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Biomedical subjects

S Khan

Publications and source records attributed to S Khan.

At least 109 records · Page 6Linked to original sources
PubMed2001

Evaluation and reinforcement of the correlation of S-phase fraction with nodal metastases, tumor grade and tumor size in breast carcinoma patients in Pakistan.

The aim of this study was to evaluate the S-phase fraction (SPF) of tumors in breast cancer patients in Pakistan. Its association with the traditional morphological prognostic markers, i.e., axillary lymph node metastasis, tumor size and grade, was also studied. Flow cytometry was used to estimate SPF on breast cancer tissues from 166 patients reported at the Aga Khan University Hospital between the years 1997 and 2000. Univariate analysis was done to find any association between SPF and the aforesaid variables. For the ease of analysis, the cases were subdivided into two categories depending on the SPF value, i.e., <10% (low-risk group) and > or = 10% (high-risk group). The mean and median SPF values were 21.45% and 20.035%, respectively, with a range of 3.26% to 54.30%. Twenty-six (15.66%) of the cases had SPF <10%, 57 (34.34%) had SPF from 10%-20%, and 83 (50%) had SPF >20%. A significant correlation between SPF and nodal metastasis was observed (p = 0.0111), but not between SPF and the number of lymph nodes involved when metastatic cases were subdivided into <4 lymph node-positive cases and > or =4 lymph node-positive cases. Significant correlations were also found between SPF and tumor grade (p = 0.0244), as well as between SPF and tumor size (p = 0.048). In conclusion, DNA flow cytometric analysis of SPF carried out in our laboratory could reasonably predict the chances of lymph node metastasis, tumor grade and size in breast cancer patients, thus proving to be an important prognostic marker in the Pakistani setting. This requires further investigations regarding the survival of patients so as to evaluate its capacity of predicting the outcome of Pakistani patients.

Adenocarcinoma↗
PubMed2001

Immunohistochemical cathepsin-D expression in breast cancer: correlation with established pathological parameters and survival.

Breast cancer is an increasingly important cause of illness and death among women. In recent years, several novel prognostic determinants of breast cancer have been identified, including Cathepsin-D (CD) protein. CD protein expression was analyzed immunohistochemically (IHC) in tumor specimens (315 patients) of infiltrating ductal breast carcinoma. These patients also had axillary lymph node sampling. Overexpression of CD was observed in 39% of the tumors. IHC results were compared with the histological grade. Seventy nine percent (n = 95; 79%) tumor positivity was seen in grade II tumors, followed by grade I (n = 13; 11%) and grade III tumors (n = 12; 10%). Axillary lymph node metastasis had no significant correlation with CD positivity (p > 0.05). Bone metastases were significantly correlated with CD positivity (p < 0.05). CD positivity showed no significant correlation with disease-free and overall survival (p > 0.05). At a median follow-up of 48 (4 years) months in CD-positive patients, overall survival was 3.17 years, and disease-free survival 2.67 years. The overall survival of CD-negative tumor patients was 3.50 years, and disease-free survival was 2.93 years. We conclude that in comparison with cytosol-based quantitative studies, CD expression is not a good prognostic marker when, as in all ICH studies, only the expression in the tumor is considered.

Adult↗
PubMed2001

Therapeutic plants of Ayurveda: a review of selected clinical and other studies for 166 species.

This paper reports on the results of a literature survey involving 166 different species of plants used in the Ayurvedic pharmacopoeia, based on a sampling of the literature available to us. We found a wide range of clinical and other in vivo studies for many of the plant-based therapies utilized in the Ayurvedic system. Of the 166 plants investigated, 72 (43%) had at least one or more human studies and 103 (62%) had one or more animal studies. These results appear to contradict the generally held notion that herbal remedies used in non-Western systems of botanical medicine have not been evaluated in human or in vivo trials. Some of these studies are not always as large or methodologically rigorous as clinical studies reported in major medical journals. Indeed, a critical assessment of the research according to the standards of evidence-based medicine would eliminate many of these studies for lack of rigor according to criteria of randomization, sample size, adequacy of controls, etc. However, the studies do suggest which species might be appropriate for larger and better-controlled trials in the future. Accordingly, a synopsis of the plants, their therapeutic applications, and their clinical or experimental evaluations is presented.

