The incidence of clinical bleeding by day 7 was similar between the two groups in patients with a platelet count of less than 10 000 per μL and less than 5000 per μL, indicating a lack of efficacy at ...any degree of thrombocytopenia. ...platelet transfusion did not expedite platelet recovery: the median time to a sustained platelet count of more than 50 000 per μL was similar between the two groups (4 days IQR 3-5 in the transfusion group vs 4 days 3-4 in the control group; p=0·39). ...this trial was not designed to study the efficacy of different doses of prophylactic platelet transfusion. Since all patients in the transfusion group received the same dose of platelets, nothing can be said about the efficacy of transfusion at doses higher than four units of pooled platelets per day. References 1 CP Simmons, JJ Farrar, VV Nguyen, B Wills, Dengue, N Engl J Med, Vol. 366, 2012, 1423-1432 2 EL de Azeredo, RQ Monteiro, LM Pinto, Thrombocytopenia in dengue: interrelationship between virus and the imbalance between coagulation and fibrinolysis and inflammatory mediators, Mediators Inflamm, Vol. 2015, 2015, 313842 3 JG Wong, TL Thein, Y-S Leo, J Pang, DC Lye, Identifying adult dengue patients at...
Chronic kidney disease (CKD) patients are at high risk of developing cardio vascular disease. Left atrial volume index (LAVi) is an indicator of left ventricular diastolic dysfunction. We conducted ...this study to find out the correlation of LAVi and other echocardio- graphic parameters with estimated glomerular filtration rate (eGFR). We prospectively enrolled 170 individuals: 69 patients with CKD and 101 controls. Echocardiographic parameters including systolic and diastolic volumes of left ventricle, LAVi, ejection fraction (EF), pulmonary artery systolic pressure (PASP), and E/e ratio were measured in all participants. The demographic, clinical, and echocardiographic parameters were examined. From the total of 170 individuals, 69 (40.5%) patients had CKD and 101 (59.5%) had normal renal profile. There were 38 (55.07%) males in the CKD group and 71 (70.29%) in the control group. Patients with CKD had higher median LAVi 33.33 mL/m
± 11.71 vs. 22.54 mL/m
± 5.82; P < 0.001, higher median E/e ratio 10.41 ± 6.28 vs. 7.48 ± 2.28; P < 0.001, higher median PASP 42.47 ± 13.64 vs. 33.59 ± 12.51; P < 0.001, and lower median EF 52.79% ± 14.37 vs. 60.7% ± 8; P < 0.001. There was a statistically significant negative correlation of eGFR with LAVi (r = -0.515, P < 0.001), PASP (r = -0.44, P = 0.001), and E/e ratio (r = -0.331, P = 0.001). Patients with CKD have higher LAVi, PASP, and E/e ratio and lower EF as compared to individuals without CKD. There is a significant negative correlation between eGFR and LAVi.
To evaluate the utility of teleconsultation in the provision of eye care services during the COVID-19 lockdown. Disparities in the consultation burden of sub-specialities and socio-demographic ...differences in teleconsultation utilization were also assessed.
Al-Shifa Trust Eye Hospital Rawalpindi began audio and video teleconsultation using broadband telecommunication services during the lockdown. Patients' and consultations' data gathered during the first three weeks after the commencement of this programme were compared with data from the four weeks prior to lockdown. The weekly consultation ratio and overall consultation burden of sub-specialities were measured. Chi-Square tests of association determined the relationship between different variables (socioeconomic status and consultation characteristics) and consultation modality (on-site vs online).
In total, 17507 on-site consultations (4377/week) were conducted compared to 1431 teleconsultations (477/week), which maintained 10.89% of the weekly pre-lockdown eye care services. The post-lockdown teleconsultation programme saw a relatively higher percentage of service utility among female (47.09% vs 44.71%), younger-age (31.33±19.45 vs 41.25±23.32 years) and higher-socioeconomic-status (32.21% vs 0.30%) patients compared to pre-lockdown on-site consultations. The most common indication for teleconsultation was red-eye (16.70%). While cornea and glaucoma clinics maintained most of the pre-lockdown services (30.42% and 29% respectively), the highest dropout was seen in optometric and vitreoretinal services supporting only 5.54% and 8.28% of pre-lockdown services, respectively.
Digital initiatives could partially maintain eye care services during the lockdown. Focused strategies to improve teleconsultation utilization are required during the pandemic and beyond.
Although most symptomatic dengue infections follow an uncomplicated course, complications and unusual manifestations are increasingly being reported due to rising disease burden. Expanded dengue ...syndrome is a new entity added into World Health Organization (WHO) classification system to incorporate this wide spectrum of unusual manifestations. We report a case of expanded dengue syndrome with subacute thyroiditis and intracerebral hemorrhage. This is the first case report of thyroiditis in dengue infection.
