Biomedical subjects

A R Qureshi

Publications and source records attributed to A R Qureshi.

At least 19 recordsLinked to original sources

PubMed2006

Human liver sinusoidal endothelial cells induce apoptosis in activated T cells: a role in tolerance induction.

BACKGROUND: The liver may have a role in peripheral tolerance, by serving as a site for trapping, apoptosis and phagocytosis of activated T cells. It is not known which hepatic cells are involved in these processes. It was hypothesised that liver sinusoidal endothelial cells (LSEC) which are strategically placed for participation in the regulation of sinusoidal blood flow, and express markers involved in recognition, sequestration and apoptosis, may contribute to peripheral tolerance by inducing apoptosis of activated T cells. METHODS: By using immunoassays and western blot analysis, the fate of activated T cells when incubated with human LSEC isolated from normal healthy livers was investigated. RESULTS: Evidence that activated (approximately 30%) but not non-activated T cells undergo apoptosis on incubation with human LSEC in mixed cell cultures is provided. No difference in the results was observed when unstimulated and cytokine-stimulated LSEC were used. T cell-LSEC contact is required for induction of apoptosis. Apoptosis induced by LSEC was associated with caspase 8 and 3 activity and strong expression of the proapoptotic molecule Bak. Transforming growth factor beta (TGFbeta) produced constitutively by LSEC is partly responsible for the caspase-induced apoptosis, as neutralising antibodies to TGFbeta markedly attenuated apoptosis, up regulated the antiapoptotic molecule Bcl-2 and partially blocked caspase-3 activity. CONCLUSION: These findings broaden the potential role of LSEC in immune tolerance and homeostasis of the immune system. This study may provide insight for exploring the mechanisms of immune tolerance by liver allografts, immune escape by some liver pathogens including hepatitis C and pathogenesis of liver diseases.

Antibodies↗

PubMed2006

Are insulin-like growth factor and its binding proteins 1 and 3 clinically useful as markers of malnutrition, sarcopenia and inflammation in end-stage renal disease?

INTRODUCTION: Malnutrition is common in end-stage renal disease (ESRD) and affects both morbidity and mortality. The growth hormone-dependent insulin-like growth factor (IGF)-I may be a good marker of malnutrition because of its short half-life. In the present study, we investigate the influence of decreasing residual renal function as well as of chronic inflammation on the IGF system to assess its usefulness in this patient group. PATIENTS AND METHODS: Cross-sectional analysis of 220 ESRD patients (140 males) with a mean age of 52+/-1 years. Biochemical analyses of insulin, IGF-I, IGFBP-1, IGFBP-3, IL-6, high sensitivity (hs)-CRP and other routine markers. Malnutrition status was recorded using subjective global assessment (SGA), body mass index, estimated protein intake from nitrogen appearance (nPNA), handgrip strength (HGS) and insulin resistance (HOMA-IR). Dual energy X-ray absorptiometry was used to assess body composition. RESULTS: Both IGF-I and IGFBP-1 showed significant and opposite correlations with most markers of nutritional status, including SGA (rho=-0.29 and 0.27; P<0.001), nPNA (rho=0.18 and -0.22; P<0.05), S-creatinine (rho=0.19 and -0.19; P<0.01) and HGS (rho=0.21 and -0.25; P<0.01). IFG-I was strongly correlated with IGFBP-3 (rho=0.62; P<0.001) and inversely correlated with IGFBP-1 (rho=0.44; P<0.001). Both IGF-I and IGFBP-3, but not IGFBP-1, were significantly correlated with age (rho=-0.25 for IGF-I and -0.35 for IGFBP-3; P<0.001) and hsCRP (rho=-0.21 and -0.32; P<0.01). In multivariate analysis, SGA and s-albumin were independent predictors of both IGF-I and IGFBP-1. CONCLUSION: Both IGF-I and IGFBP-1 appear to correlate well with markers of protein-energy malnutrition and sarcopenia. However, IGF-I is also influenced by age, whereas IGFBP-1 is influenced by glucose metabolism. IGFBP-3 does not correlate with nutritional status in ESRD, perhaps because of a strong association with inflammation.

