Prognostic significance of atypical papillary urothelial hyperplasia

Typical papillary hyperplasia, a recently recognized precursor lesion to low-grade papillary urothelial neoplasms, consists of undulating folds of cytologically benign urothelium. Well-developed, branching fibrovascular cores of a papillary neoplasm are not evident. We have noted lesions with the architectural pattern of papillary hyperplasia; however, the overlying urothelium demonstrated varying degrees of cytologic atypia. We identified 15 cases of atypical papillary hyperplasia (13 males, 2 females, age 55 to 92) with overlying urothelium showing cytologic atypia. Of these cases, 8 (53%) were received in consultation. Of the 15 cases, 8 exhibited overlying flat carcinoma in situ (CIS), 4 had overlying dysplasia, and 3 were transitional between papillary hyperplasia with atypia and the earliest lesions of papillary neoplasia. Of these cases, 5 patients had multiple specimens with atypical papillary hyperplasia (range, 2 to 8) over time. Concurrent to the diagnosis of atypical papillary hyperplasia, there were 25 different urothelial lesions: CIS (n = 11), papilloma (n = 1), papillary neoplasm of low malignant potential with CIS (n = 1), high-grade papillary urothelial carcinoma (n = 10; 3 with CIS), small-cell carcinoma (n = 1), and infiltrating urothelial carcinoma (n = 1). Of 11 patients with known prior history, 2 had 12 prior urothelial neoplasms (9 low-grade papillary neoplasms, 2 papillary urothelial neoplasms of low malignant potential, and 1 high-grade papillary cancer). Of 10 patients with atypical papillary hyperplasia and a minimum of 1 year of follow-up, 9 had 19 recurrences: CIS (n = 4), papilloma (n = 1), papillary neoplasm of low malignant potential (n = 1), infiltrating urothelial carcinoma (n = 3; 1 with CIS), and high-grade papillary urothelial carcinoma (n = 10; 5 with invasion and 2 with CIS). Whether the papillary hyperplasia had overlying CIS or dysplasia did not affect the correlation with urothelial neoplasms. Immunohistochemical analysis of p53 and Ki-67 expression in 8 cases demonstrated overexpression of p53 (n = 2; 1 with overlying dysplasia and 1 with overlying CIS), and Ki-67 (n = 5; 2 with overlying dysplasia and 3 with overlying CIS). Taken together, these results suggest that atypical papillary hyperplasia is most frequently associated with CIS and high-grade papillary cancer. In some cases, CIS or dysplasia may evolve into atypical papillary hyperplasia, with further progression to high-grade papillary cancer. This process may be analogous to papillary hyperplasia without cytologic atypia progressing to low-grade papillary urothelial neoplasms.     

Stratification based on language-related endophenotypes in autism: attempt to replicate reported linkage.

The identification of autism susceptibility genes has been hampered by phenotypic heterogeneity of autism, among other factors. However, the use of endophenotypes has shown preliminary success in reducing heterogeneity and identifying potential autism-related susceptibility regions. To further explore the utility of using language-related endophenotypes, we performed linkage analysis on multiplex autism families stratified according to delayed expressive speech and also assessed the extent to which parental phenotype information would aid in identifying regions of linkage. A whole genome scan using a multipoint non-parametric linkage approach was performed in 133 families, stratifying the sample by phrase speech delay and word delay (WD). None of the regions reached suggested genome-wide or replication significance thresholds. However, several loci on chromosomes 1, 2, 4, 6, 7, 8, 9, 10, 12, 15, and 19 yielded nominally higher linkage signals in the delayed groups. The results did not support reported linkage findings for loci on chromosomes 7 or 13 that were a result of stratification based on the language delay endophenotype. In addition, inclusion of information on parental history of language delay did not appreciably affect the linkage results. The nominal increase in NPL scores across several regions using language delay endophenotypes for stratification suggests that this strategy may be useful in attenuating heterogeneity. However, the inconsistencies in regions identified across studies highlight the importance of increasing sample sizes to provide adequate power to test replications in independent samples.     

