Pulmonary function in patients with exogenous bronchial asthma treated with cyproheptadine

AIM: To study changes in FEV (forced vital capacity), FRC (functional residual capacity), CC (closing capacity) and MEFVC (maximal expiratory flow volume curve) of exogenous bronchial asthma treated with cyproheptadine.     

Cardiovascular risk with cyclooxygenase inhibitors: general problem with substance specific differences?

Randomised clinical trials and observational studies have shown an increased risk of myocardial infarction, stroke, hypertension and heart failure during treatment with cyclooxygenase inhibitors. Adverse cardiovascular effects occurred mainly, but not exclusively, in patients with concomitant risk factors. Cyclooxygenase inhibitors cause complex changes in renal, vascular and cardiac prostanoid profiles thereby increasing vascular resistance and fluid retention. The incidence of cardiovascular adverse events tends to increase with the daily dose and total exposure time. A comparison of individual selective and unselective cyclooxygenase inhibitors suggests substance-specific differences, which may depend on differences in pharmacokinetic parameters or inhibitory potency and may be contributed by prostaglandin-independent effects. Diagnostic markers such as N-terminal pro brain natriuretic peptide (NT-proBNP) or high-sensitive C-reactive protein might help in the early identification of patients at risk, thus avoiding the occurrence of serious cardiovascular toxicity.     

Curing diabetes with transplantation?

Type 1 diabetes affects >1 million people in the United States, where it accounts for up to 10% of all diabetes cases. Glycemic control via the use of exogenous insulin injections in diabetic patients is incomplete, resulting in multiple long-term complications such as retinopathy, neuropathy, vasculopathy, and nephropathy. The goal of beta-cell replacement by whole-pancreas or islet transplantation is to achieve long-term insulin independence, and the proposed benefits are improved quality of life, prevention of recurrent diabetic nephropathy, stabilization or improvement in secondary complications, and improved mortality. No other regimen of insulin delivery can achieve this level of physiologic regulation.     

Is combination therapy with lamivudine and interferon-alpha superior to monotherapy with either drug?

For the treatment of chronic hepatitis B (CHB) two drugs have been licensed world-wide: interferon-alpha (IFN) and lamivudine. Both drugs significantly increase the hepatitis B e-antigen (HBeAg) seroconversion rate, but a sustained treatment response occurs in less than 40% of patients. To explore whether there is an additional benefit of combining these two drugs, we reviewed the literature on lamivudine-IFN combination therapy in comparison to the two monotherapies in compensated, HBeAg-positive, CHB patients. We focussed on two clinically relevant outcome measures: HBeAg seroconversion, and change in liver histology. Candidates for lamivudine-IFN combination therapy were, previously untreated, patients with moderately elevated alanine aminotransferase (ALT). Such regimen should still be considered experimental. Viral kinetics may provide insight into how long therapy should be continued; prolongation of therapy to 52 weeks currently appears a reasonable approach. According to principles of anti-viral therapy today, simultaneously dosing of both drugs is to be preferred, since rapid maximal virus suppression is thought to be essential to prevent drug resistance and enhance seroconversion. From an immunological point of view, pre-treatment with lamivudine or IFN may alter the virus-host balance and set the stage for the other drug to enhance the effect of treatment. Further clinical research on lamivudine-IFN combination therapy appears warranted.     

Linking academic institutions with commercial organizations

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No cardiovascular effects of single-dose pseudoephedrine in patients with essential hypertension treated with β-blockers

OBJECTIVE: The use of the decongestant pseudoephedrine has been cautioned in patients with arterial hypertension, due to the possible rise in blood pressure induced by the sympathostimulatory properties of the drug. This effect could be enhanced in hypertensives treated with beta-blockers, in whom the vasoconstrictor effect of alpha-adrenergic stimulation is unbalanced. The purpose of this study was to investigate the cardiovascular response to pseudoephedrine in hypertensive patients treated with different types of beta-blockers. METHODS: We recruited 29 (18 males) mild-to-moderate essential hypertensive patients [mean age 49(2) years] in a randomized, placebo-controlled, crossover trial. All participants received either placebo, or a nonselective (propranolol 160 mg once daily) or a selective (atenolol 100 mg once daily) beta-blocker for 1 week. At the end of each period, all patients received a single oral dose of pseudoephedrine (60 mg) and their blood pressure and heart rate were monitored at repeated intervals for 2 h. RESULTS: After 1 week of propranolol or atenolol, patients had significantly lower systolic blood pressure and heart rate than after placebo, whereas diastolic blood pressure was not significantly modified. The acute administration of pseudoephedrine did not change systolic and diastolic blood pressure and heart rate from baseline at the end of any of the treatment periods. CONCLUSIONS: A standard oral dose of pseudoephedrine does not significantly affect blood pressure values in hypertensive patients treated with beta-blockers, and therefore may be safely used in this subset of patients.     

The safety of studies with intravenous Δ9-tetrahydrocannabinol in humans, with case histories

Rationale

Delta-9-tetrahydrocannabinol (THC) is one of the few cannabinoid receptor ligands that can be used to probe the cannabinoid system in humans. Despite increasing interest in the cannabinoid receptor system, use of intravenous THC as a research tool has been limited by concerns about its abuse liability and psychoactive effects.

Objectives

This study aims to evaluate the safety of all intravenous THC studies conducted at this center for the past 13?years.

Methods

Included were 11 studies with 266 subjects (14 schizophrenia patients and 252 healthy subjects, of whom 76 were frequent cannabis users), 351 active THC infusions, and 226 placebo infusions. Subjects were monitored for subjective and physical adverse events and followed up to 12?months beyond study participation.

Results

There was one serious and 70 minor adverse events in 9.7% of subjects and 7.4% of infusions, with 8.5% occurring after the end of the test day. Nausea and dizziness were the most frequent side effects. Adverse events were more likely to be associated with faster infusion rates (2?C5?min) and higher doses (>2.1?mg/70?kg). Of 149 subjects on whom long-term follow-up data were gathered, 94% reported either no change or a reduction in their desire to use cannabis in the post-study period, 18% stated that their cannabis use decreased, and 3% stated that it increased in the post-study period.

Conclusions

With careful subject selection and screening, risk to subjects is relatively low. Safeguards are generally sufficient and effective, reducing both the duration and severity of adverse events.