PubMed Health⌕ Search

Biomedical subjects

A Helmy

Publications and source records attributed to A Helmy.

At least 19 recordsLinked to original sources
PubMed2006

Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome.

Hepatic sinusoidal obstruction syndrome is frequently linked to high-dose chemotherapy/total-body irradiation in recipients of haematopoietic stem cell transplantation, long-term use of azathioprine after organ transplantation and other chemotherapeutic agents. The incidence of hepatic sinusoidal obstruction syndrome varies from 0% to 70%, and is decreasing. Disease risk is higher in patients with malignancies, hepatitis C virus infection, those who present late, when norethisterone is used to prevent menstruation, and when broad-spectrum antibiotics and antifungals are used during and after the conditioning therapy. Hepatic sinusoidal obstruction syndrome presents with tender hepatomegaly, hyperbilirubinaemia and ascites, and diagnosis is mainly clinical (Seattle and Baltimore Criteria). Imaging excludes biliary obstruction and malignancy, but cannot establish accurate diagnosis. Hepatic sinusoidal obstruction syndrome may be prevented by avoiding the highest risk regimens, using non-myelo-ablative regimens, and reducing total-body irradiation dose. Treatment is largely symptomatic and supportive, because 70-80% of patients recover spontaneously. Tissue plasminogen activator plus heparin improves outcome in <30% of cases. Defibrotide, a polydeoxyribonucleotide, is showing encouraging results. Transjugular intrahepatic porto-systemic shunt relieves ascites, but does not improve outcome. Liver transplantation may be an option in the absence of malignancy. Prognosis is variable and depends on disease severity, aetiology and associated conditions. Death is most commonly caused by renal or cardiopulmonary failure.

Animals↗
PubMed2005

Metal-induced oxidative damage in cultured hepatocytes and hepatic lysosomal fraction: beneficial effect of a curcumin/absinthium compound.

OBJECTIVE: Metals undergo redox cycling and there is increasing evidence of free radical generation and oxidative injury in the pathogenesis of liver injury and fibrosis in metal storage diseases. The aim of the present study was to test a natural hepatoprotective compound in metal-induced liver injury. METHODS: Hepatocytes were isolated from Wistar rats by collagenase perfusion method and cultured as such and also with alpha-linolenic acid (LNA)-bovine serum albumin (BSA). Hepatocytes were then cultured with a graded dilution of PN-M001 (100 microg/mL and 200 microg/mL), which is a curcuma/absinthium-containing compound, or sylibin (100 microg/mL) dissolved in dimethyl sulfoxide for 10 min before the addition of metallic salts (iron, copper and vanadium). Lysosomal fractions were prepared for lysosome fragility tests in which beta-galactosidase activity and lactate dehydrogenase (LDH) leakage were measured, as well as oxidative damage tests in the presence of hydrophilic and lipophilic free radical generators. Quenching activity by 1,1-diphenyl-2-picrylhydrazyl (DPPH) was also assessed. RESULTS: Malonildialdehyde accumulation in the medium showed a direct time-course increase with incubation time. Both PN-M001 and sylibin showed a significant protective effect against all challenge metal ions, as expressed by the half inhibition concentration (IC(50)) against lipid peroxidation. However, on a molar ratio, sylibin seemed to be more effective than PN-M001 in Fe-induced peroxidative damage (P < 0.05). Both test compounds, irrespective of the concentration, significantly reduced the LDH and beta-galactosidase concentration in the lysosomal fractions. As compared with untreated lysosomal fractions challenged with the two peroxide radicals generators, either PN-M001 or sylibin exerted significant protection However, PN-M001 was significantly better than sylibin in suppressing acid phosphatase enzyme activity. Both compounds showed comparable and significant DPPH radical-scavenging activity. CONCLUSION: These data support the potential clinical application of curcumin-containing compounds.

Animals↗
PubMed2004

Randomised controlled trial of long term portographic follow up versus variceal band ligation following transjugular intrahepatic portosystemic stent shunt for preventing oesophageal variceal rebleeding.

