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Biomedical subjects

S Khan

Publications and source records attributed to S Khan.

At least 55 records · Page 3Linked to original sources
PubMed2003

Cortisol response to a cognitive stress challenge in posttraumatic stress disorder (PTSD) related to childhood abuse.

Preclinical studies show that animals with a history of chronic stress exposure have increased hypothalamic-pituitary-adrenal (HPA) axis reactivity following reexposure to stress. Patients with posttraumatic stress disorder (PTSD) have been found to have normal or decreased function of the HPA axis, however no studies have looked at the HPA response to stress in PTSD. The purpose of this study was to assess cortisol responsivity to a stressful cognitive challenge in patients with PTSD related to childhood abuse. Salivary cortisol levels, as well as heart rate and blood pressure, were measured before and after a stressful cognitive challenge in patients with abuse-related PTSD (N=23) and healthy comparison subjects (N=18). PTSD patients had 61% higher group mean cortisol levels in the time period leading up to the cognitive challenge, and 46% higher cortisol levels during the time period of the cognitive challenge, compared to controls. Both PTSD patients and controls had a similar 66-68% increase in cortisol levels from their own baseline with the cognitive challenge. Following the cognitive challenge, cortisol levels fell in both groups and were similar in PTSD and control groups. PTSD patients appeared to have an increased cortisol response in anticipation of a cognitive challenge relative to controls. Although cortisol has been found to be low at baseline, there does not appear to be an impairment in cortisol response to stressors in PTSD.

Adolescent↗
PubMed2003

Transparency, swelling and scarring in the corneal stroma.

PURPOSE: This paper briefly reviews current explanations for corneal transparency and uses a well-developed model to try to explain the increased light scattering either accompanying corneal swelling or following phototherapeutic keratectomy (PTK). METHODS: The direct summation of fields (DSF) method was used to compute light transmission as a function of wavelength. The method requires input of a number of structural parameters. Some of these were obtained from electron micrographs and others were calculated from X-ray diffraction data. RESULTS: By swelling sections of stroma cut from different depths in the tissue, we have shown that fluid entering the cornea causes more swelling in the posterior lamellae than in the anterior lamellae. Furthermore, posterior lamellae can reach a higher final hydration than anterior lamellae. Collagen-free regions ('lakes') exist in corneas swollen in vitro and in Fuch's dystrophy corneas, many of which may be caused by the death of cells. The DSF method shows that local fibril disordering, increased refractive index mismatch, and increased corneal thickness together can account for a 20% increase in light scattering in a Fuch's dystrophy cornea at H=5.8 compared to the normal cornea. Additional scattering is probably caused by 'lakes'. The DSF method applied to PTK rabbit stroma with high levels of haze suggests that the newly deposited collagen is not the cause of the increased light scattering. CONCLUSIONS: Fluid is not uniformly distributed within the corneal stroma when the cornea swells. Increased hydration of posterior lamellae may be because of known differences in the glycosaminoglycans between the anterior and posterior stroma. Lamellar interweave in the anterior stroma probably limits the extent to which the constituent lamellae can swell. The DSF method can be used to account for increased light scattering in oedematous corneas but cannot account for haze following PTK.

Corneal Edema↗
PubMed2003

Situation analysis and epidemiology of infectious disease transmission: a South-East Asian regional perspective.

This paper analyses the situation in countries comprising the WHO South-East Asia Region with respect to water supply and sanitation services, hygiene and the epidemiology of related infectious diseases. Recently, published data from the WHO/UNICEF Global Water Supply and Sanitation Assessment 2000 report was reviewed to depict the situation with respect to consumers' access to improved water supply and sanitation services. It was shown that access to improved drinking water supplies is among the lowest in the world, and that sanitation coverage in this region is below all others. The paper also reviews selected surveys of hygiene behaviours in several countries of the region. Associations are suggested between access to services, hygienic practices and specific infectious diseases. The need is acknowledged to improve the evidence base on linkages between infectious diseases and water, sanitation and hygiene, and specific recommendations are made in this regard. There is a need now and for the foreseeable future to promote low-cost household-level interventions, including behaviour change strategies, that mitigate the health consequences of the current situation with respect to water supply, sanitation and hygiene. The role of health authorities in meeting this challenge, and as advocates for accelerating development of the water and sanitation sector, is highlighted.

Asia, Southeastern↗
PubMed2003

Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: global implications for the epidemiology of deafness.

