(1/3560) Maternal vitamin A or beta-carotene supplementation in lactating bangladeshi women benefits mothers and infants but does not prevent subclinical deficiency.
The effects of maternal postpartum vitamin A or beta-carotene supplementation on maternal and infant serum retinol concentrations, modified relative dose-response (MRDR) ratios and breast milk vitamin A concentrations were assessed during a community-based trial in Matlab, Bangladesh. At 1-3 wk postpartum, women were randomly assigned to receive either (1) a single dose of 200,000 international units [60,000 retinol equivalents (RE)] vitamin A followed by daily placebos (n = 74), (2) daily doses of beta-carotene [7.8 mg (1300 RE)] (n = 73) or (3) daily placebos (n = 73) until 9 mo postpartum. Compared to placebos, vitamin A supplementation resulted in lower maternal MRDR ratios (i.e., increased liver stores) and higher milk vitamin A concentrations at 3 mo, but these improvements were not sustained. The beta-carotene supplementation acted more slowly, resulting in milk vitamin A concentrations higher than the placebo group only at 9 mo. Irrespective of treatment group, over 50% of women produced milk with low vitamin A concentrations (=1.05 micromol/L or =0.28 micromol/g fat) throughout the study. Overall, mean maternal serum retinol concentrations were not affected by supplementation. Compared to the placebo group, the mean MRDR ratio of 6-mo-old infants was higher in the vitamin A group. Infants (33%) had serum retinol concentrations <0.70 micromol/L and 88% had MRDR ratios >/=0. 06. We conclude that while both interventions were beneficial, neither was sufficient to correct the underlying subclinical vitamin A deficiency in these women nor to bring their infants into adequate vitamin A status. (+info)
(2/3560) Acute haemodynamic and proteinuric effects of prednisolone in patients with a nephrotic syndrome.
BACKGROUND: Administration of prednisolone causes an abrupt rise in proteinuria in patients with a nephrotic syndrome. METHODS: To clarify the mechanisms responsible for this increase in proteinuria we have performed a placebo controlled study in 26 patients with a nephrotic syndrome. Systemic and renal haemodynamics and urinary protein excretion were measured after prednisolone and after placebo. RESULTS: After i.v. administration of 125-150 mg prednisolone total proteinuria increased from 6.66+/-4.42 to 9.37+/-6.07 mg/min (P<0.001). By analysing the excretion of proteins with different charge and weight (albumin, transferrin, IgG, IgG4 and beta2-microglobulin) it became apparent that the increase of proteinuria was the result of a change in size selectivity rather than a change in glomerular charge selectivity or tubular protein reabsorption. Glomerular filtration rate rose from 83+/-34 ml to 95+/-43 ml/min (P<0.001) after 5 h, whereas effective renal plasma flow and endogenous creatinine clearance remained unchanged. As a result filtration fraction was increased, compatible with an increased glomerular pressure, which probably contributes to the size selectivity changes. Since corticosteroids affect both the renin-angiotensin system and renal prostaglandins, we have evaluated the effects of prednisolone on proteinuria after pretreatment with 3 months of the angiotensin-converting enzyme inhibitor lisinopril or after 2 weeks of the prostaglandin synthesis inhibitor indomethacin. Neither drug had any effect on prednisolone-induced increases of proteinuria. CONCLUSIONS: Prednisolone increases proteinuria by changing the size selective barrier of the glomerular capillary. Neither the renin-angiotensin axis nor prostaglandins seem to be involved in these effects of prednisolone on proteinuria. (+info)
(3/3560) Placebo medication use in patient care: a survey of medical interns.
The use of placebo medication, long recognized by clinicians, often has serious practical implications, such as patient deception. Past evidence has suggested that resident physicians tend to misuse placebo medication. Interns from two consecutive years of a residency program were surveyed anonymously to assess their knowledge and use of placebos. Of the 74 interns surveyed, 44 (59%) were familiar with placebo use in patient care. Fifty percent of these interns familiar with placebo use had learned about placebos from another physician. All interns who had learned about placebos during their internships had learned from another physician, whereas interns who had gained their knowledge of placebos as medical students were as likely to have learned from the medical literature as they were to have learned from a physician (P = 0.027). Interns aware of placebo use were more likely to consider placebo administration for suspected, factitious pain (P = 0.022). The present study uncovered no relationship between interns' estimations of placebo efficacy and the utility they attributed to placebos in assessing a complaint of pain. This suggests that conceptual inconsistencies underlie their use of placebos. Interns often learn of placebos as medical students and are influenced by physician-mentors. Placebo use in patient care is an area of attention for medical educators. (+info)
(4/3560) The pharmacokinetic modelling of GI198745 (dutasteride), a compound with parallel linear and nonlinear elimination.