BACKGROUND/AIMS: Transjugular intrahepatic portosystemic stent shunt (TIPSS) is effective in the prevention of variceal rebleeding but requires invasive portographic follow up. This randomised controlled trial aims to test the hypothesis that combining variceal band ligation (VBL) with TIPSS can obviate the need for long term TIPSS surveillance without compromising clinical efficacy, and can reduce the incidence of hepatic encephalopathy. PATIENTS/METHODS: Patients who required TIPSS for the prevention of oesophageal variceal rebleeding were randomised to either TIPSS alone (n = 39, group 1) or TIPSS plus VBL (n = 40, group 2). In group 1, patients underwent long term TIPSS angiographic surveillance. In group 2, patients entered a banding programme with TIPSS surveillance only continued for up to one year. RESULTS: There was a tendency to higher variceal rebleeding in group 2 although this did not reach statistical significance (8% v 15%; relative hazard 0.58; 95% confidence interval (CI) 0.15-2.33; p = 0.440). Mortality (47% v 40%; relative hazard 1.31; 95% CI 0.66-2.61; p = 0.434) was similar in the two groups. Hepatic encephalopathy was significantly less in group 2 (20% v 39%; relative hazard 2.63; 95% CI 1.11-6.25; p = 0.023). Hepatic encephalopathy was not statistically different after correcting for sex and portal pressure gradient (p = 0.136). CONCLUSIONS: TIPSS plus VBL without long term surveillance is effective in preventing oesophageal variceal rebleeding, and has the potential for low rates of encephalopathy. Therefore, VBL with short term TIPSS surveillance is a suitable alternative to long term TIPSS surveillance in the prevention of oesophageal variceal rebleeding.

Adult↗
PubMed2003

Laparoscopic esophagogastric devascularization in bleeding varices.

BACKGROUND: Bleeding from esophageal varices is the major cause of death in patients with portal hypertension. The ideal surgical procedure should effectively control bleeding and maintain liver function with low rates of encephalopathy. Based on this objective, laparoscopic devascularization of the lower esophagus and upper stomach was studied. METHODS: Eighteen patients were studied prospectively who underwent a laparoscopic esophagogastric devascularization procedure for variceal hemorrhage. The diaphragmatic hiatus and esophagus are dissected. The lower 7 or 8 cm of esophagus is devascularized. Devascularization of the gastric fundus is then accomplished by meticulous dissection and ligation of the short gastric vessels. The hepatogastric ligament is opened, permitting identification and isolation/ligation of the left gastric vessels. The dissection and ligation of the vessels at lesser curvature proceeded up to the diaphragmatic hiatus with devascularization of the external varices from the retroperitoneum or mediastinum at the esophagogastric junction. RESULTS: Mean operating room time was 111 min (range, 80-140 min) (6 emergent/12 elective). Mean blood loss 388 ml (range, 150-650 ml). Intensive care unit stay averaged 48 h, with a mean hospitalization of 11 days. Liver function and coagulation parameters remained stable postoperatively. Duplex sonography on the portal and splenic veins revealed patency in all patients. The flow velocity in the portal vein decreased from 15.5 +/- 4.1 to 13.4 +/- 3.5 cm/s postoperatively ( p = 0.021). Splenic vein velocity was unchanged. Bleeding recurred in 6 patients, and grade 1 encephalopathy developed in 1 patient. Follow-up endoscopy (8-24 months) demonstrated substantial reduction in variceal grade. CONCLUSION: Laparoscopic devascularization of the lower esophagus and the upper stomach is technically feasible and promising. Rapid recovery and control of variceal hemorrhage are accomplished in most patients without exposing them to the risk of open surgery.

Adult↗
PubMed2003

Enhanced vasodilatation to endothelin antagonism in patients with compensated cirrhosis and the role of nitric oxide.

BACKGROUND AND AIMS: Patients with advanced cirrhosis have systemic vasodilatation and increased nitric oxide (NO) production despite activated vasopressor systems, including the endothelin system. The aims of this study were to assess the contribution of endogenous endothelin 1 (ET-1) and NO to the maintenance of basal forearm vascular tone in patients with preascitic cirrhosis (n=7) and in age and sex matched healthy controls (n=7). METHODS: Using venous occlusion plethysmography, forearm blood flow (FBF) responses to subsystemic locally active intra-arterial infusion of BQ-123 (a selective endothelin type A receptor (ET(A)) receptor antagonist; 10 nmol/min) were measured before and during application of an "NO clamp": a balanced co-infusion of L-N(G)-monomethyl-arginine (a selective NO synthase inhibitor) and sodium nitroprusside (an exogenous NO donor) to block endogenous NO production and restore NO mediated basal FBF, respectively. RESULTS: L-NMMA infusion produced a reduction in FBF (p<0.001) which was similar in both groups. Before applying the "NO clamp", BQ-123 caused an increase in FBF in both groups (p<0.001) that was greater in patients with cirrhosis (p<0.01). During the "NO clamp", BQ-123 induced vasodilatation was abolished in controls and attenuated in patients (p<0.001) but remained significantly greater in patients with cirrhosis (p<0.01). CONCLUSIONS: These findings indicate a greater ET(A) mediated contribution of endogenous ET-1 to the maintenance of basal forearm vascular tone in patients with preascitic cirrhosis. In addition, enhanced vasodilatation to ET(A) receptor antagonism in cirrhosis cannot be entirely attributed to NO release but is likely to be related to reversal of direct ET-1 mediated tone.

