Azithromycin reverses airflow obstruction in established bronchiolitis obliterans syndrome

INTRODUCTION: A recent pilot study noted clinical benefit of macrolide therapy in the management of six lung transplant recipients with bronchiolitis obliterans syndrome (BOS), a condition previously regarded as irreversible. OBJECTIVE: To examine the effect of low-dose macrolides on lung function in lung allograft recipients with established BOS and to assess whether this benefit is sustained. METHODS: We retrospectively evaluated the effect of azithromycin (250 mg alternate days) on clinical status and lung function in 20 allograft recipients with established BOS, confirmed by decline in FEV(1) or FEF(25-75); consistent high-resolution computed tomography findings; and exclusion of acute rejection, infection, or anastomatic complications. Azithromycin was introduced at mean 82 months after transplantation. BOS staging at initiation of treatment was BOS 3 (10), BOS 2 (2), BOS 1 (6), and BOS0-p (2). All patients were on maintenance immunosuppression comprising cell-cycle inhibitor, oral corticosteroids, and calcineurin inhibitor. RESULTS: There was a significant increase in FEV(1) of median 110 ml (range, -70 to 730 ml) between baseline and 3 months of azithromycin therapy (p = 0.002). This improvement was sustained beyond 3 months in the majority of patients, who had initially benefited from azithromycin (up to 11 months follow up). CONCLUSIONS: This case series confirms the benefit of azithromycin in not only halting, but reversing the declining lung function seen in patients with BOS. This benefit appears to be maintained over time. Low-dose macrolides offer a new and exciting therapeutic strategy for the treatment of progressive BOS, and further clinical and translational mechanistic studies are required.     

Fragmentary blackouts: their etiology and effect on alcohol expectancies

BACKGROUND: Fragmentary blackouts, or memory loss for intoxicated events that may be later recalled with the provision of cues, are common sequelae of heavy drinking, yet understanding of their characteristics, correlates, and consequences is limited. Consequently, this alcohol-administration study addressed questions regarding the etiology of fragmentary blackouts and their effect on alcohol outcome expectancies. METHODS: A placebo-controlled design addressed the etiology of fragmentary blackouts through assessment of memory formation before and after alcohol consumption. The effect of fragmentary blackouts on prospective beliefs about alcohol was assessed by way of a self-report outcome expectancy questionnaire and a measure of response latency for alcohol concepts presented after beverage consumption. RESULTS: Although participants performed similarly on memory indices before consuming beverages, those who reported past fragmentary blackouts and consumed alcohol displayed marked difficulty with recall of a narrative when this was attempted both during intoxication and after detoxification, as well as with a source memory task presented during intoxication. Those reporting fragmentary blackouts also endorsed stronger outcome expectancies for a range of alcohol effects and exhibited greater accessibility for positive alcohol concepts presented after beverage administration. Further, source recall contributed significantly to the episodic recall both during intoxication and after detoxification, as well as to positive outcome expectancies of those receiving alcohol. CONCLUSIONS: Findings suggest that fragmentary blackouts result from poor retrieval and that individual differences in retrieval emerge after alcohol is consumed. Further, one's recall of source aspects of material-its time and social context-is an important determinant of recall of stimuli and events encountered during intoxication, as well as of prospective expectations for positive alcohol effects. The collective findings expand our understanding of this complex yet common neuropsychological consequence of heavy drinking.     

Effects of short-term exposure to fine and ultrafine particles from indoor sources on arterial stiffness – A randomized sham-controlled exposure study

ObjectivesParticulate air pollution is linked to adverse cardiovascular effects, including arterial stiffness. The aim of the study was to investigate the effect of short-term exposure to indoor fine and ultrafine particles on augmentation index (AIx), augmentation pressure (AP), and pulse wave velocity (PWV), early signs of vascular damage.MethodsWe analyzed the association of particle emissions from typical indoor sources (candle burning - CB, toasting bread - TB, and frying sausages - FS) with changes in pulse wave analysis indices in 55 healthy adults in a randomized cross-over controlled exposure study. Particle mass concentration (PMC), size-specific particle number concentration (PNC) and lung-deposited particle surface area concentration (PSC) were measured during the 2 h exposure. AIx and AP were measured before, directly, 2, 4 and 24 h after exposure. PWV was measured directly and 24 h after exposure. We performed multiple mixed linear regression analyses of different particle metrics and AIx, AP and PWV.ResultsThe highest mean PMC was observed during FS reaching a maximum of 210 μg/m³ PM₁₀. The maximal PNC for UFP <100 nm was reached during CB with 2.3 million particles/cm³. PSC was similar across all three exposures (about 3000 μm²/cm³). Strongest associations between different particles metrics and arterial stiffness indices could be observed for UFP from CB and FS and for PMC from TB. The highest mean increase could be observed for the UFP fraction <10 nm, measured during CB, and AIx with an increase of 9.5%-points (95%-CI: 3.1; 15.9). PSC seemed to follow the pattern of PNC. PM₁₀ and PM_2.5 from TB led to clear changes in AIx with biggest increases for PM₁₀ of 5.8%-points (95%-CI: 3.2; 8.4) 2 h after exposure and for PM_2.5 of 8.1%-points (95%-CI: 2.5; 13.7) directly after exposure.ConclusionsOur study indicates effects of indoor exposure to fine and ultrafine particles on systemic arterial stiffness indices that depend on the indoor source as well as on particle metric. Differences in size-specific physical characteristics of source-specific particles might account for these differential effects. We did not observe clear and stable associations of indoor particle exposure and PWV.     

Advancing the use of patient-reported outcomes in practice: understanding challenges,opportunities, and the potential of health information technology

Quality of Life Research - The effective use of patient-reported outcomes (PROs) can play a critical role in improving health care delivery and patient experience with care. However, PROs are not...     

Current trends in the diagnosis and management of syndesmotic injury

Ideal management of the various presentations of syndesmotic injury remains controversial to this day. High quality evidentiary science on this topic is rare, and numerous existing studies continue to contradict one another. The primary reasons for these discrepancies are that previous studies have failed to (1) properly distinguish between isolated (non-fractured) and non-isolated injuries, (2) accurately define stable from unstable injuries, and (3) sufficiently differentiate between acute and chronic injuries. The purpose of this review is to summarize today’s body of literature regarding diagnosis and management of syndesmotic injury and discuss current trends and important future directions to optimize care of this very heterogeneous population.     

Early exposure to haloperidol or olanzapine induces long‐term alterations of dendritic form

Exposure of the developing brain to a wide variety of drugs of abuse (e.g., stimulants, opioids, ethanol, etc.) can induce life‐long changes in behavior and neural circuitry. However, the long‐term effects of exposure to therapeutic, psychotropic drugs have only recently begun to be appreciated. Antipsychotic drugs are little studied in this regard. Here, we quantitatively analyzed dendritic architecture in adult mice treated with paradigmatic typical‐ (haloperidol) or atypical (olanzapine) antipsychotic drugs at developmental stages corresponding to fetal or fetal plus early childhood stages in humans. In layer 3 pyramidal cells of the medial and orbital prefrontal cortices and the parietal cortex and in spiny neurons of the core of the nucleus accumbens, both drugs induced significant changes (predominantly reductions) in the amount and complexity of dendritic arbor and the density of dendritic spines. The drug‐induced plasticity of dendritic architecture suggests changes in patterns of neuronal connectivity in multiple brain regions that are likely to be functionally significant. Synapse 64: 191–199, 2010. © 2009 Wiley‐Liss, Inc.