Fast-particle-driven Alfvénic modes in a reversed field pinch.

Alfvénic modes are observed due to neutral beam injection for the first time in a reversed field pinch plasma. Modeling of the beam deposition and slowing down shows that the velocity and radial localization are high. This allows instability drive from inverse Landau damping of a bump-on-tail in the parallel distribution function or from free energy in the fast ion density gradient. Mode switching from a lower frequency toroidal mode number n=5 mode that scales with beam injection velocity to a higher frequency n=4 mode with Alfvénic scaling is observed.

Effect of advanced glycation end products on endotoxin-induced TNF-alpha, IL-1beta and IL-8 in human peripheral blood mononuclear cells.

BACKGROUND/AIMS: Advanced glycated end products (AGE) are endogenous proteins that have formed covalent complexes with sugars by a nonenzymatic process. Being proinflammatory molecules, AGE are thought to contribute to chronic systemic and local inflammatory processes associated with pathological changes in various diseases. In patients with end-stage renal disease, AGE are believed to play a role in the progression of atherosclerosis and worsening of renal failure. In patients receiving hemodialysis, AGE are thought to contribute to the inflammatory components of the therapy, particularly in diabetic patients. METHODS: In the present study, AGE were produced using 5% human serum albumin (HSA) and 50% glucose, both used for intravenous infusion into humans and both released after strict control for endotoxin content. The presence of AGE formed by HSA and glucose was confirmed using 2 independent assays. The inflammatory properties of these AGE were assessed using synthesis and release of the proinflammatory cytokines interleukin-1 (IL-1), tumor necrosis factor (TNF) and IL-8, a chemokine. RESULTS: Alone, AGE did not induce these cytokines from peripheral blood mononuclear cells (PBMC) obtained from 14 healthy human donors. However, in the presence of 1 or 10 ng/ml of endotoxin, AGE augmented the production of IL-1 and TNF above that induced by endotoxin alone. Although the amount of augmentation of LPS-induced cytokines by AGE varied between the blood donors, the response was consistently observed and reached statistical significance. The augmentation of cytokine production was confirmed using AGE prepared with different lots of HSA and glucose. CONCLUSION: These results demonstrate that in the strict absence ofendotoxins, AGE are formed that do not stimulate cytokine production from PBMC of healthy donors, however, AGE significantly augment the synthesis and release of proinflammatory cytokine in the presence of low concentrations of endotoxins. The data suggest that renal replacement therapies should consider the role of microbial products in potentiating the biological consequences of naturally formed AGE and their potential to contribute to systemic and local inflammation in renal replacement therapies. Therefore, although the formation of AGE is unavoidable, excluding microbial products during renal replacement therapy should reduce the pathological consequences of AGE.

Acute myocardial infarction associated with amphetamine use.

Myocardial infarction is a rarely reported complication of amphetamine use. We report the case of a healthy 31-year-old man who presented to our emergency department with no clinical evidence of an acute coronary event after intravenous injection of amphetamines. However, he subsequently experienced a non-Q-wave anterior wall myocardial infarction associated with the use of amphetamines.

Ibuprofen liquigel for oral surgery pain.