Age Factors↗

PubMed2006

Elevated resistin levels in chronic kidney disease are associated with decreased glomerular filtration rate and inflammation, but not with insulin resistance.

In the present study, we explore the role of decreased renal function and a genetic polymorphism on the recently discovered protein resistin, apparently able to inhibit hepatic insulin action in mice. We also investigate possible links with inflammation and the insulin resistance present in patients with chronic kidney disease (CKD). This is a post hoc, cross-sectional study comparing 239 prevalent CKD patients with varying degrees of renal function impairment with an age- and gender-matched randomly selected control group of 25 individuals. Glomerular filtration rate (GFR) was estimated by the mean of urea and creatinine clearance (24-h urine samples) (n=204) or by iohexol clearance (n=60). Plasma analysis of blood lipids, insulin, glucose, inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, vascular cellular adhesion molecule, intercellular adhesion molecule) and resistin (kit from LINCO Research, St Charles, MS) was performed using commercially available assays or routine methods. Insulin resistance was estimated by quantitative insulin-sensitivity check index (QUICKI) and homeostasis model assessment for insulin resistance (HOMA-IR) and body composition by dual-energy X-ray absorptiometry. Genotyping of a C/G promoter single nucleotide polymorphism (n=168) at position -180 of the resistin gene was performed by PyroSequencing. Serum levels of resistin were markedly elevated in the CKD patients with both advanced (39.9+/-1.3 ng/ml) and mild to moderate (23.2+/-1.0 ng/ml) renal function impairment, as compared to controls (8.5+/-0.7 ng/ml; P<0.001). In a multiple linear regression model in patients (adjusted r(2)=0.60), only GFR (beta=3.4; P<0.0001), lean body mass (beta=2.2; P<0.001) and the inflammatory markers were independently associated with circulating resistin levels. There was a weak but significant impact of -180 C/G genotype on plasma levels of resistin (median 43.0+/-2.4 ng/ml in CC, 37.5+/-2.0 ng/ml in CG, and 41.1+/-4.9 ng/ml in GG; P<0.05). Univariate analysis of non-diabetic patients and controls showed that serum resistin was associated with markers of glucose metabolism. However, in a multiple regression model, resistin, as well as all the measured markers of inflammation, was only associated with insulin resistance if GFR was not taken into account. Circulating resistin levels are strongly associated with both GFR and inflammatory biomarkers in CKD. As the significant relationship between plasma resistin levels and insulin resistance was lost following the correction for GFR, resistin is not a likely mediator of insulin resistance in patients with CKD. Renal function is an important factor to take into account in clinical studies relating insulin sensitivity to inflammatory biomarkers in CKD as well as in patients with diabetes mellitus, who often have an impaired renal function.

Adult↗

PubMed2006

Plasma pentosidine and total homocysteine levels in relation to change in common carotid intima-media area in the first year of dialysis therapy.

