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Biomedical subjects

S A Shah

Publications and source records attributed to S A Shah.

At least 19 recordsLinked to original sources
PubMed2007

Selective use of older adults in right lobe living donor liver transplantation.

Many centers are reluctant to use older donors (>44 years) for adult right-lobe living donor liver transplantation (RLDLT) due to concerns about possible increased morbidity in donors and poorer outcomes in recipients. Since 2000, 130 adult RLDLTs have been performed at our institution. Recipients were divided into those who received a right lobe graft from a donor </=age 44 (n = 89, 68%; median age 30) and those who received a liver graft from a donor age >44 (n = 41, 32%; mean age 52). The two donor and recipient populations had similar demographic and operative profiles. With a median follow-up of 29 months, the severity and number of complications in older donors were similar to those in younger donors. No living donor died. Older donor allografts had initial allograft dysfunction compared to younger donors. Complication rates were similar among recipients in both groups but there was a higher bile duct stricture rate with older donor grafts (27% vs. 12%; p = 0.04). One-year recipient graft survival was 86% for older donors and 85% for younger donors (p = 0.95). Early experience with the use of selected older adults (>44 years) for RLDLT is encouraging, but may be associated with a higher rate of biliary complications in the recipient.

Adolescent↗
PubMed2007

Biliary strictures in 130 consecutive right lobe living donor liver transplant recipients: results of a Western center.

Biliary strictures remain the most challenging aspect of adult right lobe living donor liver transplantation (RLDLT). Between 04/2000 and 10/2005, 130 consecutive RLDLTs were performed in our center and followed prospectively. Median follow-up was 23 months (range 3-67) and 1-year graft and patient survival was 85% and 87%, respectively. Overall incidence of biliary leaks (n = 19) or strictures (n = 22) was 32% (41/128) in 33 patients (26%). A duct-to-duct (D-D) or Roux-en-Y (R-Y) anastomosis were performed equally (n = 64 each) with no difference in stricture rate (p = 0.31). The use of ductoplasty increased the number of grafts with a single duct for anastomosis and reduced the biliary complication rate compared to grafts >/=2 ducts (17% vs. 46%; p = 0.02). Independent risk factors for strictures included older donor age and previous history of a bile leak. All strictures were managed nonsurgically initially but four patients ultimately required conversion from D-D to R-Y. Ninety-six percent (123/128) of patients are currently free of any biliary complications. D-D anastomosis is safe after RLDLT and provides access for future endoscopic therapy in cases of leak or stricture. When presented with multiple bile ducts, ductoplasty should be considered to reduce the potential chance of stricture.

Adult↗
PubMed2006

HIV-infected workers deported from the Gulf States: impact on Southern Pakistan.

HIV prevalence is still very low in Pakistan, but its south Asian location and subgroups with recognized lifestyle risk factors suggest that Pakistan will experience expanded diffusion of HIV. We report the frequency of HIV infections identified by the AIDS Control Programme in the Sindh province of Pakistan. Most HIV positive cases currently reported to the Sindh AIDS Control Programme are found among Pakistani workers deported from the Gulf States and among foreigners. The 58 returned workers with HIV represent 61 to 86% of reported cases in any given year during the 1996-1998 period. Five wives of returning workers have been identified with HIV. Expatriate workers in the Gulf States are tested for HIV routinely, unlike other subgroups in Pakistan. Considering the risk of HIV/AIDS due to regular introduction of HIV from returned workers, and the limited awareness surrounding sexual health and HIV/STD transmission issues in Pakistan, intervention programmes targeted at overseas workers need to be implemented to control the expansion of the HIV epidemic in Pakistan (Int J STD AIDS 1999;10:812-14).

Journal Article↗
PubMed2005

Analysis of long-term gene expression in neurons of the hippocampal subfields following traumatic brain injury in rats.

After experimental traumatic brain injury (TBI), widespread neuronal loss is progressive and continues in selectively vulnerable brain regions, such as the hippocampus, for months to years after the initial insult. To clarify the molecular mechanisms underlying secondary or delayed cell death in hippocampal neurons after TBI, we compared long-term changes in gene expression in the CA1, CA3 and dentate gyrus (DG) subfields of the rat hippocampus at 24 h and 3, 6, and 12 months after TBI with changes in gene expression in sham-operated rats. We used laser capture microdissection to collect several hundred hippocampal neurons from the CA1, CA3, and DG subfields and linearly amplified the nanogram samples of neuronal RNA with T7 RNA polymerase. Subsequent quantitative analysis of gene expression using ribonuclease protection assay revealed that mRNA expression of the anti-apoptotic gene, Bcl-2, and the chaperone heat shock protein 70 was significantly downregulated at 3, 6 (Bcl-2 only), and 12 months after TBI. Interestingly, the expression of the pro-apoptotic genes caspase-3 and caspase-9 was also significantly decreased at 3, 6 (caspase-9 only), and 12 months after TBI, suggesting that long-term neuronal loss after TBI is not mediated by increased expression of pro-apoptotic genes. The expression of two aging-related genes, p21 and integrin beta3 (ITbeta3), transiently increased 24 h after TBI, returned to baseline levels at 3 months and significantly decreased below sham levels at 12 months (ITbeta3 only). Expression of the gene for the antioxidant glutathione peroxidase-1 also significantly increased 6 months after TBI. These results suggest that decreased levels of neuroprotective genes may contribute to long-term neurodegeneration in animals and human patients after TBI. Conversely, long-term increases in antioxidant gene expression after TBI may be an endogenous neuroprotective response that compensates for the decrease in expression of other neuroprotective genes.

