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Biomedical subjects

A Khalil

Publications and source records attributed to A Khalil.

At least 109 records · Page 6Linked to original sources

Platelet aggregation and lipid profile in offsprings of young ischemics.

OBJECTIVE: To study the platelet aggregation and lipid profile in offsprings of young ischemic parents. DESIGN: Cross sectional. SETTING: Hospital based. METHODS: 40 adults under 45 years of age with proven CHD and their 50 offsprings comprised the study group. In the control group, 40 age matched adults with normal maximal treadmill test and their 50 off springs were included. All were screened for lipid profile and platelet aggregation. RESULTS: Platelet aggregation was significantly elevated in adults with CHD (44.0 +/- 15.5%) compared to controls (32.22 +/- 9.1%). Children of CHD adults also had significantly elevated aggregation (34.9 +/- 12.5%) compared to control offsprings (27.8 +/- 9.9%). Adult CHD subjects had significantly elevated serum cholesterol, LDL-cholesterol (LDL-C) and atherogenic index compared to control adults. The children in both groups had similar lipid profiles. CONCLUSION: Platelet aggregation is enhanced in offsprings of young ischemics. The potential of this index as a marker for early development of CHD needs to be explored.

Adolescent↗

Cytokine gene expression during experimental Escherichia coli pyelonephritis in mice.

PURPOSE: We studied nine inflammatory and immunoregulatory cytokines in acute pyelonephritis and urethral obstruction in mice to better understand the processes underlying kidney inflammation and scarring. MATERIALS AND METHODS: Experimental acute pyelonephritis was established in Bki NMRI outbred mice by bladder inoculation of Escherichia coli, followed by 6 h urethral obstruction. The numbers of cytokine mRNA expressing cells for interleukin-1 (IL-1), IL-4, IL-6, IL-10, IL-12, tumor necrosis factor alpha (TNF-alpha), TNF-beta, transforming growth factor beta (TGF-beta) and interferon gamma (IFN-gamma) were determined in the kidneys and spleens from the infected, non-infected but obstructed and untouched mice using in situ hybridization with radio-labelled oligonucleotide probes at 12 h, 48 h and 6 d after release of the urethral obstruction. RESULTS: Kidney cell expression of IL-1, IL-6 and TNF-alpha mRNA was observed already at 12 h and persisted on day 6 in the infected animals. A significant proinflammatory cytokine response occurred also in the non-infected obstructed animals, albeit later and at lower levels. A marked increase of IL-4, IL-10, TGF-beta and IFN-gamma mRNA producing cells was also found in the kidneys of these two groups again with higher levels in the infected animals. Very high numbers of splenocytes expressing mRNA for IL-1 were observed especially in the infected animals. A high proportion of splenocytes further expressed mRNA for IL-6, TNF-alpha, IL-4, IL-10, IFN-gamma and TGF-beta, again with highest numbers in the infected group of animals. CONCLUSIONS: The present study extends previous knowledge about the local and systemic cytokine expression profiles during acute pyelonephritis and after urethral obstruction. Of particular interest was the marked kidney cell expression of mRNA for TGF-beta, presumed to be important both for obstructive and post-infectious renal scarring.

Acute Disease↗

Diagnostic embryoscopy and fetoscopy in the first trimester of pregnancy.

Embryoscopy is the examination of the embryo at 9-10 weeks' gestation through the intact membranes by introducing an endoscope into the exocoelomic space transcervically or transabdominally. This is likely to remain confined to the management of early pregnancy in selected families affected by recurrent genetic syndromes with recognizable external fetal abnormalities. The procedure-related risk of fetal loss is around 12 per cent. Fetoscopy is the examination of the fetus after 11 weeks' gestation. This is performed transabdominally in the amniotic fluid. The technique has evolved with the miniaturization of the optical device by using fibre-optics technology. This procedure is likely to find new applications with the development of ultrasound examination at 10-14 weeks' gestation in order to, either confirm, or rule out suspected external fetal abnormalities. Amniocentesis can be performed at the same time. The procedure-related risk is likely to remain below 10 per cent but no accurate figures can be drawn from the literature.

Amniocentesis↗

Cyclosporin A-induced coronary artery vasoconstriction through myogenic and endothelium-dependent mechanisms.

