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Biomedical subjects

A Mahmood

Publications and source records attributed to A Mahmood.

At least 19 recordsLinked to original sources

Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes.

BACKGROUND: Zinc carnosine (ZnC) is a health food product claimed to possess health-promoting and gastrointestinal supportive activity. Scientific evidence underlying these claims is, however, limited. AIM: To examine the effect of ZnC on various models of gut injury and repair, and in a clinical trial. METHODS: In vitro studies used pro-migratory (wounded monolayer) and proliferation ([(3)H]-thymidine incorporation) assays of human colonic (HT29), rat intestinal epithelial (RIE) and canine kidney (MDCK) epithelial cells. In vivo studies used a rat model of gastric damage (indomethacin/restraint) and a mouse model of small-intestinal (indomethacin) damage. Healthy volunteers (n = 10) undertook a randomised crossover trial comparing changes in gut permeability (lactulose:rhamnose ratios) before and after 5 days of indomethacin treatment (50 mg three times a day) with ZnC (37.5 mg twice daily) or placebo coadministration. RESULTS: ZnC stimulated migration and proliferation of cells in a dose-dependent manner (maximum effects in both assays at 100 micromol/l using HT29 cells), causing an approximate threefold increase in migration and proliferation (both p<0.01). Oral ZnC decreased gastric (75% reduction at 5 mg/ml) and small-intestinal injury (50% reduction in villus shortening at 40 mg/ml; both p<0.01). In volunteers, indomethacin caused a threefold increase in gut permeability in the control arm; lactulose:rhamnose ratios were (mean (standard error of mean)) 0.35 (0.035) before indomethacin treatment and 0.88 (0.11) after 5 days of indomethacin treatment (p<0.01), whereas no significant increase in permeability was seen when ZnC was coadministered. CONCLUSION: ZnC, at concentrations likely to be found in the gut lumen, stabilises gut mucosa. Further studies are warranted.

Animals↗

Sorption of lead from aqueous solution by chemically modified carbon adsorbents.

An indigenously prepared, steam activated and chemically modified carbon from husk and pods of Moringa oleifera (M. oleifera), an agricultural waste, was comparatively examined as an adsorbent for the removal of lead from aqueous solutions. Studies were conducted as a function of contact time, initial metal concentration, dose of adsorbent, agitation speed, particle size and pH. Maximum uptake capacities were found to be, 98.89, 96.58, 91.8, 88.63, 79.43% for cetyltrimethyl ammonium bromide (CTAB), phosphoric, sulfuric, hydrochloric acid treated and untreated carbon adsorbents, respectively. Bangham, pseudo-first- and second-order, intra-particle diffusion equations were implemented to express the sorption mechanism by utilized adsorbents. Adsorption rate of lead ions was found to be considerably faster for chemically modified adsorbents than unmodified. The results of adsorption were fitted to both the Langmuir and Freundlich models. Satisfactory agreement between the metal uptake capacities by the adsorbents at different time intervals was expressed by the correlation coefficient (R(2)). The Langmuir model represented the sorption process better than the Freundlich one, with R(2) values ranging from 0.994 to 0.998.

Adsorption↗

Auditory brainstem response findings and peripheral auditory sensitivity in adrenoleukodystrophy.

Measurements of the auditory brainstem response (ABR) were obtained in 96 individuals with X-linked adrenoleukodystrophy (X-ALD). The patients were divided into five diagnostic groups on the basis of neurologic diagnosis. The five groups were cerebral childhood and adolescent, pure adrenomyeloneuropathy (pure AMN), adrenomyeloneuropathy cerebral (AMN cerebral), Addison's only and symptomatic female heterozygotes. Results indicated the presence of marked ABR abnormalities for all groups most frequently involving Wave V, followed by Wave III and Wave I. Abnormalities of all interpeak latency intervals (i.e., I-III, III-V and I-V) were observed for all groups. ABR abnormalities were most frequently seen in the AMN-cerebral and pure AMN groups but were also common in the symptomatic female heterozygote group. The ABRs in the cerebral childhood and adolescent group were the least impaired of the five groups examined. Age was found to be a significant independent predictor of bilateral ABR abnormalities but VLCFA levels, MRI Loes score, and duration of symptoms were not found to be independent predictors of bilateral ABR abnormalities after adjusting for ALD phenotype. Patients with AMN were significantly more likely to have bilateral ABR abnormalities than the cerebral childhood and adolescent group after adjusting for age, duration of symptoms, EDSS score, VLCFA levels and MRI Loes scores. The prevalence of peripheral hearing loss was not found to exceed that present in age and sex matched normal control groups derived from the NHANES (1999-2000), indicating a lack of association between peripheral hearing loss and X-linked adrenoleukodystrophy. It was concluded that: (1) auditory sensitivity in X-ALD is not significantly impaired; (2) ABR abnormalities are a frequent finding and may be caused by abnormalities of fiber tracts in the region of the lateral lemniscus and inferior colliculus; and, (3) the abnormalities progress slowly and appear to be associated mainly with the AMN phenotype.