A 20 years old man presented with fever, myalgias, arthralgias, retro-orbital pain, vomiting and gum bleeding during a large dengue outbreak in Lahore, Pakistan. On 7th day of illness patient became afebrile, but he developed severe headaches, unconsciousness followed by altered behavior. On 9th day of illness patient developed painful neck swelling accompanied by fever, tremors, palpitations, hoarseness of voice and odynophagia. Examination revealed acutely swollen, tender thyroid gland along with features of hyperthyroidism. Laboratory evaluation revealed stable hematocrit, thrombocytopenia and leukopenia. Patient had seroconverted for anti-dengue IgM antibodies on the 10th day of illness. A non-contrast Computed Tomogram (CT) of the brain showed right frontal lobe hematoma. Thyroid profile showed increased free T3 and T4 and low TSH. Technetium thyroid scan showed reduced tracer uptake. He was diagnosed as having subacute thyroiditis and treated with oral prednisolone and propranolol. Follow up CT brain showed resolving hematoma. Patient's recovery was uneventful.
Subacute thyroiditis may develop during the course of dengue fever and should be included as a manifestation of expanded dengue syndrome. It should be suspected in patients with dengue fever who develop painful thyroid swelling and clinical features of hyperthyroidism.
Peroxisomes, single-membrane intracellular organelles, play an important role in various metabolic pathways. The translocation of proteins from the cytosol to peroxisomes depends on peroxisome import ...receptor proteins and defects in peroxisome transport result in a wide spectrum of peroxisomal disorders. Here, we report a large consanguineous family with autosomal recessive congenital cataracts and developmental defects. Genome-wide linkage analysis localized the critical interval to chromosome 12p with a maximum two-point LOD score of 4.2 (
θ
= 0). Next-generation exome sequencing identified a novel homozygous missense variant (c.653 T > C; p.F218S) in peroxisomal biogenesis factor 5 (
PEX5
), a peroxisome import receptor protein. This missense mutation was confirmed by bidirectional Sanger sequencing. It segregated with the disease phenotype in the family and was absent in ethnically matched control chromosomes. The lens-specific knockout mice of
Pex5
recapitulated the cataractous phenotype. In vitro import assays revealed a normal capacity of the mutant PEX5 to enter the peroxisomal Docking/Translocation Module (DTM) in the presence of peroxisome targeting signal 1 (PTS1) cargo protein, be monoubiquitinated and exported back into the cytosol. Importantly, the mutant PEX5 protein was unable to form a stable trimeric complex with peroxisomal biogenesis factor 7 (PEX7) and a peroxisome targeting signal 2 (PTS2) cargo protein and, therefore, failed to promote the import of PTS2 cargo proteins into peroxisomes. In conclusion, we report a novel missense mutation in
PEX5
responsible for the defective import of PTS2 cargo proteins into peroxisomes resulting in congenital cataracts and developmental defects.
To elucidate the novel molecular cause in two unrelated consanguineous families with autosomal recessive intellectual disability.
A combination of homozygosity mapping and exome sequencing was used ...to locate the plausible genetic defect in family F162, while only exome sequencing was followed in the family PKMR65. The protein 3D structure was visualized with the University of California–San Francisco Chimera software.
All five patients from both families presented with severe intellectual disability, aggressive behavior, and speech and motor delay. Four of the five patients had microcephaly. We identified homozygous missense variants in LINGO1, p.(Arg290His) in family F162 and p.(Tyr288Cys) in family PKMR65. Both variants were predicted to be pathogenic, and segregated with the phenotype in the respective families. Molecular modeling of LINGO1 suggests that both variants interfere with the glycosylation of the protein.
LINGO1 is a transmembrane receptor, predominantly found in the central nervous system. Published loss-of-function studies in mouse and zebrafish have established a crucial role of LINGO1 in normal neuronal development and central nervous system myelination by negatively regulating oligodendrocyte differentiation and neuronal survival. Taken together, our results indicate that biallelic LINGO1 missense variants cause autosomal recessive intellectual disability in humans.
Objective: The objective of this study was to determine the prevalence of obesity among students of medical colleges of Lahore and to study its correlation with high-caloric diet intake and physical ...inactivity. Study Design: A cross-sectional survey was conducted at four medical colleges of Lahore, Pakistan between March and June 2012. Methods: A total of 244 medical students (85 males, 159 females) of the median age of 20 years (range: 18-25) were randomly included in the study. Anthropometric measures were obtained. High-caloric diet intake and physical profile were assessed through a self-reported questionnaire. The relationships between obesity indices (body mass index BMI, waist-to-hip ratio) were investigated and correlated with the studied dietary and physical activity factors. Results: Approximately, 30.5% males and 16% females had BMI ≥25.0 kg/m2 overall affecting 21% of total medical students. Central obesity was found in 46% of male and 31.4% of female students. Central obesity was associated with a higher total daily caloric intake, studying at private medical college and male gender. Overall, 197 of 244 (80.7%) students played no sports in college. Median time to watch television or work on the computer was 120 min a day (range: 30-420). Only 70 (28.7%) students had regular walk or jogging. Conclusion: A substantial proportion of Pakistani medical students were overweight or obese. Higher total daily caloric intake was associated with central obesity but not a BMI >25. Physical activity parameters favored an overall sedentary aptitude for medical students.