BACKGROUND: Homocysteine and advanced glycation end-products (AGEs), which accumulate in chronic kidney disease (CKD), are recently proposed cardiovascular risk factors. In this study, we evaluated the association between changes in calculated intima media (cIM) area of the common carotid artery during the first year of dialysis therapy and plasma total homocysteine (tHcy) level as well as circulating AGEs such as plasma pentosidine level. METHODS: We studied 63 CKD patients (38 males) aged 52 +/- 12 years at a time-point close to start of dialysis treatment and after 12 months of dialysis treatment (41 on peritoneal and 22 on hemodialysis). The tHcy and plasma pentosidine levels were measured by HPLC. Change in cIM area was evaluated by non-invasive B mode ultrasonography. Malnutrition was assessed by subjective global assessment (SGA). RESULTS: At basal, 70% of the patients had carotid plaques, 32% had symptomatic CVD, 38% had malnutrition, 30% had inflammation (CRP > or = 1 mg/dl) and 23% had diabetes mellitus, respectively. At baseline, the mean plasma pentosidine levels were similar in the patients with and without carotid plaques (36 +/- 21 vs 36 +/- 19 pmol/mg albumin, respectively), whereas the median plasma tHcy was significantly lower in the patients with carotid plaques than in the patients without carotid plaques (32 +/- 21 vs 52 +/- 42 pmol/l, p < 0.01, respectively). The prevalence of hyperhomocysteinemia (tHcy level > 13.7 micromol/l) was 95%. In univariate analysis, the change in cIM area during the first year of dialysis was significantly correlated with basal plasma pentosidine level (p = 0.31, p = 0.01), but not with basal tHcy (p = -0.11). However, neither pentosidine nor tHcy levels were correlated with cIM area at basal or at 12 months. In a stepwise multiple regression model, age and plasma pentosidine content, but not the tHcy level, associated with changes in the cIM area. CONCLUSION: Progression of atherosclerosis, as indicated by changes in carotid intima-media area during the course of dialysis treatment, was associated with pentosidine, but not with tHcy, levels at baseline in these CKD patients. This suggests that the accumulation of AGEs in CKD patients may have a role in the pathogenesis of CVD in these patients. Since almost all CKD patients have hyperhomocysteinemia, this finding, however, does not exclude a role ofhomocysteine as a risk factor for CVD in CKD patients.

Adult↗

PubMed2005

Peroxisome proliferator-activated receptor gamma polymorphisms affect systemic inflammation and survival in end-stage renal disease patients starting renal replacement therapy.

BACKGROUND: Inflammation may contribute to the markedly increased cardiovascular morbidity and mortality in end-stage renal disease (ESRD). However, the prevalence of inflammation varies in different ESRD populations. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is an important nuclear signaling protein that may regulate inflammatory response, and recent studies have revealed genetic polymorphisms that have significant effect on PPAR-gamma signaling. The aim of this study was to clarify whether the PPAR-gamma 161C/T and PPAR-gamma2 Pro12Ala single-nucleotide polymorphisms (SNPs) influence the inter-individual variance of inflammation and mortality in ESRD patients. METHODS: The present prospective study included 229 incident Caucasian ESRD patients (62% males) just prior to starting renal replacement therapy and 207 healthy controls (62% males). Blood samples were taken for measuring systemic inflammatory (CRP, TNF-alpha, IL-6) and nutritional (S-albumin) parameters. The presence of diabetes mellitus, malnutrition (subjective global assessment (SGA)) and cardiovascular disease (CVD) were also assessed. Genotyping of the two PPAR-gamma SNPs was performed using Pyrosequencing. During follow-up (1621+/-63 days), both all-cause and CVD-mortality were investigated. RESULTS: ESRD patients had a higher prevalence of both the PPAR-gamma 161 CC and PPAR-gamma2 Pro12Pro genotypes than the general population (p<0.01). Whereas the Pro12Pro genotype was associated with higher median serum levels of both hs-CRP (p<0.05) and TNF-alpha (p<0.01) the 161CC genotype was associated with a significantly higher (6.6 mg/L versus 3.3 mg/L; p<0.01) median hs-CRP level. Following adjustment for age, gender, SGA and CVD a significantly higher mortality rate was observed in patients with the Pro12Pro genotype. CONCLUSION: This study demonstrates significant differences in PPAR-gamma genotype distribution between ESRD patients and healthy controls. Furthermore, as the PPAR-gamma2 Pro12Pro genotype was associated with both higher levels of biomarkers of inflammation as well as shorter survival, genetic polymorphisms seem to play a role in determining systemic inflammatory status and outcome in this patient group.

Adult↗

PubMed2001

Acute effects of peritoneal dialysis solutions on appetite in non-uremic rats.