Recessive mutations of SLC26A4 (PDS) are a common cause of Pendred syndrome and non-syndromic deafness in western populations. Although south and east Asia contain nearly one half of the global population, the origins and frequencies of SLC26A4 mutations in these regions are unknown. We PCR amplified and sequenced seven exons of SLC26A4 to detect selected mutations in 274 deaf probands from Korea, China, and Mongolia. A total of nine different mutations of SLC26A4 were detected among 15 (5.5%) of the 274 probands. Five mutations were novel and the other four had seldom, if ever, been identified outside east Asia. To identify mutations in south Asians, 212 Pakistani and 106 Indian families with three or more affected offspring of consanguineous matings were analysed for cosegregation of recessive deafness with short tandem repeat markers linked to SLC26A4. All 21 SLC26A4 exons were PCR amplified and sequenced in families segregating SLC26A4 linked deafness. Eleven mutant alleles of SLC26A4 were identified among 17 (5.4%) of the 318 families, and all 11 alleles were novel. SLC26A4 linked haplotypes on chromosomes with recurrent mutations were consistent with founder effects. Our observation of a diverse allelic series unique to each ethnic group indicates that mutational events at SLC26A4 are common and account for approximately 5% of recessive deafness in south Asians and other populations.

Asia, Southeastern↗
PubMed2003

Cefaclor AF vs Clarithromycin in acute exacerbation of chronic bronchitis (B3M-PK-AJBG).

OBJECTIVE: To compare the efficacy and safety of Cefaclor AF vs Clarithromycin in the treatment of acute exacerbation of chronic bronchitis in adult subjects. PATIENTS AND METHODS: This study was conducted on 300 patients suffering from acute exacerbation of chronic bronchitis, who attended the out patient clinics of ten different hospitals throughout Pakistan. Pneumonia, bronchiectasis and tuberculosis were excluded with the help of chest radiography and sputum smear examination. Pretherapy sputum culture and sensitivity (c/s) were tested and patients were randomized and supplied with either tablet Cefaclor 375 mg or tablet Clarithromycin 250 mg to be taken twice daily. Patients were evaluated at day 0 and then at day 3-5 and day 10-11. Post therapy sputum c/s was done on day 10-11. A fourth and final visit was planned on day 20-24 which was optional. At each visit, the severity of disease and the signs and symptoms were recorded on the clinical report forms according to the preset standards. RESULTS: Of 136 patients in the Cefaclor group and 142 patients in the Clarithromycin group, cure was achieved in 44 vs 35 subjects, improvement in 78 vs 91 subjects and failure in 16 vs 18 subjects among Cefaclor vs Clarithromycin groups respectively. The overall clinical efficacy (cure and improvement combined ) was 88.4% in the Cefaclor group and 87.5% in the Clarithromycin group. Nine patients in the Cefaclor group and patients in the Clarithromycin group had one adverse event whereas twelve patients in each group had two or more adverse events. CONCLUSIONS: The above results show that both Cefaclor AF and Clarithromycin are equally effective and safe in the treatment of acute exacerbation of chronic bronchitis in adult patients.

Acute Disease↗
PubMed2002

An overview on fermentation, downstream processing and properties of microbial alkaline proteases.

Microbial alkaline proteases dominate the worldwide enzyme market, accounting for a two-thirds share of the detergent industry. Although protease production is an inherent property of all organisms, only those microbes that produce a substantial amount of extracellular protease have been exploited commercially. Of these, strains of Bacillus sp. dominate the industrial sector. To develop an efficient enzyme-based process for the industry, prior knowledge of various fermentation parameters, purification strategies and properties of the biocatalyst is of utmost importance. Besides these, the method of measurement of proteolytic potential, the selection of the substrate and the assay protocol depends upon the ultimate industrial application. A large array of assay protocols are available in the literature; however, with the predominance of molecular approaches for the generation of better biocatalysts, the search for newer substrates and assay protocols that can be conducted at micro/nano-scale are becoming important. Fermentation of proteases is regulated by varying the C/N ratio and can be scaled-up using fed-batch, continuous or chemostat approaches by prolonging the stationary phase of the culture. The conventional purification strategy employed, involving e.g., concentration, chromatographic steps, or aqueous two-phase systems, depends on the properties of the protease in question. Alkaline proteases useful for detergent applications are mostly active in the pH range 8-12 and at temperatures between 50 and 70 degrees C, with a few exceptions of extreme pH optima up to pH 13 and activity at temperatures up to 80-90 degrees C. Alkaline proteases mostly have their isoelectric points near to their pH optimum in the range of 8-11. Several industrially important proteases have been subjected to crystallization to extensively study their molecular homology and three-dimensional structures.

