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Biomedical subjects

S Aziz

Publications and source records attributed to S Aziz.

At least 37 records · Page 2Linked to original sources

A multicenter, randomized, controlled trial of Celsior for flush and hypothermic storage of cardiac allografts.

BACKGROUND: A multicenter, randomized, controlled, open-label trial was conducted to evaluate the safety and efficacy of Celsior when used for flush and hypothermic storage of donor hearts before transplantation. METHODS: Heart transplant recipients were randomized to one of two treatment groups in which donor hearts were flushed and stored in either Celsior or conventional preservation solution(s) (control). Study subjects were followed for 30 days after transplantation. RESULTS: A total of 131 heart transplant recipients were enrolled (Celsior, n = 64; control, n = 67). The treatment groups were evenly distributed in donor and recipient base line characteristics. Graft loss rate was lower in the Celsior group on day 7 (3% versus 9%) and on day 30 (6% versus 13%), but the difference was not statistically significant based on 95% confidence interval analysis. No significant difference was measured between the Celsior and control groups in 7-day patient survival (97% versus 94%) and the proportion of patients with one or more adverse events (Celsior, 88%; control 87%) or serious adverse events (Celsior, 38%; control, 46%). Significantly fewer patients in the Celsior group developed at least one cardiac-related serious adverse event (13% versus 25%). CONCLUSIONS: Celsior was demonstrated to be as safe and effective as conventional solutions for flush and cold storage of cardiac allografts before transplantation.

Adult↗

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↗

Bilirubin-IXalpha and -IXbeta pigments, coproporphyrins and bile acids in meconium and stools from full-term and preterm neonates during the first month of life.

UNLABELLED: Individual bilirubin pigments in the excreta were quantitated by newly developed methods. In meconium, bilirubin-IXbeta predominated, whereas bilirubin-IXgamma and -IXdelta remained undetectable. The daily excretion of bilirubin-IXalpha plus -IXbeta was 0.03-1.00 and 0.04-2.00 micromoles kg(-1) of birthweight in preterm and full-term infants, respectively. The ratio of bilirubin-IXalpha to -IXbeta in meconium was 0.25 +/- 0.34, 0.32 +/- 0.30 and 0.46 +/- 0.55 in newborns of gestational ages below 30, from 31 to 36 and above 36 wk, respectively. The predominance of bilirubin-IXbeta disappeared within the first week in those with gestational age >31 wk but more slowly in the very preterm group. The ratio of monoconjugated to diconjugated bilirubin-IXalpha was 4 to 5 in full-term infants, whereas this ratio was only reached after 1 mo in preterm infants. The ratio of glucuronide or glucoside to xyloside varied widely, independent of gestational age. No correlation between faecal UCB-IXalpha and beta-glucuronidase was observed. The daily coproporphyrin excretion fell from a median of 500 microg on day 1 to below 20 microg from day 7 onwards; this decrease correlated with that of bilirubin-IXbeta. The daily 3alpha-hydroxylated bile acid loss in the excreta was two- to fivefold higher than in the adult; this, together with the higher neonatal serum levels (12-90 nmoles ml(-1)), indicates an immature intestinal reabsorption and an enhanced bile acid synthesis. CONCLUSION: Both zinc coproporphyrin and bilirubin-lXbeta are characteristic compounds of human meconium, diconjugated bilirubin-IXalpha is low or absent in meconium of very preterm infants, and faecal and serum bile acids are high.

Bile Acids and Salts↗

Bilirubin-IXbeta is a marker of meconium, like zinc coproporphyrin.