BACKGROUND: Standard peritoneal dialysis (PD) solutions may contribute to anorexia in PD patients due to the peritoneal absorption of glucose from the dialysate, abdominal discomfort and other factors. New PD solutions containing alternative osmotic agents, neutral pH and bicarbonate as buffer were recently developed. To test the effect of these solutions on appetite, we investigated how intraoral (IO) intake of sucrose via an IO cannula was influenced by intraperitoneal (IP) infusion of different PD solutions in an appetite model in rats. METHODS: The IO intake was measured in male Wistar rats after an IP dwell of 30 and 120 minutes with the following PD solutions: 1.36%, 2.27% and 3.86% glucose based and lactate buffered solutions (D); 1.36%, 2.27% and 3.86% glucose based and bicarbonate/lactate buffered solutions (P); 7.5% icodextrin based solution (E); 1.1% amino acid-based solution (N); and, 2.5% glucose-based lactate-buffered solution (GB), using sham injection (injection without infusion) as control. Prior to the tests, rats were provided with an IO cannula, and were trained for two weeks until the rate of IO intake had stabilized. RESULTS: The D and N solutions inhibited IO intake. For the D solutions, the degree of appetite suppression was higher with the higher concentration of glucose. P 3.86%, but not P 1.36% and P 2.27% solutions, inhibited the IO intake. However, a comparison of the degree of appetite inhibition between D and P showed less inhibition with P 1.36%, 2.27% and 3.86% solutions than with corresponding D solutions. The E solution did not seem to suppress appetite. Finally, no significant difference in IO intake was found between rats given GB 2.5% and D 2.27%. CONCLUSIONS: In this appetite model in rats, the measurement of IO intake after the IP infusion of different dialysis solutions showed that (1) N and D solutions may reduce appetite, and for the D solutions the degree of appetite inhibition was related to the dialysate concentrations of glucose; (2) the P solutions had less impact on appetite than the D solutions; (3) the E solution had no impact on appetite during the short dwells of 30 and 120 minutes. The demonstrated differences between the different solutions appear to be due to different concentrations, and type, of nutrients used as osmotic agent (glucose, amino acids, icodextrin) or buffer (lactate), although differences in dialysate pH, tonicity and concentration of glucose degradation products also may be important. The present studies suggest a possible positive effect on appetite by using bicarbonate/lactate buffered solutions instead of lactate buffered solutions.

Administration, Oral↗

PubMed2000

Hyperhomocysteinemia, nutritional status, and cardiovascular disease in hemodialysis patients.

BACKGROUND: Hyperhomocysteinemia, cardiovascular disease (CVD), and malnutrition are common in patients with end-stage renal disease (ESRD). This study was designed to assess possible relationships between total plasma homocysteine (tHcy), nutritional status, and ischemic CVD. METHODS: We performed a cross-sectional study in 117 unselected patients on maintenance hemodialysis (HD) treatment, among whom there was a high prevalence of malnutrition (56%), as assessed by the subjective global nutritional assessment (SGNA), and a high prevalence of CVD (60%), and prospectively, we followed-up the overall mortality for four years. RESULTS: The level of tHcy was elevated in 95% of the HD patients, and that of total plasma cysteine (tCys) was also significantly elevated, while the plasma concentrations of methionine (Met), serine (Ser), and taurine (Tau) were significantly lower than those in healthy controls. The 65 patients who were malnourished according to the SGNA score had significantly lower levels of serum albumin (SAlb), plasma IFG-1 (p-IGF-1), tHcy, tCys, and Met than the 52 patients with normal nutritional status, whereas the levels of Ser, Tau, plasma folate, and vitamin B12 were similar in the two groups. The prevalence of malnutrition was 30% in the 47 patients without CVD and was significantly higher (70%, P < 0.001) in the 70 patients with CVD, who also had lower tHcy, SAlb, plasma IGF-1, serum creatinine (SCr), and blood hemoglobin. The tHcy levels were positively correlated with SAlb, Met, tCys, and SCr. Stepwise, multiple-regression analysis showed that tCys, SAlb, and normalized protein equivalent of nitrogen appearance (nPNA), an indicator of protein intake, were independent predictors of tHcy. The patients with tHcy <24 micromol/L (median value) had a significantly worse four-year survival than those with a higher tHcy (> or =24 micromol/L). CONCLUSIONS: Our results demonstrate that most of HD patients have grossly elevated tHcy levels, but that the absolute level appears to be dependent on nutritional status, protein intake, and SAlb. The results also suggest that the lower tHcy levels in patients with CVD than in those without CVD may be related to the higher prevalence of malnutrition and hypoalbuminemia in the CVD patients. This is also in accordance with our observation that the patients with lower tHcy had a worse survival rate than those with higher tHcy, considering that malnutrition is a strong risk factor for mortality and that CVD is the most common cause of death in ESRD patients.

