Skin reaction in antiviral therapy for chronic hepatitis C: a role for polyethylene glycol interferon?

In the past decade, different modalities of antiviral therapy have been adopted aimed at eradicating hepatitis C virus infection. Initially, interferon was used in monotherapy, then interferon combined with ribavirin and amantadine. Recently, interferon has been conjugated with polyethylene glycol to allow optimization of its pharmacokinetic properties and to improve its antiviral activity. This study focused on the characteristics of the skin reactions that we observed in 27 patients with na?ve hepatitis C who received polyethylene glycol interferon-ribavirin-amantadine or polyethylene glycol interferon-ribavirin and in 10 previous non-responders to interferon monotherapy who were retreated with triple therapy. In 9 patients (7 on triple therapy) dermatitis-like lesions were observed, and in 5 the severity of the lesions necessitated withdrawal from therapy.     

Localized Panniculitis and Subsequent Lipoatrophy with Subcutaneous Glatiramer Acetate (Copaxone®) Injection for the Treatment of Multiple Sclerosis

Glatiramer acetate (copolymer 1, Copaxone) is a mixture of synthetic polypeptides and is used for the treatment of multiple sclerosis. It has been shown to possess beneficial effects in reducing the relapse rate in relapsing-remitting multiple sclerosis. Its main mechanism of action is regarded as a switch of the immune reaction from a T helper (Th)1 to a Th2 cell type. Glatiramer acetate is administered by subcutaneous injection once daily. As described in previous reports, the most common adverse effects are pain, inflammation, and induration at the injection site, occurring in approximately 20-60% of patients. A rare adverse effect is a localized lipoatrophy at the site of injection, which has previously been observed and described in 11 patients. It has been reported that these atrophic areas remain unchanged and localized lipoatrophy may be preceded by a subcutaneous panniculitis. In this article, we describe another case of subcutaneous changes following repeated glatiramer acetate injection, presented as localized panniculitis in the area around the injection sites, in a 46-year-old female patient who was treated with glatiramer acetate for 18 months.     

The effects of cardiovascular dynamics monitoring in the outpatient management of pregnancy hypertension

OBJECTIVE: Our purpose was to assess the effects of the adjunctive use of cardiovascular dynamics monitoring in the ambulatory management of 199 pregnant patients with severe hypertension. STUDY DESIGN: A prospective, observational study was performed. Determinants of mean arterial pressure were computed by using the Hon monitor. Indicators of arterial compliance and effective blood volume were developed. All patients were monitored in the outpatient clinic; additionally, 19 patients self-tested at home. No rigid medication protocol was followed, but furosemide was used in most cases when cardiovascular dynamics monitoring patterns were consistent with volume loading. Otherwise, vasodilators were prescribed. The t test for independent samples was used to compare the home-monitored subgroup with the outpatient-only group. RESULTS: Pregnancy was prolonged by 74 +/- 63.9 days (mean +/- SD). Mean gestation was 37.6 +/- 2.9 weeks, and mean birth weight was 2882.4 +/- 837 g. The primary cesarean delivery rate was 23.7%, but only 15 (7.5%) cesarean deliveries were performed because of failed therapy. The 19 home-monitored patients gained 108 +/- 75 days (83.1 +/- 42.2 days beyond 20 weeks). CONCLUSION: Adjunctive cardiovascular dynamics monitoring may have a role in the evaluation and management of hypertension during pregnancy.     

An unusual family with multiple movement disorders

Multiple movement disorders presenting in the same family are rare. We present an unusual family where generalized dystonia, Huntington's disease, progressive supranuclear palsy and secondary paroxysmal dyskinesia co-exist. The index case presented with young-onset dystonia and tested negative for the DYT1 gene deletion. Her father was similarly affected. The father's brother (paternal uncle of the index) also had abnormal movements-a mixture of chorea and dystonia-and tested positive for the HD expansion. His son had secondary paroxysmal dyskinesia, and tested negative for the HD expansion. The index case and her father were also negative for the HD expansion. A paternal aunt of two of the cases had a clinical diagnosis of progressive supranuclear palsy.Dystonia is known to be a genetically heterogeneous condition. The co-existence of inherited generalized dystonia with other movement disorders may provide clues to its genetic localization.     