BACKGROUND: Ibuprofen liquigel is a solubilized potassium ibuprofen 200-mg gelatin capsule formulation that was approved for over-the-counter use in 1995. OBJECTIVE: This study compared the analgesic efficacy and tolerability of ibuprofen liquigel 200 mg, ibuprofen liquigel 400 mg, acetaminophen caplets 1000 mg, and placebo in patients experiencing moderate or severe pain after surgical removal of impacted third molars. METHODS: This randomized, double-blind, parallel-group, 6-hour study was conducted in 210 patients experiencing moderate or severe postoperative pain. Ratings of pain intensity and pain relief were recorded every 15 minutes for the first hour, at 90 and 120 minutes, and then hourly through hour 6. The onsets of first perceptible relief and meaningful relief were recorded using 2 stopwatches. An analysis of variance model was employed to test for significant differences (P < or = 0.05) between treatment groups with respect to pain relief, pain intensity difference, total pain relief (TOTPAR), and summed pain intensity difference (SPID). Stopwatch measures were analyzed using the Cox proportional hazards model. Drug tolerability was assessed by monitoring the occurrence of adverse events. RESULTS: During the first 2 hours of the study (TOTPAR 2 and SPID 2), all active treatments were significantly more efficacious than placebo (P < 0.001), with ibuprofen liquigel 200 and 400 mg significantly more efficacious than acetaminophen 1000 mg (P < 0.05 and P < 0.01, respectively). For the entire duration of the study (TOTPAR 6 and SPID 6), only the 2 doses of ibuprofen liquigel were significantly more efficacious than placebo (P < 0.001). Ibuprofen liquigel 200 and 400 mg were also significantly more efficacious than acetaminophen 1000 mg on the summary measures TOTPAR 6 and SPID 6 (P < 0.01 and P < 0.001, respectively). Analysis of the stopwatch data revealed that all active treatments displayed significantly more rapid onsets to confirmed first perceptible relief (P < 0.001 to < 0.05) and meaningful relief (P < 0.001 to < 0.01) than did placebo, with ibuprofen liquigel 400 mg displaying a significantly more rapid onset to meaningful relief than acetaminophen 1000 mg (P < 0.05) and a significantly more rapid onset to confirmed first perceptible relief than acetaminophen 1000 mg (P < 0.001) and ibuprofen liquigel 200 mg (P < 0.01). All adverse events were considered mild or moderate, with an overall incidence of 11.5% in the ibuprofen liquigel 200-mg group, 6.8% in the ibuprofen liquigel 400-mg group, 19.0% in the acetaminophen 1000-mg group, and 25.9% in the placebo group. CONCLUSIONS: Ibuprofen liquigel provided greater peak and overall analgesic effects and a more rapid onset to analgesia than did acetaminophen 1000 mg.

The safety profile of nonprescription ibuprofen in multiple-dose use: a meta-analysis.

A meta-analysis was performed to compare the incidence of adverse experiences (AEs) during the multiple-dose use of nonprescription ibuprofen to a placebo. Eight studies, with doses ranging from 800 to 1200 mg/day and durations of 1 to 10 days, met the criteria for inclusion. AEs were classified according to COSTART, except that "abdominal pain" was conservatively reassigned to the digestive system. In each study, the overall AE frequency among ibuprofen-treated subjects (n = 1094) was numerically less than or equal to the placebo (n = 1093). Pooled across all studies, placebo subjects reported AEs significantly (p = 0.018) more often (31.7%) than ibuprofen subjects (27.4%). The frequency of digestive system AEs was comparable (p = 0.420) for the placebo (11.0%) and ibuprofen (12.1%); there was no significant difference for any specific digestive system AE. AE frequency in the "body-as-a-whole" category was significantly higher (p < 0.001) in the placebo (20.4%) than in ibuprofen (14.8%). The number of severe AEs in all of these categories was lower for ibuprofen than for the placebo. These data indicate that nonprescription ibuprofen has an excellent side effect profile in multiple-dose use, with a frequency of gastrointestinal AEs comparable to a placebo.

Evaluating the process of tailoring the global HIV/AIDS practice guidelines for use in developing countries.

OBJECTIVE: To describe a systematic procedure for adapting, or 'tailoring' the World Health Organisation's 'global guidelines for the management of HIV/AIDS in adults and children' for use in two developing countries: Malawi and Barbados. DESIGN: In order for these guidelines to achieve reproducibility, clinical flexibility, and clinical applicability, a systematic procedure is needed to tailor the guidelines to the local practice conditions of specific settings. METHODS: A group of local experts in each country used a nominal group process to modify the global program on AIDS (GPA) guidelines for local use. Semantic analysis techniques, known as clinical algorithm nosology (CAN), were used to compare the two modified guidelines with the global ones to determine the extent and type of differences between sets of guidelines. RESULTS: Standard, locally-tailored algorithm map guidelines (AMG) were developed within 4 months. CAN semantic analysis showed that guideline structure was maintained; 572/858 (66.6%) decision nodes were found to be the same in the GPA/Malawi, GPA/Barbados and Malawi/Barbados comparisons. However, different guideline versions managed patients quite differently, as evidenced by clinical algorithm patient abstraction (CAPA) scores of between 0 and 8.46 (0 = different; 8 = similar; 10 = identical). Analysis of the 197 specific differences found in these abstractions showed that 83% were in approaches to diagnosis and therapy, while the remaining 17% related to disease prevalence. CONCLUSIONS: Standard techniques involving consensus used to develop clinical guidelines can also be employed to tailor these guidelines to local settings. Semantic analysis shows that the tailoring preserves structure but may involve significant modification to the processes of clinical care that could in turn affect care outcomes.