Transplantation of pig metanephroi

To determine whether pig metanephroi grow and differentiate after allotransplantation or xenotransplantation across a highly disparate barrier, we implanted metanephroi from embryonic day 28 (E28) pig embryos into the omentum of unilaterally nephrectomized adult pigs or C57Bl/6J mice (hosts). Some mouse hosts received anti-CD45RB, anti-CD154, and anti-CD11a (costimulatory blockade). E28 pig metanephroi were < 0.2 mm in diameter and contained only metanephric blastema and segments of ureteric bud. Pig metanephroi transplanted into pigs underwent growth and differentiation of nephrons over a 2 week period without the need for costimulatory blockade of hosts. In contrast, pig metanephroi did not grow or differentiate in mice that received no costimulatory blockade. However, by 2 weeks posttransplantation in mice in which costimulation was blocked, metanephroi from E28 pigs had enlarged, become vascularized, and had formed mature tubules and glomeruli. By 3 weeks posttransplantation in mice, metanephroi had grown to the point that they were approximately half the volume of the native mouse kidney. Here we show that growth and development of pig metanephroi occurs posttransplantation across an allogeneic or highly disparate xenogeneic barrier.     

Experimental analysis of the annotation of promoters in the public database

The ability to identify and examine promoter elements is important to researchers who wish to understand how gene expression is regulated in normal and pathological states. Unfortunately, the number of human promoters that have been directly experimentally defined is small. In order to determine if promoter sequences can be identified by simply aligning mRNA and genomic sequences, we have used a reporter gene assay to assess the promoter activity of the immediate 5' region flanking 38 mRNAs mapping to chromosome 21. For comparison, we have measured the activities of 19 sequences not thought to be promoters and 39 sequences taken from the Eukaryotic Promoter Database. Our results suggest that alignment of reference mRNAs to genomic sequence allows promoters to be identified for at least 75% of genes. These data provide the first empirical evidence that the current state of annotation of the genome is sufficient to allow molecular geneticists to correctly identify promoter sequences for most genes for which reference mRNA and genomic sequences are available.     

Combating the stress of residency: one school's approach.

Residency is a time of stress and turmoil for many residents. The stresses are varied and great, often involving both personal and professional issues. One institutional mechanism that has been shown to help residents cope with stress is the use of residents' wellness, or assistance, programs. The University of South Florida (USF) College of Medicine developed the USF Residency Assistance Program (RAP) in 1997, modeled after business employee assistance programs but tailored to enhance the well-being of residents. The program was developed in an organized, thoughtful manner starting with a Request for Proposals to all local employee assistance programs and the selection of one of these to run the program. The RAP is broad-based, readily available, easily accessible, totally voluntary and confidential, and not reportable to the state board of medicine. It is well integrated into all residency programs and has had excellent acceptance from the administration; information about access to the RAP is available to all residents through multiple venues. The cost is minimal, at only seven cents a day per resident.The authors present data from the eight years the RAP has been operating, including information on program use, referral rates, acceptance, and types of problems encountered. One suicide occurred during this time period, and the RAP provided a significant role in grief counseling. Assistance programs are critical to the well-being of residents. The USF program presents a model that can be used by other programs around the country.     

Health seeking behavior by families of children suspected to have malaria in Kabale: Uganda

Background

Malaria is common among communities of Kabale district, and many young children die of the illness. Despite a good distribution of health facilities, able to handle malaria patients, families and individuals tend to depend on self-treatment, or private clinics where drugs used may be of doubtful quality. This study reports on health seeking behaviour by families with children suspected to have malaria.

Methodology

A community-based, cross-sectional survey among 209 rural peasant families living in 12 villages, chosen from the 5 most malaria-affected sub-counties was done. Using a questionnaire, respondents'' reactions to the disease and what decisions they took were recorded. Reasons for choices such as drugs used, location of treatment and malaria control methods were recorded.