AIMS: To characterize the pharmacokinetics of the dual 5alpha-reductase inhibitor GI198745 (dutasteride) to allow for more accurate predictions of GI198745 concentrations after different dosing schedules. METHODS: In this randomized, single-blind, parallel group study, 32 healthy male volunteers received single oral doses of GI198745 ranging from 0.01 to 40 mg. Data were analysed by nonlinear mixed effects modelling using NONMEM where both linear and nonlinear pharmacokinetic models were examined. RESULTS: The time course of GI198745 serum concentrations indicated concentration dependent elimination, with the apparent half-life increasing with dose. Data were best described by a two-compartment model with first order absorption and parallel linear and nonlinear elimination pathways. Drug absorption was rapid, and was followed by a short distribution phase. A high volume of distribution (511 l) and a low linear clearance (0.58 l h(-1)) combined to give a half-life of up to 5 (1-7) weeks at high concentrations. As concentrations declined towards Km (0.96 ng ml(-1)), the proportion eliminated by the relatively rapid saturable elimination pathway, with a maximum clearance of 6.2 l h(-1), increased and the half-life reduced to about 3 days. The estimated inter individual variability for the linear clearance was high (CV = 70%). CONCLUSIONS: G1198745 pharmacokinetics are well described by a pharmacokinetic model with parallel linear and nonlinear elimination. Simulations using this model show that at daily doses of 0.1 mg the steady state drug concentrations, and the rate at which these are achieved, are mainly influenced by the nonlinear pathway, while at daily doses above 1 mg they are almost entirely influenced by the linear pathway. (+info)
(5/3560) Ketotifen and cardiovascular effects of xamoterol following single and chronic dosing in healthy volunteers.
AIMS: To study whether desensitization occurs after long-term administration of the 1-adrenoceptor partial agonist xamoterol and, if so, whether this can be influenced by ketotifen. METHODS: In a double-blind, randomized design 10 young, healthy males received ketotifen (2 x 1 mg day(-1) p.o.) or placebo for 3 weeks with xamoterol (2 x 200 mg day(-1) p.o.) administered concomitantly during the last 2 weeks. 'l1-adrenoceptor mediated responses were assessed as exercise-induced tachycardia and isoprenaline-induced shortening of heart rate corrected electromechanical systole (QS2c); isoprenaline-induced tachycardia was measured as a mixed beta1-/beta2-adrenoceptor-mediated effect. RESULTS: The first dose of xamoterol significantly increased resting heart rate and systolic blood pressure and significantly shortened QS2c. The last dose of xamoterol after 2 weeks of treatment still produced the same responses. Ketotifen did not influence these effects of xamoterol on resting haemodynamics. The first dose of xamoterol caused a rightward shift of the exercise- and isoprenaline-induced tachycardia (mean dose ratios+/-s.e.mean: 1.20+/-0.05 and 2.46+/-0.23) and the isoprenaline-evoked shortening of QS2c (dose ratio 3.59+/-0.68). This rightward shift was even more pronounced after 2 weeks xamoterol treatment. This additional rightward shift after 2 weeks of xamoterol was not affected by ketotifen (mean difference (95% CI) of log transformed dose ratios between placebo and ketotifen: exercise tachycardia 0.001 (-0.03; 0.04); isoprenaline tachycardia 0.03 (-0.15; 0.21); isoprenaline induced shortening of QS2c 0.13 (-0.22; 0.48)). CONCLUSIONS: In humans xamoterol is a partial beta1-adrenoceptor agonist with positive chrono- and inotropic effects at rest and antagonistic properties under conditions of beta-adrenoceptor stimulation. These effects were well maintained after chronic dosing with no signs of beta1-adrenoceptor desensitization. Ketotifen does not change the beta-adrenoceptor mediated responses of xamoterol after chronic dosing. (+info)
(6/3560) Differential vascular alpha1-adrenoceptor antagonism by tamsulosin and terazosin.