Adult↗
PubMed2001

Bradykinin contributes to the vasodilator effects of chronic angiotensin-converting enzyme inhibition in patients with heart failure.

BACKGROUND: Bradykinin, an endogenous vasodilator peptide, is metabolized by ACE. The aims of the present study were to determine the doses of B9340, a bradykinin receptor antagonist, that inhibit vasodilatation to exogenous bradykinin and to assess the contribution of bradykinin to the maintenance of basal vascular tone in patients with heart failure receiving chronic ACE inhibitor therapy. METHODS AND RESULTS: Forearm blood flow was measured using bilateral venous occlusion plethysmography. On three occasions in a double-blind randomized manner, 8 healthy volunteers received intrabrachial infusions of placebo or B9340 (at 4.5 and 13.5 nmol/min). On each occasion, placebo or B9340 was coinfused with bradykinin (30 to 3000 pmol/min) and substance P (4 to 16 pmol/min). B9340 caused no change in basal FBF but produced dose-dependent inhibition of the vasodilatation to bradykinin (P<0.001) but not substance P. The effects of bradykinin antagonism were studied in 17 patients with NYHA grade II through IV heart failure maintained on chronic ACE inhibitor therapy. Incremental doses of B9340, but not HOE-140, produced a dose-dependent vasoconstriction (P=0.01). After withdrawal of ACE inhibitor therapy, B9340 produced no significant change in forearm blood flow. After reinstitution of therapy, B9340 again resulted in vasoconstriction (P<0.03). CONCLUSIONS: B9340 is a potent and selective inhibitor of bradykinin-induced vasodilatation. Bradykinin does not contribute to the maintenance of basal peripheral arteriolar tone in healthy humans or patients with heart failure but contributes to the vasodilatation associated with chronic ACE inhibitor therapy in patients with heart failure via the B(1) receptor.

Adrenergic beta-Antagonists↗
PubMed2001

Review article: current endoscopic therapeutic options in the management of variceal bleeding.

Variceal bleeding is a frequent and life-threatening complication of portal hypertension. The first episode of variceal bleeding is not only associated with a high mortality, but also with a high recurrence rate in those who survive. Therefore, many studies and randomized clinical trials have focused on different therapeutic strategies aiming to prevent the first episode of variceal bleeding (primary prophylaxis), to control haemorrhage during the acute bleeding episode (emergency treatment), and to prevent re-bleeding (secondary prophylaxis). These strategies involve pharmacological, endoscopic, surgical, and interventional radiological modalities. This review concentrates on the clinical aspects of the endoscopic modalities used to treat oesophageal variceal haemorrhage, including variceal injection sclerotherapy, variceal band ligation, and the use of tissue adhesives (glue) and their substitutes. We also draw conclusions from the available literature regarding the use of endoscopic modalities in primary prophylaxis, emergency treatment, and secondary prophylaxis of variceal re-bleeding. The management of gastric varices and variceal bleeding during pregnancy is also addressed.

Clinical Trials as Topic↗
PubMed2001

Altered peripheral vascular responses to exogenous and endogenous endothelin-1 in patients with well-compensated cirrhosis.

