Comparing sulindac with indomethacin for closure of ductus arteriosus in preterm infants

Objectives: A prospective study comparing the efficiacy and side-effects of oral sulindac with intravenous indomethacin in clinically stable preterm infants (<1750 g) requiring non-invasive closure of haemodynamically significant patent ductus arteriosus.
Methodology: As maturity and birthweight are the two major determinants of ductal closure, infants were matched as closely as possible for these parameters. An eligible patient was first assigned to the sulindac group and a subsequent patient with similar gestational age (± 1 week) and birthweight (±100 g) to the previously recruited infant would automatically receive indomethacin. A total of eight infants were enrolled in each group.
Results: The ductus arteriosus was successfully closed in all eight infants receiving indomethacin, and in seven of eight infants receiving sulindac. No significant differences were found with regards to the ductal size between the two groups at diagnosis or on each of the consecutive days of treatment ( P >0.25). More renal adverse effects were encountered in the indomethacin group. Significant differences in changes from baseline value for urine output, plasma sodium, urea and creatinine concentrations were noted at 24, 48 and 72 h after commencement of treatment between the two groups ( P <0.05). All the parameters returned to normal or pre-treatment levels 48 h after stopping therapy. Unexpectedly, severe gastrointestinal complications were encountered in the sulindac group.
Conclusions: Sulindac is capable of promoting ductal constriction in clinically stable preterm infants without compromising the renal function. The spectrum of gastrointestinal complications observed in sulindac treated infants were similar to those described for indomethacin. The use of sulindac for ductal closure in the preterm infant should remain experimental.     

Aberrant crypt focus promotion and glucose intolerance: correlation in the rat across diets differing in fat, n-3 fatty acids and energy

McKeown-Eyssen (Cancer Epidemiol. Biomarkers Prevent., 3, 687-695, 1994) and Giovannucci (Cancer Causes Control, 6, 164-179, 1995), noting the striking similarity in lifestyle risk factors for colorectal cancer and insulin resistance, proposed that the hyperinsulinemia, glycemia and hypertriglyceridemia associated with insulin resistance promotes colon cancer. To compare the effect of diet on colon cancer promotion and insulin resistance in the F344 rat, we assessed the effect of fat, n-3 fatty acids and energy in pairwise comparisons on average size of aberrant crypt foci (ACF) and on glucose intolerance in the same animals in a single experiment. Diets high in fat and energy increased and diets with increased n-3 fatty acids and calorie restriction decreased both ACF growth and glucose intolerance compared with control diets. The measures of promotion of colon cancer and insulin resistance were strongly correlated (n = 98, r = 0.67, P < 0.001). In addition, both were highly correlated with daily energy intake (r = 0.62 and 0.66) and were also correlated with basal (post-prandial) insulin, glucose and triglycerides (r = 0.31-0.53, P < 0.01). We concluded that ACF growth and glucose intolerance are correlated for a wide range of diets and that increased circulating energy (glucose and triglycerides) may lead to both colon cancer promotion and insulin resistance.      

Angiogenesis is an early event in the development of chemically induced skin tumors

In this study we have analyzed the vascular response induced in the two- stage carcinogenesis model in SENCAR mice. The role of angiogenesis has not been explored in this model, which is the paradigm of multistage carcinogenesis and a model for neoplastic lesions derived from exophytic premalignant lesions (e.g. colon carcinoma, bladder papilloma). We investigated if angiogenesis is involved in the formation of papillomas and in the progression from papilloma to carcinoma. To this end we analyzed the vasculature of normal and hyperplastic skin, focal epidermal hyperplasias that are precursors of papillomas, papillomas at different stages and squamous cell carcinomas. We also analyzed the vascularization of papillomas induced in two strains of mice that differ in their susceptibility to malignant progression. We show here that angiogenesis is turned on in the earliest stages of papilloma formation. In late stages, regardless of state of progression, the predominant response is an increase in the size of blood vessels. Thus, in the SENCAR mouse model, representative of exophytic tumors, the angiogenesis switch is a very early event, probably mechanistically related to the development of the primarily exophytic lesions. Therefore, the density of blood vessels cannot be used as a predictor of malignant progression in this model.      