AIMS: In patients with lower urinary tract symptoms suggestive of benign prostatic obstruction the alpha1-adrenoceptor antagonist terazosin lowers blood pressure whereas only very small if any alterations were reported with the alpha1-adrenoceptor antagonist tamsulosin. Therefore, we have compared the vascular alpha1-adrenoceptor antagonism of tamsulosin and terazosin directly. METHODS: Ten healthy subjects were investigated in a randomized, single-blind, three-way cross-over design and received a single dose of 0.4 mg tamsulosin, 5 mg terazosin or placebo on 3 study days at least 1 week apart. Before and 1, 3, 5, 7, 10 and 23.5 h after drug intake, alterations of diastolic blood pressure and other haemodynamic parameters in response to a graded infusion of the alpha1-adrenoceptor agonist phenylephrine were determined non-invasively. RESULTS: At most time points tamsulosin inhibited phenylephrine-induced diastolic blood pressure elevations significantly less than terazosin (5 h time point: median difference in inhibition 35%, 95% CI: 18.7-50.3%). On the other hand, phenylephrine-induced changes of cardiac output, heart rate and stroke volume were similar during both active treatments. CONCLUSIONS: In doses equi-effective for treatment of lower urinary tract symptoms tamsulosin causes less inhibition of vasoconstriction than terazosin. (+info)
(7/3560) Filtration leukocytapheresis therapy in rheumatoid arthritis: a randomized, double-blind, placebo-controlled trial.
OBJECTIVE: To determine the efficacy and safety of filtration leukocytapheresis (LCP) for the treatment of rheumatoid arthritis (RA). METHODS: Twenty-five patients with drug-resistant RA were randomly assigned to undergo filtration LCP and 7 to undergo sham apheresis (control group) in a randomized, double-blind, placebo-controlled study. Three apheresis procedures were performed, with 1-week intervals between procedures. The efficacy of filtration LCP was evaluated according to the American College of Rheumatology definition of improvement in RA. Medications for each patient were unchanged for at least 6 months prior to enrollment and throughout the study. RESULTS: Tender joint counts, swollen joint counts, patient assessment of pain and global severity, physician assessment of global severity, and Health Assessment Questionnaire Disability Index were significantly improved in the LCP group compared with the control group (P < 0.05 for patient assessment of pain; P < 0.01 for all others). Seventy-nine percent of the patients in the LCP group exhibited significant overall improvement, while none of the patients in the control group were improved (P < 0.001). CONCLUSION: The results indicate that filtration LCP is an effective and well-tolerated treatment for patients with drug-resistant RA. (+info)
(8/3560) The cost-effectiveness of ibutilide versus electrical cardioversion in the conversion of atrial fibrillation and flutter to normal rhythm.
Atrial fibrillation and atrial flutter are cardiac rhythm disorders that are often symptomatic and may interfere with the heart's function, limiting its effectiveness. These arrhythmias are responsible for a large number of hospitalizations at a significant cost to the healthcare system. Electrical cardioversion (EC) is the most common nonpharmacologic intervention used to convert atrial fibrillation and atrial flutter to normal rhythm. Electrical cardioversion is highly successful in converting patients to normal rhythm; however, it is more traumatic and resource intensive than pharmacologic treatment. Recently, a new rapid-acting drug, ibutilide, was approved for the conversion of atrial fibrillation and atrial flutter. Ibutilide is administered through intravenous infusion and does not require anesthetization of the patient, as is required for EC. A decision-tree model was developed to estimate the cost-effectiveness of ibutilide therapy compared with EC therapy. Clinical outcomes were based on a phase III trial of ibutilide, and resource use was based on the literature and physician clinical judgment. A stepped conversion regimen of first-line ibutilide followed by EC for patients who fail to convert is less expensive and has a higher conversion rate than first-line EC. Sensitivity analysis shows that our results are robust to changes in cost and effectiveness estimates. (+info)