Plasma endothelin concentrations are elevated in cirrhosis and correlate with disease severity. This study assessed forearm vascular responses to exogenous endothelin-1 (ET-1), and evaluated the contribution of endogenous ET-1 to the maintenance of basal peripheral vascular tone in patients with well-compensated cirrhosis (n = 11) and matched healthy controls (n = 8). Bilateral forearm blood flow (FBF) was measured at baseline and following unilateral, subsystemic, intrabrachial artery infusions of ET-1 (2 and 6 pmol/min); BQ-123, a selective ET(A) receptor antagonist (3 and 10 nmol/min); and BQ-788, a selective ET(B) receptor antagonist (0.3 and 1 nmol/min) using venous occlusion plethysmography. Baseline systemic hemodynamics and plasma ET-1 and big ET-1 concentrations were measured using electrical bioimpedance and radioimmunoassay, respectively. Patients and controls had similar baseline FBF, systemic hemodynamics, and plasma ET-1 and big ET-1 concentrations. In both groups, ET-1 and BQ-788 caused significant vasoconstriction (P < .001) and BQ-123 caused significant vasodilatation (P < .001). Compared with controls, cirrhotic patients had attenuated ET-1 responses (P < .001), augmented BQ-123 responses (P < .001), and similar BQ-788 responses (P = .62). Despite normal systemic hemodynamics and plasma ET-1 concentrations, forearm vascular responses to exogenous ET-1 are reduced in cirrhotic patients. The augmented vasodilatation to BQ-123 in cirrhotic patients is consistent with a compensated vasodilated state, and a greater contribution of ET-1 to the maintenance of basal vascular tone acting through the ET(A) receptor.

Antihypertensive Agents↗
PubMed2001

Transjugular intrahepatic portosystemic stent-shunt insufficiency and the role of diabetes mellitus.

BACKGROUND/AIMS: Maintenance of long-term patency of transjugular intrahepatic portosystemic stent-shunts (TIPSS) has proved problematic. Various prognostic variables have been assessed as predictors, but the role of diabetes mellitus, which induces vascular endothelial cell dysfunction, has not been assessed. METHODS: We analysed the records of 248 patients who underwent TIPSS between July 1991 and July 1997, followed-up through to August 1998. Patients with at least one shunt assessment by portography and available blood glucose levels were eligible (177 patients; median follow-up, 15.0 months). Fourteen patients had a pre-procedural diagnosis of diabetes (one insulin dependent, seven oral hypoglycaemic treated and six diet controlled). In another 14 patients, diabetes was diagnosed at TIPSS insertion, giving a 28/177 (15.8%) prevalence of diabetes in our patients. Fifty-nine patients were excluded from the final analysis (including five diabetics), as they either died or had early shunt insufficiency (within 1 month of stent placement), leaving 118 patients (including 23 diabetics) to be included in the final analysis. RESULTS: Mean age, sex distribution, median follow-up (months) and pre-shunt portal pressure gradient were comparable in the two groups (diabetics versus non-diabetics). Child-Pugh classes A and B were more common in the diabetic group (P < 0.01), and the mean inserted stent diameter was larger in the diabetic group (P < 0.05). The presence of diabetes was associated with a higher incidence of delayed shunt insufficiency (P = 0.02), but there was no evidence of an association between presence of diabetes and variceal haemorrhage post TIPSS. Kaplan-Meier analyses revealed earlier insufficiency in diabetic patients compared with those without diabetes (P = 0.04). Age, gender and presence of diabetes are included in the final logistic regression model. Individuals who have diabetes are more likely to experience shunt insufficiency independent of age and gender. CONCLUSIONS: Diabetes mellitus is common in patients undergoing TIPSS and is associated independently with increased incidence of primary delayed shunt insufficiency.

Diabetes Complications↗
PubMed2000

Postoperative hepatic catabolic stress response in patients with cirrhosis and chronic hepatitis.

Open (OC) or laparoscopic (LC) cholecystectomy is considered a relative contraindication in patients with liver cirrhosis. The effect of LC and OC on the hepatic catabolic stress response was studied in patients with postnecrotic liver cirrhosis and chronic hepatitis to define the most suitable procedure from a metabolic point of view. Altogether 14 patients with cirrhosis and 14 with chronic hepatitis were randomized to LC or OC (n = 7 in each group). The increase in the functional hepatic nitrogen clearance (FHNC) was quantified. Changes in glucose, insulin, glucagon, cortisol, epinephrine, norepinephrine, and prostaglandin E(2) (PGE(2)) were observed. There was no difference in FHNC between LC and OC in any of the patients. Among cirrhotic patients OC caused a 132% increase in FHNC (p < 0.05) and among the hepatitis patients a 69% increase (p < 0.05). In contrast, there was no significant increase following LC in any of the patients. OC increased fasting glucose and insulin in the hepatitis patients (p < 0.01 and p < 0.001, respectively) and in the cirrhosis group (p < 0.01 and p < 0.05, respectively). Alanine stimulation increased glucose in hepatitis patients after OC (p < 0.05) and after LC (p < 0.01). Stimulated glucagon increased after OC in the hepatitis group (p < 0.05). During stimulation cortisol was higher following LC in hepatitis patients (p < 0.01) and cirrhotic patients (p < 0.05). Fasting PGE(2) was down-regulated after LC in hepatitis patients (p < 0.05) and cirrhotic patients (p < 0.01) and after OC in the hepatitis group (p < 0.001). FHNC is similar after LC and OC. Thus from a metabolic point of view, LC has no advantage over OC.

