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.     

Topical treatment of actinic keratosis with fluorouracil: is irritation associated with efficacy?

Actinic keratoses (AKs) are common dysplastic epidermal lesions that share clinical, histologic, and molecular features with squamous cell carcinoma. Therapeutic options include destructive modalities (i.e., cryosurgery, curettage) or topical fluorouracil treatment. The efficacy of topical fluorouracil for the treatment of widespread AK lesions has been demonstrated in multiple studies, but treatment is often associated with significant skin irritation. Various approaches to decrease irritation while maintaining efficacy have been attempted, including altered treatment regimens, combination therapies, and variations in vehicle formulations. Recently, a novel topical fluorouracil cream that contains 0.5% 5-fluorouracil in a microsphere vehicle has been approved for the treatment of AK. Data demonstrate that this low-dose formulation is effective in reducing AK lesions while maintaining a tolerable irritation profile.     

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.     

Is weight loss possible in patients treated with thiazolidinediones? Experience with a low-calorie diet

BACKGROUND: Weight gain is a frequent side-effect of thiazolidinediones, possibly related to fluid retention and stimulation of pre-adipocyte differentiation. METHODS: We report our experience with a low-calorie diet (800 cal, sodium content 1500 mmol/day) combined with behavior modification on eight patients treated with thiazolidinediones (six pioglitazone and two rosiglitazone). RESULTS: All patients had reported previous weight gain following treatment with thiazolidinediones. All patients lost weight over 12 weeks in the program with their mean +/- SD body weight falling from 270 +/- 54 lbs (123 +/- 25 kg) to 244 +/- 61 lbs (111 +/- 28 kg) (p < 0.01). The weight loss observed was no different from that observed in 16 age- and gender-matched patients with type 2 diabetes not treated with thiazolidinediones (from 263 +/- 54 lbs (120 +/- 25 kg) to 239 +/- 52 lbs (109 +/- 24 kg); p < 0.01). Glycemic control improved while reducing insulin treatment. Blood pressure control also improved and antihypertensive medications were decreased. The degree and time course of weight loss is no different from that in patients treated with other diabetic therapies and is associated with improved glycemic and blood pressure control. CONCLUSIONS: We conclude that a program of caloric restriction and behavior modification is effective in leading to weight loss in patients treated with thiazolidinediones. This effect is reassuring, since thiazolidinediones stimulate adipogenesis.     

Surfactant therapy in children with pneumonia

After the impressive results in the treatment of respiratory failure in premature babies, natural surfactant has been proposed for the treatment of several lung pathologies in which surfactant deficiency could be suspected. Lung pathologies connected with instability of terminal bronchioles and alveoli have been studied,