Stool antigen testing for the diagnosis and confirmation of eradication of Helicobacter pylori infection: a prospective blinded trial.

BACKGROUND AND AIMS: Helicobacter pylori is an established pathogen for a wide spectrum of gastroduodenal diseases. We investigated the usefulness of H. pylori stool antigen test (HpSA) before and after eradication therapy on patients referred for gastroscopy. METHODS: Over a 12-month period, 127 adult patients (47% males) underwent HpSA and gastroscopy with dual biopsies from the antrum and proximal body of the stomach for urease and histology. The positive patients (histology, urease or combined positive) received triple therapy consisting of clarithromycin 500 mg, amoxycillin 1 g and omeprazole 20 mg, each given twice daily for 7 days. Six weeks post-therapy, eradication was verified with the 13C-urea breath test (UBT) and the HpSA results compared on a second stool sample. RESULTS: Pre-therapy, 23/113 patients were positive by urease test, 22/112 by histology and 22/112 were combined positive. For the HpSA, compared to combined urease and histology as the reference standards, the sensitivity and specificity were 79 and 92% while the positive and negative predictive values (PPV and NPV) were 68 and 96%, respectively. Post-therapy, UBT was adopted as the reference standard and 18 paired samples were available for analysis: three were positive and 15 were negative. Sensitivity and specificity were 67 and 100% while the PPV and NPV were 100 and 94%, respectively. CONCLUSIONS: In this prospective study, HpSA was found to be a reasonably useful diagnostic test for H. pylori infection. Post-eradication, it was highly specific and similar to UBT in terms of PPV and NPV. The test is non-invasive and cheaper than the urease test or the UBT, making it a candidate in the investigation of dyspepsia.

Safety of intravenous immunoglobulin preparations: a prospective multicenter study to exclude the risk of non-A, non-B hepatitis.

The risk of non-A, non-B hepatitis transmission by an intravenous immunoglobulin (IVIG) preparation was assessed in a prospective multicenter trial in 68 patients with primary immunodeficiency disorders (40 children or adolescents and 28 adults). During the 4-week prestudy evaluation period the clinical examinations and liver function tests including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, and bilirubin were normal in all patients. The treatment consisted of three infusions of 200 mg IVIG (pH 4; pepsin procedure) per kilogram body weight at 2-week intervals. During the observation period of 24 weeks following the first infusion of the study IVIG, the patients were monitored at regular time intervals. No clinical and laboratory signs of hepatitis or liver dysfunction were noticed. All patients completed the study. In 5 patients, one isolated alanine aminotransferase value and in another patient one gamma-glutamyl transpeptidase value were moderately elevated, but always below 2.5 times the upper limit of the reference range. Similar isolated and transient elevations were observed for aspartate aminotransferase and alkaline phosphatase. It was concluded that the IVIG preparation did not transmit non-A, non-B hepatitis or other viral liver diseases.

Pharmacokinetics of cytomegalovirus specific IgG antibody following intravenous immunoglobulin in bone marrow transplant patients.

Cytomegalovirus (CMV) associated interstitial pneumonitis is a major cause of death among bone marrow transplant patients. A variety of intravenous immunoglobulin (IVIg) preparations have shown some promise in preventing this complication. As part of a multicenter trial of Sandoglobulin, the pharmacokinetics of CMV specific IgG was measured in order to guide future dosing schedules. A dose of 500 mg/kg was administered weekly beginning 1 week before transplant and continuing until day 98 following transplant. The half-life of CMV specific IgG was measured by an ELISA method after the first, third and fifth doses of IVIg. CMV seronegative patients received only screened CMV negative blood products, which permitted assessment of the half-life of IVIg CMV antibody. Peak titers achieved were comparable to those of the CMV seropositive patients averaging 1:2702 (range 1:596-1:10 514). Total IgG levels rose to a peak of about 75% above baseline. After the first dose of IVIg, the half-life of CMV IgG antibody was 3.4 +/- 2.0 (SD) days, although it lengthened to 6.1 +/- 5.1 days after the fifth dose of IVIg. The half-life of total IgG was estimated to be between 5 and 10 days, depending on the assumptions made regarding endogenous production. If high levels of IVIg are necessary for protection from CMV associated interstitial pneumonitis, weekly dosing will be important in order to maintain sufficient levels to be protective.

Unexpected differences between mazindol and its homologs on biochemical and behavioral responses.

Mazindol and two homologs of mazindol were tested for their effects as uptake inhibitors in rat tissue slices for [3H]dopamine in the neostriatum, for [3H]norepinephrine in occipital cortex and for [3H]serotonin in whole brain. All three drugs were potent inhibitors of [3H]dopamine uptake (ED50 values between 57 and 280 nM), [3H]norepinephrine uptake (ED50 values less than 19 nM) and were somewhat weaker against [3H]serotonin uptake (ED50 values between 550 and 4100 nM). All three drugs were in contrast very weak as releasing agents for previously accumulated 3H-biogenic amines. Mazindol injection resulted in a large increase in locomotor activity in mice, but its two homologs were without effect. Mazindol was able to counteract amphetamine-induced increases in activity in reserpinized mice, but its homologs were inactive. Mazindol also caused a vigorous ipsilateral rotation in rats with an unilateral 6-hydroxydopamine lesion of the nigrostriatal system, but again the homologs had no such effect. However, all three drugs were potent inhibitors of prolactin secretion in rats (ID50 values 1-2 mg/kg orally). Correlations between the capacities of the drugs to inhibit 3H-biogenic amine uptake and the various in vivo responses are made.

Pharmacological studies with several analogs of mazindol: correlation between effects on dopamine uptake and various in vivo responses.

Several structural analogs of mazindol were tested as inhibitors of the uptake of [3H] dopamine in rat neostriatum, of [3H] norepinephrine in rat occipital cortex and of [3H] serotonin in whole rat brain. A rather wide range of potencies was observed but a number of the drugs were even more potent than mazindol as uptake inhibitors. All of the drugs studied were weak releasing agents for previously accumulated [3H]amines. Several of the drugs caused large increases in motor activity in normal mice but not in reserpinized mice. However, these same drugs were able to prevent amphetamine-induced increases in activity in reserpinized mice, and were able to induce ipsilateral circling in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. Two of these same drugs were tested and found to be potent inhibitors of prolactin secretion. Correlations will be made between the capacities of the drugs to inhibit dopamine uptake and the in vivo responses mentioned above.