Isradipine Twice Daily Lowers Blood Pressure Over 24 H

The objective of this study was to compare the effects of isradipine and placebo on blood pressure (BP) at the end of the dosing interval (‘trough'). Following a three-week placebo period, 187 patients who had previously shown a response to treatment with isradipine (based on office BP measurements) were randomized to double-blind treatment with 2.5 mg isradipine twice daily or placebo for six weeks. Four of these patients withdrew from the study during the double-blind phase because of adverse events (one taking isradipine and three taking placebo). Blood pressure during the double-blind study was always measured 12 h after drug administration (trough values). The rate of normalization [defined as diastolic BP (DBP) ≤ 90 mm Hg] was 52/96 (54%) in the isradipine-treated group compared with 30/87 (33%) in the placebo group. A further 12/96 (12%) patients taking isradipine showed a fall in DBP of ≥ 10 mm Hg, although their DBP was still not < 90 mm Hg, compared with 5/87 (6%) patients receiving placebo. This difference was statistically significant (P = .003). Thus, isradipine in a dose of 2.5 mg twice daily lowers blood pressure over 24 h. Am J Hypertens 1991;4:131S-134

Motivational determinants of physical activity in disadvantaged populations with (pre)diabetes: A cross-cultural comparison

Understanding motivational determinants of physical activity (PA) is essential to guide the implementation of PA at individual and population level. Knowledge about the cross-cultural generalizability of these determinants is lacking and they have mostly been studied as separate factors. This study compares a motivational process model across samples from diverse populations with, or at risk of diabetes.Measurement invariance of barrier identified regulation, barrier self-efficacy and social support was assessed in a rural Ugandan sample (n=712) and disadvantaged samples with high proportions of immigrants in urban South Africa (n=566) and Sweden (n=147). These motivational determinants were then compared through multigroup structural equation modeling

Prospective Analysis in GIST Patients on the Role of Alpha-1 Acid Glycoprotein in Imatinib Exposure

Background: For imatinib, a relationship between systemic exposure and clinical outcome has been suggested. Importantly, imatinib concentrations are not stable and decrease over time, for which several mechanisms have been suggested. In this study, we investigated if a decrease in alpha-1 acid glycoprotein (AGP) is the main cause of the lowering in imatinib exposure over time. Methods: We prospectively measured imatinib trough concentration (Cmin) values in 28 patients with gastrointestinal stromal tumours, at 1, 3 and 12 months after the start of imatinib treatment. At the same time points, AGP levels were measured. Results: Overall, imatinib Cmin and AGP levels were correlated (r2 = 0.656; P < 0.001). However, AGP levels did not fluctuate significantly over time, nor did the change in AGP levels correlate with the change in the imatinib Cmin. Conclusion: We showed that systemic AGP levels are not likely to be a key player in the decrease in systemic imatinib exposure over time. As long as intra-individual changes in imatinib exposure remain unexplained, researchers should standardize the sampling times for imatinib in order to be able to assess the clinical applicability of therapeutic drug monitoring

Persistence of clones of coagulase-negative staphylococci among premature neonates in neonatal intensive care units: two-center study of bacterial genotyping and patient risk factors

From 1 January 1995 until 1 January 1996, we studied the molecular epidemiology of blood isolates of coagulase-negative staphylococci (CoNS) in the Neonatal Intensive Care Units (NICUs) of the Sophia Children's Hospital (SCH; Rotterdam, The Netherlands) and the Wilhelmina Children's Hospital (WCH; Utrecht, The Netherlands). The main goal of the present study was to detect putatively endemic clones of CoNS persisting in these NICUs. Pulsed-field gel electrophoresis was used to detect the possible presence of endemic clones of clinical significance. In addition, clinical data of patients in the SCH were analyzed retrospectively to identify risk factors for the acquisition of positive blood cultures. In both centers, endemic CoNS clones were persistently present. Thirty-three percent of the bacterial isolates derived from blood cultures in the SCH belonged to a single genotype. In the WCH, 45% of all bacterial strains belonged to a single clone. These clones were clearly different from each other, which implies that site specificity is involved. Interestingly, we observe that the clonal type in the SCH differed significantly from the incidentally occurring strains with respect to both the average pH and partial CO2 pressure of the patient's blood at the time of bacterial culture. We found that the use of intravascular catheters, low gestational age, and a long hospital stay were important risk factors for the development of a putative CoNS infection. When the antibiotic susceptibility of the bacterial isolates was assessed, a clear correlation between the nature of the antibiotics most frequently used as a first line of defense versus the resistance profile was observed. We conclude that the intensive use of antibiotics in an NICU setting with highly susceptible patients causes selection of multiresistant clones of CoNS which subsequently become endemic

Efficacy and safety of an intravenous monoclonal anti-HBs in chronic hepatitis B patients

