Streptolysin O enhances keratinocyte migration and proliferation and promotes skin organ culture wound healing in vitro

ML-05, a modified form of the hemolytic and cytotoxic bacterial toxin, streptolysin O, is currently being investigated as a treatment for collagen-related disorders such as scleroderma and fibrosis. Furthermore, ML-05 may be effective in promoting wound healing and alleviating the formation of hypertrophic scars and keloids. To investigate the effects of ML-05 on wound-healing processes, in vitro wound-healing scratch assays (using human primary epidermal keratinocytes and dermal fibroblasts) and a human skin organ culture wound model were utilized. ML-05 markedly enhanced keratinocyte migration and proliferation in wound scratch assays. ML-05 did not affect either proliferation or migration of dermal fibroblasts, indicating that ML-05's effects on cell migration/proliferation may be keratinocyte-specific. ML-05 was tested in a dose-dependent manner in a skin organ culture wound model using two different application methods: Through the culture media (dermal exposure) or direct topical treatment of the wound surface. ML-05 was found to accelerate wound healing as measured by reepithelialization, particularly after topical application. Therefore, ML-05 may have potential as a wound-healing agent that promotes reepithelialization through stimulation of keratinocyte migration and proliferation.     

Bone Mineral Density Determinations by Dual-Energy x-ray Absorptiometry in the Management of Patients with Marfan Syndrome—Some Factors Which Affect the Measurement

Reduced bone mineral density (BMD) was sporadically reported in patients with Marfan syndrome. This may or may not place the Marfan patient at increased risk for bone fracture. In comparing the BMDs of our patients with those reported in the literature, it seemed that agreement between values, and hence the degree of osteoporosis or osteopenia reported, was dependent on the instrumentation used. The objective of this study was to statistically assess this impression. Bone mineral density measurements from our previously published study of 30 adults with Marfan syndrome performed on a Lunar DPXL machine were compared with studies published between 1993–2000 measured using either Lunar or Hologic bone densitometry instruments. The differences of our measurements compared with those made on other Lunar machines were not statistically significant, but did differ significantly with published results from Hologic machines (P < 0.001). Before progress can be made in the assessment of BMD and fracture risk in Marfan patients and in the evidence-based orthopedic management of these patients, standardization of instrumental bone density determinations will be required along with considerations of height, obesity, age, and sex.     

Asymmetric dimethyl-arginine and coronary artery calcification in young adults entering middle age: the CARDIA Study.

BACKGROUND: Normal endothelial function depends on nitric oxide (NO) release by endothelial cells. Asymmetric dimethylarginine (ADMA), by competing with L-arginine, inhibits NO production and may lead to endothelial dysfunction and atherosclerotic development. Our aim was to ascertain the association between ADMA and coronary artery calcification (CAC), a marker of atherosclerotic coronary disease burden. DESIGN: A nested case-control study within the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, an observational study among young adults residing in four US cities. METHODS: Participants were 263 white and black male and female cases with the presence of CAC and 263 sex and race-matched controls without evidence of CAC by computed tomography, 33-47 years old in 2000-2001. RESULTS: The median level (range) of ADMA was significantly higher in cases (0.55; 0.20-2.22 micromol/l) than in controls (0.53; 0.32-1.30 micromol/l; P=0.03). In conditional logistic regression adjusting for age, field center, educational attainment, smoking status, alcohol consumption, body mass index, waist circumference, hypertension, diabetes, low-density lipoprotein and high-density lipoprotein-cholesterol, triglycerides, renal function and C-reactive protein, the highest tertile of ADMA, compared with the lowest tertile, was associated with 1.80 (95% confidence interval 1.03-3.15) increased odds of the presence of any CAC. By linear regression, a significant independent relationship was also found between ADMA and the degree of CAC. CONCLUSION: These results support a role for ADMA as a biochemical marker of CAC.     

Scalp electrical recording during paralysis: quantitative evidence that EEG frequencies above 20 Hz are contaminated by EMG.

OBJECTIVE: To identify the possible contribution of electromyogram (EMG) to scalp electroencephalogram (EEG) rhythms at rest and induced or evoked by cognitive tasks. METHODS: Scalp EEG recordings were made on two subjects in presence and absence of complete neuromuscular blockade, sparing the dominant arm. The subjects undertook cognitive tasks in both states to allow direct comparison of electrical recordings. RESULTS: EEG rhythms in the paralysed state differed significantly compared with the unparalysed state, with 10- to 200-fold differences in the power of frequencies above 20 Hz during paralysis. CONCLUSIONS: Most of the scalp EEG recording above 20 Hz is of EMG origin. Previous studies measuring gamma EEG need to be re-evaluated. SIGNIFICANCE: This has a significant impact on measurements of gamma rhythms from the scalp EEG in unparalysed humans. It is to be hoped that signal separation methods will be able to rectify this situation.     

Measurement in clinical trials: A neglected issue for statisticians?

Biostatisticians have frequently uncritically accepted the measurements provided by their medical colleagues engaged in clinical research. Such measures often involve considerable loss of information. Particularly, unfortunate is the widespread use of the so‐called ‘responder analysis’, which may involve not only a loss of information through dichotomization, but also extravagant and unjustified causal inference regarding individual treatment effects at the patient level, and, increasingly, the use of the so‐called number needed to treat scale of measurement. Other problems involve inefficient use of baseline measurements, the use of covariates measured after the start of treatment, the interpretation of titrations and composite response measures. Many of these bad practices are becoming enshrined in the regulatory guidance to the pharmaceutical industry. We consider the losses involved in inappropriate measures and suggest that statisticians should pay more attention to this aspect of their work. Copyright © 2009 John Wiley & Sons, Ltd.