Chromosomal Mosaicism in Cleavage-Stage Human Embryos and the Accuracy of Single-Cell Genetic Analysis

Purpose: Our purpose was to assess the effect of chromosomal mosaicism in cleavage-stage human embryos on the accuracy of single-cell analysis for preimplantation genetic diagnosis. Methods: Multicolor fluorescence in situ hybridization with X, Y, and 7 or X, Y, 7, and 18 chromosome-specific probes was used to detect aneuploidy in cleavage-stage human embryos. Results: Most nuclei were diploid for the chromosomes tested but there was extensive mosaicism including monosomic, double-monosomic, nullisomic, chaotic, and haploid nuclei. Conclusions: Identification of sex by analysis of a single cleavage-stage nucleus is accurate but 7% of females are not identified. One or both parental chromosomes 7 were absent in at least 6.5% of the nuclei. With autosomal recessive conditions such as cystic fibrosis, carriers would be misdiagnosed as normal or affected. With autosomal dominant conditions, failure to analyze the affected parents allele (1.6–2.5%) would cause a serious misdiagnosis and analysis of at least two nuclei is necessary to reduce errors.     

Retinal function and histologic changes following intravitreal injection of indocyanine green in a rabbit model.

The aim of this animal study was to investigate the effects of intravitreal injection of indocyanine green (ICG) applied in macular hole surgery on retinal functional, morphology, and histologic changes. Eighteen (18) New Zealand albino rabbits were divided equally into three groups (6 rabbits in each). In Group A, both eyes of each rabbit were vitrectomized by perflouropropane gas compression. One (1) month later, 0.1 cc of different doses of ICG was injected into the vitreous in the left eyes. In the right eyes, 0.1 cc of balanced salt solution was injected intravitreally, allowing them to serve as control eyes. In Group B, the same doses of ICG were injected intravitreally. ICG was washed out by fluid-fluid exchange 3 minutes after injection. In Group C, the same doses of ICG were injected intravitreally in nonvitectomized eyes. Scotopic and photopic electroretinogram (ERG) recordings and indirect ophthalmoscopy examinations were performed to detect any functional and morphologic changes. Rabbit eyes were enucleated 4 months after ICG injections to observe histologic changes. Significant decreased of scotopic and photopic ERG amplitude and marked histologic changes were noted in eyes injected with 0.5 mg/cc and 0.1 mg/cc of ICG in nonvitrectomized eyes (Group C). In vitrectomized eyes (Group A), decreased scotopic and photopic ERGs and mild histologic changes were noted in eyes injected with 0.5 mg/cc, but no histologic changes were noted in eyes injected with 0.1 mg/cc. There was a transient, mild decrease in scotopic and photopic ERGs and no morphologic changes were noted in the eyes with fluid-fluid exchange (Group B). The toxicity of intravitreous ICG is dose- and time-dependent. ICG at 0.5 mg/cc, with short exposure time, is recommended in macular hole surgery.     

Risk factors for wound infection after cholecystectomy.

BACKGROUND AND PURPOSE: Surgical site infection (SSI) after cholecystectomy is a common problem. The aim of this study was to identify the possible risk factors for the development of SSI. METHODS: 545 consecutive patients who received open (125) or laparoscopic (420) cholecystectomy due to gallbladder disease during the years 1998 to 2000 were included in the study. Potential risk factors including clinical features, biochemical data, and operative types were analyzed by univariate and multivariate analysis. RESULTS: The overall incidence of SSI was 4.4% (24/545). The wound complication rate was significantly lower in the laparoscopic group than in the open group (1.4% vs 14.4%, respectively). Factors associated with SSI found by univariate analysis (p < 0.05) included age, gender, acute cholecystitis, white blood cell count, serum albumin, blood glucose and bilirubin level, type of surgery, operative time and positive bile culture. Stepwise logistic regression analysis showed that abnormal blood glucose [odds ratio (OR), 4.7; 95% confidence interval (CI), 1.6 to 13.5], positive bile culture (OR, 3.5; 95% CI, 1.2 to 10.4), and open cholecystectomy (OR, 4.3; 95% CI, 1.3 to 13.6) were the most significant predictors of SSI. CONCLUSION: Poor control of diabetes mellitus before surgery, positive bile culture and open cholecystectomy significantly increased the rate of SSI. These findings indicate that better control of diabetes mellitus, and appropriate selection of surgical procedure and antibiotic regimen in the management of high-risk patients may reduce the incidence of postoperative SSI.