Background Aims: In this study the safety and efficacy of a monoclonal anti-HBs, Tuvirumab (Mab), were investigated. Tuvirumab is a human monoclonal antibody recognizing the stable 'a'-determinant of the HBsAg. Methods: We included ten chronic hepatitis B patients: four received monotherapy, and six combination therapy with interferon alpha 2b. Results: Because the development of insoluble [HBsAg-HBsAb] complexes led to adverse events, the Mab dose had to be reduced in seven patients. In nine patients treatment was stopped prematurely because of lack of efficacy, i.e. neutralization of HBsAg in serum. However, temporary HBsAg levels were reduced by at least 50% in all patients; in three patients receiving combination therapy, background levels of HBsAg in serum were reached. A loss of serum HBV-DNA was seen in three patients in the combination group, followed by HBeAg seroconversion in two patients. Conclusions: We conclude that Mab was not effective in achieving primary efficacy as assessed by neutralization of circulating HBsAg. Whether a combination of Mab with an antiviral agent that reduces the HBsAg load - and therefore minimizes the risk of adverse events - may result in clinical efficacy should be investigated

Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension

We studied the hemodynamic, neurohumoral, and biochemical effects of the novel angiotensin type 1 (AT1) receptor antagonist irbesartan in 86 untreated patients with essential hypertension on a normal sodium diet. According to a double-blind parallel group trial, patients were randomized to a once-daily oral dose of the AT1 receptor antagonist (1, 25, or 100 mg) or placebo after a placebo run-in period of 3 weeks. Randomization medication was given for 1 week. Compared with placebo, 24-hour ambulatory blood pressure did not change with the 1-mg dose, and it fell (mean and 95% confidence interval) by 7.0 (4.2-9.8)/6.1 (3.9-8.1) mm Hg with the 25-mg dose and by 12.1 (8.1-16.2)/7.2 (4.9-9.4) mm Hg with the 100-mg dose. Heart rate did not change during either dose. With the 25-mg dose, the antihypertensive effect was attenuated during the second half of the recording, and wi

Marine Low Cloud Sensitivity to An Idealized Climate Change: The CGILS LES Intercomparison

Subtropical marine low cloud sensitivity to an idealized climate change is compared in six large-eddy simulation (LES) models as part of CGILS. July cloud cover is simulated at three locations over the subtropical northeast Pacific Ocean, which are typified by cold sea surface temperatures (SSTs) under well-mixed stratocumulus, cool SSTs under decoupled stratocumulus, and shallow cumulus clouds overlying warmer SSTs. The idealized climate change includes a uniform 2 K SST increase with corresponding moist-adiabatic warming aloft and subsidence changes, but no change in free-tropospheric relative humidity, surface wind speed, or CO2. For each case, realistic advective forcings and boundary conditions are generated for the control and perturbed states which each LES runs for 10 days into a quasi-steady state. For the control climate, the LESs correctly produce the expected cloud type at all three locations. With the perturbed forcings, all models simulate boundary-layer deepening due to reduced subsidence in the warmer climate, with less deepening at the warm-SST location due to regulation by precipitation. The models do not show a consistent response of liquid water path and albedo in the perturbed climate, though the majority predict cloud thickening (negative cloud feedback) at the cold-SST location and slight cloud thinning (positive cloud feedback) at the cool-SST and warm-SST locations. In perturbed climate simulations at the cold-SST location without the subsidence decrease, cloud albedo consistently decreases across the models. Thus, boundary-layer cloud feedback on climate change involves compensating thermodynamic and dynamic effects of warming and may interact with patterns of subsidence change

Marine Low Cloud Sensitivity to An Idealized Climate Change: The CGILS LES Intercomparison

Subtropical marine low cloud sensitivity to an idealized climate change is compared in six large-eddy simulation (LES) models as part of CGILS. July cloud cover is simulated at three locations over the subtropical northeast Pacific Ocean, which are typified by cold sea surface temperatures (SSTs) under well-mixed stratocumulus, cool SSTs under decoupled stratocumulus, and shallow cumulus clouds overlying warmer SSTs. The idealized climate change includes a uniform 2 K SST increase with corresponding moist-adiabatic warming aloft and subsidence changes, but no change in free-tropospheric relative humidity, surface wind speed, or CO2. For each case, realistic advective forcings and boundary conditions are generated for the control and perturbed states which each LES runs for 10 days into a quasi-steady state. For the control climate, the LESs correctly produce the expected cloud type at all three locations. With the perturbed forcings, all models simulate boundary-layer deepening due to reduced subsidence in the warmer climate, with less deepening at the warm-SST location due to regulation by precipitation. The models do not show a consistent response of liquid water path and albedo in the perturbed climate, though the majority predict cloud thickening (negative cloud feedback) at the cold-SST location and slight cloud thinning (positive cloud feedback) at the cool-SST and warm-SST locations. In perturbed climate simulations at the cold-SST location without the subsidence decrease, cloud albedo consistently decreases across the models. Thus, boundary-layer cloud feedback on climate change involves compensating thermodynamic and dynamic effects of warming and may interact with patterns of subsidence change