Evaluation of indapamide 1.25 mg once daily in elderly patients with mild to moderate hypertension.

The objective of this study was to evaluate the safety and efficacy of indapamide 1.25 mg once daily as monotherapy in elderly patients (65 years and older) with mild to moderate essential hypertension. Two hundred and seventy-nine (279) elderly patients were enrolled in a washout period, during which patients received single-blind placebo for 4 weeks. Patients demonstrating supine diastolic pressures between 95 mm Hg and 114 mm Hg at the end of the 4-week placebo washout period were entered into the 8-week double-blind treatment period. Two hundred and four (204) patients qualified for the study and were randomized to the double-blind treatment; 103 patients received indapamide 1.25 mg and 101 patients received placebo for 8 weeks. Overall, 177 patients (92 indapamide and 85 placebo) completed the study. The primary efficacy criterion was the mean change in supine diastolic blood pressure (DBP) from double-blind baseline to the end of 8 weeks of therapy. By week 8 of the double-blind treatment period, indapamide 1.25 mg produced a statistically significant (P = 0.0037) decrease in supine DBP of 8.2 mm Hg compared to a decrease of 5.3 mm Hg produced in the placebo group. Additionally, indapamide 1.25 mg was statistically (P = 0.0028) more effective than placebo in reducing supine systolic BP (SBP) (-10.1 vs -4.2 mm Hg). The incidence of drug-related adverse events during the double-blind treatment period was similar between the two treatment groups. A low dose of indapamide, 1.25 mg, given once daily for 8 weeks was effective as monotherapy with respect to BP reduction in an elderly population with mild to moderate hypertension. Indapamide 1.25 mg was safe and generally well tolerated in this elderly patient population.

Measurement of the 5-hydroxyindoleacetic acid/creatinine ration in the urine of patients with coeliac disease.

Urinary excretion of 5-hydroxyindoleacetic acid and creatinine has been measured in 8-hour collections from adult patients with coeliac disease, and results have been compared with a group of healthy adult controls. Results were expressed as 5-HIAA/creatinine and significantly higher values of this ratio were found in patients with coeliac disease. Measurement of this ratio is a non-invasive technique which is useful in selecting patients with suspected coeliac disease for further investigation.

Identification of Bacteroides gingivalis by fluorescent antibody staining.

Reactivity with the conjugates to the 4 serogroups A, B, C and C-1 of the former taxon Bacteroides melaninogenicus and with antisera to B. gingivalis and to oral strains of B. melaninogenicus subsp. intermedius, was studied by fluorescent antibody staining (FAS) on strains representative of the black-pigmented Bacteroides: B. asaccharolyticus, B. melaningogenicus subsp. intermedius, B. melaninogenicus subsp. melaninogenicus, B. melaninogenicus subsp. levii, B. melaninogenicus subsp. macacae and B. gingivalis. The strains of B. gingivalis only reacted with the homologous antiserum and failed to react with any of the other immunoreagents tested indicating that the oral strains of asaccharolytic black- pigmented Bacteroides belong to a serogroup distinct from those currently serogrouped. This serological characteristic corroborates the definition of the new species B. gingivalis which has been proposed on the basis of phenotypic and genetic characteristics different from that of B. asaccharolyticus and can be used for their discrimination. FAS appears to be a reliable method for identification of B. gingivalis, a suspected major periodontopathic organism.

Serum antibodies to oral Bacteroides asaccharolyticus (Bacteroides gingivalis): relationship to age and periondontal disease.

An enzyme-linked immunosorbent assay microplate method was used for measuring levels of antibody specific for the oral serotype of Bacteroides asaccharolyticus (Bacteroides gingivalis) in serum samples obtained from umbilical cords, infants, children, periodontally normal adults, and edentulous adults. Serum from patients with various periodontal diseases, including adult periodontitis, localized juvenile periodontitis, generalized juvenile periodontitis, post-localized juvenile periodontitis, and acute necrotizing ulcerative gingivitis, were also studied. A positive correlation between increase in age and increase in both prevalence and level of specific antibody in the G, A, and M classes of immunoglobulins was observed. This indicates that antibodies reactive with oral B. asaccharolyticus found in up to 84% of normal adults are natural antibodies, presumably with a protective role. Among the patient groups, those with adult periodontitis were found to have levels of immunoglobulin G antibodies to oral B. asaccharolyticus that were five times higher than the antibody levels found in control subjects. The levels of IgG antibodies to this organism in the other patient groups were comparable to the levels found in the control group. However, 50% of the individuals in the generalized juvenile periodontitis group had high levels of immunoglobulin G antibodies to B. asaccharolyticus, suggesting heterogeneity with respect to immune response in these patients. These results indicate that antibodies to oral B. asaccharolyticus (B. gingivalis) occur at low levels in most normal children and adults and that the rise in titer of the specific antibodies of each major class of immunoglobulins parallels the ontogenic change in serum levels of that isotype. In contrast, there is a marked increase in titer of immunoglobulin G antibodies to oral B. asaccharolyticus in the group of patients with adult periodontitis and in patients with the generalized form of juvenile periodontitis.

Activation of monocytes by portal serum and its relationship to immunoglobulin, immune complex and endotoxin content.

To investigate the possibility that a "spillover effect" of substances from the portal vein into the systemic circulation accounts for the abnormal monocyte function in patients with liver disease, we have incubated human peripheral blood monocytes with paired specimens of portal and systemic serum from humans and rabbits. Monocytes incubated with portal serum released more of a lysosomal enzyme, N-acetyl-B-glucosaminidase, than those incubated with systemic serum (p less than 0.05). In order to delineate the factors responsible for this increased activity, the content of immune complexes, immunoglobulins and endotoxin in the paired specimens of portal and systemic serum was measured. Endotoxin was found in none of 16 human specimens of portal blood and five of the 16 rabbit specimens. Modestly increased levels of immune complexes, particularly of the IgG class, were found in the portal serum compared to the systemic serum (p less than 0.01). Corresponding studies on immunoglobulins showed a higher concentration of IgA in portal serum (p less than 0.05), but no difference in other classes of immunoglobulins or complement levels. There was good correlation between the enzyme production by monocytes and the concentration of immune complexes, particularly IgA (r = 0.687, p less than 0.001), but there was no relationship to the presence or absence of endotoxin. This evidence suggests that portal serum contains substances, particularly immune complexes, which under normal circumstances are sequestered by the liver. These are capable of "activating" monocytes in vitro and may play a role in the pathogenesis of certain types of liver disease.