Quantitative analysis of microvascular changes in diffuse astrocytic neoplasms with increasing grade of malignancy

BACKGROUND: Despite concerns about its prevalence and ramifications, harassment has not been well quantified among physicians. Previous published studies have been small, have surveyed only 1 site or a convenience sample, and have suffered from selection bias. METHODS: Our database is the Women Physicians' Health Study, a large (4501 respondents; response rate, 59%), nationally distributed questionnaire study. We analyzed responses concerning gender-based and sexual harassment. RESULTS: Overall, 47.7% of women physicians reported ever experiencing gender-based harassment, and 36.9% reported sexual harassment. Harassment was more common while in medical school (31% of gender-based and 20% for sexual harassment) or during internship, residency, or fellowship (29% for gender-based and 19% for sexual harassment) than in practice (25% for gender-based and 11% for sexual harassment). Respondents more likely to report gender-based harassment were physicians who were now divorced or separated and those specializing in historically male specialties, whereas those of Asian and other (nonwhite, nonblack, non-Asian, non-Hispanic) ethnicity, those living in the East, and those self-characterized as politically very conservative were less likely to report gender-based harassment. Being younger, born in the United States, or divorced or separated were correlated with reporting ever experiencing sexual harassment; those who were Asian or who were currently working in group or government settings were less likely to report it. Those who felt in control of their work environments, were satisfied with their careers, and would choose again to become physicians reported lower prevalences of ever experiencing harassment. Those with histories of depression or suicide attempts were more likely to report ever having been harassed. CONCLUSIONS: Women physicians commonly perceive that they have been harassed. Experiences of and sensitivity to harassment differ among individuals, and there may be substantial professional and personal consequences of harassment. Since reported rates of sexual harassment are higher among younger physicians, the situation may not be improving.     

Current concepts: spinal injuries and rehabilitation

Spinal cord injuries and their catastrophic effects require a treatment infrastructure able to provide an integrated process of management, including rehabilitation from injury and on an ongoing basis. This is particularly important because the incidence of spinal cord injuries is small. Better outcomes and cost efficiency with such an infrastructure have been established, but further knowledge is required to solve the remaining controversies in some aspects of management.     

Demonstration of tank effect on growth indices of juvenile rainbow trout (Oncorhynchus mykiss) during an ad libitum feeding trial

Growth indices were examined in 24 identically managed tanks, each containing 120 diploid juvenile rainbow trout (initial mean body weight, 9.3 g) during a 12-week study to examine tank effects associated with tank location in a multi user research facility. Growth indices included mean body weight, feed intake, feed conversion index, and specific growth rate. The null hypothesis that tank effect had no effect on growth over the 12-week period was rejected (P = 0.038), and mean weight in individual tanks differed by as much as 18.7%). During the study it was determined that the proximity of tanks to common-use walkways in the facility could affect growth indices. This was indicated by significant differences in the mean fish weights among blocks of tanks served by different header tanks after 4 (P = 0.001) and 8 (P = 0.024) week. The block containing tanks of fish with the highest them weight was nearest to the 2 common-use walkways in the facility. Fish in this block of tanks, compared with those in other blocks, had significantly greater feed intake but no significant differences in conversion efficiency. Compensatory growth, a well known growth attribute in fishes, diminished the difference in mean weight be tween these blocks of tanks by the end of the study. Comparison of paired ranks within header tank blocks indicated that fish in those located nearest to walkways had higher feeding rates over the 12-week period (P = 0.048), but less efficient feed conversion (P = 0.040) than did fish in matched tanks located farthest from walkways. However, there were no differences in mean weight of fish. Results of this trial document the risks involved in identifying fish in a tank as the experimental unit when treatments are administered to the tank of fish, the latter being the true experimental unit.     