Animals↗
PubMed2001

Acamprosate is neuroprotective against glutamate-induced excitotoxicity when enhanced by ethanol withdrawal in neocortical cultures of fetal rat brain.

BACKGROUND: Acamprosate reduces relapse, and the drug may interact with glutamate transmission and with glutamate/NMDA receptors. Because these systems are implicated in excess calcium entry leading to alcohol withdrawal-induced neurotoxicity, we evaluated the effects of acamprosate on these parameters in neuronal cultures. METHODS: Primary cultures of neocortical neurons from fetal Sprague-Dawley rats were maintained either in normal medium or in medium containing 100 mM ethanol for 4 days. After this time, cultures were challenged with glutamate for 10 min and then returned to medium (all in the absence of ethanol). 45Ca2+ uptake was measured during the challenge, and glutamate-induced toxicity was assessed after 20 hr. The effects of acamprosate present during the glutamate challenge were measured on both parameters. RESULTS: In controls, acamprosate did not significantly affect glutamate-induced neurotoxicity but produced a significant inhibition of calcium entry. The NMDA receptor antagonists dizocilpine and d-amino-phosphonovalerate (D-APV) inhibited both glutamate neurotoxicity and calcium entry. In cultures previously exposed to ethanol, glutamate-induced neurotoxicity and calcium entry were both significantly enhanced. Dizocilpine reduced both these parameters to unstimulated control values, and D-APV reduced both calcium entry and neurotoxicity with the same relation that we obtained in control cultures. In the ethanol-withdrawn cultures, acamprosate reduced both the enhanced glutamate-induced calcium entry and the enhanced neurotoxicity in a concentration-dependent manner. Acamprosate also significantly reduced calcium entry caused by 80 mM K+ in control and ethanol-exposed cultures. CONCLUSIONS: Acamprosate had protective effects against glutamate-induced neurotoxicity only in ethanol-withdrawn cultures. The neuroprotective effects of the drug did not correlate with its effects on calcium entry, making it unlikely that acamprosate directly affects NMDA receptors via the glutamate binding site or the receptor-operated calcium channel. The results are, however, compatible with other inhibitory effects on NMDA receptor function.

Acamprosate↗
PubMed2001

Ultrasound-mediated disruption of cell membranes. II. Heterogeneous effects on cells.

Ultrasound has been shown to reversibly and irreversibly disrupt membranes of viable cells through a mechanism believed to involve cavitation. Because cavitation is both temporally and spatially heterogeneous, flow cytometry was used to identify and quantify heterogeneity in the effects of ultrasound on molecular uptake and cell viability on a cell-by-cell basis for suspensions of DU145 prostate cancer and aortic smooth muscle cells exposed to varying peak negative acoustic pressures (0.6-3.0 MPa). exposure times (120-2,000 ms), and pulse lengths (0.02-60 ms) in the presence of Optison (1.7% v/v) contrast agent. Cell-to-cell heterogeneity was observed at all conditions studied and was classified into three subpopulations: nominal uptake (NUP), low uptake (LUP), and high uptake (HUP) populations. The average number of molecules within each subpopulation was generally constant: 10(4)-10(5) molecules/cell in NUP, approximately 10(6) molecules/cell in LUP, and approximately 10(7) molecules/cell in HUP. However, the fraction of cells within each subpopulation showed a strong dependence on both acoustic pressure and exposure time. Varying pulse length produced no significant effect. The distribution of cells among the three subpopulations correlated with acoustic energy exposure, which suggests that energy exposure may govern the ability of ultrasound to induce bioeffects by a nonthermal mechanism.

Cell Membrane↗
PubMed2001

Ultrasound-mediated disruption of cell membranes. I. Quantification of molecular uptake and cell viability.