Animals↗
PubMed2005

Study of dust pollution caused by traffic in Aligarh city.

In the present study the dust pollution caused by vehicles in Aligarh city was estimated. Four major national roads viz. Anoopshahar road, Delhi road, Agra road and Kanpur road of Aligarh city were selected. The dust pollution was maximum on Kanpur road (46.44 gm/m2/ month) followed by Agra road (38.94 gm/m2/month) and Delhi road (34.52 gm/m2/month). The least dust pollution was recorded on Anoopshahar road (20.10gm/m2/month). In general, the dust fall rate per unit area was highest at 3 km inside city (38.66 gm/m2/month) closely followed by starting point (37.27gm/m2/month) and least at 3 km outside city (29.09 gm/m2/ month). The average dust fall rate per unit area was estimated to be about 35 gm/m2/month in Aligarh city.

Air Pollutants↗
PubMed2003

Cutaneous wound analysis using hyperspectral imaging.

A correlative bright-field and hyperspectral analysis of full-thickness, cutaneous wounds in a porcine model was undertaken to investigate the efficacy of hyperspectral imaging as an alternate method for wound identification. Analysis of a randomly selected specimen yielded distinct spectral signatures for cutaneous regions of interest including the epidermis, injured dermis, and normal dermis. The scanning of the entire specimen group using these hyperspectral signatures revealed an exclusionary, pseudo-color pattern whereby a central wound region was consistently defined by a unique spectral signature. An algorithm was derived as an objective tool for the comparison of the wound regions defined by the hyperspectral classification versus the pathologists' manual tracings. The dimensions of the wound identified in the hyperspectral assay did not differ significantly from the wound region identified by the pathologists using standard bright-field microscopy. These data indicate that hyperspectral analysis may provide a high-throughput alternative for wound estimation that approximates standard bright-field imaging and pathologist evaluation.

Algorithms↗
PubMed2003

Prevalence of pulmonary tuberculosis in Karachi juvenile jail, Pakistan.

Jail inmates may be at increased risk of contracting tuberculosis (TB). We studied 386 detainees (mean age 17.7 years) in Karachi juvenile jail to determine the prevalence of TB and possible risk factors for contracting TB. We found a 3.9% prevalence of TB among the inmates, significantly higher than the estimated 1.1% prevalence in the general population of Pakistan. Positive family history of TB was a significant risk factor for TB. Poor adherence of previously diagnosed patients to anti-TB treatment was found. Our study highlights the vulnerability of inmates to TB owing to the presence of highly infectious cases, along with environmental conditions such as overcrowding and poor ventilation. This study strongly indicates the need for an effective treatment programme in the jails as well in the general community.

Adolescent↗
PubMed2002

Methemoglobinemia induced by topical benzocaine: a warning for the endoscopist.

Benzocaine is used routinely for topical pharyngeal anesthesia prior to upper endoscopy, to improve patient tolerance. A potentially fatal, although often unrecognized, complication of benzocaine use is methemoglobinemia. Here, we report a case of methemoglobinemia induced by benzocaine given before upper endoscopy. Rapid recognition of this complication and immediate treatment is essential to prevent complications related to significant tissue hypoxia. This case serves as an important reminder to physicians, especially endoscopists, about this serious side effect. Furthermore, we question the need for topical anesthesia for upper endoscopy in sedated patients.

Aged↗
PubMed2001

Impaired bioavailability of rifampicin in presence of isoniazid from fixed dose combination (FDC) formulation.