Adult↗

PubMed2000

Hand-grip muscle strength, lean body mass, and plasma proteins as markers of nutritional status in patients with chronic renal failure close to start of dialysis therapy.

We studied 115 patients (69 men, 46 women) with chronic renal failure (CRF) aged younger than 70 years close to the start of dialysis therapy to assess the prevalence of malnutrition and study the relationship between various nutritional parameters in these patients. Nutritional status was classified by means of subjective global assessment. Anthropometric measurements (AMs) were performed, and hand-grip strength (HGS) was measured using the Harpenden dynamometer. Body composition, including lean body mass (LBM), was evaluated by dual-energy x-ray absorptiometry (DXA), and LBM was also estimated by means of AMs and creatinine kinetics (CK). The mean age of the patients was 52 +/- 12 years, and creatinine clearance was 9 +/- 3 mL/min. Malnutrition was seen in 53 patients (48%). As expected, malnourished patients differed in several aspects from well-nourished patients. LBM (estimated by all methods), fat mass (FM), HGS, creatinine clearance, and transthyretin and vitamin A levels were less in malnourished patients, whereas serum albumin levels did not differ. Estimates of LBM by means of DXA, AMs, and CK correlated well with each other. Although DXA and AMs gave similar mean values, LBM was an average of 8 kg less estimated by means of CK, and Bland-Altman plots showed the best agreement between AMs and DXA. HGS showed a strong correlation to LBM (regardless of method) in both men and women. Serum albumin level was not related to HGS or LBM, whereas significant correlations were found between serum albumin level and albumin losses in urine, C-reactive protein (CRP) level, and creatinine clearance. Multiple logistic regression showed that low HGS, low percentage of FM, female sex, and high serum CRP levels were independent factors associated with malnutrition, whereas serum albumin level and percentage of LBM did not reach statistical significance. In conclusion, the present study shows a high prevalence of malnutrition in predialysis patients with CRF and suggests that HGS is a reliable, inexpensive, and easy-to-perform nutritional parameter in patients with CRF. Conversely, serum albumin level seems to be a poor nutritional marker in patients with advanced CRF.

Blood Proteins↗

PubMed1999

Physiological saline is not a biocompatible peritoneal dialysis solution.

UNLABELLED: We have previously demonstrated that daily exposure to dialysis fluid results in significantly increased peritoneal lymphatic flow. In this study, we investigated if daily intraperitoneal infusion of saline (isotonic, glucose free) could cause similar changes. METHODS: Sixteen male SD rats received daily infusion (i.p.) of 20 ml saline for ten days (Saline group). Twenty-four hours after the last infusion, a 4 hour dwell study using 25 ml 3.86% glucose dialysis solution with frequent dialysate and blood sampling was done in each rat as well as in rats which did not receive daily infusion (Control, n=8). Radiolabeled human albumin (RISA) was added to the solution as an intraperitoneal volume marker. Radioactivity, glucose, urea, sodium, and potassium were measured for each sample. In a separate study, the RISA absorption to peritoneal tissue was also determined. RESULTS: The net ultrafiltration was significantly decreased in the daily infusion group (p<0.05). However, the apparent volume at 3 minutes of the dwell was markedly increased; this was due to a significant increase in the RISA binding (1.5-12.0% in the Saline group vs. 0.45-1.12% in the Control group) to peritoneal tissues as assessed by measurement of RISA recovery at 3 min of the dwell. This resulted in a significant overestimation both of the intraperitoneal volume (IPV) at 3 min and the (apparent) fluid absorption rate (as estimated by the transport of RISA out of peritoneal cavity): 0.087+/-0.026 ml/min in the Saline group vs. 0.052+/-0.007 ml/min in the Control group, p<0.001. The direct lymphatic flow as estimated by the clearance of RISA to plasma (which should not be affected by the RISA binding) also increased markedly (0.021+/-0.005 ml/min in the Saline group vs. 0.008+/-0.001 ml/min in the control group). There was no significant difference in the D/P values for small solutes (urea, sodium, potassium, urate) and D/D0 for glucose between the two groups. CONCLUSIONS: 1) Daily infusion of physiological saline into peritoneal cavity may increase the peritoneal lymphatic flow; 2) The significant (apparent) increase in IPV shortly after infusion may suggest increased RISA binding to peritoneal tissues (which may be related to the damage of the tissues, and results in overestimation of the peritoneal fluid absorption rate); 3) Saline is not a biocompatible peritoneal dialysis solution, and should therefore not be used as a control or flush solution.