BACKGROUND: The exact mechanism of vascular toxicity of cyclosporin A (CSA) remains unknown. It has been reported that an impairment of endothelium-mediated vascular reactivity may be involved. METHOD AND RESULTS: We studied the response to intracoronary injections of acetylcholine (ACh) (30 ng/kg), adenosine (100 ng/kg), and nitroglycerin (NTG) (1.7 micrograms/kg) before and after intracoronary infusion of CSA (20 mg over 20 minutes) and of L-arginine (10 mg.kg-1.min-1). Experiments were performed on 11 open-chest dogs anesthetized and instrumented for measurements of coronary blood flow (CBF) in the left anterior descending (LAD) and left circumflex (LCx) coronary arteries, left ventricular dP/dt, mean aortic pressure, and coronary sinus pressure. CSA, L-arginine, ACh, adenosine, and NTG were injected into the LAD, and the LCx served as control. The increase in CBF in the LAD with ACh administration averaged 21 +/- 11 mL/min before CSA, 15 +/- 10 mL/min after CSA, and 15 +/- 8 mL/min during L-arginine injection (P = .2). Adenosine caused an increase in CBF in the LAD averaging 20 +/- 10 mL/min before CSA, 10 +/- 8 mL/min after CSA, and 17 +/- 12 mL/min during L-arginine injection (P = .004). NTG caused an increase in CBF in the LAD averaging 21 +/- 10 mL/min before CSA, 13 +/- 11 mL/min after CSA, and 14 +/- 7 after administration of L-arginine (P = .009). CONCLUSIONS: These results suggest that direct intracoronary injection of CSA induces a vasoconstrictive response through endothelium-dependent and myogenic mechanisms. The muscarinic endothelial response was not affected by CSA, whereas the purinergic action of CSA was restored after L-arginine administration.

Acetylcholine↗

Increased susceptibility of low-density lipoprotein (LDL) to oxidation by gamma-radiolysis with age.

The susceptibility to oxidation of freshly isolated LDL from healthy normolipidemic individuals in three age groups was estimated by exposure of LDL to ionizing radiation followed by analyses of vitamin E, TBARS, conjugated dienes, and fluorescent products. The results clearly showed that LDL from elderly subjects was the most susceptible to oxidative damage in vitro. In particular, the greater susceptibility of LDL from elderly subjects in comparison to that from young subjects may be attributed to the much lower (4-fold) concentration of LDL vitamin E in the elderly subjects. The present study reinforces the notion that the susceptibility of LDL to oxidation increases with age.

Adult↗

Effect of L-arginine on metabolic recovery of the ischemic myocardium.

BACKGROUND: The release of nitric oxide is decreased after myocardial ischemia and reperfusion. Whereas the precursor L-arginine can stimulate the release of nitric oxide, its effect on metabolic recovery after myocardial ischemia is unknown. METHODS: To study the effect of L-arginine on metabolic recovery after myocardial ischemia, cardioplegia infusion, and reperfusion, 33 dogs were placed on cardiopulmonary bypass and subjected to a sequence of 30 minutes of normothermic global ischemia, 30 minutes of warm blood cardioplegic arrest, and 30 minutes of reperfusion. A pH probe was inserted in the anterior wall of the left ventricle, and tissue pH was measured throughout the experiment. Coronary blood flow in the left anterior descending coronary artery and the circumflex coronary artery was measured. Blood samples from the coronary sinus were taken to measure blood pH and levels of lactate, creatine kinase, and troponin T. RESULTS: In the control group of 9 dogs, tissue pH averaged 6.4 +/- 0.1, 6.5 +/- 0.1, and 6.8 +/- 0.1 after the end of global ischemia, cardioplegia, and reperfusion, respectively. Tissue pH averaged 6.4 +/- 0.1, 6.6 +/- 0.1, and 6.9 +/- 0.1, respectively, in the experimental group of 9 animals with 2 mmol/L of L-arginine added to the cardioplegic solution. Tissue pH averaged 6.2 +/- 0.1, 6.7 +/- 0.1, 7.1 +/- 0.1, respectively, in the third group of 9 animals that received an additional infusion of L-arginine (10 mg.kg-1.min-1) during reperfusion. Tissue pH recovered faster in groups with L-arginine (p = 0.00001). A hyperemic response of coronary blood flow was shown at reperfusion in animals in the control group only. In 6 dogs, L-NAME (N-nitroarginine methyl ester), an inhibitor of nitric oxide synthesis, was injected and resulted in a slower pH recovery on reperfusion compared with that of animals that received L-arginine. CONCLUSIONS: The addition of L-arginine to the cardioplegic solution and the systemic circulation during reperfusion resulted in a significant increase in coronary blood flow during cardioplegia infusion and in a faster recovery of myocardial tissue pH, possibly by increasing coronary blood flow through the release of nitric oxide.

