Gleb Haynatzki

Accuracy of Pubertal Tanner Staging Self-Reporting

OBJECTIVES Previous studies examining the reliability of self-reported Tanner stages have given conflicting results. We report on the reliability of self-reported Tanner stages in lean healthy children. METHODS Self-reported Tanner staging of 240 children (130 girls, 110 boys) were compared to the ratings of a pediatric endocrinologist who was unaware of the childrens self-assessments. The correlation between the two approaches was analyzed using kappa statistics. RESULTS 40% (kappa coeffcient = 0.49, p <0.001) and 23% (kappa coefficient = 0.68, p <0.001) of the girls rated their breast and pubic Tanner stage incorrectly, respectively; 39% of the boys (kappa coefficient = 0.49, p <0.001) rated their pubic stage incorrectly. The age of the children who self-rated correctly and incorrectly was not different; no independent predictors for correct Tanner staging self-assessment were found. CONCLUSIONS The results of this analysis suggest that self-rated Tanner pubertal staging is not influenced by age and is not a reliable method of assessing Tanner stage.

Progression of visual field loss in untreated glaucoma patients and glaucoma suspects in St. Lucia, West Indies

PURPOSE A 1986-1987 survey found 8.8% prevalence of open-angle glaucoma in the black population of St. Lucia, West Indies. This follow-up study assessed visual field loss progression in untreated glaucoma patients and glaucoma suspects 10 years later. DESIGN Cohort study. METHODS Subjects were 205 glaucoma patients and suspects; 1987 data included age, sex, visual acuity, and visual fields measured by automated threshold perimetry (Humphrey C 30-2 test), and 1997 data included intraocular pressure, visual acuity, and visual fields measured by the same test. Exclusion criteria included field unreliability, field improvement due to vision improvement, nonglaucomatous vision deterioration, glaucoma treatment since 1988, and scoring of a visual field as end stage in 1987. Visual fields were scored by algorithms for the Advanced Glaucoma Intervention Study (AGIS) and Collaborative Initial Glaucoma Treatment Study (CIGTS). RESULTS By AGIS criteria, 55% of 146 right eyes and 52% of 141 left eyes showed progression of visual field loss. In linear regressions, progression severity was unassociated with sex, intraocular pressure, or baseline visual field score, but was positively associated with age (P <.001, right; P =.002, left). The cumulative probability of reaching end stage in 10 years in at least one eye was approximately 16% by AGIS criteria. By CIGTS criteria, 73% of 146 right eyes and 72% of 141 left eyes progressed. CONCLUSIONS These data provide a unique opportunity to study progression of untreated glaucoma. The percentage of eyes showing visual field loss progression and the percentage reaching end stage were considerably higher than in studies of visual field progression in treated eyes.

Effect of Vitamins D2 and D3 Supplement Use on Serum 25OHD Concentration in Elderly Women in Summer and Winter

Vitamin D2 and D3 are generally considered equipotent in humans. A few studies have reported that serum 25OHD levels are higher in vitamin D3- compared with vitamin D2-supplemented subjects. As both vitamin D2 and D3 supplements are commonly used by elderly in United States, in the present study we determined the effect of self-reported vitamin D2 and vitamin D3 supplement use on serum total 25OHD levels according to season in elderly women aged 65–77 years. Serum total 25OHD levels were determined in winter and summer in unsupplemented women (N = 307) and in women who reported taking vitamin D2 (N = 56) and vitamin D3 (N = 55) supplements by competitive protein binding assay. In vitamin D2-supplemented women, the contribution of vitamin D2 and D3 to the mean serum total 25OHD level was assessed by HPLC. In summer, there were no significant differences in the mean total serum 25OHD levels (ng/ml) among the vitamin D2 (32 ± 2.1), vitamin D3 (36.7 ± 1.95), and unsupplemented (32.2 ± 0.95) groups. In winter, the mean serum total 25OHD levels were higher in women on vitamin D2 (33.6 ± 2.34, P < 0.05) and vitamin D3 (29.7 ± 1.76, NS) supplements compared with unsupplemented women (27.3 ± 0.72). In vitamin D2-supplemented women, about 25% of the mean serum total 25OHD was 25OHD2, in both summer and winter. Twelve percent of unsupplemented women and 3.6% of vitamin D-supplemented women had a mean serum total 25OHD level below 15 ng/ml in winter. In elderly subjects, both vitamin D2 and Vitamin D3 supplements may contribute equally to circulating 25OHD levels, with the role of vitamin D supplement use being more predominant during winter.

Response to preoperative chemoradiation in Stage II and III rectal cancer

AbstractPURPOSE: The purpose of this study was to determine whether a complete pathologic response after neoadjuvant therapy in rectal cancer patients improves disease control and survival. METHODS: The study reviewed Stage II and III rectal cancer patients treated with preoperative chemoradiation and resected for cure. Complete pathologic response was defined as no cancer in the resected specimen. The main outcome measures were cancer-specific and disease-free survival in patients achieving a complete pathologic response and a noncomplete pathologic response. Kaplan-Meier curves were evaluated using log-rank analysis. RESULTS: Eighty-nine rectal cancer patients received neoadjuvant chemoradiation followed by radical resection for cure. Twenty-one patients (24 percent) achieved a complete pathologic response. Median follow-up for the complete pathologic response group was 23.5 months and 31 months for the noncomplete pathologic response group. There were more Stage III patients in the noncomplete pathologic response group than the complete pathologic response group (P = 0.005). Complete pathologic response patients were less likely to receive postoperative adjuvant chemotherapy than noncomplete pathologic response patients (P = 0.004). Cancer-specific and disease-free survival were not statistically different between the two groups. However, a trend was noted toward improved survival and decreased recurrence in association with a complete pathologic response. CONCLUSION: Stage III patients were less likely to be in the complete pathologic response group than Stage II patients. Complete pathologic response patients were less likely to receive postoperative adjuvant chemotherapy than noncomplete pathologic response patients. Complete pathologic response after neoadjuvant chemoradiation for rectal cancer patients demonstrated a trend toward improved survival and decreased recurrence compared with noncomplete pathologic response patients.