Compliance with primary prevention in private practice: creating a tobacco-free environment

A sample of private orthodontic practices (n = 40) from a controlled trial for clinician-initiated tobacco-use prevention was used to test the effectiveness of preventive medicine representative (PMR) visits in creating and maintaining an anti-tobacco office environment. Clinical staff of 20 offices, randomly assigned to the experimental group, were trained by a PMR on the use of anti-tobacco materials (no-smoking signs, posters, and print materials). Twenty control-group offices did not receive any training or special treatment. Subsequently, experimental-group offices were visited by a PMR once every three months and were telephoned six weeks after each visit over a 12-month period. During visits and phone calls, PMRs prompted offices to order anti-tobacco materials. Visits served to introduce offices to new materials and to encourage their continued use. Data from direct observations and self-report measures showed significant differences between experimental and control offices for display of anti-tobacco materials at 1.5 months and 12 months (P < .001). Results suggest that PMR visits may serve as an effective method of introducing and maintaining preventive medicine procedures in clinical environments.     

The role of dermabrasion and chemical peels in the treatment of patients with xeroderma pigmentosum

We describe our experience with two patients with xeroderma pigmentosum who underwent periodic trichloroacetic acid chemical peels. One also received a full-face dermabrasion. The effect of chemical peeling was more transient than dermabrasion but was associated with less morbidity. Both chemical peeling and dermabrasion provided a prophylactic effect against the development of skin malignancies; the latter had a more pronounced effect.     

Multiple virus genes involved in the nematode transmission of pea early browning virus

Gorlin syndrome is an autosomal dominant disorder characterized by multiple basal cell carcinomas, medulloblastomas, ovarian fibromas, and a variety of developmental defects. All affected individuals share certain key features, but there is significant phenotypic variability within and among kindreds with respect to malformations. The gene (NBCCS) maps to chromosome 9q22, and allelic loss at this location is common in tumors from Gorlin syndrome patients. Two recessive cancer-predisposition syndromes, xeroderma pigmentosum group A (XPAC) and Fanconi anemia group C (FACC), map to the NBCCS region; and unusual, dominant mutations in these genes have been proposed as the cause of Gorlin syndrome. This study presents cytogenetic and molecular characterization of germ-line deletions in one patient with a chromosome 9q22 deletion and in a second patient with a deletion of 9q22-q3l. Both have typical features of Gorlin syndrome plus additional findings, including mental retardation, conductive hearing loss, and failure to thrive. That Gorlin syndrome can be caused by null mutations (deletions) rather than by activating mutations has several implications. First, in conjunction with previous analyses of allelic loss in tumors, this study provides evidence that associated neoplasms arise with homozygous inactivation of the gene. In addition, dominant mutations of the XPAC and FACC1 genes can be ruled out as the cause of Gorlin syndrome, since the two patients described have null mutations. Finally, phenotypic features that show variable expression must be influenced by genetic background, epigenetic effects, somatic mutations, or environmental factors, since these two patients with identical alterations (deletions) of the Gorlin syndrome gene have somewhat different manifestations of Gorlin syndrome.     

Reciprocal regulation of neu tyrosine kinase activity and caveolin-1 protein expression in vitro and in vivo. Implications for human breast cancer

Neu (c-erbB2) is a proto-oncogene product that encodes an epidermal growth factor-like receptor tyrosine kinase. Amplification of wild-type c-Neu and mutational activation of Neu (Neu T) have been implicated in oncogenic transformation of cultured fibroblasts and mammary tumorigenesis in vivo. Here, we examine the relationship between Neu tyrosine kinase activity and caveolin-1 protein expression in vitro and in vivo. Recent studies have suggested that caveolins may function as negative regulators of signal transduction. Our current results show that mutational activation of c-Neu down-regulates caveolin-1 protein expression, but not caveolin-2, in cultured NIH 3T3 and Rat 1 cells. Conversely, recombinant overexpression of caveolin-1 blocks Neu-mediated signal transduction in vivo. These results suggest a reciprocal relationship between c-Neu tyrosine kinase activity and caveolin-1 protein expression. We next analyzed a variety of caveolin-1 deletion mutants to map this caveolin-1-dependent inhibitory activity to a given region of the caveolin-1 molecule. Results from this mutational analysis show that this functional in vivo inhibitory activity is contained within caveolin-1 residues 32-95. In accordance with these in vivo studies, a 20-amino acid peptide derived from this region (the caveolin-1 scaffolding domain) was sufficient to inhibit Neu autophosphorylation in an in vitro kinase assay. To further confirm or refute the relevance of our findings in vivo, we next examined the expression levels of caveolin-1 in mammary tumors derived from c-Neu transgenic mice. Our results indicate that dramatic reduction of caveolin-1 expression occurs in mammary tumors derived from c-Neu-expressing transgenic mice and other transgenic mice expressing downstream effectors of Neu-mediated signal transduction, such as Src and Ras. Taken together, our data suggest that a novel form of reciprocal negative regulation exists between c-Neu and caveolin-1.     

