R1 (rs2060793, rs10500804 and rs10766197) on susceptibility to TB, and to investigate whether these SNPs modify the association between vitamin D status and disease susceptibility. RESULTS: Profound vitamin D deficiency (serum 25-hydroxyvitamin D concentration ≤ 20 nmol/L) was common among TB patients (118/260, 45 %), and was independently associated with susceptibility to TB (adjusted odds ratio 1.87, 95 % CI 1.15 to 3.04, P = 0.01). However, none of the SNPs investigated associated with susceptibility to TB, either in main effects analysis, or in interaction with vitamin D status. CONCLUSION: Profound vitamin D deficiency was common among TB patients in this high-burden setting, and was independently associated with disease susceptibility. However, no statistically significant associations between SNPs in the vitamin D pathway and disease susceptibility was demonstrated.

Genotype-independent association between profound vitamin D deficiency and delayed sputum smear conversion in pulmonary tuberculosis.

BACKGROUND: Both vitamin D deficiency and genetic variants in the vitamin D receptor (VDR) have been reported to associate with delayed response to intensive-phase therapy for pulmonary tuberculosis. Studies investigating the influence of genetic variants in vitamin D binding protein (DBP) and vitamin D 25-hydroxylase (CYP2R1) on vitamin D status and response to antituberculous therapy are lacking. METHODS: We conducted a longitudinal study in 260 patients initiating treatment for smear-positive pulmonary tuberculosis in Lahore, Pakistan. Vitamin D status and genotypes for polymorphisms in VDR (rs2228570, rs731236, rs1544410), DBP (rs7041, rs4588) and CYP2R1 (rs2060793, rs10500804, rs10766197) were determined at baseline. Sputum smear microscopy was performed at 2, 4, 6 and 8 weeks, and time to sputum smear conversion was estimated for each participant. Analyses were conducted to determine demographic, clinical and genetic determinants of baseline vitamin D status and time to sputum smear conversion. RESULTS: Profound vitamin D deficiency (serum 25[OH]D < 25 nmol/L) was highly prevalent at TB diagnosis (present in 54 % of patients), and was independently associated with female vs. male sex (adjusted OR 2.60, 95 % CI 1.50 to 4.52, P = 0.001), recruitment in October to March inclusive (adjusted OR 1.75, 95 % CI 1.00 to 3.04, P = 0.047) and bilateral vs. unilateral disease (adjusted OR 1.89, 95 % CI 1.49 to 4.52 P = 0.025). Profound vitamin D deficiency was also independently associated with impaired response to antituberculous therapy (median time to sputum smear conversion 22.5 vs. 7.5 days for patients with serum 25[OH]D < 25 nmol/L vs. ≥ 25 nmol/L, respectively; aHR 4.36, 95 % CI 3.25 to 6.65, P < 0.001). No polymorphisms in VDR, CYP2R1 and DBP studied associated with either baseline vitamin D status or time to sputum smear conversion. CONCLUSIONS: Profound vitamin D deficiency is very common among TB patients in Lahore, Pakistan, and is independently associated with significantly delayed sputum smear conversion. Polymorphisms in VDR, CYP2R1 and DBP did not associate with baseline vitamin D status or response to intensive-phase treatment in this patient group.

Use of non invasive ventilation to avoid re-intubation in myasthenia gravis; a case report and review of literature.

Myasthenia Gravis (MG) in the elderly is an uncommon finding, especially when it is not related to thymoma. A case is presented with late onset Myasthenia Gravis treated with steroids, immunosuppressives and mechanical ventilation. This 61 year Asian hypertensive lady clinically diagnosed as MG presented to emergency room with difficulty in swallowing liquid, diplopia, drooping of eyelids and generalized weakness.Within 24 hours in the ward developed respiratory distress and CO2 narcosis, for which she was immediately intubated and shifted to ICU and managed by invasive ventilation and inotropic support. After stabilization and extubation BiPAP was applied successfully. BiPAP use is an established, non invasive ventilation technique for Myasthenia Gravis. Its application to avoid reintubation has not been thoroughly investigated. We intend to highlight this area for further research as it may change the total length of ICU and hospital stay and more importantly the outcome for this subset of patients.

Use of isoniazid chemoprophylaxis in renal transplant recipients.

BACKGROUND: The use of isoniazid (INH) as chemoprophylaxis for tuberculosis (TB) in renal transplant recipients has not been widely studied or reported from a country where TB is endemic. We are reporting here the results of the largest ever-reported randomized, prospective study of the use of INH in renal transplant recipients. METHODS: Four hundred consecutive live related renal transplant recipients between April 2001 and September 2004, from this single center, were randomized to receive or not receive INH for 1 year after transplantation. RESULTS: There were 12 dropouts. Of the remaining 388, 181 recipients received INH for 1 year post-transplant and 207 did not. The primary disease, comorbidities, HLA (human leucocyte antigen) match, immunosuppression, episodes of rejection, the use of anti-rejection agents, a past history of TB in the donor, the recipients and in family members living in same house and a history of TB in the family were factors compared in the two groups. The only significant difference between the two groups was that there was an increased family history of TB in recipients who received INH (P = 0.01). One recipient from the INH group and 16 recipients from the non-INH group developed TB (P = 0.0003). Discontinuation of INH for hepatotoxicity was not required in any patient. CONCLUSION: These results provide evidence that the use of INH following renal transplantation should be considered mandatory in geographical areas where the prevalence of TB is high. Furthermore, these results have important implication in patients from such areas who are immunosuppressed following other kinds of transplantation and for those who are immunocompromised for any other reason.

Dextrocardia associated with left hemidiaphragmatic eventration.

A rare case of dextrocardia in association with eventration of left hemidiaphragm who failed to thrive is presented. Growth retardation could not be attributed to these congential anomalies.

Coagulation factors and antithrombin levels in young and elderly subjects in Pakistani population.

Aging is associated with increased levels of coagulation factors and decrease in natural anticoagulant factors. This strongly supports that age-related hypercoagulable state occurs in elderly. This study aimed to measure the plasma levels of coagulation factors and anticoagulant levels in young and elderly to observe the effect of age on haemostatic system. Ninety healthy individuals, both men and women were divided into two groups on the basis of age. Group I included participants of less than 40 years of age, whereas, group II comprised of participants more than 60 years of age. Fibrinogen activity was assessed by using Clauss technique. Coagulation factor VII, and factor VIII activity by corresponding one stage assay based on prothrombin time and activated partial thromboplastin time. Antithrombin III was measured by the chromogenic method. Our results showed that significantly increased levels of fibrinogen (P = 0.001) were observed in the elderly population as compared to young. Higher fibrinogen levels in younger women than men and comparatively higher level than other races was observed in our local population. Increase in factor VII levels (P = 0.05) was also observed in the elderly group. This increase was statistically significant with age in women (P = 0.03). Factor VIII rose with age in both sexes (P = 0.001). Higher antithrombin activity was observed in the younger group whereas the older group demonstrated significantly lower antithrombin activity (P = 0.001). We conclude that considerable effects of age and sex are observed on coagulation factors and naturally occurring inhibitors.