Acoustic Stimulation↗

Trial of trefoil factor 3 enemas, in combination with oral 5-aminosalicylic acid, for the treatment of mild-to-moderate left-sided ulcerative colitis.

BACKGROUND: Current treatment of ulcerative colitis is imperfect. Trefoil peptides are known to stimulate repair in many models of injury, including animal models of colitis. AIM: To assess the efficacy of trefoil factor family-3 enema treatment in a clinical trial. METHODS: A total of 16 patients with mild-to-moderate left sided ulcerative colitis were recruited into a double-blind randomized placebo-controlled study. Patients taking steroids or with proctitis only were excluded. Patients received 75 mL enemas containing either human recombinant trefoil factor family-3 (10 mg/mL) or saline alone once a day for 14 days. All patients also received an oral dose-increment of 1.2 g of mesalazine daily above their normal usage. Patients were assessed at 0, 2, 4 and 12 weeks. Remission was defined as Ulcerative Colitis Disease Activity Index of 0 or 1 with no blood in stool. Individual clinical improvement was defined as a Ulcerative Colitis Disease Activity Index reduction of >3. Data was analysed using chi-square test and anova. RESULTS: Median Ulcerative Colitis Disease Activity Index at entry were 8.5 (trefoil factor family-3 group) and 8 (placebo group). Analysed on an intention-to-treat basis, only one patient went into remission (in trefoil factor family-3 group at day 28). Clinical improvement was seen in two trefoil factor family-3 and three placebo patients on day 14 and two patients in each group on day 28. CONCLUSION: Increasing the dose of 5-aminosalicylic acid was moderately effective in reducing the Ulcerative Colitis Disease Activity Index but was insufficient to induce remission. Trefoil factor family-3 enemas were well-tolerated but did not provide additional benefit above that of adding additional 5-aminosalicylic acid alone.

Administration, Oral↗

Influence of zinc on the status of hepatic trace elements and biokinetics of 65Zn in ethanol treated rats.

Whole body counting studies of 65Zn indicated that the Tb1 (the faster component) was significantly decreased while the slower component (Tb2) was increased significantly following ethanol treatment. Interestingly, following zinc treatment to ethanol treated rats, slower component (Tb2) of 65Zn came back to within normal limits while the faster component (Tb1) got significantly elevated in comparison to ethanol treatment. Percent uptake values of 65Zn were found to be increased in liver, intestine, muscle, brain and kidney, and decreased in bone under alcoholic conditions. Interestingly, the uptake values of 65Zn in all the organs except muscle were reverted back to within normal limits upon zinc supplementation to these ethanol intoxicated animals. A significant decrease in zinc contents was noticed in ethanol treated rats, which, however, were raised to normal levels upon zinc supplementation: Copper levels, on the other hand, were significantly enhanced in both ethanol fed and combined ethanol + zinc treated rats. Calcium levels were significantly decreased in both ethanol and zinc treated rats, which however were further reduced upon zinc supplementation to ethanol fed rats. However, no significant change was observed in the concentrations of sodium and potassium in any of the treatment groups. In conclusion, zinc appears to play a protective role by normalizing the turnover of 65Zn in whole body as well as in its uptake in different organs under alcoholic conditions.

Animals↗

The use of microsatellite markers for the detection of genetic similarity among winter bread wheat lines for chromosome 3A.

