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Biomedical subjects

M A Chaudhary

Publications and source records attributed to M A Chaudhary.

12 recordsLinked to original sources

Long term clinical and echocardiographic results of mitral balloon valvotomy in children and adolescents.

AIMS: To assess the safety, efficacy, and long term results of mitral balloon valvotomy (MBV) for rheumatic mitral stenosis in children and adolescents in comparison to adults. METHODS: The results of 468 patients with mitral stenosis who underwent successful MBV and were followed up for 0.5-13 years were analysed. Patients were divided according to age at the time of MBV into group 1 consisting of 84 patients < or = 20 years of age (children and adolescents) and group 2 that included 384 patients, age > 20 (adults). RESULTS: Patients in group 1 had a lower mitral echo score (mean (SD) 7.5 (1.3) v 8 (1.1), p < 0.001), smaller Doppler mitral valve area (MVA) (0.84 (0.17) v 0.92 (0.18) cm2, p < 0.001), and higher Doppler mitral valve gradient (15.0 (5.3) v 12.7 (4.5) mm Hg, p < 0.001) than group 2. Immediately after MBV group 1 had larger MVA, whether measured by Doppler (2.0 (0.30) v 1.96 (0.28) cm2, p < 0.05) or by catheter (2.0 (0.59) v 1.8 (0.52) cm2, p < 0.001), and similar complication rates, compared to group 2. After a mean follow up of 5 (3.5) years there was no significant difference between groups 1 and 2 in the incidence of restenosis (14.3% v 16.1%, NS). Event-free survival rates at 5, 10, and 12.5 years were 93%, 79%, and 79% for group 1 and 94%, 90%, and 84% for group 2 (p = 0.18). CONCLUSIONS: MBV is safe and effective in children and adolescents with rheumatic mitral stenosis. It provides better immediate results than in adults and excellent long term results that are comparable to those seen in adults.

Adolescent↗

Concurrent methylation of multiple genes in childhood ALL: Correlation with phenotype and molecular subgroup.

Multiple genes have been shown to be independently hypermethylated in lymphoid malignancies. We report here on the extent of concurrent methylation of E-cadherin, Dap-kinase, O(6)MGMT, p73, p16, p15 and p14 in 129 pediatric ALL cases. While most of these genes demonstrated methylation in a proportion of cases, O(6)MGMT, p16 and p14 were infrequently methylated (11, 7 and 3%, respectively). Methylation of at least one gene was found in the vast majority (83%) of cases. To determine the extent and concordance of methylation we calculated a methylation index (MI=number of methylated genes/number of studied genes) for each sample. The average MI was 0.28, corresponding to 2/7 methylated genes. MI was correlated with standard prognostic factors, including immunophenotype, age, sex, WBC and presence of specific translocations (TEL-AML1, BCR-ABL, E2A-PBX1 or MLL-AF4). We determined that children >/=10 years old and children presenting with high WBC (>/=50 x 10(9)/l) both associated with a higher MI (P<0.01 and <0.05, respectively). T-ALLs demonstrated a lower MI (median=0.17) than precursor B ALLs (median=0.28). Among the different molecular subgroups, MLL-ALLs had the highest MI (mean=0.35), while ALLs carrying the t(1;19) had the lowest MI (mean=0.07). The most common epigenetic lesion in childhood ALL was methylation of E-cadherin (72%) independent of the molecular subtype or other clinicopathological factors.

Adolescent↗

Hepatitis B virus reactivation with clinical flare in allogeneic stem cell transplants with chronic graft-versus-host disease.

We conducted a retrospective study with the aim of identifying risk factors and clinical characteristics associated with HBV reactivation and clinical flare after allogeneic stem cell transplantation (aSCT). We reviewed the King Faisal Specialist Hospital and Research Center International Bone Marrow Transplant Registry database from January 1998 to June 2000. Complete serological screening for HBV was available in 128 of 131 patients transplanted during that period. Fifty-four (42%) had evidence of prior infection and recovery from HBV before transplant (hepatitis B core antibody positive, B surface antigen negative). Forty-two were evaluable for HBV reactivation and clinical flare. Six (14%) reactivated with clinical flare as documented by seroconversion and/or positive HBV DNA in the serum with biochemical hepatitis at 5.5, 18, 18, 19, 21 and 23 months post-transplant. Five of fifteen patients with chronic graft-versus-host disease (cGVHD) reactivated with clinical flare in contrast to 1/27 without cGVHD (RR: 9.0, 95% CI: 1.2-70.1 P < 0.02). HBV reactivation with clinical flare occurred during immunosuppressive therapy tapering or withdrawal in all patients. In conclusion, hepatitis B core antibody positive allogeneic stem cell recipients with cGVHD are at significant risk of HBV reactivation with clinical flare.

Adolescent↗

Evidence of DNA repair/processing defects in cultured skin fibroblasts from breast cancer patients.

Cultured skin fibroblasts from 14 breast cancer (BC) patients were compared with those from 8 healthy subjects and 4 ataxia-telangiectasia (A-T) cases for sensitivity to low dose-rate (0.007 Gy/min) gamma-irradiation assessed by a colony-forming assay and for postirradiation DNA synthesis inhibition determined by the method of [(3)H]thymidine incorporation. Fibroblasts from all but two BC patients exhibited moderately enhanced radiosensitivity in the colony-forming assay, occupying an intermediate position between the controls and the A-T cases. Fibroblasts from the radiosensitive BC patients also showed an intermediate response with respect to radio-induced DNA synthesis inhibition compared with those from controls and A-T cases. In a host cell reactivation assay using an irradiated herpes simplex virus for plaque-forming ability, the fibroblasts from 7 BC patients, used as host cells, resulted in a significantly reduced (P < 0.0001) recovery of the virus relative to the 8 control fibroblasts, suggesting a deficiency in DNA repair in the former. A number of the BC fibroblasts analyzed in an assay for potentially lethal damage repair confirmed the repair deficiency in the fibroblasts from the BC patients. Defects in DNA repair and/or DNA processing after exposure to genotoxic agents would lead to genomic instability and hence would be responsible for cancer predisposition. Our data suggest that most BC patients may carry various genes resulting in such defects, and additional studies on normal cells from a larger cohort of BC patients and their family members are warranted to establish a connection between mutations or polymorphisms in specific DNA repair genes and susceptibility to breast cancer.

