A human skin equivalent burn model to study the effect of a nanocrystalline silver dressing on wound healing.

In this study, a deep burn wound model was established using a 3D human skin equivalent (HSE) model and this was compared to native skin. HSEs were constructed from dermis derived from abdominoplasty/breast surgery and this dermal template was seeded with primary keratinocytes and fibroblasts. The HSE model was structurally similar to native skin with a stratified and differentiated epidermis. A contact burn (60 °C, 80 °C, 90 °C) was applied with a modified soldering iron and wounds were observed at day 1 and 7 after burn. The HSEs demonstrated re-growth with keratinocyte proliferation and formation of a neo-epidermis after burn injury, whereas the ex vivo native skin did not. To assess the suitability of the 3D HSE model for penetration and toxicity studies, a nanocrystalline silver dressing was applied to the model for 7 days, with and without burn injury. The effect of silver on skin re-growth and its penetration and subcellular localization was assessed in HSEs histologically and with laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS). The silver treatment delayed or reduced skin re-growth, and silver particles were detected on the top of the epidermis, and within the papillary dermis. This novel in vitro 3D multicellular deep burn wound model is effective for studying the pathology and treatment of burn wound injury and is suitable for penetration and toxicity studies of wound healing treatments.

Quantitative EEG findings in patients with chronic renal failure.

OBJECTIVE: Chronic renal failure frequently causes uremic encephalopathy with impairment of various cognitive functions, but the pathophysiology of uremic syndrome is complex and poorly understood. In this study, we wished to establish a reliable tool and monitor system to evaluate the central nervous system dysfunction of patients with uremic encephalopathy. METHODS: A group of 31 patients with chronic renal failure was assessed with online real time brain mapping using the CATEEM technology to detect deviations and abnormal EEG patterns. Quantitative EEG data were compared with those of an age-matched healthy control group and correlated to laboratory markers and various dosages of erythropoietin. RESULTS: Electrical power was most prominent in delta, theta and alpha frequencies in the temporal and central brain areas (electrode positions T5, T6, C3 and C4). Explorative statistical comparison of the two data sets with respect to these brain areas revealed that the increases in electrical power in delta, theta and alpha frequency bands were different from healthy people with p-values of p<0.003 (delta), p<0.0003 (theta), p<0.01 (alpha 1) and p<0.01 (alpha 2). In addition, high levels of hemoglobin were significantly correlated with higher theta activity. CONCLUSION: We detected distinct EEG deviations from normality in patients with chronic renal failure. Online real time brain mapping using the CATEEM technology provides a unique possibility to monitor mental impairment and serves as a control for therapeutical intervention.

Multiple sclerosis coinciding with Machado-Joseph disease.

Although inflammatory demyelination is considered to be the key feature in multiple sclerosis (MS) pathogenesis, histopathological investigations and MRI studies recently highlighted the extent of neuronal damage that occurs even in the early stages of the disease. We report the unusual case of a patient with Machado-Joseph disease (MJD; spinocerebellar ataxia (SCA) III) and discuss this coincidence in light current pathogenetic paradigms of CNS autoimmunity.

Factors associated with fetal growth and body composition as measured by ultrasound.

OBJECTIVE: This study seeks to determine which parental demographic and metabolic factors best correlate with fetal growth and body composition as estimated by ultrasound. STUDY DESIGN: Thirty-one gravid patients had ultrasound estimates of fetal anthropometry in mid-third trimester. These measurements included estimated fetal weight, abdominal subcutaneous fat, and/or thigh subcutaneous fat thickness. Independent variables included diagnosis of gestational diabetes, parental demographic factors, neonatal sex, and late gestation estimates of carbohydrate metabolism. RESULTS: In the multivariate stepwise model the strongest predictor of ultrasound estimated fetal weight was basal hepatic glucose production, followed by late gestation insulin sensitivity (total R (2) = 0.27). The strongest predictors of abdominal subcutaneous fat thickness were weight gain and presence of gestational diabetes (total R (2) = 0.25). CONCLUSION: Measures of maternal carbohydrate metabolism, rather than fat mass, explain sonographic measurements of fetal weight. We speculate that factors other than maternal carbohydrate metabolism further explain the variances of fetal adiposity.

Chronic administration of single-agent paclitaxel in gynecologic malignancies.

OBJECTIVE: There are currently limited published data available on the safety and feasibility of the prolonged administration of paclitaxel. The goal of this study was to review the cumulative toxicity associated with the continuous long-term administration of this agent to women with gynecologic cancers. METHODS: Eleven patients with gynecologic malignancies of varying histologic subtypes who received >15 consecutive courses of paclitaxel were identified in a retrospective review of individuals treated between 1994 and 1999 in the Gynecologic Oncology Program of the Cleveland Clinic Taussig Cancer Center. The analysis excluded paclitaxel delivered as a component of an initial chemotherapy regimen for the cancer. Paclitaxel was administered at doses ranging from 80 to 175 mg/m(2) every 3-4 weeks as a 3-h infusion. RESULTS: In general, the patients included in this report were heavily pretreated and were continued on therapy either as a result of documentation of an objective response or with evidence of stabilization of disease (e.g., physical examination, radiographic evaluation, CA-125 antigen level) and the maintenance of a satisfactory quality of life. In the 11 patients, the median duration of therapy was 20 cycles (range: 16-36 cycles). Alopecia was observed in all patients. A single patient experienced grade 3 anemia and grade 4 neutropenia. Of note, there was 1 case of grade 2 and no cases of grade 3 peripheral neuropathy in this population. CONCLUSION: Prolonged delivery of paclitaxel for >15 consecutive cycles can be safely administered to carefully selected patients with persistent or recurrent advanced gynecologic cancers.