We investigated an outbreak of darkening of skin, bleeding from multiple sites, leucopenia and thrombocytopenia in ischaemic heart disease patients. Case patients were defined as patients who had ...received medicines from the pharmacy of Punjab Institute of Cardiology between 1 December 2011 and 12 January 2012 and who developed any one of the following: darkening of skin, bleeding from any site, thrombocytopenia and leucopenia. Clinical and drug‐related data were ed. All 664 case patients had received iso‐sorbide‐mono‐nitrate contaminated with about 50 mg of pyrimethamine, and 151 (23%) died. The median age of 117 patients admitted at Jinnah Hospital Lahore was 57 years (range, 37–100) and 92 (79%) were male. The median time from intake of medicine to presentation was 37 days (range 13–72). Symptoms and signs included bleeding (in 95% of the patients), skin hyperpigmentation (in 61%), diarrhoea (in 53%) and abdominal pain (in 48%). At presentation, the median white cell count was 2.3 × 109/L (range, 0.1 × 109–16.0 × 109), the median hemoglobin concentration was 109 g/L (range 58–169) and the median platelet count was 18 × 109/L (range, 0 × 109–318 × 109). Bone marrow examination revealed trileneage dysplasia and severe megaloblastosis. The predictors of mortality included presentation prior to 15 January 2012, age more than 57 years, hypotension and leukocyte count less than 1.5 × 109/L. None of the patients who died received Calcium folinate because all deaths occurred prior to contaminant identification. We describe an outbreak of pyrimethamine toxicity in ischaemic heart disease patients receiving medicines from a single pharmacy due to accidental contamination of iso‐sorbide mono‐nitrate tablets at industrial level. Late recognition of illness resulted in high mortality.
Background: Scientific data regarding effects of platelet transfusion on platelet count in dengue-related thrombocytopenia is scanty. Methods: A single center, randomized non-blinded trial was ...conducted on adult patients with dengue fever and platelet counts less than 30,000/μl. Patients were randomized to treatment and control group. Treatment group received single donor platelets. Patients with post-transfusion platelet increment (PPI) ≥10,000/μl and/or corrected count increment (CCI) ≥5,000/μl 1 h post-transfusion were considered responders. Primary outcome was platelet count increments at 24 and 72 h. Results: 87 patients were enrolled, and 43 (48.2%) received platelet transfusion. Mean PPI and CCI at 1 h post-transfusion in the treatment group were 18,800/μl and 7,000/μl respectively. 22 (53.6%) patients in the treatment group were non-responders. Mean platelet increments at 24 and 72 h were higher in the treatment group as compared to the control group. Responders showed significantly higher increments when compared to non-responders and the control group at 24 h (p = 0.004 and p < 0.001, respectively) and 72 h (p = 0.001 and p < 0.001, respectively). Significant differences were found between non-responders and the control group at 24 h (p < 0.001), but not at 72 h (p = 0.104). Patients with lower baseline platelet count were more likely to be non-responders. Platelet transfusion neither prevented development of severe bleeding nor shortened time to cessation of bleeding. Three severe transfusion reactions and two deaths occurred in treatment group. Conclusion: In this trial, almost half the patients showed no response to a high-dose platelet transfusion. Platelet transfusion did not prevent development of severe bleeding or shorten time to cessation of bleeding and was associated with significant side effects. Therefore, platelet transfusion should not be routinely done in the management of dengue fever.
Short stature is defined as height below 3
centile. Causes of short stature can range from familial, endocrine disorders, chronic diseases to chromosomal disorders. Most common cause in literature ...being idiopathic short stature. Early detection and management of remedial disorders like malnutrition and vitamin D deficiency, Endocrine disorders like growth hormone deficiency & hypothyroidism can lead to attainment of expected height. Pakistani data shows idiopathic short stature as the most common cause of short stature. Our study aimed at detecting causes of short stature in children/adolescents at an Endocrine referral center.
A retrospective study was conducted at WILCARE Center for Diabetes, Endocrinology & Metabolism, Lahore on 70 well-nourished children/adolescents. The patients had been evaluated clinically, biochemically and radiologically as needed. Biochemical testing included hormonal testing as well to detect endocrine causes. Data was entered and analyzed in SPSS 20.0.
Leading cause of short stature in our population was Growth Hormone (GH) deficiency seen in 48 out of 70 (69%) patients. Second most common endocrine abnormality seen in these patients was Vitamin D deficiency 44 out of 70 patients (63%). Primary hypothyroidism; pan-hypopituitarism & adrenal insufficiency were other endocrine causes. The weight for age was below 3
percentile in 57 (81%) patients, with no association with other major causes.
Growth hormone and Vitamin D deficiency constitute one of the major causes of short stature among well-nourished children with short stature in Pakistan.
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