BACKGROUND: Because meconium accumulates continuously in the fetal intestine, analysis of the postnatally excreted material could yield important information of intrauterine metabolism and maturation. Therefore, a study of the bilirubin pigments in meconium and in the first neonatal stools was carried out. METHODS: Meconium and stools from 37 neonates of various gestational ages were collected carefully, and stored at -20 degrees C, protected by aluminium foil. Samples were defrosted, vortex mixed with an equal amount of dimethyl sulfoxide, centrifuged, and submitted to analysis by high-pressure liquid chromatography using newly developed methods to identify and to quantitate the bilirubin-IXalpha, -IXbeta, -IXgamma, and -IXdelta isomers. In addition, samples were also submitted to diazo coupling with ethyl anthranilate. Total coproporphyrins and zinc coproporphyrin were assayed for comparison. RESULTS: Unconjugated bilirubin-IXalpha and -IXbeta were detected in meconium but not the -IXgamma or the -IXbeta isomer. Bilirubin-IXbeta was the predominant pigment and comprised 63% to 96% of the unconjugated bilirubins in the first sample of meconium excreted. Its amount decreased rapidly during the first 5 days in full-term newborns, but this occurred more slowly in preterm neonates, especially in those with a gestational age less than 30 weeks. The decrease of bilirubin-IXbeta over time correlated with that of coproporphyrin. CONCLUSIONS: Bilirubin-IXbeta is the prevailing bile pigment in the first excreted sample of meconium. It gradually decreases after birth and can be considered a biochemical marker of meconium, like zinc coproporphyrin.

Bile Acids and Salts↗

Emerging anticoagulant and thrombolytic drugs.

Since its discovery, heparin has been used intensely as an anticoagulant for several medical and surgical indications. However, efforts are in progress to replace heparin because of its serious complications, such as intraoperative and postoperative bleeding, osteoporosis, alopecia, heparin resistance, heparin rebound, heparin-induced thrombocytopenia (HIT) and thrombosis syndrome (HITTS), and other disadvantages. Significant developments in the field of new anticoagulants have resulted in the evaluation and introduction of low molecular weight heparins (LMWHs) and heparinoids, hirudin, ancrod, synthetic peptides and peptidomimetics. However, despite significant progress in the development of these new anticoagulants, a better or an ideal anticoagulant for cardiovascular patients is not yet available and heparin still continues to amaze both basic scientists and the clinicians. To minimise the adverse effects of heparin, newer approaches to optimise its use in combination with the new anticoagulants may provide better clinical outcome. In our experience, the off-label use of argatroban at a dose of 300 microg/kg iv. bolus followed by 10 microg/kg/minute infusion in combination with aggrastat (a glycoprotein [GP] IIb/IIIa inhibitor) at a dose of 10 microg/kg iv. bolus followed by an infusion of 0.15 microg/kg/minute in patients with HIT undergoing percutaneous coronary interventions resulted in elevation of celite activated clotting time (ACT) to 300 seconds followed by a gradual decline and the ACT remained above 200 seconds even after 200 min of drug administration. A bewildering array of newer anticoagulants now exist, such as LMWHs and heparinoids, indirect or direct thrombin inhibitors, oral thrombin inhibitors, such as melagatran (AstraZeneca) and HC-977 (Mitsubishi Pharmaceuticals), Factor IXa inhibitors, indirect or direct Factor Xa inhibitors, Factor VIIa/tissue factor (TF) pathway inhibitor, newer antiplatelet agents, such as GPIIb/IIIa inhibitors, fibrin specific thrombolytic agent, such as tenecteplase and modulation of the endogenous fibrinolytic activity by thrombin activatable fibrinolytic inhibitor (TAFI), Factor XIIIa inhibitors and PAI-1 inhibitors. The quest for newer anticoagulant, antiplatelet and fibrinolytic agents will continue until ideal agents are found.

Journal Article↗

Determination of pesticide residues in fruits and vegetables in Islamabad market.

Pesticide residues in fruits and vegetable from Islamabad market, Pakistan were determined by GLC using Perkin Elmer Autosystem equipped with 63NECD and capillary column. Dimethoate was determined in the quantity of 0.032 mg kg-1 in apple, 0.110 mg kg-1 in banana, 0.004 mg kg-1 in brinjal, 1.80 mg kg-1 in cauliflower and 0.13 mg kg-1 in arvi, fenvalerate 0.010 mg kg-1 in apple and chlorpyrifos 0.004 mg kg-1 in brinjal. The importance of these pesticide residues with reference to human health is also briefly discussed.

Food Contamination↗

Impact of socioeconomic conditions on perinatal mortality in Karachi.