The present study describes comparative bioavailability of rifampicin (RIF) after administration of a single component RIF (450 mg) capsule and rifampicin-isoniazid (RIF-INH) (450+300 mg) fixed dose combination (FDC) capsule formulations. Six healthy male volunteers participated in a single dose, two treatment, two period, cross-over study. A sensitive, specific and accurate HPTLC method was developed, validated and employed for estimation of RIF and its major active metabolite, 25-Desacetylrifampicin (25-DAR) levels, in urine. Using the urinary excretion data various pharmacokinetic parameters: AUC(0-24), AUC(0-infinity), cumulative amount excreted in 24 h, peak excretion rate, etc. for both RIF and 25-DAR were calculated and compared statistically (ANOVA, 90% confidence interval for ratio). Significant decrease in the bioavailability ( approximately 32% as RIF and approximately 28% as 25-DAR) of RIF from FDC capsules was observed. The present bioavailability study confirms our serious doubts about the stability of RIF in presence of INH in acidic environment of stomach, which probably is the main factor responsible for the reduced bioavailability of RIF from RIF-INH combination formulations. This study underlines the fact that there is an urgent need to reconsider the formulation of the FDC product in order to minimize or avoid the decomposition of RIF in gastrointestinal tract.

Adult↗
PubMed2001

Molecular genetics of ulcerative colitis-associated colon cancer in the interleukin 2- and beta(2)-microglobulin-deficient mouse.

Mice deficient in beta(2)-microglobulin and interleukin 2 (beta(2)m(null) x IL-2(null)) spontaneously develop colon cancer in the setting of chronic ulcerative colitis (UC). We investigated mutations of the Apc and p53 genes and microsatellite instability in colonic adenocarcinomas arising in this model. Mutations of the Apc and p53 genes in the regions corresponding to mutation hot spots in human colorectal cancer were determined by sequencing in 11 colonic adenocarcinomas. Microsatellite instability was determined in matched normal and neoplastic DNA at five loci. All 11 adenocarcinomas harbored Apc mutations. Of these 11 tumors, 5 harbored truncating mutations. A total of 67 Apc mutations were found in these 11 tumors; 59 were missense mutations, whereas 8 were frameshift or nonsense mutations. Six of the 11 adenocarcinomas harbored p53 mutations. A total of seven p53 mutations were found in these 11 tumors; all mutations were transitions, 4 of which were C:G-->T:A transitions occurring in codon 229 at cytosine-guanine dinucleotides. Nine adenocarcinomas exhibited microsatellite instability in at least one of the five loci examined; 1 tumor had microsatellite instability in two loci. Molecular genetics, as well as clinical features, of colon cancer in the beta(2)m(null) x IL-2(null) mice are similar to those of human UC-associated colorectal cancer. As such, this model appears to be an excellent animal model to study UC-associated colorectal carcinogenesis.

Adenocarcinoma↗
PubMed2001

Protective effects of ischemic preconditioning on the cold-preserved liver are tyrosine kinase dependent.

BACKGROUND: Little data exist regarding the use of ischemic preconditioning before sustained hepatic cold storage. We hypothesized that ischemic preconditioning protects hepatic grafts via a tyrosine kinase-dependent pathway. METHODS: Six porcine livers underwent routine harvest (control). Five other livers underwent 15 min of in situ ischemia followed by 15 min of reflow before harvest (ischemic preconditioning). Another five livers were pretreated with a tyrosine kinase inhibitor (genistein) before preconditioning. Upon reperfusion and after 2 hours of cold storage, graft function, graft circulatory impairment, and markers of cellular damage were analyzed. Tissue cytoplasmic extracts were analyzed for tyrosine phosphorylation with Western blot. Significance was determined with t tests. RESULTS: Ischemic-preconditioned grafts demonstrated enhanced bile production, augmented responses to a bile acid challenge, and elevated O2 consumption (P<0.05) compared to controls. Also, preconditioned grafts demonstrated improved hepatic tissue blood flow and decreased hepatic vascular resistance (P<0.005) compared to controls. Endothelial cell preservation (factor VIII immunostain) was improved in preconditioned graft biopsies compared to controls. With genistein pretreatment, all observed improvements returned to control levels. Analysis of cytoplasmic extracts demonstrated an increase in tyrosine phosphorylation before cold ischemia in preconditioned grafts only, but not in control or genistein-pretreated grafts. CONCLUSIONS: The data indicate that ischemic preconditioning protects the liver from sustained cold ischemia and that tyrosine kinases are involved in preconditioning responses.

Alanine Transaminase↗
PubMed2001

Protein kinase C inhibition abrogates hepatic ischemic preconditioning responses.