Previous studies with chromosome substitution and recombinant inbred chromosome lines identified that chromosome 3A of wheat cv. Wichita contains alleles that influence grain yield, yield components and agronomic performance traits relative to alleles on chromosome 3A of Cheyenne, a cultivar believed to be the founder parent of many Nebraska developed cultivars. This study was carried out to examine the genetic similarity among wheat cultivars based on the variation in chromosome 3A. Forty-eight cultivars, two promising lines and four substitution lines (in duplicate) were included in the study. Thirty-six chromosome 3A-specific and 12 group-3 barley simple sequence repeat (SSR) primer pairs were used. A total of 106 polymorphic bands were scored. Transferability of barley microsatellite markers to wheat was 73%. The coefficient of genetic distance (D) among the genotypes ranged from 0.40 to 0.91 and averaged D=0.66. Cluster analysis by the unweighted pair-group method with arithmetic averages showed one large and one small cluster with eight minor clusters in the large cluster. Several known pedigree relationships largely corresponded with the results of SSR clusters and principal coordinate analysis. Cluster analysis was also carried out by using 22 alleles that separate Wichita 3A from Cheyenne 3A, and three clusters were identified (a small cluster related to Cheyenne of mainly western Nebraska wheat cultivars; a larger, intermediate cluster with many modern Nebraska wheat cultivars; a large cluster related to Wichita with many modern high-yielding or Kansas wheat cultivars). Using three SSR markers that identify known agronomically important quantitative trait loci (QTL) regions, we again separated the cultivars into three main clusters that were related to Cheyenne or Wichita, or had a different 3A lineage. These results suggest that SSR markers linked to agronomically important QTLs are a valuable asset for estimating both genetic similarity for chromosome 3A and how the chromosome has been used in cultivar improvement.

Bread↗

The Lubinus patellofemoral arthroplasty: a series of 17 cases.

INTRODUCTION: The Lubinus patellofemoral arthroplasty was introduced in our institution in 1994. The first 17 patients were followed-up in order to identify the short-term outcome for this prosthesis. MATERIALS AND METHODS: The average age at surgery was 66 years (range 37-82 years). The mean follow-up was 19 months. The indications for surgery were strictly limited to radiographically proven primary osteoarthritis affecting only the patellofemoral joint (13) and secondary arthritis due to maltracking, subluxation (3) or trauma to the patella (1). At review, the range of movement and Lysholm and Tegner scores were recorded and radiographs obtained. Patients were also asked if their outcome was satisfactory or unsatisfactory. RESULTS: At review, only 9 (53%) knees were classified as satisfactory by the patients. Further surgery had been carried out in 6 cases (35%) including revision to total knee arthroplasty in 4 (24%). Other complications included clicking and subluxation in 3 cases (18%), extension block in 3 (18%) and infection in 1 (6%). Progression of osteoarthritis to involve other compartments occurred in 2 cases (12%). CONCLUSIONS: Many of these early problems are related to the unforgiving nature of the prosthesis on insertion. These poor early results have led us to stop using the prosthesis.

Adult↗

Are renal microgranulomas related to inflammatory tubular destruction?

Two cases of renal microgranuloma formation are reported, one in a patient with known Crohn's disease and another in a case of acute renal allograft rejection. In both cases, the microgranulomas arose as a result of inflammatory tubular destruction, in a manner analogous to that seen in patients with ulcerative colitis arising adjacent to ruptured epithelial crypts in the large intestine. Microgranulomas may occur at multiple anatomical sites in Crohn's disease, although renal microgranulomas are very rare. Non-specific inflammatory tubular destruction should be considered as a cause of renal microgranuloma formation, in addition to systemic granulomatous diseases, such as tuberculosis, sarcoid, or Crohn's disease, when granulomas are seen in the presence of inflammatory tubular destruction in renal biopsies.

Adult↗

Role of zinc on lipid peroxidation and antioxidative enzymes in intestines of ethanol-fed rats.