OBJECTIVE: To study and compare the perinatal mortality (PNM) in hospitals located in various socio-economic areas of Karachi. DESIGN: A prospective review of all births was done from May 1996 to April 1997. Precoded proformas were provided to each hospital and the birth and details of each mother and baby delivered recorded. SETTING: All mothers and their newborn delivered during the time period mentioned. OUTCOME MEASURES: Comparison of PNM in hospitals located in various socio-economic areas of Karachi. RESULTS: A total of 4957 proformas were filled, 63.5% by doctors, 32% by LHVs, 2.9% by administrator and 2.3% by paramedics. Overall 92.3% mothers were housewives, less than 45% of the mothers received primary/secondary education; 42% mothers were of the age 21 to 25 years. More than 52.3% fathers were unskilled labourers. Only 27% mothers were booked while the rest were unbooked or came to deliver on walk in basis. Majority (62%) of the mothers had a > 37 week duration of pregnancy and 51% newborns were male and 49% female. Twenty three percent of the newborns weighed < 2500 grams, remaining weighed > 2500 grams but less than 4500 grams; 24.5% newborns died on day one of birth. The PNM per 1000 births in the high, middle and low socioeconomic hospital was 16.4 +/- 23.6, 24.9 +/- 51.20 and 80.4 +/- 177.78 respectively. A statistical significance (p < 0.0000) by the Chi-square for several proportions was seen between the high middle and low socioeconomic hospitals of Karachi. CONCLUSION: The present socioeconomic conditions will take some time to change. However, this study indicates that perinatal mortality rate may be changed by an improvement in antenatal care of the mother, hence the fetus.

Chi-Square Distribution↗

Induction of the urokinase plasminogen activator system by oncostatin M promotes endothelial migration.

Oncostatin M (OSM) is an inflammatory cytokine produced by activated macrophages and T-lymphocytes. We have previously demonstrated that OSM-induced endothelial cell migration, unlike endothelial cell proliferation and spindle formation, is independent of basic fibroblast growth factor expression (Wijelath et al. [1997] J. Cell. Sci. 110:871-879). To better understand the mechanism of OSM-induced endothelial cell migration, this study examined the potential role of the plasminogen activator system in promoting OSM mediated endothelial cell migration. OSM stimulated increased mRNA levels of urokinase-plasminogen activator (uPA) and urokinase-plasminogen activator receptor (uPAR) in a time and dose-dependent manner. Transcriptional run-off and mRNA stability analysis demonstrated that the increase in uPA and uPAR mRNA levels was due to both increased gene transcription and mRNA stability. The increase in mRNA correlated with increased protein levels of both uPA and uPAR. This increase was reflected in elevated levels of membrane-bound plasmin activity. OSM-induced endothelial cell migration was only partially dependent on plasmin activity since incubating endothelial cells without plasminogen or, in the presence of aprotinin, resulted in suppression of endothelial cell migration, indicating that OSM promoted endothelial cell migration through both a plasmin-dependent and -independent mechanism. Our results imply a role for OSM in promoting endothelial cell migration via a plasmin-dependent pathway and a uPAR-mediated pathway. Together, these and other recent studies support a role for OSM in modulating the different phases of angiogenesis.

Cells, Cultured↗

Multiple factors other than p53 influence colon cancer sensitivity to paclitaxel.

PURPOSE: To determine factors which influence the sensitivity of human colorectal carcinoma cell lines to paclitaxel. METHODS: The paclitaxel sensitivity of ten human colorectal carcinoma cell lines, and a panel of RKO colon carcinoma cell lines, isogenic except for p53 status, were studied. The inhibitory concentrations causing a 50% decrease in growth (IC50) were assayed after 3, 24, and 96 h after paclitaxel exposure. The doubling time (DT) and cell cycle parameters of cells were also measured. The expression of the multidrug resistance glycoprotein-1 (MDR-1), bcl-2 and bax was quantitatively assessed by immunoblotting. RESULTS: Mean IC50 values at 24 and 96 h drug exposure were about 1.5 logs lower than the IC50 values at 3 h, regardless of the p53 status. No difference was found between the IC50 values of wild-type and mutant p53 cells, or among the RKO panel of cells. Correlation analysis showed that: (1) resistance was associated with longer DTs, but this was generally abated by a 96-h exposure; (2) with a 3-h exposure, the combination of MDR, bcl-2 and bax parameters with DT (DT + MDR + bcl-2 bax) best correlated with IC50 values (r = 0.77); (3) with a 96-h exposure, in spite of the generally decreased IC50 values, a combination of MDR-1, bcl-2 and bax parameters (MDR + bcl-2-bax) best correlated with the IC50 values (r = 0.71). CONCLUSIONS: These results suggest that the exposure duration, DT, and expression of MDR-1, bcl-2 and bax each contribute to paclitaxel sensitivity of human colorectal carcinoma cells. In assessing paclitaxel drug resistance, multiple factors should always be considered. There may be a therapeutic window for taxanes in colon cancer by optimizing pharmacokinetics and modulating MDR-1 and bcl-2 resistance factors.