INTRODUCTION: A transient period of warm ischemia prior to a longer ischemic episode (ischemic preconditioning) protects the hepatic graft from cold ischemia. The mechanism for this protection is unknown, as is the role of protein kinase C in ischemic preconditioning responses. METHODS: Livers from 40 kg Yorkshire pigs were harvested and subjected to 2 h of cold ischemia (n = 6) (control). Another group of harvested livers was pretreated with a 15-min ischemic period followed by 15 min of in situ perfusion with (n = 5) or without (n = 5) a protein kinase C inhibitor, chelerythrine. Following cold ischemia, all grafts were reperfused on a perfusion circuit and the following variables evaluated: (1) hepatic graft function, (2) graft circulatory impairment, (3) hepatocellular damage, and (4) endothelial cell damage. Protein kinase C levels were also evaluated by Western blot in the cytoplasm of all grafts. RESULTS AND DISCUSSION: Ischemic preconditioned grafts demonstrate improved graft function, reduced graft circulatory impairment, and reduced endothelial cell damage as compared to cold ischemia controls. When preconditioned grafts were pretreated with chelerythrine, graft function, graft circulatory impairment, and endothelial cell damage were no different than cold ischemia controls. Ischemic preconditioned grafts demonstrated decreased levels of protein kinase C prior to cold ischemia. There was no change in protein kinase C levels in cold ischemia controls or chelerythrine-pretreated grafts prior to cold ischemia. These data indicate that modulation of protein kinase C is essential for ischemic preconditioning responses in the cold preserved hepatic graft.

Alkaloids↗
PubMed2001

FRAP-p70s6K signaling is required for pancreatic cancer cell proliferation.

BACKGROUND: FRAP-p70s6K signaling regulates mitogenic responses to growth factors in eukaryotic cells. Constitutive p70s6K activation occurs in some human malignancies and may contribute to dysregulated cell growth. We examined whether inhibition of this pathway affects mitogen-induced proliferation and cell cycle progression of human pancreatic cancer cells in vitro. METHODS: Quiescent BxPC3 and Panc-1 human pancreatic cancer cells treated with or without 20 ng/mL rapamycin (FRAP inhibitor) were repleted with 10% FCS to induce cell cycle entry. Proliferation was measured with MTT assay. Cell cycle and apoptosis were determined by FACS analysis. Phosphorylation of p70s6K, Akt, and cdc2 was evaluated by Western blot. Statistical analysis was by two-tailed t test (P < 0.05). RESULTS: Rapamycin (Rapa) inhibited the phosphorylation of p70s6K while inducing G(1) cell cycle arrest (P < 0.005). In both cell lines, Rapa inhibited serum-induced proliferation (P < 0.05) without affecting apoptosis. Cdc2 phosphorylation was inhibited by 15 min with Rapa (not shown), consistent with cell cycle arrest. Akt phosphorylation was not affected, indicating FRAP specificity of Rapa. CONCLUSIONS: FRAP-p70s6K signaling appears to be necessary for G(1)-to-S phase progression and proliferation in pancreatic cancer cells. This supports earlier work demonstrating a similar regulatory role for PI-3' kinase, an upstream activator of FRAP-p70s6K.

Adenocarcinoma↗
PubMed2001

Endotoxin (LPS) stimulates 4E-BP1/PHAS-I phosphorylation in macrophages.

INTRODUCTION: Translational control of cytokine production in endotoxin (LPS)-stimulated macrophages is poorly characterized but likely important. An early step in protein translation is engagement of mRNA by eukaryotic initiation factor 4E (eIF-4E). Translation initiation can be prevented by small 4E-binding proteins (4E-BP1 or PHAS-I) which must be phosphorylated in order to disengage eIF-4E. We examined whether LPS alters 4E-BP1 phosphorylation in macrophages. MATERIALS AND METHODS: Elicited rat peritoneal macrophages and Raw 264.7 macrophages were treated with signal transduction inhibitors and then LPS. Cells were harvested and equal protein amounts were electrophoresed (SDS-PAGE). Western blots (WB) were developed with 4E-BP1 antibody. Alternatively cell lysates were exposed to 7-methyl GTP Sepharose beads in order to isolate the cap-binding protein eIF-4E. The relative amounts of 4E-BP1 associated with eIF-4E were then determined by WB. RESULTS: Macrophage 4E-BP1 is phosphorylated upon stimulation by LPS as evidenced by the appearance of a more slowly migrating gamma (hyperphosphorylated) band on gel electrophoresis. Inhibition of both the p42/p44 MAPK pathway (PD 98059) and the p38 MAPK pathway (SB 203580) failed to alter LPS-induced 4E-BP1 phosphorylation. Rapamycin (FRAP/mTOR inhibitor) blocked 4E-BP1 phosphorylation causing a predominance of the alpha (hypophosphorylated) band. This was confirmed further by 7-methyl-GTP Sepharose isolation of eIF-4E with which 4E-BP1 coprecipitates. CONCLUSION: LPS stimulates 4E-BP1 phosphorylation in macrophages through FRAP/mTOR signaling. This pathway may contribute to the translational control of cytokine gene expression in macrophages.

Animals↗