Bacteria↗
PubMed2002

CDH23 mutation and phenotype heterogeneity: a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness.

Usher syndrome type I is characterized by congenital hearing loss, retinitis pigmentosa (RP), and variable vestibular areflexia. Usher syndrome type ID, one of seven Usher syndrome type I genetic localizations, have been mapped to a chromosomal interval that overlaps with a nonsyndromic-deafness localization, DFNB12. Mutations in CDH23, a gene that encodes a putative cell-adhesion protein with multiple cadherin-like domains, are responsible for both Usher syndrome and DFNB12 nonsyndromic deafness. Specific CDH23 mutational defects have been identified that differentiate these two phenotypes. Only missense mutations of CDH23 have been observed in families with nonsyndromic deafness, whereas nonsense, frameshift, splice-site, and missense mutations have been identified in families with Usher syndrome. In the present study, a panel of 69 probands with Usher syndrome and 38 probands with recessive nonsyndromic deafness were screened for the presence of mutations in the entire coding region of CDH23, by heteroduplex, single-strand conformation polymorphism, and direct sequence analyses. A total of 36 different CDH23 mutations were detected in 45 families; 33 of these mutations were novel, including 18 missense, 3 nonsense, 5 splicing defects, 5 microdeletions, and 2 insertions. A total of seven mutations were common to more than one family. Numerous exonic and intronic polymorphisms also were detected. Results of ophthalmologic examinations of the patients with nonsyndromic deafness have found asymptomatic RP-like manifestations, indicating that missense mutations may have a subtle effect in the retina. Furthermore, patients with mutations in CDH23 display a wide range of hearing loss and RP phenotypes, differing in severity, age at onset, type, and the presence or absence of vestibular areflexia.

Adolescent↗
PubMed2002

Stage-specific transcription of distinct repertoires of a multigene family during Plasmodium life cycle.

Members of a multigene family in the rodent malaria parasite Plasmodium yoelii yoelii code for 235-kilodalton proteins (Py235) that are located in the merozoite apical complex, are implicated in virulence, and may determine red blood cell specificity. We show that distinct subsets of py235 genes are expressed in sporozoites and hepatic and erythrocytic stages. Antibodies to Py235 inhibited sporozoite invasion of hepatocytes. The switch in expression profile occurred immediately after transition from one stage to another. The results suggest that this differential expression is driven by strong biological requirements and provide evidence that hepatic and erythrocytic merozoites differ.

Amino Acid Sequence↗
PubMed2002

Aerosol scavenging: model application and sensitivity analysis in the Indian context.

Sulfate aerosols have been found to be the major contributors to precipitation acidity. Thus, in view of the long-term ecological repercussions they have on aquatic ecosystems and their acidity-potential, the present analysis focuses on a case study application of the layer-averaged aerosol-scavenging model (Okita et al., 1996) for predicting values of the wet scavenging coefficient and sulfate concentrations in precipitation samples on the basis of the information available for some selected Indian cities. Through sensitivity analysis (Pandey et al., 1997) the scavenging coefficient has been found to be very strongly dependent on precipitation intensity. Comparison of model predictions has been done with the measured values for Delhi, Mumbai, Calcutta and Chennai in India.

Acid Rain↗
PubMed2002

Guillain-Barré syndrome after allogeneic hematopoietic stem cell transplantation.

Guillain-Barré syndrome is a rare complication in the setting of hematopoietic stem cell transplantation. We report three children with T cell lymphoma/leukemia in whom this syndrome developed soon after they received unrelated donor transplants. The rapid onset of symptoms raises the concern that the bone marrow transplant conditioning regimen (ie, total body irradiation, cyclophosphamide and cytosine arabinoside) might have precipitated the clinical syndrome of ascending polyneuropathy. Although central nervous system toxicity has been well described with high-dose cytosine arabinoside therapy, peripheral neuropathy of the Guillain-Barré type has been reported only infrequently. We review possible factors contributing to the development of this syndrome in these three patients.

