Efficacy and safety of becaplermin (recombinant human platelet-derived growth factor-BB) in patients with nonhealing, lower extremity diabetic ulcers: a combined analysis of four randomized studies.

The results of a combined analysis and separate analyses of four multicenter, randomized, parallel group studies that evaluated the effects of once-daily topical administration of becaplermin gel for the treatment of chronic, full thickness, lower extremity diabetic ulcers are presented. The four studies included a total of 922 patients with nonhealing lower extremity diabetic ulcers of at least 8 weeks' duration. Following initial complete sharp debridement of the ulcer, patients were randomized to receive a standardized regimen of good ulcer care alone, good ulcer care plus placebo gel, or good ulcer care plus becaplermin gel-30 microg/g, or good ulcer care plus becaplermin gel-100 microg/g, with various combinations of regimens used in the four studies. Safety was assessed by monitoring adverse events and by clinical laboratory evaluations. Meta-analytic statistical techniques were used in the combined analysis to establish homogeneity of treatment comparisons across studies. Based on an analysis of patients with baseline ulcer area common to all trials (

Becaplermin gel in the treatment of pressure ulcers: a phase II randomized, double-blind, placebo-controlled study.

Pressure ulcers are associated with significant rates of morbidity and mortality, particularly in the geriatric and spinal cord-injured populations. Newer pharmacologically active therapies include the use of topically applied recombinant human platelet-derived growth factor-BB (becaplermin), the active ingredient in REGRANEX) (becaplermin) Gel 0.01%, which has been approved in the United States for treatment of lower extremity diabetic neuropathic ulcers that extend into the subcutaneous tissue or beyond and have an adequate blood supply. In this study, the efficacy of becaplermin gel in the treatment of chronic full thickness pressure ulcers was compared with that of placebo gel. A total of 124 adults (>/= 18 years of age) with pressure ulcers were assigned randomly to receive topical treatment with becaplermin gel 100 microg/g (n = 31) or 300 microg/g (n = 32) once daily alternated with placebo gel every 12 hours, becaplermin gel 100 microg/g twice daily (n = 30), or placebo (sodium carboxymethylcellulose) gel (n = 31) twice daily until complete healing was achieved or for 16 weeks. All treatment groups received a standardized regimen of good wound care throughout the study period. Study endpoints were the incidence of complete healing, the incidence of >/= 90% healing, and the relative ulcer volume at endpoint (endpoint/baseline). Once-daily treatment of chronic pressure ulcers with becaplermin gel 100 microg/g or 300 microg/g significantly increased the incidences of complete and >/= 90% healing and significantly reduced the median relative ulcer volume at endpoint compared with that of placebo gel (p < 0.025 for all comparisons). Becaplermin gel 300 microg/g did not result in a significantly greater incidence of healing than that observed with 100 microg/g. Treatment with becaplermin gel was generally well tolerated and the incidence of adverse events was similar among treatment groups. In conclusion, once-daily application of becaplermin gel is efficacious in the treatment of chronic full thickness pressure ulcers.

Tretinoin emollient cream for photodamaged skin: results of 48-week, multicenter, double-blind studies.

BACKGROUND: The ability of topical tretinoin to improve certain signs of skin photodamage has been shown previously. OBJECTIVE: Our purpose was to assess the effectiveness of tretinoin emollient cream in maintaining or further improving photodamaged skin during extended use. METHODS: Photodamaged subjects who completed 24 weeks of once-daily use of tretinoin emollient cream 0.05% (n = 149) or 0.01% (n = 149) continued to use the same strength formulation in a 24-week double-blind extension. RESULTS: Maintenance of improvement or continued reduction in signs of photodamage was noted in both investigators' and subjects' evaluations of the 0.05% and 0.01% preparations; these results were confirmed by skin replica analyses. Cutaneous side effects were less common during the extension study than during the first 24 weeks of therapy. CONCLUSION: Both strengths of tretinoin emollient cream (0.05% and 0.01%) appeared safe and effective in the treatment of photodamaged skin during a 48-week treatment period.

Skin replica analysis of photodamaged skin after therapy with tretinoin emollient cream.