Ultrasound-mediated drug delivery is a nonchemical, nonviral, and noninvasive method for targeted transport of drugs and genes into cells. Molecules can be delivered into cells when ultrasound disrupts the cell membrane by a mechanism believed to involve cavitation. This study examined molecular uptake and cell viability in cell suspensions (DU145 prostate cancer and aortic smooth muscle cells) exposed to varying peak negative acoustic pressures (0.6-3.0 MPa), exposure times (120-2000 ms), and pulse lengths (0.02-60 ms) in the presence of Optison (1.7% v/v) contrast agent. With increasing pressure and exposure time, molecular uptake of a marker compound, a calcein, increased and approached equilibrium with the extra cellular solution, while cell viability decreased. Varying pulse length produced no significant effect. All viability and molecular uptake measurements collected over the broad range of ultrasound conditions studied correlated with acoustic energy exposure. This suggests that acoustic energy exposure may be predictive of ultrasound's nonthermal bioeffects.

Cell Membrane↗
PubMed2001

Generation and characterization of a defined mutant of Streptococcus suis lacking suilysin.

A defined allelic-replacement mutant of the sly gene, encoding a thiol-activated cytolysin, from a European isolate of Streptococcus suis serotype 2 was generated and characterized. Unlike the parental strain, it is nonhemolytic, noncytotoxic for cultured macrophage-like cells, avirulent in a mouse infection model, yet only slightly attenuated in a porcine model of systemic infection.

Animals↗
PubMed2001

A comparison of the palliative care needs of patients dying from chronic respiratory diseases and lung cancer.

This paper reports on data from the Regional Study of Care for the Dying, conducted in 1990, and compares symptoms, care and service utilization for patients with chronic lung diseases (CLD) and lung cancer (LC) in the final 12 months of life. Post-bereavement structured interviews were conducted with informal carers of 449 LC patients and 87 CLD patients. The LC patients were significantly younger than those with CLD (P = 0.001) and these respondents were more likely to have been a spouse (P = 0.034). No differences were found in the mean number of symptoms reported by the two groups in the final year or week of life, although the CLD patients were more likely to have experienced these symptoms for longer. Significantly more patients with CLD than LC experienced breathlessness in the final year (94% CLD vs 78% LC, P < 0.001) and final week (91% CLD vs 69% LC, P < 0.001) of life. Significantly more LC patients were reported to have experienced anorexia (76% LC vs 67% CLD, P = 0.06) and constipation (59% LC vs 44% CLD, p = 0.01) in the final year of life. There were no differences in general practitioner use, but LC patients were reported to have received more help from district nurses (52% LC vs 39% CLD, P = 0.025) and from a palliative care nurse (29% LC vs 0% CLD, P < 0.001). More CLD patients were reported to have received help from social services (29% CLD vs 18% LC, P = 0.037). LC patients were reported to be more likely to have known they might die (76% LC vs 62% CLD, P = 0.003) and to have been told this by a hospital doctor (30% LC vs 8% CLD, P = 0.001). Among those that knew, LC patients were told earlier prior to death than CLD patients. This study suggests that patients with CLD at the end of life have physical and psychosocial needs at least as severe as patients with lung cancer.

Aged↗
PubMed2001

Neuroparalysis and oxime efficacy in organophosphate poisoning: a study of butyrylcholinesterase.

The temporal profile of butyrylcholinesterase (BuChE) and in vitro pralidoxime-reactivated BuChE was studied in a cohort of 25 organophosphate-poisoned patients to examine their relationship to the development of intermediate syndrome and to understand reasons for lack of efficacy of oxime treatment. The clinical severity of poisoning (assessed by the Namba Scale) correlated significantly with the severity of intermediate syndrome. BuChE activity increased significantly over time and showed significant relationship to muscle power. The temporal profile of the enzyme was correlated to the clinical severity of poisoning. Reactivation potentials of BuChE (the difference between oxime-reactivated and -unreactivated enzyme activity) declined significantly with time after organophosphate ingestion. The reactivation potential of the enzyme at admission decreased significantly with increasing severity of poisoning and was lower in patients who developed intermediate syndrome. Patients who received oxime prior to hospitalization had a higher rate of intermediate syndrome and lower levels of BuChE at admission than those who had not. The study suggests that (i) BuChE reflects the clinical course of poisoning, confirming earlier studies; (ii) intermediate syndrome may be associated with a persistent inhibition of BuChE; and (iii) the lack of oxime efficacy in our patients maybe due to their severity of poisoning and the timing of oxime treatment.