Influence of cell polarity on retrovirus-mediated gene transfer to differentiated human airway epithelia

Gene transfer with recombinant murine leukemia viruses (MuLV) provides the potential to permanently correct inherited lung diseases, such as cystic fibrosis (CF). Several problems prevent the application of MuLV-based recombinant retroviruses to lung gene therapy: (i) the lack of cell proliferation in mature pulmonary epithelia, (ii) inefficient gene transfer with a vector applied to the apical surface, and (iii) low titers of many retroviral preparations. We found that keratinocyte growth factor (KGF) stimulated proliferation of differentiated human tracheal and bronchial epithelia. Approximately 50% of epithelia divided in response to KGF as assessed by bromodeoxyuridine histochemistry. In airway epithelia stimulated to divide with KGF, high-titer ampho- and xenotropic enveloped vectors preferentially infected cells from the basal side. However, treatment with hypotonic shock or EGTA transiently increased transepithelial permeability, enhancing gene transfer with the vector applied to the mucosal surfaces of KGF-stimulated epithelia. Up to 35% of cells expressed the transgene after gene transfer. By using this approach, cells throughout the epithelial sheet, including basal cells, were targeted. Moreover, the Cl- transport defect in differentiated CF airway epithelia was corrected. These findings suggest that barriers to apical infection with MuLV can be overcome.     

Laparoscopic splenectomy: outcome and efficacy in 103 consecutive patients

OBJECTIVE: To study the safety and efficacy of laparoscopic splenectomy (LS) in patients with predominantly benign hematologic disorders. SUMMARY BACKGROUND DATA: The technical feasibility of LS has been recently established. However, data regarding the efficacy of the procedure in a large cohort of patients are scarce. METHODS: One hundred three consecutive patients underwent LS between June 1992 and October 1997. Data were collected prospectively on all patients. RESULTS: Indications were idiopathic thrombocytopenic purpura (ITP), hereditary spherocytosis, autoimmune hemolytic anemia, thrombotic thrombocytopenic purpura, and others. Mean spleen size was 14 cm and mean weight was 263 g. Accessory spleens were found in 12 patients with ITP and in 5 patients without ITP. There were no deaths. Complications occurred in six patients, one requiring a second procedure for small bowel obstruction. Six patients received transfusions, and four procedures were converted to open splenectomy for bleeding. Mean surgical time was 161 minutes and was greater in the first 10 cases than the last 10. Mean postsurgical stay was 2.5 days. Thrombocytopenia resolved after surgery in 84% of patients with ITP, and hematocrit levels increased significantly in 70% of patients with chronic hemolytic anemias. A positive response was noted in 92% of patients with hereditary spherocytosis, without relapse for the duration of the observation. ITP relapsed in four patients during follow-up, three within 12 months. CONCLUSIONS: LS can be performed safely and effectively in a teaching institution. Rigorous technique will minimize capsular fractures, reducing the risk of splenosis. Accessory spleens can be successfully localized, thus improving response and limiting recurrence of ITP. LS should become the technique of choice for treatment of intractable benign hematologic disease.     

Factors affecting high-density lipoproteins

Although it is well established that a low-circulating level of high-density lipoprotein (HDL) cholesterol is strongly associated with the likelihood of developing atherosclerotic coronary heart disease (CHD), the causal nature of this association has not been shown. Low levels of HDL cholesterol frequently are associated with other CHD risk factors, whose correction, often by hygienic means, may reduce CHD risk with minimal risk of adverse side-effects. However, other recommended hygienic interventions may lower HDL cholesterol levels. Specific safe and effective drugs for correcting a low HDL cholesterol level are not available and the potential value of specific pharmacologic treatment of this condition in the treatment or prevention of CHD remains unproven. Thus, while HDL measurement should be incorporated routinely in risk-assessment, intervention efforts should focus primarily on lowering low-density lipoprotein cholesterol.