Activity of telithromycin against key pathogens associated with community-acquired respiratory tract infections

OBJECTIVES: To investigate the correlation between in vitro susceptibility of isolates and clinical outcomes with telithromycin in respiratory tract infections. METHODS: The activity of telithromycin was determined by in vitro susceptibility testing of key respiratory tract pathogens isolated from patients with community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute maxillary sinusitis enrolled in 14 Phase III/IV clinical trials evaluating the clinical efficacy of telithromycin. RESULTS: In this pooled analysis, telithromycin mode minimum inhibitory concentration (MIC) and MIC90, respectively, were: 0.016 and 0.03 mg/l against Streptococcus pneumoniae (n=626); 0.03 and 0.5 mg/l for penicillin-resistant S. pneumoniae (n=56); 0.03 and 1 mg/l for erythromycin-resistant S. pneumoniae (n=81); 2 and 4 mg/l against Haemophilus influenzae (including beta-lactamase producers; n=627); both 0.12 mg/l for Moraxella catarrhalis (n=159) and both 0.25 mg/l for Staphylococcus aureus (n=124). Telithromycin (5 or 7-10 days) resulted in overall clinical and bacteriologic success rates of 88.1% (1593/1808) and 89% (1593/1789), respectively. CONCLUSIONS: High levels of in vitro susceptibility to telithromycin are paralleled by high rates of clinical cure and bacteriologic eradication.     

High‐frequency vibration for the recanalization of guidewire refractory chronic total coronary occlusions

Background: Recanalization of coronary chronic total occlusions (CTOs) remains a clinical challenge, particularly when standard guidewire attempts fail. Objectives: We sought to determine the safety and efficacy of a novel method that used high‐frequency (20 kHz) vibration to fragment occlusive fibrous tissue and facilitate guidewire crossing into the distal vessel. Methods: A total of 125 patients with CTO, who failed at attempts of conventional guidewire recanalization after more than 5 min of fluoroscopy time, were enrolled in the study. The primary efficacy endpoint was the advancement of the CROSSER? catheter through the occlusion and attainment of coronary guidewire positioning in the distal coronary lumen. The primary safety endpoint was the occurrence of death, myocardial infarction, clinical perforation, or target vessel revascularization within the first 30 days. Results: The average fluoroscopy time while delivering the CROSSER catheter was 12.4 min. CROSSER‐assisted guidewire recanalization was achieved in 76 (60.8%) procedures and a final diameter stenosis <50% was obtained in 68 (54.4%) of cases. Major adverse events occurred in 11 (8.8%) patients, lower than the predefined objective performance criteria. Angina frequency and quality of life were improved in patients with successful guidewire recanalization. Conclusions: We conclude that high‐frequency vibration using the CROSSER catheter is a safe and effective therapy for patients with CTO, which are refractory to standard guidewire recanalization. © 2008 Wiley‐Liss, Inc.     

Discordant atrial natriuretic peptide and brain natriuretic peptide levels in lone atrial fibrillation

OBJECTIVES: We sought to characterize natriuretic peptide levels in a cohort of rigorously characterized subjects with lone atrial fibrillation (AF). BACKGROUND: Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are sensitive biomarkers of cardiac contractile dysfunction. Both peptides have been reported to be elevated in cohorts with AF, but previous studies have included subjects with underlying structural heart disease. We studied these hormones in 150 subjects with lone AF. METHODS: Study subjects had electrocardiographic evidence of at least one episode of AF and a structurally normal heart on echocardiography. Subjects were excluded if they had a history of a myocardial infarction, rheumatic heart disease, cardiomyopathy, significant valvular disease, hyperthyroidism, or hypertension that preceded the onset of AF. Control subjects were obtained from a healthy outpatient primary care population. Plasma pro-ANP and N-terminal pro-BNP (nt-pro-BNP) levels were determined using commercially available immunoassays. RESULTS: A total of 150 serial subjects with lone AF were enrolled and studied, the majority during normal sinus rhythm. Median levels of nt-pro-BNP were significantly elevated in subjects with lone AF as compared with control subjects (166 vs. 133 fmol/ml, p=0.0003). There was no significant difference in pro-ANP levels between subjects with lone AF and control subjects (1,730 vs. 1,625 fmol/ml, p=0.90). CONCLUSIONS: Discordant natriuretic peptide levels were observed in this homogeneous population of subjects with lone AF. This biomarker pattern, which is present even in sinus rhythm, may represent an underlying subclinical predisposition to this common arrhythmia.     

Early identification of axial spondyloarthritis in a multi-ethnic Asian population

Clinical Rheumatology - To address the diagnostic delay in axial spondyloarthritis (axSpA), we have cross-culturally adapted the Hamilton axSpA questionnaire, a self-administered screening...     

Recurrent aortic aneurysms following thoracic aortic stent-graft repair in a patient with Cogan syndrome.

PURPOSE: To report the need for multiple surgical interventions to treat recurrent aortic aneurysms in a patient with Cogan syndrome. CASE REPORT: A 17-year-old Chinese man with clinical Marfanoid features had a left common carotid artery pseudoaneurysm electively repaired with an autologous saphenous vein graft. Four months later, he presented with acute chest pain. Computed tomography (CT) revealed a 1-cm pseudoaneurysm at the mid descending aorta; a 24 x 100-mm Talent stent-graft was implanted to exclude the pseudoaneurysm. He was also found to have increasing left-sided hearing loss. A month later, the patient was re-admitted with vertigo and keratitis, which were treated appropriately. Nine months following stent-graft insertion, he was admitted with acute hemoptysis. Urgent CT showed a rupture at the proximal end of the stent-graft, with hemorrhage into the lung parenchyma. In an emergent procedure, the stent-graft was removed, and the descending thoracic aorta was repaired. Intraoperatively, a large pseudoaneurysm was found arising from the proximal part of the stented aorta, which appeared thickened. His postoperative recovery was uneventful. Nine months after the thoracotomy, a routine CT revealed an aneurysm at the distal descending thoracic aorta. On re-thoracotomy, a de novo saccular aneurysm was found 2.5 cm from the distal anastomosis. The affected segment was replaced with a Dacron graft. The distal aorta appeared thickened and edematous; histology confirmed aortitis. The patient was subsequently diagnosed with Cogan syndrome and given corticosteroids and methotrexate. There is no evidence of recurrence at nearly 2 years after the last intervention. CONCLUSION: This case highlights the pitfalls of stent-graft repair in a patient with presumed connective tissue disease.     

