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Biomedical subjects

S Hussain

Publications and source records attributed to S Hussain.

At least 19 recordsLinked to original sources
PubMed2006

Cross section dependence of event rates at neutrino telescopes.

We examine the dependence of event rates at neutrino telescopes on the neutrino-nucleon cross section for neutrinos with energy above 1 PeV, and contrast the results with those for cosmic ray experiments. Scaling of the standard model cross sections leaves the rate of upward events essentially unchanged. Details, such as detector depth and cross section inelasticity, can influence rates. Numerical estimates of upward shower, muon, and tau event rates in the IceCube detector confirm these results.

Journal Article↗
PubMed2006

Interaction of the guidance molecule Slit with cellular receptors.

Slits are large secreted glycoproteins characterized by an unusual tandem of four LRR (leucine-rich repeat) domains in their N-terminal half. Slit proteins were initially described as repulsive guidance cues in neural development, but it has become clear that they have additional important functions, for instance in the vasculature and immune system. Genetic studies have identified two types of cellular receptors for Slits: Robos (Roundabout) and the HS (heparan sulphate) proteoglycan syndecan. The intracellular signalling cascade downstream of Robo activation is slowly being elucidated, but the mechanism of transmembrane signalling by Robo has remained obscure. No active signalling role for syndecan has yet been demonstrated. Slit-HS interactions may be important for shaping the presumed Slit gradient or presenting Slit at its target cell surface. Recent studies have mapped the binding sites for Robos and HS/heparin to discrete Slit domains. Robos bind to the second LRR domain of Slit, whereas HS/heparin binds with very high affinity to the C-terminal portion of Slit. Slit activity is likely to be modulated by physiological proteolytic cleavage in the region separating the Robo and HS/heparin-binding sites.

Animals↗
PubMed2006

Gastric carcinoma presenting with extensive bone metastases and marrow infiltration causing extradural spinal haemorrhage.

Gastric carcinoma is the third most common gastrointestinal (GI) malignancy after colon and pancreatic carcinoma. A Japanese study showed that the incidence of bone metastases of gastric cancer was 13.4% among autopsies. It is very rare for the primary presentation of a gastric malignancy to be with bone metastases. This case report is of a 46-year-old female patient, who presented with a thoracic vertebral wedge fracture and was subsequently found to have widespread vertebral metastatic deposits with marrow infiltration. The infiltration and suppression of marrow function was complicated by an acute bleed into the extradural space causing spinal cord compression. This case demonstrates two important features. First, that gastric cancer, although far less common than breast, kidney, thyroid, prostate and bronchial cancer, is a cause of metastases to bone. Second, it highlights the complications of bone metastases, marrow suppression, leukoerythroblastic anaemia, spinal canal haematoma and cord compression. The case is illustrated by axial and sagittal MRI slices.

Back Pain↗
PubMed2005

Self management of oral anticoagulation: randomised trial.

OBJECTIVE: To determine the clinical effectiveness of self management compared with routine care in patients on long term oral anticoagulants. DESIGN: Multicentre open randomised controlled trial. SETTING: Midlands region of the UK. PARTICIPANTS: 617 patients aged over 18 and receiving warfarin randomised to intervention (n = 337) and routine care (n = from 2470 invited; 193/337 (57%) completed the 12 month intervention. INTERVENTION: Intervention patients used a point of care device to measure international normalised ratio twice a week and a simple dosing chart to interpret their dose of warfarin. MAIN OUTCOME MEASURE: Percentage of time spent within the therapeutic range of international normalised ratio. RESULTS: No significant differences were found in percentage of time in the therapeutic range between self management and routine care (70% v 68%). Self managed patients with poor control before the study showed an improvement in control that was not seen in the routine care group. Nine patients (2.8/100 patient years) had serious adverse events in the self managed group, compared with seven (2.7/100 patient years) in the routine care arm (chi2(df = 1) = 0.02, P = 0.89). CONCLUSION: With appropriate training, self management is safe and reliable for a sizeable proportion of patients receiving oral anticoagulation treatment. It may improve the time spent the therapeutic range for patients with initially poor control. Trial registration ISRCTN 19313375.

Administration, Oral↗
PubMed2004

Novel mutations in the EXT1 gene in two consanguineous families affected with multiple hereditary exostoses (familial osteochondromatosis).