This study was undertaken to investigate the effects of zinc on lipid peroxidation and various antioxidative enzymes in the intestines of male Wistar rats fed on ethanol. It was observed that NADPH-dependent lipid peroxidation (LP) was significantly increased upon ethanol treatment for 4 and 8 wk. The concentration of glutathione as well as the activities of catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) were also found to be significantly increased upon ethanol feeding at all of the treatment intervals. The glutathione levels were found to be further elevated upon combined zinc and ethanol treatments. Interestingly, the administration of zinc to ethanol-fed rats was able to bring down the elevated levels of LP, catalase, SOD, and GPx, thus indicating the antiperoxidative potential of zinc under such conditions.

Administration, Oral↗

Leprosy patients with lepromatous disease have an up-regulated IL-8 response that is unlinked to TNF-alpha responses.

Tumor necrosis factor (TNF-alpha) in conjunction with interferon-gamma (IFN-gamma) plays an important role in lymphocyte recruitment and granuloma formation in mycobacterial diseases. Lepromatous leprosy infections are typically associated with low to absent T cell responses and the absence of INF-gamma secretion. Chemokines such as IL-8, MCP-1, and MIP-1beta, have also been shown to recruit neutrophils and lymphocytes to the site of mycobacterial infections. We have studied IL-8 expression in relation to TNF-alpha and TGF-beta in monocytes from lepromatous patients (LL) as compared with healthy endemic controls. In endemic controls, no spontaneous expression of IL-8, TNF-alpha, and TGF-beta was observed, but BCG and M. leprae induced activation of all three cytokines. Lepromatous leprosy monocytes spontaneously expressed high levels of IL-8 and TGF-beta but negligible levels of TNF-alpha. A further increase in IL-8 secretion or gene expression by BCG or M. leprae was not significant. BCG, but not M. leprae, was able to stimulate TNF-alpha activation in lepromatous leprosy subjects. TGF-beta responses in LL were parallel to those of IL-8. This suggests a vigorous and active ongoing IL-8 response in lepromatous disease that is independent of TNF-alpha activation. Therefore, in the absence of IFN-gamma and TNF-alpha activation, IL-8 may assume a pivotal role in cell recruitment in leprosy patients with disseminated mycobacterial infections.

Adult↗

Rapid diagnosis of pulmonary tuberculosis by mycobacteriophage assay.

We evaluated FASTPlaqueTB, a recently introduced bacteriophage assay for rapid detection of Mycobacterium tuberculosis complex in sputum specimens, using 169 non-duplicate sputum specimens from patients suspected of pulmonary tuberculosis. The results of 160 specimens were analysed. FASTPlaqueTB assay detected tuberculosis in 77% (46/60) of culture-positive cases. Among the AFB smear-positive cases (n = 47) it had a sensitivity of 76% and specificity of 60% while among AFB smear-negative cases (n = 113) its sensitivity and specificity were 78% and 98%, respectively. The overall sensitivity and specificity of the technique were 77% and 96%, respectively, and the positive and negative predictive values were respectively 92% and 87%. The overall efficiency of the test was 89%. Test results were available in 48 h.

Bacteriological Techniques↗

Stevens Johnson syndrome in Pakistan: a ten-year survey.

OBJECTIVE: A pre-tested questionnaire-based, retrospective study to highlight the causative factors, mode of presentation, complications and outcome of patients with Stevens Johnson syndrome. SETTING: Aga Khan University Hospital over a 10 year period. METHODS: All case records with a diagnosis of Steven Johnson Syndrome in the period 1990 to 2000 were retrospectively reviewed. Data was retrieved on a comprehensive questionnaire. The demographic variatbles and drugs taken within the previous 21 days were noted. Date analysis was done by Epi-Info Version 6.0. RESULTS: Of the 101 studied patient files, the most common offender was found to be the Penicillins as a group and Sulfadoxine-Pyrimethamine (Fansidar) when considering all drugs individually. Most common complications included electrolyte disturbances (13.9%) and congestive heart failure (6.9%). Mortality rate was high at 10.1%. CONCLUSION: SJS was found to be a rare condition but having a mortality rate of 10.1%. As it can be induced by a large number of drugs, caution should be practiced while prescribing.

Adult↗

Rapid detection of rifampicin susceptibility of Mycobacterium tuberculosis in sputum specimens by mycobacteriophage assay.