Social Factors Associated with Readiness for Sexual Activity in Adolescents: A Population-Based Cohort Study

Archives of Sexual Behavior - Various factors are associated with sexual activity in adolescence and it is important to identify those that promote healthy and adaptive romantic and sexual...     

Interrater and intrarater reliability of the wheelchair skills test version 4.2 for power wheelchair users

Purpose: The purpose of this study is to estimate the interrater and intrarater reliability of the Wheelchair Skills Test (WST) Version 4.2 for powered wheelchairs operated by adult users.

Materials and methods: Cohort study with a convenience sample of occupational therapists (n?=?10). For the main outcome measure, participants viewed and scored eight videos of adult power wheelchair users completing the 30 skills of the WST Version 4.2 on two occasions, a minimum of two weeks apart. Using these scores, we calculated intraclass correlation coefficients to estimate interrater and intrarater reliability.

Results: The interrater reliability intraclass correlation coefficient was 0.940 (95%CI 0.862–0.985). Intrarater reliability intraclass correlation coefficients ranged from 0.923 to 0.998.

Conclusions: The WST Version 4.2 has excellent interrater and intrarater reliability and is a reliable tool for use in clinical and research practice to evaluate a power wheelchair user’s skill capacity.

• Implications for Rehabilitation

• The Wheelchair Skills Test for Powered Wheelchair Users (WST-P 4.2) is a useful addition to the clinical tools available for clinicians who assess and train for powered wheelchair use.

• The WST-P 4.2 has excellent reliability and potential for clinical use as a pre-post measure of powered wheelchair skills.

• Clinicians using the WST-P 4.2 should attempt to maintain consistent scoring procedures, particularly for those skills that may require subjective assessment of skill safety.

     

The isolation rate of Escherichia coli 0157:H7 in Toronto and surrounding communities

Verocytotoxin-producing strains of Escherichia coli, most often serotype 0157:H7, have been associated with both sporadic and epidemic diarrheal disease in Canada. In order to determine the isolation rate of E coli 0157:H7 in outpatients with diarrhea, all stool specimens submitted for culture to Med-Chem Laboratories in Metropolitan Toronto between June 1988 and September 1989 were cultured on MacConkey-Sorbitol agar in addition to standard enteric media. A total of 46 (0.3%) of 16,125 stool specimens yielded E coli 0157:H7 or verotoxin-producing E coli 0157:H(-). These isolates came from 31 patients with diarrhea; only 16 (52%) had a history of hemorrhagic colitis and one patient developed hemolytic uremic syndrome. Although MacConkey-Sorbitol agar was useful as a differential medium for detecting E coli 0157:H7, 14.5% of all specimens yielded nonsorbitol-fermenting isolates. It is not certain whether the routine use of MacConkey-Sorbitol agar is justified when isolation rates of E coli 0157:117 are very low.     

Morphological and functional characterization of vascular muscle cells enzymatically dispersed from dog mesenteric arteries.

The objective of this study was to compare the properties of single smooth muscle cells enzymatically dispersed from the dog mesenteric arteries to the properties of similar cells functioning in tissue strips. The isolated cells remained relaxed in nominally Ca(2+)-free medium for about 1-2 h after exposure to 1 mM Ca2+ and like intact mesenteric artery rings did not contract spontaneously. Enzymatically dispersed cells maintained all the characteristic morphological features observed in strips of muscle prior to isolation except that the amorphous materials covering the smooth muscle cell surfaces (basal lamina) were absent after enzymatic dispersion. Addition of 100 mM KCl to these vascular muscle cells elicited maximal shortening in the presence but not in the absence of extracellular Ca2+ and KCl-induced cell shortening was prevented by 10(-7) M nifedipine indicating the presence of functional voltage-operated Ca2+ channels. However, in contrast to the vascular muscle strips, in which graded contractile responses were observed with increasing KCl concentrations, isolated vascular muscle cells underwent nearly maximal contraction at concentrations as low as 15 mM KCl. Both intact tissue and isolated cell preparations responded similarly to phenylephrine in a concentration-dependent manner and the responses were blocked by prazosin. In contrast to muscle strips, the isolated cells did not shorten in response to phenylephrine in Ca(2+)-free medium. Isolated muscle shortened in the presence of sarcoplasmic reticulum selective Ca2+ transport ATPase inhibitors, cyclopiazonic acid or thapsigargin. Ryanodine also caused contraction. We conclude that enzymatically dispersed smooth muscle cells from dog mesenteric arteries are potentially useful for studies of the regulation of smooth muscle contractility, but have significantly increased sensitivity to external K+, implying an altered membrane potential or voltage dependence of ion channels. Their impaired ability to contract to phenylephrine in Ca(2+)-free medium implies some alteration in intracellular Ca2+ stores of their coupling to cellular activation. These differences will affect how the data obtained from freshly isolated enzymatically dispersed vascular muscle cells may be extrapolated to cell studies in intact tissues.