Antineoplastic Agents, Phytogenic↗

Secondary pulmonary hypertension does not adversely affect outcome after single lung transplantation.

OBJECTIVE: Primary and secondary pulmonary hypertension have been associated with poor outcomes after single lung transplantation. Some groups advocate double lung transplantation and the routine use of cardiopulmonary bypass during transplantation in this population. However, the optimal procedure for these patients remains controversial. The goal of our study was to determine the safety of single lung transplantation without cardiopulmonary bypass in patients with secondary pulmonary hypertension. METHODS: We retrospectively reviewed 76 consecutive patients with pulmonary parenchymal disease who underwent single lung transplantation from 1992 to 1998. Recipients were stratified according to preoperative mean pulmonary artery pressure. Secondary pulmonary hypertension was defined as parenchymal lung disease with a preoperative mean pulmonary artery pressure of 30 mm Hg or more. Patients with primary pulmonary hypertension or Eisenmenger's syndrome were excluded from analysis. RESULTS: Eighteen of 76 patients had secondary pulmonary hypertension. No patient with secondary pulmonary hypertension required cardiopulmonary bypass, whereas 1 patient without pulmonary hypertension required bypass. After the operation, no significant differences were seen in lung injury as measured by chest radiograph score and PaO(2)/FIO(2) ratio, the requirement for inhaled nitric oxide, the length of mechanical ventilation, the intensive care unit or hospital length of stay, and 30-day survival. There were no differences in the forced expiratory volume in 1 second or 6-minute walk at 1 year, or the incidence of rejection, infection, or bronchiolitis obliterans syndrome greater than grade 2. Survival at 1, 2, and 4 years after transplantation was 86%, 79%, and 65%, respectively, in the low pulmonary artery pressure group and 81%, 81%, and 61%, respectively, in the group with secondary pulmonary hypertension (P >.2). CONCLUSION: We found that patients with pulmonary parenchymal disease and concomitant secondary pulmonary hypertension had successful outcomes as measured by early and late allograft function and appear to have acceptable long-term survival after single lung transplantation. Our results do not support the routine use of cardiopulmonary bypass or double lung transplantation for patients with this disorder.

Adult↗

Cardiovascular surgery in the elderly.

The elderly segment of the population is increasing rapidly, and surgeons are more frequently being requested to operate on this group of patients. A number of reports suggest that elderly patients have a significantly higher incidence of operative mortality and 30-day hospital mortality as compared with younger patients. Elderly patients also had a significantly higher increased incidence of complications, such as renal failure, prolonged ventilation, and incidence of strokes and postoperative cardiac arrest. Regarding coronary artery disease, elderly patients are more acutely sick on admission, are more likely to have triple-vessel disease, more likely have comorbid disease, and are usually less likely to receive an internal mammary artery graft. The presence of valvular disorders with concomitant coronary disease (especially mitral ischemic related valve disease) increases operative time, morbidity, and mortality. Efforts must continue to be made to gather data on outcomes of cardiac surgery in the elderly. Consideration must be given to modify the operative approach that minimizes cardiopulmonary bypass time, mitigates the multisystem organ injury associated with cardiopulmonary bypass, and decreases the likelihood of embolization from the ascending aorta. Future efforts must be made to develop measures to decrease the complications rate identified in elderly patients.

Aged↗

Generation and characterization of human smooth muscle cell lines derived from atherosclerotic plaque.