Absorption↗

PubMed1998

Factors predicting malnutrition in hemodialysis patients: a cross-sectional study.

Signs of protein-energy malnutrition are common in maintenance hemodialysis (HD) patients and are associated with increased morbidity and mortality. To evaluate the nutritional status and relationship between various parameters used for assessing malnutrition, we performed a cross-sectional study in 128 unselected patients treated with hemodialysis (HD) thrice weekly for at least two weeks. Global nutritional status was evaluated by the subjective global nutritional assessment (SGNA). Body weight, skinfold thicknesses converted into % body fat mass (BFM), mid-arm muscle circumference, hand-grip strength and several laboratory values, including serum albumin (SA1b), plasma insulin-like growth factor I (p-IGF-I), serum C-reactive protein (SCRP) and plasma free amino acids, were recorded. Dose of dialysis and protein equivalence of nitrogen appearance (nPNA) were evaluated by urea kinetic modeling. The patients were subdivided into three groups based on SGNA: group I, normal nutritional status (36%); group II, mild malnutrition (51%); and group III, moderate or (in 2 cases) severe malnutrition (13%). Clinical factors associated with malnutrition were: high age, presence of cardiovascular disease and diabetes mellitus. nPNA and Kt/V(urea) were similar in the three groups. However, when normalized to desirable body wt, both were lower in groups II and III than in group I. Anthropometric factors associated with malnutrition were low body wt, skinfold thickness, mid-arm muscle circumference (MAMC), and handgrip strength. Biochemical factors associated with malnutrition were low serum levels of albumin and creatinine and low plasma levels of insulin-like growth factor 1 (IGF-1) and branched-chain amino acids (isoleucine, leucine and valine). The serum albumin (SAlb) level was not only a predictor of nutritional status, but was independently influenced by age, sex and SCRP. Plasma IGF-1 levels also reflected the presence and severity of malnutrition and appeared to be more closely associated than SAlb with anthropometric and biochemical indices of somatic protein mass. Elevated SCRP (> 20 mg/liter), which mainly reflected the presence of infection/inflammation and was associated with hypoalbuminemia, was more common in malnourished patients than in patients with normal nutritional status, and also more common in elderly than in younger patients. Plasma amino acid levels, with the possible exception of the branched-chain amino acids (isoleucine, leucine, valine), seem to be poor predictors of nutritional status in hemodialysis patients.

Adult↗

PubMed1997

Dioctyl sodium sulphosuccinate increases net ultrafiltration in peritoneal dialysis.