Adult↗
PubMed2001

Factors affecting employment after whiplash injury.

Of 586 employed patients with a whiplash injury 40 (7%) did not return to work. The risk was increased by three times in heavy manual workers, two and a half times in patients with prior psychological symptoms and doubled for each increase of grade of disability. The length of time off work doubled in patients with a psychological history and trebled for each increase in grade of disability. The self-employed were half as likely to take time off work, but recovered significantly more slowly than employees.

Anxiety↗
PubMed2001

Glypican-3 (GPC3) expression in human placenta: localization to the differentiated syncytiotrophoblast.

The expression of glypican-3 (GPC3), a heparan-sulfate proteoglycan associated with the Simpson-Golabi-Behmel fetal overgrowth syndrome, was studied in normal human placental tissue and cell lines derived from human placentae. Cytotrophoblasts derived from term placentae expressed GPC3 mRNA at low levels in culture. GPC3 mRNA expression increased markedly during trophoblast differentiation. By contrast, fibroblast cell lines derived from normal placentae did not express GPC3 in culture. Similarly, choriocarcinoma cell lines derived from human placentae (BeWo, JAR, and JEG) failed to express GPC3 mRNA. In situ hybridization confirmed the localization of GPC3 mRNA to the syncytiotrophoblast. Furthermore, immunohistochemical staining of paraffin imbedded placental tissue demonstrated intense staining of the syncytiotrophoblast cell layer and less intense staining of cytotrophoblasts. No staining of mesenchymal elements was noted. These data confirm the presence of GPC3 in human placenta and suggest it is expressed by the differentiated syncytiotrophoblast at term.

Adult↗
PubMed2001

Unique sensitivities to cytokine regulated expression of adhesion molecules in human heart-derived endothelial cells.

The expression of adhesion molecules by endothelial cells is crucial in many inflammatory processes and plays an active role in the development of reperfusion injury, acute and chronic rejection. The expression of adhesion molecules in different parts of the coronary tree to cytokine stimulation is not known. We describe here a detailed study of the effects of the inflammatory cytokines TNFalpha and IL-1beta on the expression of adhesion molecules vascular cell adhesion molecule-1 (VCAM-1), E-selectin and intracellular cell adhesion molecule-1 (ICAM-1) on human aortic root (HAEC), coronary artery (HCAEC) and heart microvascular (HHMEC)) endothelial cells in culture, using flow cytometry. We found constitutive levels of both VCAM-1 and E-Selectin on HCAEC and HHMEC (approximately 20%) which were significantly higher compared to HAEC (approximately 3%). There was an extreme sensitivity of HCAEC and HHMEC to 0.002 ng/ml TNFalpha: (VCAM-1 approximately 40%, E-Selectin approximately 25%) respectively, compared to HAEC (VCAM-1 approximately 5%, E-selectin approximately 5%). IL-1beta showed a similar pattern of expression at low doses (5 U/ml), but was less potent. We also observed prolonged expression of these adhesion molecules, especially on the HHMEC (>48 hours) compared to HAEC. There was also increased binding of peripheral blood mononuclear cells (PBMC) to both non-stimulated and TNFalpha stimulated HCAEC and HHMEC compared to HAEC. This data suggest that endothelial cells in different regions of the coronary tree express different patterns of basal and cytokine-stimulated adhesion molecule expression.

Aorta, Thoracic↗
PubMed2001

Weight gain with risperidone among patients with mental retardation: effect of calorie restriction.