OBJECTIVE: To evaluate the performance of FASTPlaqueTB-RIF, a newly introduced bacteriophage assay for rapid detection of rifampicin susceptibility of Mycobacterium tuberculosis in sputum specimens. METHODS: A comparative study of 40 sputum specimens from patients of pulmonary tuberculosis, using FASTPlaqueTB-RIF and Bactec 460 TB system carried out at the Armed Forces Institute of Pathology, Rawalpindi between September and November 2001. RESULTS: Of the 40 clinical isolates of Mycobacterium tuberculosis tested for rifampicin (RIF) susceptibility using the Bactec 460 TB system, 28 isolates were resistant to RIF and 12 isolates were susceptible. FASTPlaqueTB-RIF identified 24 specimens as resistant to RIF. Three specimens that revealed susceptible isolates on Bactec 460, were resistant by FASTPlaqueTB-RIF while four specimens which revealed resistant isolates on Bactec 460, demonstrated susceptibility to RIF by FASTPlaqueTB-RIF. The sensitivity and specificity of FASTPlaqueTB-RIF were 86% and 73% respectively. The predictive values of positive and negative tests were 0.89 and 0.67 respectively. The overall accuracy of the technique was 82%. The phage assay took 48 hours to perform. CONCLUSION: Early detection of rifampicin resistance by the mycobacteriophage technique direct from sputum specimens is a potentially useful new test which would allow decision regarding appropriate therapy to be made early thus having a positive impact on patient care and on prevention of spread of MDR TB.

Antibiotics, Antitubercular↗

In-vitro activity of nitrofurantoin in enterococcus urinary tract infection.

OBJECTIVE: To compare in-vitro antimicrobial susceptibility of nitrofurantoin against commonly used antimicrobials for the treatment of urinary tract infection caused by enterococci. METHODS: A total of 144 enterococci (Enterococcus faecalis, n=130, Enterococcus faecium, n=14) isolated and confirmed by biochemical tests at the department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi, for a period of three years were included in the study. The antimicrobial susceptibility tests of isolated organisms were performed by standard disc diffusion method as recommended by NCCLS. In addition to nitrofurantoin (NIT), doxycycline (DOX), co-trimoxazole (COT), ampicillin (AMP), imipenem (IPM) and vancomycin (VAN) were used for antimicrobial susceptibility testing. RESULTS: One hundred and twenty seven (88%) isolates of Enterococci were susceptible to NIT while 72% (n = 103) to AMP, 13% to COT, 11% to DOX, 91% to IPM and 99% to VAN. Among the strains resistant to AMP, COT, DOX, IPM and VAN, 50-88% were susceptible to NIT. CONCLUSION: Nitrofurantoin is an effective antimicrobial in vitro and can be used for treatment of Enterococcus urinary tract infections.

Anti-Bacterial Agents↗

The effect of mycobacterial virulence and viability on MAP kinase signalling and TNF alpha production by human monocytes.

SETTING: The success of Mycobacterium tuberculosis as a human pathogen depends on its ability to tolerate and perhaps manipulate host defense mechanisms. OBJECTIVE: To determine the induction of tumour necrosis factor-alpha (TNF alpha), a central mediator of immunity, by human monocytes infected with virulent M. tuberculosis, M. leprae and attenuated M. bovis BCG. DESIGN: Mycobacteria-induced cellular activation pathways of TNF alpha production was investigated using an inhibitor of protein tyrosine kinase (PTKs) and an inhibitor of mitogen-activated protein (MAP) kinases. RESULTS: TNF alpha production was significantly lower during infection with virulent M. tuberculosis than with BCG and this differential response was independent of mycobacterial viability. TNF alpha production involved the PTK and MAP kinase pathways. Reduced TNF alpha induction by M. tuberculosis was associated with a reduction in the extent and duration of phosphorylation of extracellular-signal regulated kinases (ERK 1/2). Infection with M. leprae triggered low and transient ERK 1/2 activation as well as low TNF alpha production. CONCLUSION: Maintenance of the differential response in both live and heat-killed preparations suggests that the reduced TNF alpha response associated with virulent mycobacteria is due to differences in the presence of components capable of triggering host pattern recognition receptors, rather than events associated with phagosome trafficking or the active release of intracellular modulators.

BCG Vaccine↗

Microtibial embolectomy.

