Endobronchial volume reduction: a myth or a marvel?

Recently, several techniques and devices have been suggested for achieving endobronchial volume reduction in patients with emphysema. The proposed devices include bronchial blockers, bronchial valves, glues, biomodulators, and stents for bronchial fenestration; all could be positioned only with flexible bronchoscopy. The current available evidence on safety and efficacy for these methods is based on animal studies and patient case series at best; therefore, all the results should be seen with caution. However, the preliminary work reviewed here suggests that most of the proposed techniques can work, and seem to be safer than surgical volume reduction. We do not yet have a proven, widely applicable endobronchial palliative treatment for severe emphysema, but we have a rapidly growing area of new research in interventional pneumology with preliminary results that challenge traditional medical thinking.     

An epidemiologically-based needs assessment for stroke services

Stroke is amenable to the entire spectrum of health services, ranging from prevention of its risk factors, to the treatment of acute stroke and rehabilitation and palliation of stroke. The aim of this study was to determine the number of persons with the capacity to benefit from evidence-based effective stroke services. Population-based survey and registry data along with published, evidence-based recommendations for services were used to determine the number of persons in Eastern Ontario with stroke (including risk factors, acute stroke and chronic stroke) and their related need for services (including prevention programs, diagnostic services, treatment of acute stroke and rehabilitation). These estimates were then compared to the actual provision of these services. Estimates of the need for effective services exceeded the provision of all services with the exception of pharmacologic treatment for diabetes mellitus and carotid endarterectomy for acute stroke. The approach was able to identify both the under-provision and over-provision of evidence-based effective services for stroke. This study has shown that an epidemiologically-based needs assessment could be a useful basis for the planning of health services.     

The effect of varying tonicity on nasal epithelial ion transport in cystic fibrosis

There is reasonable evidence that the fluid layer of the airway epithelium is exposed to changes in tonicity. The inspiration of cool, dry air causes an increased tonicity, whereas this tonicity may be decreased by glandular secretions. We hypothesized that the cystic fibrosis transmembrane conductance regulator (CFTR) is involved in the responses to changes in tonicity and that these may be altered in cystic fibrosis (CF). Using nasal potential difference (PD) protocols in 8 subjects with CF and 10 subjects without CF, we investigated the effects of hyper- and hypotonicity on ion transport processes. We found significant differences between the two groups. In response to a hypertonic challenge (mannitol 500 mM), there was a decreased PD in both groups, suggesting decreased sodium absorption. However, after the prior inhibition of sodium transport using amiloride, there was an increased PD in the non-CF group alone, suggesting CFTR-mediated chloride secretion in response to luminal hypertonicity. For the hypotonic solution, we found that hypotonicity inhibited CFTR-mediated chloride secretion in the non-CF group. These data suggest that CFTR plays a role in the recognition and regulation of airway fluid tonicity.     

Potential difference measurements in the lower airway of children with and without cystic fibrosis

Nasal potential difference measurements are valuable endpoint assays in clinical studies of novel treatments for cystic fibrosis (CF). Similar measurements made on the lower airway via the bronchoscope have been successful in adults, but have not been reported in children, the group most likely to benefit from such therapies. Here we report the design and validation of a small, single-lumen catheter technique allowing baseline potential difference and chloride secretion to be assessed in the distal airways of children as young as 1 year of age. Tracheal baseline values were significantly higher in children with CF than those without, although this was not the case more distally. In airways between the third and seventh generation, perfusion with a zero chloride solution containing isoprenaline led to a significant change in potential difference in children without CF, whereas no change was seen in those with CF. This measure provided a reliable distinguishing test between the two disease groups. We confirm that invasive bronchoscopic techniques can be performed safely and reliably in small children. Potential difference measurements could form a useful functional endpoint assay for future studies of either the CFTR gene or protein-based therapies in future trials in the pediatric age group.     

Multiscale, resurgent epidemics in a hierarchical metapopulation model

Although population structure has long been recognized as relevant to the spread of infectious disease, traditional mathematical models have understated the role of nonhomogenous mixing in populations with geographical and social structure. Recently, a wide variety of spatial and network models have been proposed that incorporate various aspects of interaction structure among individuals. However, these more complex models necessarily suffer from limited tractability, rendering general conclusions difficult to draw. In seeking a compromise between parsimony and realism, we introduce a class of metapopulation models in which we assume homogeneous mixing holds within local contexts, and that these contexts are embedded in a nested hierarchy of successively larger domains. We model the movement of individuals between contexts via simple transport parameters and allow diseases to spread stochastically. Our model exhibits some important stylized features of real epidemics, including extreme size variation and temporal heterogeneity, that are difficult to characterize with traditional measures. In particular, our results suggest that when epidemics do occur the basic reproduction number R(0) may bear little relation to their final size. Informed by our model's behavior, we suggest measures for characterizing epidemic thresholds and discuss implications for the control of epidemics.     

Plasma lipids predict myocardial infarction, but not stroke, in patients with established cerebrovascular disease.