BACKGROUND: The atypical antipsychotics cause weight gain, which is poorly understood in terms of its mechanism and treatment. A usual recommendation for treatment of antipsychotic-induced weight gain includes calorie restriction and exercise. The authors describe their recent clinical experience with calorie restriction in adults with mental retardation treated with risperidone. METHOD: A retrospective chart review was performed on the records of 50 adult patients with mental retardation treated with risperidone while residing at a habilitation center. We assessed dose and duration of risperidone treatment, weight, changes in calorie intake, and frequency of aggressive behavior. RESULTS: Of the 50 patients, 39 had adequate data for analysis. Thirty-seven of the 39 patients gained weight with a mean of 18.8 lb (8.3 kg) over about 2 years. Twenty of the 37 patients were calorie restricted. Three of the 20 calorie-restricted patients lost weight at a rate of 0.2 lb (0.1 kg) per month. The other 17 calorie-restricted patients and the 17 patients who were not calorie restricted continued to gain weight at a rate of 0.8 lb (0.4 kg) per month over about another 2 years of treatment. The amount of weight gain was not dose related. Calorie restriction led to no deterioration in behavior. CONCLUSION: The current investigation lends support to data that note weight gain with risperidone in adults with mental retardation. It suggests that calorie restriction does not lead to weight loss or behavioral deterioration and that weight gain is not dose related.

Aggression↗
PubMed2001

Acute colonic perforation associated with colorectal cancer.

Our purpose was to evaluate long-term outcome in patients presenting with acute colonic perforation in the setting of colorectal cancer. We conducted a retrospective review of 48 consecutive patients presenting with acute colonic perforation associated with colorectal cancer at a single institution. Patients presented either with free air or acute peritonitis. No patients with colonic obstruction were included. Forty-eight patients presented with colon perforation. Thirty-six had perforation at the tumor, 11 proximal to the tumor, and one distal to the primary tumor. Patients who perforated proximal to the tumor were older (74.5 +/- 2 vs 64.7 +/- 3; P < 0.04) and had a longer length of stay (46.8 +/- 17 vs 11.6 +/- 1 P < 0.001). Fourteen patients had stage II disease, 19 stage III, and 15 stage IV. Thirty-day mortality was 14 per cent (n = 7) with nine in-hospital deaths. Of 30-day survivors 29 (60%) had curative resection (21 with local perforation and nine with proximal perforation). Of these 14 received adjuvant chemotherapy. Eleven patients (33%) had either unresectable or metastatic disease on exploration. Mean follow-up was 21.5 months. Ten patients developed metastatic disease after potentially curative resections. Of these nine patients had perforations of the primary tumor. Three patients developed local recurrence and all had local tumor perforations. One-year survival was 55 per cent (n = 16). Five-year disease-free survival was 14 per cent (n = 4). There were no long-term survivors after perforation proximal to the tumor, although disease stage was comparable in both groups. We conclude that perforation proximal to a cancer is associated with a higher perioperative mortality and worse long-term outcome when compared with acute perforations at the site of the tumor. Long-term survival requires both aggressive management of the concomitant sepsis and definitive oncologic surgery.

Acute Disease↗
PubMed2001

A survival analysis of metastatic breast cancer in Pakistani patients.

OBJECTIVE: To determine the overall survival of metastatic breast cancer in the Pakistani patients and compare it with published information. METHOD: The design was a retrospective analysis of metastatic breast cancer patients from breast cancer database. A total of 137 patient based information was available for review and analysis. RESULTS: An overall median survival of 2.83 years was noted in metastatic breast cancer patients. CONCLUSION: This survival figure in this study compares favorably to those published in the literature.

Adult↗
PubMed2001

Ulcerative colitis and colonic lymphoma: a theoretical link.

Ulcerative colitis (UC) is an inflammatory disease of the colon and rectum. Although colonic adenocarcinoma is a recognized complication of UC there have been few reported cases of gastrointestinal lymphoma arising in this setting. We describe our experience with such a case and review the literature that attempts to explain possible genetic etiologies for the malignant transformation of gastrointestinal lymphoid tissue to lymphoma as well as a link between UC and lymphoma.

Colitis, Ulcerative↗