Carboplatin desensitization.

BACKGROUND: IgE-mediated carboplatin hypersensitivity reactions occur in up to 30% of patients receiving this agent for chemotherapy of solid tumors, thus limiting therapeutic options. OBJECTIVE: To describe our experience with intravenous carboplatin desensitization regimens, which culminated in a standardized, successful protocol for safe administration. METHODS: Eight consecutive patients with ovarian cancer who had experienced severe anaphylactic reactions to carboplatin were referred to our hospital. Intradermal skin testing was performed by raising a 3-mm bleb by injection of undiluted carboplatin at 10 mg/mL, and the wheal size was read at 20 minutes. The outcomes of the various desensitization regimens were documented prospectively, and the experience gained was used to develop a standardized protocol for administration. RESULTS: All patients had positive intradermal skin test results. The first 3 patients were treated with short (90 minutes to 6 hours) desensitization protocols, and all protocols failed on the first or second infusions. These 3 and a subsequent 5 patients were given intravenous carboplatin according to a protocol of gradual dose escalation over a 4-log dose range given during a 4-day period, with subsequent 3-weekly infusions given more rapidly by omitting the most dilute log dose on each occasion. All patients tolerated the longer infusion protocol without event, and all but 1 patient experienced appropriate tumor marker response. CONCLUSIONS: Short carboplatin desensitization protocols (less than 6 hours) have an unacceptable failure rate in patients with carboplatin allergy, but longer infusion times (days) are well tolerated without recurrence of the allergic reaction and with good tumor response. In cases where carboplatin is the optimal therapeutic agent, clinicians should not be deterred by an anaphylactic reaction to it or by failure of shorter desensitization regimens.     

Growth hormone effects on hypertrophic scar formation: a randomized controlled trial of 62 burned children

The hypercatabolism after massive pediatric burns has been effectively treated with recombinant human growth hormone, an anabolic agent that stimulates protein synthesis and abrogates growth arrest. While experimental studies have shown increased potential for fibrosis induced by growth hormone therapy, adverse effects on human scars have not been investigated. Our aim was to evaluate hypertrophic scar formation in 62 patients randomized to receive injections of 0.05 mg/kg/day of recombinant human growth hormone or placebo, from discharge until 1 year after burn. Scar scales were used to evaluate scar-severity at discharge, 6, 9, 12, and 18-24 months after burn, by three observers blinded to treatment. Computer-assisted planimetry allowed quantification of percentage of hypertrophic scar formation. Types I and III collagens were localized and quantified in scars and normal skin of patients from both groups, using immunohistochemistry with confocal laser microscopy analysis. Insulin-like growth factor-1 blood levels helped assess compliance. Statistical analysis showed that scar hypertrophy significantly increased from 6 to 12 months after injury in both groups, while decreasing at 18-24 months postburn. Types I and III collagens were statistically increased in the reticular layer of scars from both groups when compared to paired normal skin. Insulin-like growth factor-1 was significantly increased in the recombinant human growth factor-treated group. No differences were seen when recombinant human growth factor and control groups were compared using the scar scales, planimetry, or immunohistochemistry. We concluded that recombinant human growth hormone therapy did not adversely affect scar formation and should not contraindicate the administration of recombinant human growth hormone as a therapeutic approach to severely burned children.     

Changing health status and health expectancies among older adults in China: Gender differences from 1992 to 2002

Numerous studies document improvements in health status and health expectancies among older adults over time. However, most evidence is from developed nations and gender differences in health trends are often inconsistent. It remains unknown whether changes in health in developing countries resemble Western trends or whether patterns of health improvement are unique to the country's epidemiologic transition and gender norms. Using two nationally representative samples of non-institutionalized adults in China aged 65 years and older, this study investigates gender differences in the improvements in disability, chronic disease prevalence, and self-rated health from 1992 to 2002. Results from multivariate logistic regression models show that all three indicators of health improved over the 10-year period, with the largest improvement in self-rated health. With the exception of disability, the health of women improved more than men. Using Sullivan's decomposition methods, we also show that active life expectancy, disease-free life expectancy, and healthy life expectancy increased over this decade and were patterned differently according to gender. Overall, the findings demonstrate that China experienced broad health improvements during its early stages of the epidemiologic transition and that these changes were not uniform by gender. We discuss the public health implications of the findings in the context of China's rapidly aging population.     

Verbal Working Memory and Atherosclerosis in Patients with Cardiovascular Disease: An fMRI study

BACKGROUND AND PURPOSE: Intimal-medial thickening (IMT) of the carotid wall is an accepted peripheral marker of atherosclerosis. It is associated with increased risk for myocardial infarction and stroke, and lower attention-executive-psychomotor functioning. The purpose of this study was to examine the relationship between IMT and brain activity during a verbal working memory (VWM) task in patients with cardiovascular disease (CVD). METHODS: Thirteen CVD patients underwent functional magnetic resonance imaging (fMRI) during a 2-Back VWM task, and B-mode ultrasound of the carotid arteries. IMT was calculated using an automated algorithm based on a validated edge-detection technique. The relationship between IMT and 2-Back-related brain activity was modeled using partial correlations controlling for age and small vessel disease as measured by white matter signal hyperintensities on MRI (WMH). RESULTS: Higher IMT was associated with lower 2-Back-related signal intensity and in the right middle frontal gyrus, independent of age and WMH. CONCLUSIONS: IMT may be one mechanism contributing to brain dysfunction in CVD. The blood oxygenation level-dependent (BOLD) contrast appears to be highly sensitive to peripheral vascular health as measured by IMT. Future studies should examine the sensitivity and specificity of the BOLD response for predicting cognitive decline in CVD.