BACKGROUND: The surface-active substance dioctyl sodium sulphosuccinate (DSS) has been reported to increase the peritoneal clearances of urea and creatinine. This study investigated the effects of DSS on the fluid and solute transport characteristics of the peritoneum. DESIGN: A 4-h single-dwell experiment session of peritoneal dialysis using 25 ml of 3.86% glucose dialysis solution with an intraperitoneal volume maker was performed in 16 male Sprague-Dawley rats. In eight rats, 0.005% (50 p.p.m.) DSS was added to the dialysis fluid. No DSS was given to the other eight rats (control group). The transport of fluid, glucose, potassium, sodium, urea, phosphate and urate were analysed. RESULTS: There was a significant increase in the intraperitoneal volume in the DSS group. At 240 min, the drain volume in DSS group (33.0 +/- 2.9 ml) was significantly higher compared to the control group (28.8 +/- 2.1 ml, P < 0.01). This increase in the drain volume was mainly due to a decrease in peritoneal fluid absorption rate in the DSS group (0.040 +/- 0.013 ml/min) as compared to the control group (0.054 +/- 0.010 ml/min, P < 0.05). There was no significant difference in the diffusive permeability and sieving coefficient for the small solutes between these two groups. However, the clearances for urea and sodium were higher in the DSS group, mainly due to the increase in the dialysate volume. CONCLUSION: Our results suggest that DSS significantly increases the net ultrafiltration of peritoneal dialysis. This effect, which was mainly due to a decrease in the fluid absorption rate, contributed to the increased clearances for urea and sodium. DSS did not alter the diffusive permeability and sieving coefficient for the small solutes.

Animals↗

PubMed1996

Community acquired and post-transfusion hepatitis C "is there a difference?".

We analyzed 77 consecutive hepatitis C antibody positive patients to compare the history, laboratory data and histological features of community acquired (CA) and post-transfusion (PT) hepatitis C. Forty-six patients had "CA" and 31 "PT" hepatitis C. Mean age in both groups was same (45.67 vs 46 years). Male to female ratio was 2:1 in the CA group and 1:2.4 in the PT group. Mean duration between jaundice and first presentation was 8.9 years in the CA group and the mean duration between transfusion and first presentation was 9.8 years in PT group. No significant difference was found between two groups in the laboratory data. Liver biopsy was done in 32 patients (19 CA and 13 PT group). Mean histological score for disease activity was 9.3 in both groups, although more (68%) patients in the CA group had cirrhosis with chronic active hepatitis, (CAH) as compared to the PT (54%) group. Hepatitis C is an important cause of CA hepatitis. PT hepatitis C is more common in females because of increased likelihood of receiving transfusion for obstetric and gynaecological reasons. There is no significant difference in the laboratory and histological features between CA and PT hepatitis C.

Adult↗

PubMed1995

Thrombolytic therapy in acute myocardial infarction in Pakistan.

To characterize features of acute myocardial infarction (AMI) in a Pakistani population, and assess the role of thrombolysis in our country, we studied 194 consecutive admitted patients with enzyme positive AMI. Males were affected three times more frequently; women, although affected less, had a higher incidence of complications than men. Premature coronary artery disease (CAD) was present in 50% patients presenting with AMI. An unusually high incidence of anterior wall myocardial infarction (39%) was seen. Complications were frequent with a predominance of LV failure symptoms. Cardiogenic shock was associated with a very high mortality, in excess of 93%. Streptokinase (SK) was administered in 60% patients with suspected transmural AMI. A statistically significant reduction in mortality was seen in the group that received SK (15.2%) compared to those who did not receive SK (24.7%), (p = < 0.05).

Adult↗

PubMed1994

Tryptophan and its metabolites in patients on continuous ambulatory peritoneal dialysis and following renal transplantation.

Plasma tryptophan (Trp) concentration in its total (TTrp) and non-protein-bound free form (FTrp) and its metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) as well as muscle Trp contents (MTrp) were studied in 12 uraemic patients undergoing continuous ambulatory peritoneal dialysis (CAPD), 10 renal transplant patients, and 10 healthy control subjects. The CAPD patients exhibited signs of muscle weakness, as assessed by dynamometry, and signs of protein malnutrition with a decreased ratio of alkali-soluble protein relative to DNA in muscle as well as low serum albumin concentration. In the uraemic patients TTrp was markedly reduced, whereas in the transplant patients it did not differ from the controls. The FTrp, which was separated by the process of equilibrium dialysis, was less in the uraemic (P < 0.01) as well as transplant patients (P < 0.01) than in the controls. The plasma FTrp/TTrp ratio was increased in the uraemic patients (40 +/- 8%) but less in the transplant patients (16 +/- 4%), as compared to the controls (25 +/- 5%). The uraemic patients had increased plasma concentrations of 5-HIAA, whereas this metabolite could not be found in the plasma of renal transplant patients and healthy controls. MTrp was increased by an average of 33% in the uraemic patients whereas it did not differ between the transplant patients and the controls. The results indicate that the abnormal Trp metabolism in uraemic patients is to a large extent corrected by a successful renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Nutritional status, muscle composition and plasma and muscle free amino acids in renal transplant patients.