A Study on the Mechanisms by Which Minocycline Protects Against MDMA (‘Ecstasy’)-Induced Neurotoxicity of 5-HT Cortical Neurons

3,4-Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is a selective 5-HT neurotoxin in rat brain which has been shown to produce acute neuroinflammation characterized by activation of microglia and release of interleukin-1beta (IL-1β). We aimed to determine whether or not minocycline, a semi-synthetic tetracycline antibiotic capable of inhibiting microglial activation, could prevent the inflammatory response and reduce the toxicity induced by MDMA. Adult male Dark Agouti rats were given minocycline twice a day for 2 days (45 mg/kg on the first day and 90 mg/kg on the second day; 12-h apart, i.p.). MDMA (12.5 mg/kg; i.p.) was given after the third minocycline injection and animals were killed either 1 h later for the determination of NFκB binding activity, 3 h later for the determination of IL-1β, 24 h later for the determination of microglial activation or 7 days later for the determination of [³H]-paroxetine binding as a measure of 5-HT neurotoxicity. MDMA increased NFκB activation, IL-1β release and microglial activation both in the frontal cortex and in the hypothalamus and 7 days later produced a reduction in the density of 5-HT uptake sites in both these brain areas. Minocycline prevented the MDMA-induced increase in NFκB activation, IL-1β release and microglial activation in the frontal cortex and prevented the 5-HT neurotoxicity 7 days later. However, in the hypothalamus, in spite of preventing MDMA-induced microglial activation, minocycline failed to prevent MDMA-induced NFκB activation, IL-1β release and neurotoxicity. This suggests that the protective mechanism of minocycline against MDMA-induced neurotoxicity in frontal cortex involves inhibition of MDMA-induced NFκB activation possibly through a reduction in IL-1β signalling.     

Non-coronary chest pain: esophageal evaluation in 27 patients

The authors analyse the clinical features of 27 patients with non-coronary chest pain. They applied specific questionnaire and used esophageal function tests. The pain features were very similar to coronary patients, but there was a strict relationship with emotional stress. Esophageal symptoms were found in about 50% of patients. Eighty-five, one percent of the patients, presented with some abnormalities; 33.3% of the total group with esophagitis and 66.6% with motor disorders; some patients presented overlapping pictures. Three patients had duodenal ulcer. The patients were classified as having pain of proved (18.5%), or suspected (66.6%) esophageal origin. Twenty of these patients were followed and those with esophagitis and/or duodenal ulcer had a good response to specific treatment. The author stress the importance of showing the patients the benign nature of this disease. In the present group of patients, the actual diagnosis was more important in obtaining good therapeutic response than classifying the pain as above.     

Molecular Imaging of Angiogenesis in Cardiac Regeneration

Purpose of Review

Myocardial infarction (MI) leading to heart failure displays an important cause of death worldwide. Adequate restoration of blood flow to prevent this transition is a crucial factor to improve long-term morbidity and mortality. Novel regenerative therapies have been thoroughly investigated within the past decades.

Recent Findings

Increased angiogenesis in infarcted myocardium has shown beneficial effects on the prognosis of MI; therefore, the proangiogenic capacity of currently tested treatments is of specific interest. Molecular imaging to visualize formation of new blood vessels in vivo displays a promising option to monitor proangiogenic effects of regenerative substances.

Summary

Based on encouraging results in preclinical models, molecular angiogenesis imaging has recently been applied in a small set of patients. This article reviews recent literature on noninvasive in vivo molecular imaging of angiogenesis after MI as an integral part of cardiac regeneration.