Pregnancy in patients with cystic fibrosis.
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Adult↗
Biomedical subjects
S Fitzsimmons
Publications and source records attributed to S Fitzsimmons.
Clonal diversity of Streptococcus mitis biovar 1 isolates from the oral cavity of human neonates.
The clonal diversity of 101 isolates of the pioneer bacterium Streptococcus mitis biovar 1 obtained from the oral cavities of 40 human neonates 1 to 3 days, 2 weeks, and 1 month postpartum was examined by using rRNA gene restriction patterns. There was a high degree of genetic diversity, with the 101 isolates comprising 93 unique PvuII ribotypes. There were eight identical pairs of ribotype patterns, and seven of the eight pairs were obtained from individual neonates. Only one identical pair comprised isolates obtained from different neonates. In all but two cases, isolates with matching ribotypes were obtained at one visit. Two pairs of isolates with matching ribotype patterns were obtained from neonates on successive visits. The ribotype patterns of the isolates were examined by cluster analysis. The isolates forming each cluster were very similar, yet each cluster was well separated from its neighbors. When several isolates were obtained from individual neonates at a particular visit, in some instances they were contained in a single cluster, whereas in other cases each isolate was contained in a separate cluster. Isolates obtained from individual neonates on successive visits tended to be contained in different clusters. This high degree of diversity, which has been observed in other mucosal commensal bacteria, may serve as a mechanism for avoiding immune elimination of these bacteria.
Cloning, Molecular↗
Pioneer oral streptococci produce immunoglobulin A1 protease.
As part of a longitudinal study of the relationship between bacterial colonization and the secretory immune response, 367 isolates of pioneer viridans streptococci collected from 40 breast- and bottle-fed neonates within the first month postpartum were tested for the production of immunoglobulin A1 (IgA1) protease and glycosidases. Fifty percent of the streptococci isolated produced IgA1 protease, including all isolates of Streptococcus oralis and S. sanguis, 60.7% of S. mitis biovar 1 isolates, and some isolates that could not be identified. Three cleavage patterns of alpha 1 heavy chains were observed. Six isolates of S. mitis biovar 1 that did not produce IgA1 protease attacked the alpha 1 chain. Incubation of IgA1 protease-negative S. mitis biovar 1 isolates with IgA1, either prior to or together with S. sanguis, rendered the IgA1 paraprotein resistant to cleavage by the IgA1 protease of S. sanguis. The ability of some pioneer streptococci in the human oral cavity to produce IgA1 protease and of others to modify the susceptibility of IgA1 to cleavage by IgA1 protease perhaps enhances their ability to survive in this habitat.
Female↗
A phase I trial of CGS 16949A. A new aromatase inhibitor.
CGS 16949A is a new, nonsteroidal competitive inhibitor of the aromatase enzyme. In this Phase I trial, 16 heavily pretreated postmenopausal patients with metastatic breast cancer were treated with escalating doses of CGS 16949A from 0.6 to 16 mg total daily oral dose. No hematologic, biochemical, or significant clinical toxicity was encountered. Endocrinologic and pharmacologic data were available from 12 of these patients. Maximum inhibition of estrogen biosynthesis was observed at a dose of 2 mg CGS 16949A daily. At this dose, the inhibition of estrogen biosynthesis was equivalent to 1000 mg aminoglutethimide (AG). The fall in plasma and urinary estrogens without a concomitant drop in androgens confirmed the specific blockade of aromatase activity. At doses of 4 to 16 mg daily, CGS 16949A appeared to inhibit the C21-hydroxylase enzyme as well. The t1/2 of CGS 16949A in the circulation was 10.5 hours. Of 16 evaluable patients there were two partial responses and seven patients with stable disease.
Adult↗
The efficacy and safety of valsartan compared with placebo in the treatment of patients with essential hypertension.
A multicenter, randomized, placebo-controlled, double-masked, parallel-group study was performed to compare the efficacy and safety of valsartan 20, 80, 160, and 320 mg with placebo in the treatment of patients with essential hypertension. A total of 736 adults with uncomplicated essential hypertension stages 1 to 3 were randomized to receive placebo or valsartan 20, 80, 160, or 320 mg daily for 8 weeks. Assessments were made at baseline, after 4 and 8 weeks of treatment, and 2 to 3 days after stopping treatment. The primary efficacy variable was change from baseline in mean sitting diastolic blood pressure (MSDBP). Other variables included change from baseline in mean sitting systolic blood pressure (MSSBP) and responder rates (ie, MSDBP < 90 mm Hg or decrease of > or = 10 mm Hg from baseline). All doses of valsartan produced statistically significant reductions in both MSDBP and MSSBP at end point compared with placebo. A dose-response effect was seen, although the incremental reduction in blood pressure with doses of valsartan > 80 mg was relatively small. Statistically significant differences in responder rates at end point were seen for doses of valsartan of 80 mg and above compared with placebo, whereas the responder rates for valsartan 20 mg was not significantly different from that for placebo. Safety and tolerability variables included data on adverse experiences, rebound hypertension, and clinical laboratory evaluations. Tolerability was good, with headache being the most common complaint and occurring most frequently in placebo patients. The incidence of dizziness was similar among the placebo (5.4%) and valsartan 20-mg to 160-mg groups (2.1% to 3.4%); there was an increase in the incidence of dizziness in the 320-mg group (9.3%). No cases of symptomatic orthostatic hypotension occurred. Analysis of rebound showed that 11.6% of patients receiving placebo and 16.6% receiving valsartan had an increase in MSDBP to baseline levels or above 2 to 3 days after stopping treatment. No clinically significant adverse experiences were noted after stopping treatment. There were no clinically or statistically significant changes in laboratory values during treatment. Thus valsartan proved to be both effective and safe in reducing blood pressure in adults with essential hypertension. The optimal dose range is 80 to 160 mg, given once daily.
Adult↗
Valsartan, a new angiotensin II antagonist: antihypertensive effects over 24 hours.
This study was done to assess the antihypertensive efficacy of once-daily valsartan 20 mg, 80 mg, 160 mg, and 320 mg over 24 hours using ambulatory blood pressure monitoring (ABPM). A total of 217 adult outpatients with uncomplicated essential hypertension (office mean sitting diastolic blood pressure [DBP] of > or = 95 to < or = 115 mm Hg) participated in this multicenter, double-masked, placebo-controlled study. Patients were randomized to receive valsartan 20 mg, 80 mg, 160 mg, 320 mg, or placebo for 8 weeks. Twenty-four-hour ABPM was done at baseline and after 8 weeks of treatment. All valsartan doses produced significant decreases in average ambulatory systolic blood pressure (SBP) and DBP over 24 hours compared with placebo. A trend to greater reductions compared with placebo was observed for doses of valsartan 80 mg and greater (80 mg, -6.61 mm Hg DBP, -11.04 mm Hg SBP; 160 mg, -5.51 mm Hg DBP, -10.61 mm Hg SBP; 320 mg, -8.44 mm Hg DBP, -14.34 mm Hg SBP) compared with valsartan 20 mg (-3.52 mm Hg DBP, -5.92 mm Hg SBP). Valsartan produced consistent reductions compared with placebo during both day (> 6 AM to < or = 10 PM) and night (> 10 PM to < or = 6 AM). However, in all groups, the circadian pattern of blood pressure over 24 hours was preserved and was similar to that observed at baseline (but shifted into the normotensive range in a parallel fashion). The data show that single daily doses of valsartan 80 mg and greater provide effective control of both DBP and SBP over a 24-hour period without loss of diurnal variation.
Antihypertensive Agents↗