AIMS: To evaluate the role of plasma lipids in recurrent vascular events, including stroke, among individuals with established cerebrovascular disease. METHODS AND RESULTS: Plasma total cholesterol, HDL cholesterol, and triglycerides were measured at baseline among individuals participating in the Perindopril Protection Against Recurrent Stroke (PROGRESS) study, a randomized clinical trial of blood pressure lowering among patients with previous stroke or transient ischaemic attack. A series of nested case-control studies were used to investigate the association between each of these lipid variables and the risk of subsequent haemorrhagic stroke, ischaemic stroke, myocardial infarction (MI), and heart failure. A total of 895 patients were selected as cases (83 haemorrhagic stroke, 472 ischaemic stroke, 206 MI, and 258 heart failure) and each was matched with one to three controls. After adjustment for other major cardiovascular risk factors, none of the lipid variables was associated with the risk of either stroke subtype. There were significant positive and negative associations for total cholesterol and HDL, respectively, with the risk of MI; the odds ratio comparing the highest and lowest thirds of each of these lipid variables was 2.00 (95% CI: 1.30-3.09) for total cholesterol and 0.58 (95% CI: 0.37-0.90) for HDL. HDL was inversely associated with the risk of heart failure; however, this result was of borderline statistical significance (P=0.05). CONCLUSION: Lipid variables are associated with the risk of MI, but not recurrent stroke, in patients with established cerebrovascular disease.     

Dobutamine stress-induced ischemic right ventricular dysfunction and its relation to cardiac output in patients with three-vessel coronary artery disease with angina-like symptoms

We investigated markers of ischemic dysfunction and their relation to overall right ventricular (RV) performance during dobutamine stress echocardiography in patients who had coronary artery disease. Thirty-three patients (58 +/- 10 years old) who had 3-vessel coronary artery disease were compared with 17 age-matched controls (58 +/- 11 years old). RV long-axis amplitude (M mode), systolic and diastolic myocardial tissue Doppler velocities, and filling and ejection velocities were measured, and cardiac output (CO) was calculated at rest and during peak stress. There was no difference in RV size (inlet dimension <3.5 cm), RV systolic long-axis amplitude, systolic and diastolic velocities, peak early/late diastolic velocity ratio, and RV CO between patients and controls at rest. During stress, RV systolic long-axis amplitude increased in controls (from 24 +/- 6 to 30 +/- 5 mm) and CO increased significantly (from 4.9 +/- 1.2 to 12.5 +/- 2.1 L/min, p <0.001 for the 2 items). In contrast, RV amplitude did not change with stress in patients (from 24 +/- 5 to 22 +/- 6 mm, p = NS), and the stress-increment in CO was augmented (from 4.2 +/- 1.2 to 8.3 +/- 2.0 L/min, p <0.001 vs control stress increment). Failure to increase RV systolic amplitude >2 mm was 79% sensitive and 88% specific for detecting ischemic RV dysfunction, and there was a close correlation between stress-induced change in RV systolic amplitude and change in CO in patients (r = 0.56, p <0.001). Early diastolic velocity increased in controls (from 10.8 +/- 3.2 to 13.1 +/- 3.6 cm/s, p <0.01) but did not change in patients (from 11.5 +/- 3.7 to 11.3 +/- 4.8 cm/s, p = NS). RV shortening after ejection did not appear in any control subject but did develop in 8 of 33 patients, thus contributing to the decrease in RV peak early/late diastolic velocity ratio in patients (from 1.1 +/- 0.3 to 0.76 +/- 0.4, p <0.001) compared with that in controls (1.3 +/- 0.3 to 1.0 +/- 0.2, p <0.001). In conclusion, markers of RV dysfunction are not related to left ventricular wall motion score index or long-axis changes with stress.     

A national network for the tele-education of Canadian residents in pediatric cardiology.

A trial of 11 video-conferenced teaching sessions for residents in pediatric cardiology was performed by the 7 training programs in Canada in order to share expertise in specialized areas, to expose trainees to educational telemedicine, and to acquaint residents with other programs and personnel. Topics included cardiac pathology, arrhythmias, magnetic resonance imaging, fetal physiology, pulmonary hypertension, and cardiomyopathy. The sessions were evaluated by 93 residents by questionnaire for content and technology. Session content was highly rated. Videoconference picture quality was highly rated, but sound quality and visual aids were rated as neutral or unsatisfactory by a significant minority, related to problems with several early sessions, subsequently corrected. 60% of respondents rated the videoconferences as good as live presentations. Presenters were generally satisfied although they required some adjustments to videoconferencing. The average cost per session was $700 Canadian. Videoconferencing of resident educational sessions was generally well accepted by most presenters and residents, and the trial has formed the basis for a national network. Adequate organizational time, and careful attention to audiovisual needs, are most important. Videoconference guidelines are suggested for presenters based on this experience.     

Dermatomyositis and sarcoid-like reaction associated with multiple myeloma treated effectively by high-dose chemotherapy and autologous peripheral blood stem cell transplantation

We report the case of a 46-year-old male who developed dermatomyositis and a sarcoid-like reaction in association with testicular relapse of multiple myeloma. The myositis progressed despite chemotherapy directed at the underlying malignant disorder and immunosuppressive treatment. There was, however, a dramatic and sustained response to high-dose chemotherapy and autologous peripheral blood stem cell transplantation which resulted in resolution of the myopathy and partial resolution of the sarcoid-like reaction. This case report highlights the potential of autologous stem cell transplantation as treatment for para-neoplastic disorders associated with haematological malignancies.