The study of atherogenesis in humans has been restricted by the limited availability and brief in vitro life span of plaque smooth muscle cells (SMCs). We describe plaque SMC lines with extended life spans generated by the expression of the human papillomavirus (HPV)-16 E6 and E7 genes, which has been shown to extend the life span of normal adult human aortic SMCs. Resulting cell lines (pdSMC1A and 2) demonstrated at least 10-fold increases in life span; pdSMC1A became immortal. The SMC identity of both pdSMC lines was confirmed by SM22 mRNA expression. pdSMC2 were generally diploid but with various structural and numerical alterations; pdSMC1A demonstrated several chromosomal abnormalities, most commonly -Y, +7, -13, anomalies previously reported in both primary pdSMCs and atherosclerotic tissue. Confluent pdSMC2 appeared grossly similar to HPV-16 E6/E7-expressing normal adult aortic SMCs (AASMCs), exhibiting typical SMC morphology/growth patterns; pdSMC1A displayed irregular cell shape/organization with numerous mitotic figures. Dedifferentiation to a synthetic/proliferative phenotype has been hypothesized as a critical step in atherogenesis, because rat neonatal SMCs and adult intimal SMCs exhibit similar gene expression patterns. To confirm that our pdSMC lines likewise express this apparent plaque phenotype, osteopontin, platelet-derived growth factor B, and elastin mRNA levels were determined in pdSMC1A, pdSMC2, and AASMCs. However, no significant increases in osteopontin or platelet-derived growth factor B expression levels were observed in either pdSMC compared with AASMCs. pdSMC2 alone expressed high levels of elastin mRNA. Lower levels of SM22 mRNA in pdSMC1A suggested greater dedifferentiation and/or additional population doublings in pdSMC1A relative to pdSMC2. Both pdSMC lines (particularly 1A) demonstrated high message levels for matrix Gla protein, previously reported to be highly expressed by human neointimal SMCs in vitro. These results describe 2 novel plaque cell lines exhibiting various features of plaque SMC biology; pdSMC2 may represent an earlier plaque SMC phenotype, whereas pdSMC1A may be representative of cells comprising an advanced atherosclerotic lesion.

Animals↗

Prospective trial of catheter irrigation and muscle flaps for sternal wound infection.

BACKGROUND: Sternal wound infection is a relatively rare but potentially devastating complication of open heart operations. The most common treatments after debridement are rewiring with antibiotic irrigation and muscle flaps. Here we present the results of a prospective trial to determine the appropriate roles of closed-chest catheter irrigation and muscle flap closure for sternotomy infection and to assess the effect of internal mammary artery bypass grafting on the outcome of each treatment modality. METHODS: Between 1990 and 1994, 5,658 sternotomies were performed at the University of Washington Medical Center. Sternal dehiscence occurred in 43 patients, 25 of whom had infection (overall incidence, 0.44%). Because of the infrequency of this complication, a prospective, randomized trial was developed in which the initial approach to sternal dehiscence was rewiring and catheter irrigation. Muscle flaps were used as the primary treatment if the sternum could not be restabilized or as secondary treatment if catheter irrigation failed. Wound resolution, length of hospital stay, and complications were evaluated. RESULTS: Sterile dehiscences were successfully closed with irrigation in 17 of 18 patients; the other patient required flap closure. Of the 25 patients with infection, 19 had irrigation and 6, closure with flaps primarily. In the group of infected patients, 17 of the 19 who received irrigation also had internal mammary artery bypass grafting. Irrigation failed in 15 (88.2%) of these 17 patients, and salvage was accomplished with muscle flap closure. All 6 patients with infection who were closed primarily with muscle flaps had a successful outcome. Hospitalization averaged 10.2 days when muscle flaps were used primarily and 14.3 additional days for unsuccessful irrigation. When irrigation was successful, the hospital stay averaged 11.2 days. CONCLUSIONS: Catheter irrigation should be reserved for patients without infection or patients with infection but without internal mammary artery bypass grafts in whom dehiscence occurs less than 1 month after sternotomy. All others should have closure with muscle flaps.

Anti-Bacterial Agents↗

Snake bite experience at Pakistan Institute of Medical Sciences.

We reviewed 40 cases of snake bite seen from January, 1996 to December, 1996. Most of the cases survived uneventfully but many developed complications which were either haematologic, (23 patients) or neurological (5 patients). Appropriate treatment was offered in every case. Polyvalent antisnake venom was administered to 30 patients (75%). Premedication used was steroids and antihistamines to prevent anaphylactic reactions. Antifibrinolytic therapy (tranxemic acid) was given to every bleeding patient. The species of offending snake could be recognized in one patient while in all others, it was not possible due to night time incidence and poor description by the patient.

Adolescent↗