Multiple hereditary exostoses (HME) is an autosomal dominant developmental disorder exhibiting multiple osteocartilaginous bone tumors that generally arise near the ends of growing long bones. Here, we report two large consanguineous families from Pakistan, who display the typical features of HME. Affected individuals also show a previously unreported feature--bilateral overriding of single toes. Analysis using microsatellite markers for each of the known EXT loci, EXT1, EXT2, and EXT3 showed linkage to EXT1. In the first family, mutation analysis of the EXT1 gene revealed that affected individuals were heterozygous for an in-frame G-to-C transversion at the conserved splice donor site in intron 1. This mutation is predicted to disrupt splicing of the first intron and produce a frameshift that leads to a premature termination codon. In the second family, an insertion of an A in exon 8 is predicted to produce a frameshift at codon 555 followed by a premature termination, a further 10 codons downstream. In both families, an increased number of affected male subjects were observed. In affected females in family 2, phenotypic variability and incomplete penetrance were noted.

Base Sequence↗
PubMed2004

Comparison of optimal malarial test with light microscopy for the diagnosis of malaria.

OBJECTIVE: To evaluate the efficacy of a parasite lactate dehydrogenase-based immunochromatographic antigen detection assay (optimal) against conventional light microscopy in the diagnosis of malaria at Military Hospital, Rawalpindi and Department of Pathology Army Medical College Rawalpindi from August to October 2002 in patients reporting sick with history suggestive of malaria. METHODS: The blood samples were collected from 215 patients reporting with symptoms suggestive of malaria. Thick and thin blood films were prepared, stained with Leishman's stain and examined by light microscopy for the presence of malarial parasites. Parasitaemia was estimated on all positive slides. All samples were tested for presence of malarial parasite by optimal dipstick method according to the manufacturer's instructions. RESULTS: A total of 215 cases were studied. Malarial parasites were visualized in 98 (45.5%) cases with light microscopy. Optimal test revealed 93 (43.2%) of these samples as positive. Microscopy showed 61 out of 98 positive cases to be P. vivax and 37 P. falciparum. The Optimal dipstick method revealed that 58 out of 93 were positive for P. vivax and 35 positive for P. falciparum. These results demonstrated that Optimal had sensitivities of 95% and 94.5% for P. vivax and P. falciparum respectively. It has 100% specificity for both malarial species, when compared to conventional microscopy. CONCLUSION: Optimal test showed excellent correlation with microscopy in the diagnosis of P. vivax and P. falciparum. It is expensive but it has an advantage of being simple, rapid and effective test in the diagnosis of malaria especially where well trained microscopists are not available or work load is too high.

Animals↗
PubMed2003

The phototoxicity of phenothiazinium derivatives against Escherichia coli and Staphylococcus aureus.

Phenothiazinium dyes, and derivatives, were tested for toxicity to Escherichia coli and Staphylococcus aureus. The dyes were generally lipophilic (log P>1) and showed inherent dark toxicity (minimum lethal concentrations: 3.1-1000 microM). Dye illumination (total light dose of 3.15 J cm(-1) over 30 min) led to up to eight-fold reductions in minimum lethal concentrations. Most of the illuminated dyes showed significant relative singlet oxygen yields (phi'delta: 0.18-1.35) suggesting a type II mechanism of generating a phototoxic response. Although generally up to six-fold more effective against S. aureus, the dyes tested efficiently killed E. coli and may be of particular use in combating Gram-negative pathogens.

Anti-Bacterial Agents↗
PubMed2003

Expression of pituitary tumour transforming gene (PTTG) and fibroblast growth factor-2 (FGF-2) in human pituitary adenomas: relationships to clinical tumour behaviour.