BACKGROUND: microtibial embolectomy is an important technique in cases of limb threatening acute arterial occlusion affecting native crural and pedal vessels. It is particularly useful when thrombolysis is contraindicated or ineffective as in "trash foot". METHODS: in order to evaluate the efficacy of this technique, a retrospective case note review was carried out for patients undergoing microtibial embolectomy from 1990 to 1999. Data collected included the causes and degree of ischaemia, additional procedures required, vessel patency, limb salvage and complications encountered. RESULTS: twenty-two limbs underwent exploration of the crural/pedal vessels with ankle level arteriotomies under local anaesthetic in 12 cases, general anaesthetic in nine and epidural in one. The causes of ischaemia were cardiac emboli (8), "trash foot" (7), emboli from aortic and popliteal aneurysms (3) and thrombotic occlusion of crural vessels (4). The vessel patency rate was 69% and limb salvage rate 62% (13/21) up to 5-years follow-up. Six of the seven cases with "trash foot" were salvaged while one required an amputation at 3-months post-operatively. The 30-day mortality was 22% (5/22). CONCLUSIONS: microtibial embolectomy is effective in acute occlusion of the crural/pedal arteries including cases of "trash foot", offering limb salvage to a worthwhile proportion of cases.

Aged↗

Frequency and antibiotic susceptibility pattern of mycobacterial isolates from extra-pulmonary tuberculosis cases.

OBJECTIVE: To determine the frequency and antimicrobial susceptibility pattern of extra-pulmonary tuberculosis in Rawalpindi. SETTING: Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi. METHODS: Between September 2000 and August 2002, 899 pulmonary and 460 extra-pulmonary specimens from suspected cases of tuberculosis were examined. The radiometric BACTEC 460 TB system was used for culture and antimicrobial susceptibility testing. RESULTS: Mycobacteria were isolated from 291 pulmonary specimens and 98 extra-pulmonary specimens. The frequency of extra-pulmonary tuberculosis was 25.2%. The commonest source of isolation was pus (44.9%, frequency 11.3%), followed by lymph nodes (13.3%, frequency 3.3%) and pleural fluid (13.3%, frequency 3.3%). We tested the anti-microbial susceptibility of the isolates to the four first line anti-tuberculous drugs, rifampicin, isoniazid, streptomycin and ethambutol. Of the extra-pulmonary isolates 13.3% were resistant to a single drug, 21.4% were multi-drug resistant and 9.2% were resistant to all the four drugs. CONCLUSION: Increased awareness of the magnitude of the problem posed by extra-pulmonary tuberculosis is required so that appropriate control measures can be adopted.

Antitubercular Agents↗

The efficacy of aspirin in patients undergoing infra-inguinal bypass and identification of high risk patients.

AIM: Infrainguinal bypass is an effective treatment for critical lower limb ischemia but up to 1/3 of these grafts will occlude within the 1st year. The aim of this audit was to evaluate the efficacy of aspirin in maintaining graft patency and also improving patient survival. METHODS: In a single audited year (1997) 125 bypasses were carried out. Seventy-nine were on aspirin, 34 on no treatment and 12 were on other agents and hence excluded from analysis. The indication for surgery was critical ischaemia in 101 and disabling claudication in 12. Autologous vein was used in 104 and prosthetic grafts in 9. RESULTS: The overall 2-year primary graft patency, secondary graft patency and limb salvage were 50%, 71% and 83%, respectively. The 2-year secondary patency in patients with or without aspirin was 73% and 64%, respectively (p<0.12-log rank test). The corresponding patient survival from vascular death in the 2 groups was 73% and 70% (p<0.67-log rank test). Crural/ pedal bypass (51/75 on aspirin) and smoking (51/61 on aspirin) were independent risk factors for graft failure and vascular death respectively whilst those with a previous myocardial infarct (21/28 on aspirin) reached significance in univariate analysis only (p< 0.03). CONCLUSION: Aspirin was not a significant factor in preventing graft failure or vascular death in patients undergoing bypass for critical limb ischemia. Dual therapy with other antiplatelet agents needs to be considered in such patients particularly those undergoing crural/pedal bypass, smokers and those with a history of previous myocardial infarction.

Adult↗