To investigate the effects of renal transplantation (Rtx) on the nutritional status, muscle composition and the plasma and muscle free amino acid (AA) pattern, three groups of altogether 30 renal transplant patients (group I n = 10; 46 +/- 14 [SD] days after Trx), (group II n = 10; 13 +/- 2 months after Rtx) and (group III n = 10; 9 +/- 2 years after Rtx) underwent anthropometric measurements, blood sampling and percutaneous muscle biopsy. The immunosuppressive therapy consisted of prednisolone, azathioprine and cyclosporine-A. The results were compared with data from age-matched healthy subjects. Renal function was impaired in groups I, II and III. Serum albumin was decreased in groups I and II. The patients of group II had an increased percentage of body fat, triceps and subscapular skin folds and total sum of skinfolds. In group I the ratio alkaline-soluble protein (ASP) to DNA, which is a sensitive index of protein depletion on the cellular level, was decreased. Muscle magnesium content was decreased whereas the muscle DNA, sodium and chloride contents were increased. The mean plasma concentration of most essential AA (EAA) was essentially normal except phenylalanine which was increased in groups I and II.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Synthesis and use of an isoform-specific affinity matrix in the purification of glutathione S-transferases from the housefly, Musca domestica (L.).

Glutathione may be linked to an agarose matrix which has been activated by treatment with epichlorhydrin. The resulting resin displayed group selectivity for the glutathione S-transferases of the housefly Musca domestica (L). The isoenzymes of low isoelectric point, which have little activity with substrates other than 1-chloro-2,4-dinitrobenzene, bound strongly to this matrix and were eluted with 10 mM glutathione at pH 7.4. On the other hand, the group of isoenzymes of higher isoelectric point, showing activity with other substrates such as 3,4-dichloronitrobenzene, did not bind. These isoenzymes did bind to a sulfobromophthalein-glutathione conjugate immobilized on agarose and could be eluted with 5 mM sulfobromophthalein at pH 7.4. The immobilized glutathione resin bound rat liver glutathione S-transferase subunits from all three molecular weight classes.

Animals↗

PubMed1989

Determination of free amino acids in biological samples: problems of quantitation.

An automatic on-line high-performance liquid chromatographic method was developed to study the effects of various precipitating agents and delayed deproteinization procedures on the estimation of plasma levels of amino acids. The optimized method for analysis is based on pre-column derivatization with o-phthalaldehyde in the presence of 2-mercaptoethanol. The separation of 25 amino acids is accomplished within 45 min on a 5-microns C18 column, using a multi-step gradient with two solvents. The method is sensitive and reproducible, and the relationship between the fluorescence intensity and concentration is linear for each amino acid over a wide concentration range.

Adult↗

PubMed1989

Quantitation of free amino acids in plasma and muscle samples in healthy subjects and uremic patients by high-performance liquid chromatography and fluorescence detection.

An automatic on-line high-performance liquid chromatographic (HPLC) method is developed to quantitate free amino acids in the biological samples. The method is based on pre-column derivatization of amino acids with orthophthalaldehyde (OPA) in presence of 2-mercaptoethanol (2-ME). The derivatized amino acids were separated on a 5 micron C18 column using a multi-step gradient with two solvents and the detection was made at Eex = 340 nm and Eem = 450 nm. The results were highly reproducible with a relative standard deviation (RSD) between 0.5-2% for all amino acids. Each chromatographic run was completed within 40 min to separate 24 amino acids. The optimized method was applied to evaluate the levels of free amino acids in plasma and muscle samples of eight healthy subjects and 13 uremic patients under fasting conditions.

Adult↗