Muhammad Qayadat Hussain

OBJECTIVE: To evaluate the effect of maximal exercise on the level of brain natriuretic peptide (BNP) and cardiac adaptive changes in endurance trained elite athletes and sedentary healthy subjects. METHODOLOGY: This Cross-sectional comparative study was conducted at Army Medical College in collaboration with Armed Forces Institute of Cardiology (AFIC) Rawalpindi. Twenty two elite endurance athletes (Long Distance Runners) and 22 matching sedentary (from same unit having no sports activity) controls were selected by convenience (non-probability) sampling technique. Height, body weight, blood pressure, pulse rate and ECG were recorded. The blood was drawn from antecubital vein for measuring BNP and aldosterone before exercise and again after exercise. The echocardiography of left ventricle was done to measure the end-diastolic internal diameter (LVIDd), diastolic interventricular septal thickness (IVSTd), and diastolic posterior wall thickness (PWTd). The left ventricular mass (LVM) ...

Background: Top-level physical training is often associated with morphological changes in heart including increased left ventricular cavity dimension, wall thickness and mass. The objective of this study was to find out the differences in ventricular chamber size and wall thickness in Pakistani elite endurance athletes as compared to age and Body Mass Index matched controls. Material & Methods: This comparative cross-sectional study was conducted in Department of Physiology, Army Medical College, Rawalpindi from May 2003 to November 2004. A sample of 44 male subjects was selected, comprised of 22 elite endurance athletes (group 1) and 22 age and BMI matched healthy sedentary volunteers as controls (group 2). All those with cardiopulmonary diseases or having family history of these diseases were excluded. M-mode echocardiography was carried out. Age, weight, height and Body Mass Index were demographic variables while left ventricular end-diastolic internal diameter, diastolic interve...

To determine the correlation of EDN with lung function tests (FVC, FEV1, FEV1/FVC and FEF25-75%) in asthmatics and to compare these with matched controls. This study was carried out at Army Medical College & Military Hospital, Rawalpindi, Pakistan. Forty four asthmatic patients and equal number of matching controls were selected. Lung function tests were done by using compact spirometer. Severity of asthma was graded according to the American Thoracic Society (ATS) "Asthma severity code and classification…

Filippi syndrome is a rare, presumably autosomal-recessive disorder characterized by microcephaly, pre- and postnatal growth failure, syndactyly, and distinctive facial features, including a broad nasal bridge and underdeveloped alae nasi. Some affected individuals have intellectual disability, seizures, undescended testicles in males, and teeth and hair abnormalities. We performed homozygosity mapping and whole-exome sequencing in a Sardinian family with two affected children and identified a homozygous frameshift mutation, c.571dupA (p.Ile191Asnfs(∗)6), in CKAP2L, encoding the protein cytoskeleton-associated protein 2-like (CKAP2L). The function of this protein was unknown until it was rediscovered in mice as Radmis (radial fiber and mitotic spindle) and shown to play a pivotal role in cell division of neural progenitors. Sanger sequencing of CKAP2L in a further eight unrelated individuals with clinical features consistent with Filippi syndrome revealed biallelic mutations in four...

Asymmetric cell division is essential for normal human brain development. Mutations in several genes encoding centrosomal proteins that participate in accurate cell division have been reported to cause autosomal recessive primary microcephaly (MCPH). By homozygosity mapping including three affected individuals from a consanguineous MCPH family from Pakistan, we delineated a critical region of 18.53 Mb on Chromosome 1p21.3-1p13.1. This region contains the gene encoding HsSAS-6, a centrosomal protein primordial for seeding the formation of new centrioles during the cell cycle. Both next-generation and Sanger sequencing revealed a homozygous c.185T>C missense mutation in the HsSAS-6 gene, resulting in a p.Ile62Thr substitution within a highly conserved region of the PISA domain of HsSAS-6. This variant is neither present in any single-nucleotide polymorphism or exome sequencing databases nor in a Pakistani control cohort. Experiments in tissue culture cells revealed that the Ile62Th...

Centrioles are essential for ciliogenesis. However, mutations in centriole biogenesis genes have been reported in primary microcephaly and Seckel syndrome, disorders without the hallmark clinical features of ciliopathies. Here we identify mutations in the genes encoding PLK4 kinase, a master regulator of centriole duplication, and its substrate TUBGCP6 in individuals with microcephalic primordial dwarfism and additional congenital anomalies, including retinopathy, thereby extending the human phenotypic spectrum associated with centriole dysfunction. Furthermore, we establish that different levels of impaired PLK4 activity result in growth and cilia phenotypes, providing a mechanism by which microcephaly disorders can occur with or without ciliopathic features.

Prenatal diagnosis (PND) of β-thalassemia has been underutilized in Pakistan because of a number of social and economic factors. National Institute for Biotechnology and Genetic Engineering Faisalabad in collaboration with Multan Institute of Nuclear Medicine and Radiotherapy Multan introduced free PND service for carrier couples of Multan district. Multan has a population of about 4 million. More than 170 couples registered for retrospective PND and in 2 years 105 PND were carried out through first trimester chorionic villus sampling. Almost 90% of these couples were unable to afford the cost of PND and would not have undergone the test as free service was not available. Monoplex and Multiplex Amplification Refractory Mutation System-polymerase chain reaction and genomic DNA sequencing were used for detection of IVS (intervening sequence)-I-5 (G-C), FSC (frameshift codon)-8/9 (+G), FSC-41/42 (-TTCT), IVS-I-1 (G-T), 619 bp deletion, and CD-15 (G-A) β-globin mutations. Eighty-one percent (85/105) couples analyzed were in a consanguineous marriage. Twenty-three fetuses were found homozygous mutant and all couples opted for discontinuation of affected pregnancies. More families are registering for PND after establishment of this free and accessible PND service.

Autosomal recessive primary microcephaly (MCPH) is characterized by reduced head circumference (≤4 SD) and mental retardation without any other neurological manifestation. Of the four identified MCPH genes, homozygous truncating mutations in ASPM (MCPH5) account for >50% of all reported families. In spite of the high frequency of MCPH in Pakistan only one case of compound heterozygosity for mutations in ASPM has been reported yet. In this large MCPH study we ascertained 37 families including 319 persons (140 patients). Haplotype analysis of eight STS markers suggested linkage by homozygosity in 20 families, and re‐analysis of single sib ships in the remaining families demonstrated possible compound heterozygosity in two families. Direct sequencing indeed confirmed compound heterozygosity in two and homozygous mutations in 20 families, respectively, showing that up to 10% of families with MCPH caused by ASPM are compound heterozygous. In total we identified 16 different nonsense o...

Feature extraction and classification for electroencephalogram (EEG) in medical applications is a challenging task. The EEG signals produce a huge amount of redundant data or repeating information. This redundancy causes potential hurdles in EEG analysis. Hence, we propose to use this redundant information of EEG as a feature to discriminate and classify different EEG datasets. In this study, we have proposed a JPEG2000 based approach for computing data redundancy from multi-channels EEG signals and have used the redundancy as a feature for classification of EEG signals by applying support vector machine, multi-layer perceptron and k-nearest neighbors classifiers. The approach is validated on three EEG datasets and achieved high accuracy rate (95-99 %) in the classification. Dataset-1 includes the EEG signals recorded during fluid intelligence test, dataset-2 consists of EEG signals recorded during memory recall test, and dataset-3 has epileptic seizure and non-seizure EEG. The findings demonstrate that the approach has the ability to extract robust feature and classify the EEG signals in various applications including clinical as well as normal EEG patterns.