Results

Ninety seven percent lived within easy reach of a public health facility. Over 2/3 knew how malaria was transmitted and how it presented. They believed it was best treated at public heath facilities using western type of medicine. Fifty percent of the children, who attended public health units, were treated within 24 of illness. Thirty eight percent of the caretakers knew how to correctly use chloroquine. The caretakers relied on fever, vomiting and refusal to feed as the main symptoms for their diagnosis of malaria. Only 31% of the families sought treatment from government health facilities.Fifty three percent of the families sought treatment from drug shops/vendors. Unfortunately only 38% of the families knew the correct regimen of chloroquine, 4.3% for sulpha-doxine pyrimethamine and 0.5% for quinine. One quarter could afford malaria treatment, and one out of five missed treatment because of poverty. Concerning prevention, 90% stated at least one method but only 21.2% used them.

Conclusions

Despite reasonable knowledge for diagnosis of malaria, awareness of correct treatment is limited. Paradoxically government health units appear to play a minor role in the treatment of malaria.     

Book Review: Promoting Children's Health: Integrating School, Family, and Community, The Guilford Press (2003). Thomas Power, George DuPaul, Edward Shapiro, & Anne Kazak, 2003.

Pediatric, child clinical, and school psychologists will benefitfrom Promoting Children's Health, a 2003 publication by leadersin the field who have developed a practical text that is clearlybased upon a comprehensive review of theoretical models andresearch data. The work is likely to be embraced by a wide arrayof specialty psychologists. Further, Promoting Children's Healthhas the potential to unify distinctly specialized practice areas.In fact, this book will be in demand not only by practitionersin the field, but also by academic faculty who might add thisto reading lists for training graduate students. The authors     

Worker motivation and productivity in chinese (beijing) tricycle haulers: Integrating social and biological variables

Ethnographic assessment of worker lifestyle and motivation was paired with measurement of health, maximum oxygen uptake, anthropometry, and cold response to predict productivity in order to determine how well behavioral ratings and biological rankings of worker capacity predict actual productivity. The subjects were Chinese laborers hauling heavy loads on a cycle by human power during a Beijing winter. Worker productivity was measured as pay for unit of work done. This paper reports the ethnographic methods and results. Worker health was assessed through a physical examination including vital signs, echocardiogram (ECG), nutrition, hemoglobin, and hematocrit. Worker motivation was assessed during 10 weeks of participant observation, extensive interview, and a visit to the worker's household. Motivation was rated using a rank-order comparison of all 50 workers from lowest to highest. Other observational ratings (household assets, demands on worker, and health of household members) were completed at the time of the home visit using five-point scales. © 1995 Wiley-Liss, Inc.     

Ultrastructural Morphometric Study of Follicular Center Lymphocytes: II. Analyses of Cleaved-Cell Populations Do Not Support the Lukes-Collins' Concept

Ultrastructural morphometric analysis was carried out on six cases of lymph node biopsies with reactive hyperplasia to establish the frequency and depth of invaginations in nuclear profiles situated in the mantle zones and follicular centers. The frequency distribution of the depth of invaginations was similar in nuclear profiles whether in the small lymphocytes of mantle zones or the small, partially transformed (centrocytes) and fully transformed (centroblasts) lymphocytes of follicular centers. Invaginated and cleaved lymphocytes were not confined to the partially transformed (centrocytic) lymphocytes of follicular centers, and nuclear profiles with invaginations bore no resemblance to those depicted in the Lukes-Collins model. A considerable proportion of mantle zone lymphocyte nuclear profiles had invaginations (ranging from 7.5% to 53.6%) and there was no difference between the frequency of deep indentations or clefts in mantle zone lymphocytes (8.1 ± 5.4%) and the small unstimulated (9.3 ± 5.3%) and partially transformed (8.4 ± 1.4%) lymphocytes in follicular centers. Computer modeling of stylized nuclei with conical indentations indicated that all lymphocytic nuclei likely have multiple invaginations or groove-like creases.