Computerized image analysis of silicone replicas, a reproducible, objective technique for measuring skin topography, was used in addition to clinical measures in two multicenter, double-blind, randomized, controlled studies of tretinoin emollient cream, a new formulation for treating photodamaged skin. Previously, the skin replica technique had been successfully used in a pilot study of tretinoin 0.05% cream by one investigator. In the present studies, subjects treated for 24 weeks with tretinoin emollient 0.05% cream consistently showed more improvement in skin topography than did vehicle-treated patients. A 0.01% concentration of tretinoin emollient cream also improved skin topography to a greater extent than the vehicle, while the lowest concentration tested (0.001%) showed little difference from vehicle. These results, reflecting a smoothening of the skin surface in tretinoin emollient cream-treated subjects, were consistent with clinical data showing greater improvement in fine wrinkling and roughness after tretinoin emollient cream therapy than after vehicle therapy. Findings from these multicenter studies confirm the value of the skin replica technique and help establish the efficacy of tretinoin emollient 0.05% cream for photodamaged skin.

Leprosy case detection rates by age, sex, and polar type under leprosy control conditions.

The knowledge of leprosy epidemiology is still extremely limited as to basic epidemiologic characteristics. Only the infectious agent and the reservoir of infection have been firmly established. It is all the more surprising that very few studies of analytical leprosy epidemiology are reported in the literature. In order to contribute to the analysis of these characteristics, data are presented on the age and sex distribution of types of leprosy from the Pogiri Leprosy Control Project, a large leprosy control project in Andhra Pradesh, India. This data base includes records on biannual examination of some 160,000 household contacts of nearly 48,000 leprosy cases observed from five to nine years between 1962 and 1970. These data indicate a peak of leprosy prevalence and incidence in the age group 35-44 years. The sex differential in leprosy, observed in these data, appears more related to sex differences in social contact, as sex ratios of leprosy vary widely among different populations. Finally, the age distribution of tuberculoid leprosy shows a bimodal curve, with peaks at ages 10-14 and 35-44 years. The first peak appears related both to the occurrence of early and self-healing lesions in school children, and to the more frequent examination of school children. Additional observations are presented on type ratios of leprosy in single and multiple case households, and on per cent of single lesions for tuberculoid cases detected over time.

Correlates of life expectancy in less developed countries.

Analyses were performed to investigate several hypotheses concerning the multiple determinants of levels of life expectancy in developing countries in recent decades and some possible explanation for the observed variations in amount of gain in life expectancy from the 1950's to the 1970's. The findings were significant. For level of life expectancy the results of this present work conform by and large to results of other scholars in this area, although the present work is unique in that only developing countries were included. From the 1960's to the 1970's there has been a shift in the relative importance of economic indicators and general social indicators in favor of the social indicators. In the period 1960-65 some 70% of the variation in levels of life expectancy was associated with per capita income and literacy rates in a ratio of about three to two in favor of the economic variable. By 1970-75 the ratio has become six to one in favor of literacy. In addition, the multivariate model showed that the sanitation variables began to appear as significant correlates of levels of life expectancy in the more recent time period, playing a larger role than level of income per capita. Work pursued as part of a separate but concurrent project explored explicitly this three-way interaction between literacy, life expectancy and sanitation.

Effect of investments in water supply and sanitation on health status: a threshold-saturation theory.

A general theory on the relationship between water supply and sanitation investments and health, the threshold-saturation theory, is proposed. The theory takes into consideration three variables: health status, socioeconomic status, and sanitation level, and attempts to encompass, for the first time in one general theoretical framework, numerous conflicting empirical findings. The two-tiered S-shaped logistic form of the relationship that is proposed assumes that at the lower end of the socioeconomic spectrum there is a threshold below which investments in community water supplies and/or excreta disposal facilities alone result in little detectable improvement in health status. Similarly, at the higher end of the socioeconomic scale, it is suggested that a point of saturation is reached beyond which further significant health benefits cannot be obtained by investments in conventional community sanitation facilities.A preliminary attempt to validate this model using published data on sanitation level (defined as access to water supply), life expectancy, and adult literacy rates, for 65 developing countries, appears to provide preliminary support for the threshold saturation theory but further empirical validation is required before a quantitative predictive model can be developed.

DNA content and DNA-based centromeric index of the 24 human chromosomes.

The chromosomes of two human males were identified by fluorescent banding, restained, and measured by scanning microscopy and computer analysis. The two variables, DNA content and DNA-based centromeric index, provided almost complete discrimination of chromosome types. Some chromosomes showed significant differences in DNA content between the men, and for one man two pairs of chromosomes showed significant differences between homologs.