Intravenous digital subtraction renal angiography: use in screening for renovascular hypertension

Intravenous digital subtraction renal angiography (DSRA) has been compared with conventional angiography only in small, selected series of hypertensive patients. The authors prospectively examined with intravenous DSRA 94 patients at increased risk for renovascular hypertension and compared these studies with conventional angiography. A stenosis of at least one main renal artery was identified with intravenous DSRA in 22 patients and confirmed in 20 patients. No significant stenoses were seen with conventional angiography in any of the 64 patients in whom lesions were not seen with intravenous DSRA. Since inadequate DSRA studies were considered positive for renal artery stenosis, the sensitivity of intravenous DSRA was 100% (25 of 25); specificity, 93% (64 of 69); positive predictive value, 83% (25 of 30); and negative predictive value, 100% (64 of 64). The authors conclude that intravenous DSRA is a sensitive test for identifying stenosis of the main renal arteries and is appropriate to use as a screening test among patients at increased risk for renovascular hypertension.     

Electrical injuries: a 20-year review

Electrical injuries continue to present problems with devastating complications and long-term socioeconomic impact. The purpose of this study is to review one institution's experience with electrical injuries. From 1982 to 2002, there were 700 electric injury admissions. A computerized burn registry was used for data collection and analysis. Of these injuries, 263 were high voltage (> or =1000 V), 143 were low voltage (<1000 V), 277 were electric arc flash burns, and 17 were lightning injuries. Mortality was highest in the lightning strikes (17.6%) compared with the high voltage (5.3%) and low voltage (2.8%) injuries, and mortality was least in electric arc injuries without passage of current through the patient (1.1%). Complications were most common in the high-voltage group. Mean length of stay was longest in this group (18.9 +/- 1.4 days), and the patients in this group also required the most operations (3 +/- 0.2). Work-related activity was responsible for the majority of these high-voltage injuries, with the most common occupations being linemen and electricians. These patients tended to be younger men in the prime of their working lives. Electrical injuries continue to make up an important subgroup of patients admitted to burn centers. High-voltage injuries in particular have far reaching social and economic impact largely because of the patient population at greatest risk, that is, younger men at the height of their earning potential. Injury prevention, although appropriate, remains difficult in this group because of occupation-related risk.     

Best Practices for Drug Substance Stress and Stability Studies During Early-Stage Development Part I—Conducting Drug Substance Solid Stress to Support Phase Ia Clinical Trials

Regulatory guidances for drug stability testing during early development stages lack specifics. Consequently, companies either conduct more stability studies than necessary just to avoid regulatory questions or perform insufficient stability work resulting in regulatory questions and delays in drug development. Hence, there exist a pressing need and a great opportunity for pharmaceutical companies to share drug stability testing practices, rationales, and regulatory experiences for the early stages of development. This paper describes a quick, streamlined solid stress practice to support drug development from pre-clinical to Phase Ia Clinical Trials. By subjecting a few grams of drug substance to high temperature and high humidity (e.g., 70?°C/75?% RH, in open and closed containers, for three weeks) and to the ICH Q1B confirmatory photostability testing condition, the initial DS retest period and the initial shelf life of powder for oral solution can be reliably extrapolated, and a bulk packaging choice is made. In addition, the solid stress results can be used for multifaceted purposes. The solid stress practice offers a quick turnaround in obtaining adequate stability information for new drug development and achieves an optimum balance between risk and cost for Phase Ia clinical development.     

Impaired lung function and lung cancer incidence in a cohort of Swedish construction workers

BACKGROUND: Although impaired lung function in general has been associated with an increased risk of lung cancer, past studies typically have not attempted to investigate separately the obstructive and restrictive components of respiratory impairment. To deal with this question further, data from a large (n = 176 997) cohort of male Swedish construction workers, for whom spirometry measurements before follow-up were available, were analysed. METHODS: Cancer incidence for 1971-2001 was obtained through linkage with the national cancer registry. Using a modification of the Global Initiative for Chronic Obstructive Lung Disease criteria for chronic obstructive pulmonary disease (COPD), subjects were classified into five categories of lung function: normal, mild COPD, moderate COPD, severe COPD and restrictive lung disease (RLD). Rate ratios (RR) and 95% confidence intervals (CI) for lung cancer across lung function categories were calculated using Poisson regression, adjusted for age and smoking. Other end points (histological types of lung cancer, non-lung tobacco-related cancers, other cancers, total mortality) were also investigated. RESULTS: 834 incident cases of lung cancer were identified. Increased rates of lung cancer were observed for both COPD (mild: RR 1.5, 95% CI 1.2 to 1.9; moderate/severe: RR 2.2, 95% CI 1.8 to 2.7) and RLD (RR 2.0, 95% CI 1.6 to 2.5) relative to normal lung function. These associations did not meaningfully change on applying follow-up lag times of 5, 10 and 15 years after spirometry. When analysed by histological type, associations with both COPD and RLD were stronger for squamous cell carcinoma and small cell carcinoma, and weaker for adenocarcinoma. Both COPD and RLD were associated with increased rates of total mortality. CONCLUSIONS: Obstructive and restrictive impairments in lung function are associated with increased lung cancer risk.     

Congenital left atrial appendage ostial stenosis in an extremely premature infant diagnosed by transthoracic echocardiography

Congenital left atrial appendage ostial stenosis is a very rare congenital cardiac condition. We present the case of an extremely premature infant with congenital left atrial appendage ostial stenosis diagnosed by transthoracic echocardiographic imaging.     

Muscle architecture adaptations to knee extensor eccentric training: Rectus femoris vs. vastus lateralis

Introduction: Changes in muscle architecture induced by eccentric knee extensor training remain unclear, as well the adaptive responses of synergistic knee extensor muscles with different geometrical designs. Methods: Ultrasonography images were taken from rectus femoris (RF) and vastus lateralis (VL) of 20 male volunteers before and after a non‐training control period of 4 weeks, and additional evaluations were performed after 4, 8, and 12 weeks of isokinetic eccentric training. Results: RF and VL had significant changes in muscle architecture within the first 4 training weeks, and the adaptive response throughout the intervention was similar. Muscle thickness increased by around 7–10%, fascicle length increased 17–19%, and pennation angle was unchanged. Conclusions: Increased muscle thickness due to eccentric training was related to increased fascicle length and not to pennation angle changes. Although RF and VL have a different fascicular geometry, they had similar morphological adaptations to eccentric training. Muscle Nerve 48 : 498–506, 2013     

Mechanism of human accommodation as analyzed by nonlinear finite element analysis

Results of nonlinear finite element analysis support the Schachar theory of accommodation and demonstrate that the long-held Helmholtz theory of accommodation is impossible.     

Alternative macrophage activation in periprosthetic osteolysis

Several disorders characterized by macrophages accumulating non-disposable (or hard to dispose of) material or formation of multinucleated giant cell containing granulomas have been linked to elicitation of an alternative macrophage activation phenotype. Gene profiling efforts have shown that alternative macrophage activation can exist in numerous forms, each specific for the particular biological niche in which the macrophage finds itself, accentuating the plasticity of this cell type. Periprosthetic osteolysis is characterized by macrophage phagocytosis of particles of wear debris and formation of foreign body granulomas, suggesting the hypothesis that it may represent a new member of this group of diseases characterized by alternative macrophage activation. Gene profiling has provided strong supportive evidence for this hypothesis, revealing that periprosthetic tissues of osteolysis patients show the presence of a pronounced alternative macrophage activation pathway, with the classical pro-inflammatory activation pathway being less evident. These findings have important implications for our understanding of periprosthetic osteolysis and how to approach future investigations into this disease.