Cholecystectomy↗
PubMed2000

Role of angiotensin II in regulation of basal and sympathetically stimulated vascular tone in early and advanced cirrhosis.

BACKGROUND & AIMS: The renin-angiotensin and sympathetic nervous systems are activated in cirrhosis. This study aimed to establish the role of angiotensin II (ANG II) in the regulation of basal and sympathetically stimulated vascular tone in preascitic cirrhotic patients and patients with diuretic-refractory ascites compared with age- and sex-matched healthy controls. METHODS: Forearm blood flow (FBF) responses to lower body negative pressure (LBNP) and to subsystemic, intrabrachial infusions of losartan, an angiotensin II type 1 (AT(1)) receptor antagonist, norepinephrine, and ANG II were measured using venous occlusion plethysmography. RESULTS: In all groups, ANG II and norepinephrine caused dose-dependent reductions in FBF (P < 0.001); responses to norepinephrine were similar across the 3 groups but those to ANG II were less in both cirrhotic groups than in controls (P < 0.01). Losartan caused a dose-dependent increase in FBF only in patients with refractory ascites (P < 0.01). LBNP caused less reduction in FBF in refractory ascites patients than in both preascitic patients and controls (P < 0.01). CONCLUSIONS: Despite hyporesponsiveness to exogenous ANG II in both early and advanced cirrhosis, endogenous ANG II contributes to the maintenance of basal vascular tone only in advanced cirrhosis. These findings suggest a role of ANG II in the pathogenesis of ascites. Attenuated LBNP responses occurred only in advanced cirrhosis, without apparent interaction with endogenous ANG II.

Adult↗
PubMed1999

Acute and chronic haemodynamic and renal effects of carvedilol in patients with cirrhosis.

BACKGROUND/AIMS: Recent reports have suggested that the vasodilating beta-blocker carvedilol may have beneficial acute haemodynamic effects in cirrhotic portal hypertension. However, no data exist on chronic use or renal effects in this patient group. The aim of this study was to assess the acute and chronic haemodynamic and renal effects of carvedilol in cirrhotic patients. METHODS: Seventeen cirrhotic patients (mean age 55.2+/-2.8, mean Child-Pugh score 7.4+/-0.5) were studied. Hepatic venous pressure gradient, cardiac output, systemic vascular resistance, mean arterial pressure, heart rate and hepatic blood flow were measured before and 1 h after 25 mg carvedilol. After 4 weeks of therapy with carvedilol 25 mg daily, these measurements were repeated before and after rechallenge with carvedilol. Urine volume, sodium excretion and creatinine clearance were also measured before and after 4 weeks of therapy. RESULTS: Seven patients did not complete the 4-week carvedilol therapy due to hypotension or poor compliance. Hepatic venous pressure gradient fell by 20.8% acutely (p<0.001) and by 16.3% after 4 weeks of therapy (p<0.002). Heart rate, mean arterial pressure and cardiac output fell after acute administration of carvedilol, but only heart rate fell significantly after 4 weeks of treatment. Hepatic blood flow, urine volume, sodium excretion and creatinine clearance remained unchanged after therapy. CONCLUSION: Carvedilol has beneficial effects on splanchnic haemodynamics following acute and chronic administration in cirrhosis, without compromising hepatic blood flow or renal function. However, a substantial number of patients cannot tolerate 25 mg daily.

Administration, Oral↗
PubMed1998

Ultrasound-detected hepatic periportal thickening in patients with prolonged pyrexia.

