Effects of combined low-density lipoprotein apheresis and aggressive statin therapy on coronary calcified plaque as measured by computed tomography

Eight patients with heterozygous familial hypercholesterolemia who received combined long-term low-density lipoprotein apheresis and high-dose statin therapy showed a significant decrease in volume of coronary calcium over a period of 29 months as measured by, computed tomography. This suggests that the effects of aggressive lipid-lowering therapy can be assessed non-invasively and may be used as surrogate end points when testing new therapies.

In overweight patients with chronic hepatitis C, circulating insulin is associated with hepatic fibrosis: implications for therapy

Background/Aims: Host factors such as increased body mass index (BMI) and genotype-specific viral factors contribute to the development of steatosis in patients with chronic hepatitis C (HCV). We hypothesized that host metabolic factors associated with increased BMI may play a role in disease progression. Methods: Fasting serum was collected from 160 patients with chronic HCV at the time of liver biopsy and 45 age, gender and BMI matched controls, and assessed for levels of insulin, c-peptide and leptin. Results: Patients with viral genotype 3 had more severe steatosis (P = 0.0001) and developed stages 1 and 2 fibrosis at a younger age (P < 0.05) than patients with genotype 1. For both genotypes, overweight patients had significantly more steatosis and increased insulin and leptin levels. In contrast to lean patients, there was a statistically significant increase in circulating insulin levels with increasing fibrosis in overweight patients with chronic HCV (P = 0.03). Following multivariate analysis, insulin was independently associated with fibrosis (P = 0.046) but not inflammation (P = 0.83). There was no association between serum leptin levels and stage of fibrosis. Conclusions: Increasing circulating insulin levels may be a factor responsible for the association between BMI and fibrosis in patients with HCV, irrespective of viral genotype. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Left ventricular dyssynchrony predicts benefit of cardiac resynchronization therapy in patients with end-stage heart failure before pacemaker implantation

We evaluated patients with end-stage heart failure who have a high likelihood of response to cardiac resynchronization therapy (biventricular pacing). It appears that 20% of patients do not respond to this expensive therapy despite the use of selection criteria (dilated cardiomyopathy, heart failure, New York Heart Association class II or IV, left ventricular election fraction 120 ms). The presence of left ventricular dys-synchrony is needed to result in improvement after cardiac resynchronization therapy. (C)2003 by Excerpta Medica, Inc.

Antibiotic desensitization in adults with cystic fibrosis

Objective: Allergic reactions to antibiotics occur in up to 30% of patients with cystic fibrosis (CF). Repeated antibiotic exposure and immune hyper-responsiveness increase the risk of allergic reactions and may limit antibiotic choice. Desensitization may allow the successful administration of an antibiotic despite previous allergy. We aimed to determine the success of antibiotic desensitization in patients with CF in an adult CF unit over a 7-year period. Methodology: A retrospective medical record review was performed on the 19 patients who had undergone antibiotic desensitization procedures. Data collected included drug allergy and intolerance profiles, nature of allergies, and the outcome of desensitization procedures. Desensitization procedures were performed in a ward setting according to published methods. Results: Nineteen patients (13 females) reported 62 drug allergies with a mean of 3.3 per patient. Of the 71 desensitization procedures undergone by this group, 54 (76%) were successful. Fifteen of the 19 patients were allergic to two or more beta-lactam antibiotics. Over half of the patients were desensitized to more than one antibiotic. Nine different antibiotics were used in 31 different patient/drug combinations. A successful outcome was achieved in 18/31 (58%) combinations, with three requiring treatment for mild allergic reactions. Allergic reactions caused drug cessation in a total of 19 patient/drug combinations (three after initial successful desensitization and full courses of antibiotics). Over 50% of these reactions occurred on day 1. Desensitization failures were more common in patients with well-documented allergic reactions to a specific drug. Conclusion: This study demonstrates that multiple antibiotic allergies are common in adults with CE Cross-reactivity between beta-lactam antibiotics may limit antibiotic choice for the treatment of pulmonary exacerbations. Antibiotic desensitization allows safe and successful treatment in the ward setting of many patients with previous allergies to an antibiotic. In many patients symptoms of allergy still occur and result in cessation of the antibiotics. Use of corticosteroids and antihistamines may improve the success rate of desensitization procedures.

Transition to raloxifene with and without low-dose estrogen therapy in postmenopausal women: effects on serum lipids and fibrinogen - a pilot study

Objective To compare the effects of transferring from low-dose transdermal estrogen to raloxifene (RLX), with a phase of alternate-day RLX therapy with or without low-dose transdermal estrogen, on serum lipids and fibrinogen in postmenopausal women previously administered estrogen plus progestogen therapy. Methods Sixty postmenopausal women (mean age 55 years) were randomized to one of two treatment groups: RLX + low-dose transdermal estrogen (RLX + E) or RLX + placebo. The study consisted of four 8-week phases: phase I (all subjects low-dose transdermal estrogen 25 mug/day), phase II (double-blind RLX 60 mg every 2nd day in combination with either low-dose transdermal estrogen or placebo), phase III (all subjects RLX 60 mg every 2nd day + placebo) and phase IV (all subjects RLX 60 mg/day + placebo). Results No significant differences existed between groups for baseline measurements prior to phase I. In phase I, for all subjects combined, total cholesterol and low-density lipoprotem cholesterol both showed a significant increase (median increase of 0.2 mmol/l, p = 0.008 and 0.4 mmol/l, p < 0.001, respectively), while triglycerides decreased significantly (median decrease of 0.2 mmol/l, p < 0.001). For the primary analysis (phase II to phase IV), the mean change from baseline observations showed no significant differences between the therapy groups for serum lipids, fibrinogen, vital signs or weight. In the comparison phase (phase II), changes in serum lipids, fibrinogen, vital signs and weight were not significantly different between groups. Conclusion Gradual conversion to RLX from low-dose transdermal estrogen, with a phase of alternate-day RLX therapy with or without low-dose transdermal estrogen, does not have any effect on the serum lipid profile or fibrinogen level.