Adult↗

The effects of radiation on craniofacial skeletal growth: a quantitative study.

To determine whether radiation delivered to children treated for head and neck cancer causes deformity, we performed a quantitative analysis for craniofacial asymmetry. A total of 42 patients, with either rhabdomyosarcoma or nasopharyngeal carcinoma, treated between 1980 and 1991, were analyzed. Exclusions included 16 subjects, leaving 26 children of mixed race and gender with a median age at diagnosis of 13 years (range: 2-18) and a median age at follow-up of 4 years (range: 3-37). Data from 14 measurements of the cranium and facial skeleton, for which normative data exist, were recorded. Symmetry of the face and head were determined and each measurement was compared to age specific standards. Deviation occurred in the cranial vault, the anterior and mid-interorbital distances and lateral orbital wall length. Asymmetry existed in the medial and lateral orbital wall lengths and the zygomatic arches. We conclude that, children irradiated for head and neck malignancies, have significant alterations in some skeletal measurements indicative of treatment induced asymmetry and potential deformity.

Adolescent↗

Developmental alterations in auditory arousal from sleep in healthy and virus-infected cats.

To investigate the impact of respiratory-tract infections on arousability from sleep, we evaluated the auditory arousal responses of healthy and virus-infected cats in two age groups. Arousability was positively associated with stimulus intensity but negatively associated with experimental day. Infected animals were more responsive to auditory stimuli than were uninfected ones, and younger cats were less responsive than older animals. Within the younger groups, infected cats demonstrated increased arousability across the entire range of stimulus volumes during quiet sleep but not during active sleep. Young infected cats also demonstrated lower EEG delta-wave amplitudes than did uninfected animals. These effects on arousability and EEG amplitudes were not observed in older cats. Thus, under the conditions studied, cats with mild viral infections show an age-related enhancement of auditory arousability from sleep, suggesting that they sleep less deeply than do healthy, age-matched animals. The generalization of these observations to other arousing stimuli, such as hypoxia or hypercapnia, and possible implications for the pathogenesis of sudden infant death syndrome remain to be determined.

Acoustic Stimulation↗

Estimating confidence intervals for cost-effectiveness ratios: an example from a randomized trial.

Cost-effectiveness ratios usually appear as point estimates without confidence intervals, since the numerator and denominator are both stochastic and one cannot estimate the variance of the estimator exactly. The recent literature, however, stresses the importance of presenting confidence intervals for cost-effectiveness ratios in the analysis of health care programmes. This paper compares the use of several methods to obtain confidence intervals for the cost-effectiveness of a randomized intervention to increase the use of Medicaid's Early and Periodic Screening, Diagnosis and Treatment (EPSDT) programme. Comparisons of the intervals show that methods that account for skewness in the distribution of the ratio estimator may be substantially preferable in practice to methods that assume the cost-effectiveness ratio estimator is normally distributed. We show that non-parametric bootstrap methods that are mathematically less complex but computationally more rigorous result in confidence intervals that are similar to the intervals from a parametric method that adjusts for skewness in the distribution of the ratio. The analyses also show that the modest sample sizes needed to detect statistically significant effects in a randomized trial may result in confidence intervals for estimates of cost-effectiveness that are much wider than the boundaries obtained from deterministic sensitivity analyses.

Analysis of Variance↗

Pediatric skin disease in Pakistan. A study of three Punjab villages.

The population of children younger than 5 years old in three widely distributed villages in Punjab, Pakistan, was examined for skin disease in November 1980. Approximately 29% of the children had infectious skin disease, with pyoderma the predominant diagnostic category. There were significant differences in pyoderma prevalence rates between villages, with the suppressive effect of malathion spraying for malaria control on the insect population representing the most likely explanation for the observed differences. These data again emphasize the amount of skin disease, particularly in children, in rural areas of the lesser developed countries, and the desirability of focusing attention on the dermatologic needs of this vast sector of the world's population.

Age Factors↗

Endocrine sequelae of childhood craniopharyngioma.

The endocrine sequelae of 62 children with craniopharyngioma were studied retrospectively. These patients were followed for a median duration of 3 years (range 1 to 10 years). Eighteen patients had a long-term follow-up for more than 5 years (range 5 to 10 years). Complete surgical resection was achieved in 30 patients and 32 patients had residual tumor. Twenty-five patients had recurrence or progression of the residual tumor and were treated with radiotherapy. Presenting complaints suggestive of endocrinopathy were infrequent. The most common presenting symptoms were headache, nausea and vomiting, followed by growth failure. Pre-operatively, growth hormone deficiency was the most commonly encountered pituitary hormonal deficiency; however postoperatively, most children had diabetes insipidus. Multiple pituitary hormonal deficiencies were more frequently observed in children treated with extensive radical surgery than in those treated with conservative surgery and radiotherapy. The endocrine morbidity associated with craniopharyngioma and its different management modalities remains high; however, it is manageable with appropriate hormonal replacement therapy.

Adolescent↗