Adolescent↗
PubMed2002

Incidental ultrasound diagnosis of pseudomyxoma peritonei in an asymptomatic woman.

An incidental finding of pseudomyxoma peritonei is reported in a woman with a 6-month history of postmenopausal bleeding. A transvaginal ultrasound scan revealed a poorly defined echogenic mass in the right iliac fossa above the right ovary and free fluid of mixed echogenicity in the pouch of Douglas. Laparoscopic appendicectomy and aspiration of mucinous fluid was performed without adjuvant chemotherapy. Regular postoperative follow-up scans, which are needed as the disease may have an indolent course, showed no signs of recurrence. The differential diagnosis and management of pseudomyxoma peritonei are discussed.

Diagnosis, Differential↗
PubMed2002

Radiological stenting provides effective palliation in malignant central venous obstruction.

Malignant superior vena caval obstruction (SVCO) due to lung cancer carries a poor prognosis and response to palliative radiotherapy is variable. Eighteen patients presenting with the appearance of malignant SVCO (thirteen due to primary bronchial tumours) in a four year period from June 1995 to July 1999 underwent venography with a view to placement of an expanding metal stent under radiological control. Fourteen patients were male and four female with a mean age at presentation of 65 years (range 44-84 years). At venography only three patients had isolated SVC stenosis, fivealso had brachiocephalic, internal jugular or subclavian vein stenoses and one had an isolated right brachiocephalic stenosis. Venography demonstrated thrombus in eight of the remaining patients, seven in association with stenosis. In one patient stenosis of the SVC was thought to be due to radiation fibrosis as no mass was visible. All underwent Seldinger catheterization of the great veins via a right femoral puncture with deployment of the stent over a guide wire. Balloon angioplasty was performed prior to stent placement in eight patients. The eight patients with thrombus underwent thrombolysis using rt-PA (recombinant tissue-type plasminogen activator) with subsequent stent placement in seven. Radiological relief of obstruction with abolition of collateral flow was observed in all cases. One patient required further stenting for recurrent obstruction after 160 days of palliation. The median duration of palliation after stenting was 87 days. No procedure-related morbidity was observed. Thrombolysis was of value in patients with occlusive thrombus, either in isolation or complicating a malignant stricture, where radiotherapy may not have been effective. Radiological stenting is a safe technique which offers rapid palliation of SVCO.

Adult↗
PubMed2002

Metabolic activation of 4-hydroxyanisole by isolated rat hepatocytes.

A tyrosinase-directed therapeutic approach for treating malignant melanoma uses depigmenting phenolic prodrugs such as 4-hydroxyanisole (4-HA) for oxidation by melanoma tyrosinase to form cytotoxic o-quinones. However, in a recent clinical trial, both renal and hepatic toxicity were reported as side effects of 4-HA therapy. In the following, 4-HA (200 mg/kg i.p.) administered to mice caused a 7-fold increase in plasma transaminase toxicity, an indication of liver toxicity. Furthermore, 4-HA induced-cytotoxicity toward isolated hepatocytes was preceded by glutathione (GSH) depletion, which was prevented by cytochrome p450 inhibitors that also partly prevented cytotoxicity. The 4-HA metabolite formed by NADPH/microsomes and GSH was identified as a hydroquinone mono-glutathione conjugate. GSH-depleted hepatocytes were much more prone to cytotoxicity induced by 4-HA or its reactive metabolite hydroquinone (HQ). Dicumarol (an NAD(P)H/quinone oxidoreductase inhibitor) also potentiated 4-HA- or HQ-induced toxicity whereas sorbitol, an NADH-generating nutrient, prevented the cytotoxicity. Ethylenediamine (an o-quinone trap) did not prevent 4-HA-induced cytotoxicity, which suggests that the cytotoxicity was not caused by o-quinone as a result of 4-HA ring hydroxylation. Deferoxamine and the antioxidant pyrogallol/4-hydroxy-2,2,6,6-tetramethylpiperidene-1-oxyl (TEMPOL) did not prevent 4-HA-induced cytotoxicity, therefore excluding oxidative stress as a cytotoxic mechanism for 4-HA. A negligible amount of formaldehyde was formed when 4-HA was incubated with rat microsomal/NADPH. These results suggest that the 4-HA cytotoxic mechanism involves alkylation of cellular proteins by 4-HA epoxide or p-quinone rather than involving oxidative stress.

Animals↗