OBJECTIVE: Pituitary tumour transforming gene (PTTG) encodes a multifunctional protein that is implicated in initiating and perpetuating pituitary adenoma growth. PTTG appears to have key regulatory functions in determining control of many fundamental cellular events including mitosis, cell transformation, DNA repair and gene regulation. Several of these events are mediated through interactions with PTTG binding factor (PBF) and fibroblast growth factor-2 (FGF-2). Given this background, we have determined the expression of PTTG, PBF, FGF-2 and its receptor FGF-R-1 in a large cohort of pituitary adenomas and have sought associations between levels of gene expression and clinical markers of tumour behaviour. PATIENTS AND METHODS: We used real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analyses to measure PTTG, PBF, FGF-2 and FGF-R-1 expression in ex vivo pituitary tumours (N = 121). Clinical data, including accurate radiological assessment of tumour characteristics, were used to determine any associations between gene expression and tumour behaviour. RESULTS: PTTG was increased significantly (fivefold, P = 0.005) in adenomas compared with normal pituitaries. We also demonstrated that PBF was similarly raised in adenomas (sixfold, P = 0.0001), and was significantly correlated with PTTG expression. FGF-2 and its receptor FGF-R-1 were also raised in adenomas compared with normal pituitary tissue. Moreover, significantly enhanced expression of FGF-R-1 was observed in invasive adenomas compared with other pituitary tumours. CONCLUSIONS: Our data support a fundamental role for PTTG-mediated upregulation of FGF-2 signalling in pituitary tumorigenesis and growth, and suggest that receptor-mediated mechanisms of growth factor action may be critically important. Further prospective studies are required to determine whether measurement of FGF-R-1 mRNA will be of clinical use as a prognostic marker in patients with pituitary adenomas.

Adenoma↗
PubMed2003

Sonographic prevalence of acquired cystic renal disease in patients receiving haemodialysis.

OBJECTIVE: To determine the sonographic prevalence of Acquired Cystic Renal Disease (ACRD) in patients on maintenance haemodialysis and its relationship to the duration on dialysis. METHODS: All patients with end stage renal disease (ESRD) who were receiving maintenance haemodialysis in Urology Department of Mayo Hospital Lahore between November 1997 to February 1998 were screened by ultrasound for the prevalence of ACRD. RESULTS: Forty patients with ESRD on maintenance haemodialysis were evaluated. The mean age of patients was 39.9 years. The male to female ratio was 2.3:1. Four patients (10%) had documented ACRD. The proportion of patients with ACRD increased with increasing duration of dialysis; ACRD was found in 60% of patients who had dialysis for more than 3 years, 20% in those who had been dialyzed for 1-3 years, and no patient developed ACRD who was on dialysis for less than one year. All patients remained asymptomatic except one, who had intermittent macroscopic haematuria. There was no evidence of neoplasm in any of these patients on clinical grounds or on ultrasound. CONCLUSION: We found a low prevalence of ACRD in the population studied compared to previously published series. This can be explained by the fact that most of our patients were on dialysis for less than one year. A further study is suggested with greater numbers in a center where patient stay on dialysis for longer period and patient turnover is low.

Adult↗
PubMed2002

Effect of videotape feedback on anaesthetists' performance while managing simulated anaesthetic crises: a multicentre study.

The aim of this study was to examine the performance of anaesthetists while managing simulated anaesthetic crises and to see whether their performance was improved by reviewing their own performances recorded on videotape. Thirty-two subjects from four hospitals were allocated randomly to one of two groups, with each subject completing five simulations in a single session. Individuals in the first group completed five simulations with only a short discussion between each simulation. Those in the second group were allowed to review their own performance on videotape between each of the simulations. Performance was measured by both 'time to solve the problem' and mental workload, using anaesthetic chart error as a secondary task. Those trainees exposed to videotape feedback had a shorter median 'time to solve' and a smaller decrease in chart error when compared to those not exposed to video feedback. However, the differences were not statistically significant, confirming the difficulties encountered by other groups in designing valid tests of the performance of anaesthetists.

Anesthesiology↗
PubMed2002

Effects of daily variation in outdoor particulates and ambient acid species in normal and asthmatic children.

BACKGROUND: Evidence suggests that the respiratory health of children may be adversely affected by daily variation in outdoor pollutants, particularly ozone and particulates. However, data from the UK are sparse and the contribution of different particulate fractions and acid species, together with the identification of those individuals most at risk, are not clear. METHODS: One hundred and sixty two 9 year old children were enrolled from two inner city locations and recorded daily symptoms and twice daily peak expiratory flow (PEF) over 8 week periods in the winter and summer. Their results were analysed with daily pollutant levels at appropriate lags using regression models which corrected for trends, weather, pollen, and autocorrelation. RESULTS: Pollutant levels were generally low, especially in the summer. Multiple statistically significant associations were noted between health outcomes and pollutant concentrations, but no consistent patterns in identified effects were apparent between pollutants, lags, direction of observed effect, or location. There was no evidence to suggest that subgroups with atopy or pre-existing wheeze are more sensitive to pollutant effects. CONCLUSION: These data do not suggest that adverse health outcomes are associated with daily variations in pollutants [corrected]. No evidence was found to indicate that particulates or individual acid and anion species are more closely related to adverse health outcomes than other pollutants.