Animals↗

Epidemiology of adults hospitalized with burns in Karachi, Pakistan.

Burns are a leading cause of adult death in Karachi slums, therefore we reviewed 1 year's logged experience (November 1992 to October 1993) at Karachi's two adult burn units for patient age, sex, burn severity and outcome. Also 47 inpatients were interviewed regarding their circumstances of injury. We grouped these using Haddon's Matrix. The log identified 832 patients. Females (57 per cent) outnumbered males and were younger on average (25.1 vs 27.6 years, P = 0.002). Females had more severe burns than males (57 per cent vs 50 per cent total body surface area (TBSA) burn, P = 0.002). At the unit with outcome data (n = 556), the case fatality was 56 per cent. The estimated adult mortality due to burns in Karachi was 10.2/100 000, 6.8/100 000 and 14.1/100 000 for men and women, respectively. Burns of interviewed patients were most often associated with flames (33/47), but stove bursts caused the most severe injury (52 per cent TBSA). These patients were predominantly young uneducated female houseworkers, clothed in loose attire who were injured during daylight at home around a floor-level stove, unaware of fire safety, and who received no first aid. It was concluded that the high burn severity and case fatality rates demand: (1) preventive measures, such as kitchen sand buckets, safer stove design and placement and education on fire safety and first aid, and (2) risk factor analysis to refine interventions.

Accidents, Home↗

Neovascular tissue in the intertrabecular spaces in eyes with neovascular glaucoma.

AIMS/BACKGROUND: To investigate histological changes in the trabecular meshwork in eyes with neovascular glaucoma. METHODS: Light and electron microscopic studies were carried out on the trabecular meshwork of three enucleated eyes with neovascular glaucoma. The presence and distribution of factor VIII in the trabecular meshwork was assessed using the ABC method. RESULTS: Peripheral anterior synechiae covering the trabecular meshwork were detected in two eyes, which would explain the rise in intraocular pressure. In the third the angle was not completely closed by peripheral anterior synechiae. The spaces between the trabecular beams were lined by a single layer of vascular endothelium, and were filled with red blood cells in this patient. Factor VIII was positively stained in the endothelial cells, lining both these spaces and Schlemm's canal. A basal lamina and microfibrils were detected just beneath the newly formed vascular endothelial cells. CONCLUSION: The neovascular tissue found in the trabecular spaces might be one of the factors responsible for intraocular pressure elevation in eyes with neovascular glaucoma.

Adult↗

Outcome of commercial renal transplantation: two years follow-up.

The results of living non-related renal transplants from India involving unethical exploitation of the donor are inferior. We followed-up 12 patients from our unit who went to a center in Bombay for renal transplantation and compared the results with our local new renal transplant programme. Two-year graft survival was 70% compared to 88% with our new renal transplant program. Also, we emphasised the human side of the problem. We addressed the problem of shortages of organ donation locally because failure to obtain consent from relatives and the need for intensive public education is required to overcome this problem. Finally, Islamic principles and rules that are related to organ transplantation have been discussed in detail, and the main purpose is to enlighten the Western reader.

Adult↗

Ovarian effects upon maternal glucose tolerance.

Ovaries from homozygous diabetic (db/db) female mice were removed and transplanted into the empty left ovarian sacs of normal homozygous (m/m) female mice which had undergone left oophorectomies. To produce controls, the previously removed normal left ovaries were transplanted into the empty left ovarian sacs of other normal (m/m) left oophorectomized females. Glucose tolerance tests were done on the study and control mice before surgery, after surgery, during pregnancy, and after delivery. There were no significant differences in the glucose tolerance test results between study group and controls before or after surgery. However, the study group, when compared to the controls, had a statistically significant glucose intolerance during pregnancy. After delivery, the glucose levels returned to normal. The ovaries from diabetic (db/db) female mice may produce hormones which, by themselves or in concert with the fetal and placental hormones, may produce maternal glucose intolerance during pregnancy.

Animals↗

The temporal and spatial vascular endothelial growth factor expression in retinal vasculogenesis of rat neonates.