Assessment of Diaphragmatic Stressors as Risk Factors for Symptomatic Failure of Laparoscopic Nissen Fundoplication

An important limitation of antireflux surgery is a 5%–10% failure rate. We investigated the correlation between various diaphragm stressors and failure of antireflux surgery. Forty-one study cases who underwent a reoperative antireflux operation from 1997 to 2001 and 50 control patients who had undergone a successful laparoscopic Nissen fundoplication during the same period without clinical or symptomatic evidence of failure were randomly selected for comparison. A retrospective analysis was conducted utilizing a standardized diaphragm stressor questionnaire, addressing the period between the primary and secondary operation. Stressors considered in the study included height, body mass index (BMI), postoperative gagging, vomiting, weight lifting (greater than 100 pounds), coughing, hiccuping, motion sickness, retching, belching, antidepressant use, smoking, preoperative grade of esophagitis, size of hiatal hernia, lower esophageal sphincter pressure, esophageal body pressures, and preoperative response to proton pump inhibitors. Of the potential stressors investigated, the following were significantly associated with surgical failure after adjusting for other variables through multivariate analysis: gagging (P = 0.005), belching (P = 0.02), and hernia size greater than 3 cm (P = 0.04; Table 1). Other potential risk factors show trends as obvious in Fig. 2. Vomiting was significant (P = 0.01) in the earlier models but lost significance when logistic regression was applied. Patients with postoperative gagging and an intraoperative hiatal hernia (greater than 3 cm) have a poorer outcome, whereas patients with postoperative belching have a better long-term outcome.

American founder mutation for lynch syndrome : Prevalence estimates and implications

Recently, a new founder mutation, an exon 1–6 deletion in a mismatch repair gene (MMR), MSH2, in nine kindreds with Lynch syndrome was reported. In 3 of the kindreds this mutation was traced by genealogy through 11–12 generations to a common founder, and thus termed the American Founder Mutation (AFM). Since then, 13 additional ‘unrelated’ kindreds with AFM were detected by a recently designed single polymerase chain reaction. This test might serve as first‐line screening for Lynch syndrome mutations, provided AFM was prevalent, which is assessed in the current study.

The determination of genetic covariances and prediction of evolutionary trajectories based on a genetic correlation matrix

There is much interest in measuring selection, quantifying evolutionary constraints, and predicting evolutionary trajectories in natural populations. For these studies, genetic (co)variances among fitness traits play a central role. We explore the conditions that determine the sign of genetic covariances and demonstrate a critical role of selection in shaping genetic covariances. In addition, we show that genetic covariance matrices rather than genetic correlation matrices should be characterized and studied in order to infer genetic basis of population differentiation and/or to predict evolutionary trajectories.

The impact of ethanol and tobacco smoke on intranasal epithelium in the rat.

Background Investigations have shown the influence of ethanol and tobacco smoke on olfaction, epithelial metaplasia, and cancer formation in the head and neck. Analysis of ethanol and tobacco smoke-induced histopathological mucosal changes in the upper respiratory tract may provide important insight into the pathophysiology of secondary olfactory dysfunction. Methods Three groups of laboratory rats were experimentally exposed to either ethanol, tobacco smoke, or both, with a control group having no such exposure. Results Compared with controls, histopathological analysis of nasal mucosa in exposed rats revealed a decrease in the length of olfactory epithelium, especially in the rats exposed to both ethanol and tobacco smoke. Structural changes included loss of cilia and metaplasia. Conclusion The histological changes noted in rats after ethanol and tobacco smoke exposure, if relevant to human physiology, could explain the decreased olfactory ability seen in patients who use these products.

A new statistical model of tumor latency time

A new statistical parametric model of carcinogenesis is proposed. The focus is on tumor latency times. The model makes use of extreme value theory following the line initially explored by Pike [1] and further developed by Klebanov et al. [2]. In this paper, we make the first attempt to take account of the interdependence between the cells in an initiated tissue developing into a malignant tumor.

A Comparison of Statistical Approaches for Genetic Anticipation with Application to Pancreatic Cancer

Genetic anticipation for a particular disease can involve an earlier age at onset (or, diagnosis), greater severity, and/or a higher number of affected individuals in successive generations within a family. The variable of interest in our study of genetic anticipation was age at diagnosis of pancreatic cancer for different generations, with and without adjustment for time under observation. We compared nonparametric and semiparametric statistical tests for paired data. This comparison was illustrated on an example of familial pancreatic cancer where study subjects were taken from the Pancreatic Cancer Collaborative Registry (PCCR). The nonparametric test performed on our example better than the two semiparametric tests, and was more efficient in detecting risk differences at earlier ages. After adjusting for follow up time, all methods detected genetic anticipation