Acids↗
PubMed2002

Vascular endothelial growth factor, its receptor KDR/Flk-1, and pituitary tumor transforming gene in pituitary tumors.

Pituitary tumorigenesis is a poorly understood process involving dysregulation of the cell cycle, proliferation, and angiogenesis. The novel securin pituitary tumor transforming gene (PTTG) disrupts cell division and stimulates fibroblast growth factor (FGF)-2-mediated angiogenesis. We investigated expression of the angiogenic vascular endothelial growth factor (VEGF) and its receptor KDR/Flk-1 in 103 human pituitary tumors, and we assessed functional relationships between these genes in vitro. Nonfunctioning tumors (n = 81) demonstrated markedly raised VEGF mRNA (3.2-fold, P < 0.05) and protein concentrations, compared with normal pituitaries (n = 10). KDR was also highly induced in nonfunctioning tumors (14-fold, P < 0.001, n = 78) as well as in the whole cohort of pituitary tumors, compared with normal pituitary samples (14-fold, P < 0.0001, n = 100). In vitro, PTTG induced VEGF, but not KDR, expression in fetal neuronal NT2 cells (2.7-fold, P < 0.001, n = 8), MCF-7 breast carcinoma cells (1.9-fold, P = 0.03, n = 10), and choriocarcinoma JEG-3 cells (P = 0.0002, n = 8). A mutated PTTG construct that cannot be phosphorylated showed identical VEGF up-regulation (2.9-fold, P < 0.001, n = 8) in NT2 cells, compared with wild-type PTTG, but a further mutated construct with abrogation of the key protein:protein interaction domain of PTTG resulted in a significant reduction in VEGF stimulation, compared with wild-type (0.37-fold reduction, P < 0.001, n = 8). FGF-2 findings mirrored those of VEGF, although antibody depletion of secreted FGF-2 in the cell medium failed to influence VEGF up-regulation by PTTG. Overall, our findings implicate altered VEGF and KDR signaling in pituitary tumorigenesis, and we propose that PTTG stimulation of FGF-2 and VEGF expression in the presence of up-regulated growth factor receptors may account for angiogenic growth and progression of human pituitary tumors.

Adenoma↗
PubMed2002

Limb loss following the use of heparin. A lesson to be remembered.

The optimal method of prophylaxis against venous thromboembolism after total hip replacement (THR) remains uncertain. Most surgeons use some form of pharmacological prophylaxis, most commonly heparin. The precise balance of the benefits and risks is unclear, and serious complications can occur. We describe a case of heparin-induced thrombocytopenia and thrombosis syndrome in a 62-year-old woman after THR.

Amputation, Surgical↗
PubMed2002

Determination of antimicrobial activity of Cefaclor on common respiratory tract pathogens in Pakistan.

OBJECTIVE: To determine the antimicrobial activity of Cefaclor against common respiratory tract pathogens isolated from patients in Pakistan. SETTING: Department of Microbiology, Liaquat National Postgraduate Medical Centre, Karachi. METHOD: A laboratory analysis was done on 466 isolates of respiratory tract pathogens collected from 13 laboratories from all over Pakistan. Antibiotic sensitivity test was done by Kirby Bauer disc diffusion method and MIC of Cefaclor was determined by 'E' test. RESULT: Of the 163 Streptococcus pneumoniae, 87 Moraxella catarrhalis and 216 Haemophilus influenzae > 95% isolates were susceptible to Cefaclor. The MIC 90 of all these pathogens were < 2 ug. CONCLUSION: Resistance of respiratory tract pathogens to the 2nd generation Cephalosporin, Cefaclor is very low. MIC 90 of Cefaclor against all three common respiratory tract pathogens is < 2 ug, which indicates that Cefaclor would be effective in more than 90% of cases infected with these bacteria.

Cefaclor↗