Hepatic periportal thickening (HPT) detected by ultrasonography has been established as a reliable tool for measuring hepatic morbidity due to schistosomiasis. During ultrasonographic examination of patients with prolonged pyrexia, we frequently noticed minimal grades of HPT in patients without a history of schistosomiasis. This led to ultrasonographic studies of conditions other than schistosomiasis in which HPT may occur. Subjects included 460 patients with Schistosoma haematobium infection, 107 urban patients with prolonged pyrexia without previous exposure to schistosomiasis, and 288 healthy controls unexposed to schistosomiasis. Grade I HPT was more prevalent (P < 0.001) in patients with pyrexia (56.1%) than in those with S. haematobium (32.2%) and was more frequent (P < 0.001) in patients with S. haematobium than in controls (11.1%). Typhoid fever was the most common febrile illness causing HPT. Grade II lesions were rare in patients with pyrexia (2.8%) or schistosomiasis (0.9%). Grade III lesions were present in only one patient with S. haematobium. Mild grades of HPT can occur in infectious diseases other than schistosomiasis. Cellular infiltration in the portal tract from chronic infectious diseases can frequently give the ultrasonographic appearance of grade I HPT.

Adolescent↗
PubMed1997

Postpartum pulmonary embolectomy; a surgical challenge and favourable outcome.

A 23-year-old female underwent uneventful caesarian section, which was followed by massive pulmonary embolism. Pulmonary embolectomy on cardiopulmonary bypass was performed, and was complicated by massive intraabdominal haemorrhage due to a hepatic subcapsular rupture. To our knowledge, this is the first surgically orientated case of postpartum pulmonary embolectomy to be reported in the literature.

Adult↗
PubMed1997

Evaluation of an ultrasonographic score for urinary bladder morbidity in Schistosoma haematobium infection.

An ultrasonographic urinary bladder morbidity score was developed and tested in 510 patients with schistosomiasis haematobia, and then evaluated for screening 1,134 randomly selected children from villages endemic for Schistosoma haematobium. The ultrasonographic urinary bladder morbidity score had four grades ranging from normal to marked thickening of the urinary bladder wall or any polyps or masses. Among both patients and randomly screened subjects, the ultrasonographic score was greater (P = 0.01 and P < 0.01) in males than in females. Children examined in the clinic had higher (P = 0.03) ultrasonographic scores than adults. Infected subjects in communities were more likely (P < 0.001) to have urinary bladder morbidity than uninfected subjects, and clinic patients with egg counts > or = 20 eggs/10 ml of urine had higher (P = 0.03) ultrasonographic urinary bladder morbidity scores than those with lighter infections. The geometric mean egg count was higher (P = 0.04) in clinic patients with grade II and III lesions than in those with grade 0 and I lesions. There was progressive improvement of the grade of urinary bladder morbidity scores in patients treated with praziquantel at each follow-up examination (P < 0.001) and there was a positive relationship (P < 0.01) between urinary bladder morbidity scores and ultrasonographic-detected renal back pressure changes. The ultrasonographic urinary bladder morbidity score objectively measured the severity of urinary bladder morbidity and correlated with intensity of S. haematobium infection in our subjects. It can be used in evaluating both morbidity in patients and in community surveys and in following the outcome of chemotherapy.

Adolescent↗
PubMed1996

Cytokine control of parasite-specific anergy in human urinary schistosomiasis. IL-10 modulates lymphocyte reactivity.

Humans chronically infected with schistosomiasis usually have impaired parasite Ag-specific lymphocyte proliferation and IFN-gamma production that may facilitate persistence of the parasite while producing little clinical disease. The mechanisms that contribute to the immunologic hyporesponsiveness in these patients remain undefined. IL-10 has been shown to exert an inhibitory effect on cell-mediated immunity. To determine whether endogenous IL-10 has a role in regulating parasite-specific anergy in schistosomiasis, neutralizing anti-IL-10 added to PBMC from Schistosoma haematobium patients' enhanced adult worm (SWAP)- or egg Ag (SEA)-driven lymphocyte proliferation and/or IFN-gamma production by 2- to >100-fold in 32 of 38 subjects. In contrast, anti-IL-10 failed to significantly augment the mycobacterial Ag, purified protein derivative (PPD)-driven lymphocyte proliferation, or IFN-gamma production in 9 or 10 of 14 individuals, respectively. SWAP or SEA triggered IL-10 release from PBMC of both patients and healthy individuals; however, CD4+ cells were a significant source of IL-10 only in infected subjects. PPD relative to SWAP induced fivefold less IL-10 release by CD4+ cells (p < 0.01). A possible mechanism whereby IL-10 suppressed Ag-specific T cell responses was demonstrated by the ability of SWAP and not PPD to suppress B7 expression on PBMC. Anti-IL-10 completely inhibited the parasite Ag-induced down-regulation of B7 expression. These studies indicate that IL-10 contributes to parasite Ag-induced T cell hyporesponsiveness observed in patients with chronic schistosomiasis hematobia.

Adolescent↗