Vascular endothelial growth factor (VEGF) has been identified as an endothelial cell-specific mitogen with potent angiogenic properties. VEGF is overexpressed in pathologic angiogenesis observed in tumor growth, rheumatoid arthritis, and retinal angiogenic diseases such as diabetic retinopathy and retinopathy of prematurity. VEGF expression in physiologic angiogenesis, i.e., vasculogenesis, has also been reported in the embryonic organs such as brain, kidney, spleen, and lung. However, the details of VEGF expression in vasculogenesis remain largely unclear. To determine if VEGF contributes to vasculogenesis in the developing tissues, VEGF expression was studied by both immunohistochemistry and in situ hybridization in newborn rat retinas on postnatal days 3, 7, 14, and 30. Vasculogenesis was assessed by both the ink perfusion method and a histologic examination. To identify the cell types of VEGF-expressing cells, immunohistochemistry for cell markers such as glial fibrillary acidic protein and von Willebrand factor was performed. On postnatal days 3 and 7, when retinal vasculogenesis was active, VEGF mRNA and protein(s) were prominently expressed in the ganglion cell and the inner nuclear layers. In rats, as well as humans, these two layers are where the retinal vessels develop, and these two layers depend solely on the retinal vessels. In addition to the ganglion and the inner nuclear layers, VEGF protein(s) were located in the endothelial cells of the developing vessels and the angioblasts, i.e., endothelial precursors. On postnatal day 14, when vasculogenesis became inactive, VEGF mRNA expression markedly decreased. These results indicated that VEGF expression in the developing retinas is temporally and spatially correlated with retinal vasculogenesis.

Animals↗

The relation between expression of vascular endothelial growth factor and breakdown of the blood-retinal barrier in diabetic rat retinas.

In the retinas of streptozotocin-induced diabetic rats, the relationship between the expression of vascular endothelial growth factor (VEGF) and the breakdown of the blood-retinal barrier (BRB) was investigated. VEGF mRNA expression was examined by in situ hybridization and VEGF protein expression was examined by immunohistochemistry. BRB breakdown was immunohistochemically demonstrated by detecting extravasation of albumin. In diabetic retinas, VEGF mRNA was expressed by the following cells: (a) ganglion cells, (b) glial cells such as astrocytes and Muller cells, whose cell processes are closely associated with retinal vessels, (c) smooth muscle cells and pericytes in the vessel walls, and (d) the retinal pigment epithelium. In diabetic retinas, BRB breakdown was immunohistochemically detected, and VEGF protein expression was markedly increased in comparison to that in the control retinas. The rates of both BRB breakdown and VEGF immunoreactivity increased in proportion to the duration of diabetes. In addition, the rate of BRB breakdown was much higher in vessels with VEGF immunoreactivity than in vessels without VEGF immunoreactivity. These findings indicate that VEGF has a major promoting effect on BRB breakdown in simple diabetic retinopathy. VEGF immunoreactivity was distributed throughout all layers of the retinas, and were most prominently observed in the nerve fiber layer, especially near the optic disc and around large vessels. These two regions coincide with the sites wherein BRB breakdown is clinically detected by fluorescein angiography in diabetic patients. Neovascularization in proliferative diabetic retinopathy is also most commonly observed in these two regions. Because VEGF promotes endothelial proliferation, these findings suggest that VEGF plays a role in the budding of retinal neovascularization and, as a result, could induce proliferative diabetic retinopathy.

Animals↗

Metabolic recovery after global myocardial ischemia: effects of blood cardioplegic solutions.

OBJECTIVE: To determine the effect of whole blood cardioplegia (WBC) and a mix of crystalloid in blood (CB) hyperkalemic cardioplegic solutions on recovery of the myocardium following global ischemia. DESIGN: Twenty-one dogs were placed on normothermic cardiopulmonary bypass, and a pH probe was inserted in the anterior wall of the left ventricle. Global myocardial ischemia was obtained by clamping the ascending aorta until a decrease in myocardial tissue pH of 0.4 units from baseline value was obtained, at which time cardioplegic solutions were perfused over 30 mins. The aorta was then unclamped and 30 mins of reperfusion was allowed. RESULTS: The aortic cross-clamping time necessary to decrease myocardial tissue pH 0.4 units from baseline averaged 13 +/- 8 mins. Whereas myocardial tissue pH returned to baseline value (6.9 +/- 0.1) after an average of 24 mins with cold (15 degrees C) and warm (35 degrees C) WBC, it took an average of 48 mins to reach control levels when warm CB solutions were used. Moreover, tissue pH decreased temporarily from 6.97 +/- 0.35 to 6.77 +/- 0.37 (P < 0.05) at initiation of normothermic myocardial reperfusion in cold WBC protected animals, and myocardial pH remained normal in the warm WBC group but remained severely acidic in warm CB animals (6.6 +/- 0.3). CONCLUSIONS: Metabolic recovery after global ischemia was faster with WBC cardioplegic protection. Normothermic blood reperfusion in cold WBC protected animals caused a significant but temporary tissue acidosis.

Animals↗