Nonprescription ibuprofen: side effect profile.

Single doses of nonprescription analgesics are commonly used to treat self-diagnosed conditions. To evaluate the safety of single doses of nonprescription-strength ibuprofen, we examined reported side effects from 15 double-blind, randomized, controlled trials we conducted of the drug to treat various common painful conditions (e.g., headache, sore throat). All studies included placebo and another nonprescription analgesic, acetaminophen. A total of 878 subjects received ibuprofen 200 or 400 mg, 849 acetaminophen 650 or 1000 mg, and 852 placebo. The overall frequency of side effects was comparable: ibuprofen 2.4%, acetaminophen 3.2%, and placebo 2.1%. The frequency of central nervous system symptoms was 0.8%, 2.1%, and 0.9%, respectively. Upper gastro-intestinal upset ranged from 0.8-0.9% of subjects in all groups. We conclude that single doses of nonprescription ibuprofen are well tolerated and demonstrate a side effect profile indistinguishable from that of acetaminophen and placebo.

The effects of 1,2-dibromo-3-chloropropane (DBCP) on general toxicity and gonadotoxicity in rats.

This study was set to determine if there is a correlation between the general toxic effect and the gonadotoxic effect of DBCP on male rats. Groups of male rats were injected with a single dose of DBCP (50 mg kg-1) dissolved in dimethylsulfoxide (DMSO). Twenty four hours, one and four weeks post injection animals were sacrificed. Blood was collected for enzymes' and hormones' assays. Organs were weighed and testes were taken for histological examination and sperm counts. The results showed that DBCP at a dose of 50 mg kg-1 had a general toxic effect expressed by reduction in body and liver weights and reduced activities of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT). These changes show a tendency to revert to normal values with time. On the other hand, gonadotoxic effects increase in severity with time. The weight of testes and epididymides were reduced, sperm counts decreased and histological damage advanced, and FSH and LH blood levels increased 4 weeks post injection. It seems that in rats the gonadotoxic effect of DBCP is dissociated from the general toxic effects.

Double-blind, placebo-controlled trial of propranolol given once, twice and four times daily in stable angina pectoris: a multicenter study using serial exercise testing.

To determine if propranolol given twice daily (b.i.d.) or once daily (q.d.) was as effective as 4 times daily (q.i.d.) for treatment of stable angina pectoris, 78 patients with exercise-induced ST depression of 1.5 mm were randomized to q.i.d., b.i.d., q.d. and placebo groups. All patients received 5 tablets per day, and propranolol groups received 80, 160 and 320 mg/day on successive weeks. At weekly visits, patients underwent treadmill exercise testing before the 8:00 AM dose and at 2 and 9 hours afterward. Exercise duration (seconds) was significantly improved at the final visit compared with baseline by b.i.d. (120 +/- 36 [mean +/-] standard error of the mean p less than 0.001 n = 18) and q.i.d. (100 +/- 37, p less than 0.01; n = 17) regimens, but not by the q.d. (30 +/- 33; n = 18) and placebo regimens (27 +/- 37; n = 17). There was a significant decrease from baseline in the magnitude of ST depression at the final visit, measured at maximal common exercise duration in b.i.d. (-0.96 +/- 0.20 mm, p less than 0.001), q.i.d. (-0.84 +/- 0.20 mm, p less than 0.01) and q.d. (-0.58 +/- 0.18 mm, p less than 0.05) groups, but not in the placebo group (0.03 +/- 0.2 mm). Hourly heart rate by Holter was reduced in all 3 propranolol groups; however, the mean serum propranolol level was significantly lower just before the first dose with q.d. group (56 +/- 20 ng/ml) compared with b.i.d. and q.i.d. groups (146 +/- 22 and 119 +/- 28 ng/ml) with 320 mg/day (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)