Control of smooth muscle cell proliferation--the role of the basement membrane

In atherogenesis and in response to vessel injury, arterial smooth muscle cells (SMCs) are activated from a quiescent, differentiated state into an actively proliferating and synthetic phenotype which migrate into the intima where the cells participate in the formation of a fibrous plaque or intimal hyperplasia. The mechanisms involved in the control of SMC function are not clear and no preventive therapy against SMC activation is available. Interactions between SMCs and the extracellular matrix have been shown to influence SMC structure and function through integrin-mediated signaling processes. The SMC basement membrane is a specific form of extracellular matrix which seems to be crucial for the maintenance of SMC quiescence and the disruption of these interactions is part of cellular activation after atherogenic or traumatic stimuli. This concept of "negative growth control" may constitute a future target for the development of new strategies in the prevention of SMC activation in atherogenesis and restenosis formation.     

Epidemiology of child deaths due to drowning in Matlab, Bangladesh.

BACKGROUND: Although the recent decline in child mortality in Bangladesh is remarkable, death from causes other than infectious diseases and malnutrition remains an important component of child mortality. Death from drowning of children can be expected to be a problem in Bangladesh given the geographical features of the country. OBJECTIVE: The objectives of this study are to determine the trend, pattern, and correlates of drowning deaths. METHODS: Data are presented on deaths of children (1-4 years) due to drowning derived from a longitudinal, population-based surveillance system in operation in a rural area of Bangladesh in 1983-1995. Moreover, a case-control study was carried out to identify the risk factors associated with drowning. RESULTS: Deaths due to drowning ranged from about 10% to 25% of child deaths during 1983-1995. The absolute risk of dying from drowning remained almost the same over the study period but the proportion of drownings to all causes of death has increased. Drowning is especially prevalent in the second year of life. Age of the mother and parity have a significant impact on drowning. The risk of dying from drowning increases with the age of mother and much more sharply with the number of living children in the family. Two socioeconomic variables did not have an influence on the risk of drowning. CONCLUSIONS: A substantial proportion of child deaths could be averted if parents and other close relatives paid more attention to the safety of children. The Child Health Programme of the Ministry of Health and Family Welfare of Bangladesh should develop health education programmes for villagers alerting them to the dangers of drowning and measures to prevent it.     

Iodine deficiency disorders in Bangladesh

An extensive iodine deficiency disorders survery was conducted in Bangladesh in 1993 to assess the latest iodine nutriture status of the country. The clinical variables of the survey were goitre and cretinism, and the biochemical variable was urinary iodine. The “EPI-30 cluster” sampling methodology was followed for selecting the survey sites. In each survey site, the study population consisted of boys and girls, aged 5–11 years, and men and women, aged 15–44 years, in about equal populations. the total number of survey sites was 78 and the total number of respondents was 30 072. The total number of urine samples was 4512 (15% sub-sample). The current total goitre rate (grade 1+grade 2) in Bangladesh is 47.1% (hilly, 44.4%; flood-prone, 50.7%; and plains, 45.6%). The prevalence of cretinism in the country is 0.5% (hilly, 0.8%; flood-prone, 0.5%; and plains, 0.3%). Nearly 69% of Bangladeshi population have biochemical iodine deficiency (urinary iodine excretion [UIE]<10 mg/dl) (hilly, 84.4; flood-prone, 67.1%; and plains 60.4%). Women and children are more affected than men, in terms of both goitre prevalence and UIE. The widespread severe iodine deficiency in all ecological zones indicates that the country as a whole is an iodine-deficient region. Important recommendations of global interest are made from the experience of the survey. An erratum to this article is available at .     

Risk factors for retinopathy in diabetes mellitus in Kelantan, Malaysia

Few attempts have been made to determine the risk factors for diabetic retinopathy which is a major cause of visual impairment and blindness. One hundred and forty patients of diabetes mellitus were studied to determine the prevalence and types of retinopathy, and its relation to various risk factors. Nearly half (48.6%) of the patients suffered from retinopathy. The significant associated risk factors were long duration of diabetes, proteinuria and elevated serum creatinine level. However, there was no significant association between the prevalence of retinopathy and high levels of serum cholesterol, C-peptide levels, associated hypertension, and glycaemic control of diabetes mellitus. An effective screening programme for detection of retinopathy in the patients of diabetes as a regular practice is encouraged.     

Raising plasma phosphorus levels by phosphorus-enriched, bicarbonate-containing dialysate in hemodialysis patients

In 6 hemodialysis patients, enriching the "base concentrate" of a bicarbonate-containing dialysate-generating system with phosphorus succeeded in raising plasma phosphorus levels.     

A seven year experience of medical emergencies in the assessment unit.

AIMS: To analyse retrospectively all referrals to the assessment unit during a seven year period, to determine their sources and destination. METHODS: All referrals over the seven year period were analysed. Parental satisfaction was determined using a questionnaire in some of the patients. The disease pattern and the investigations performed were determined. The community nurses' working hours and type of work done were analysed. RESULTS AND CONCLUSIONS: A total of 43 496 children were seen in the unit. Over 65% of the patients were referred by the general practitioners; 13 517 (34.2%) of those referred to the unit were discharged directly from the unit. Respiratory disorders and gastrointestinal problems were commonly seen. The children discharged from the unit did not have significantly more tests done on them. Most of the parents whose children were discharged from the unit were happy to be managed at home. The community nurses attended many children who needed intravenous therapy and advice on fluid rehydration. Community nurses reduce admission to the wards by working with other members in the assessment unit. This in turn provides a single point of entry and bridges the gap between primary and secondary care. We suggest recommendations on setting up such a unit.     

Evaluation of osteopontin as biomarker for pancreatic adenocarcinoma.

OBJECTIVES: Pancreatic adenocarcinoma is a deadly disease with an overall 5-year patient survival of less than 5%. This dismal prognosis of pancreatic cancer is largely due to the advanced stage of the disease at presentation. If pancreatic cancer could be diagnosed more readily and accurately using serum markers, patient survival could theoretically be improved by enabling more patients to avail of surgical resection. One candidate tumor marker recently identified by global gene expression analysis of pancreatic cancer is the secreted glycophosphoprotein osteopontin (OPN). In this study, we evaluate OPN as a serum marker of pancreatic adenocarcinoma. METHODS: In situ hybridization for OPN was performed on a pancreatic adenocarcinoma tissue microarray. Serum OPN levels were determined in preoperative sera from 50 patients with pancreatic cancer and 22 healthy control individuals by competitive ELISA. RESULTS: In situ hybridization for OPN performed on a tissue microarray revealed strong OPN mRNA signal in tumor-infiltrating macrophages in 8 of 14 pancreatic adenocarcinomas. In contrast, OPN expression was not seen in the pancreatic cancer cells themselves, nor was it seen in normal pancreatic tissue or in the macrophages distant from the infiltrating cancer. Serum OPN levels, as measured by ELISA, were elevated in the sera of 50 patients with resectable pancreatic adenocarcinoma compared to 22 healthy control individuals (mean +/- SD for OPN was 482 +/- 170 ng/ml and 204 +/- 65 ng/ml, respectively; P < 0.001). Using a cutoff level of 2 SD above the mean for healthy individuals, elevated OPN had sensitivity of 80% and specificity of 97% for pancreatic cancer. In contrast, only 62% of these patients with resectable pancreatic cancer had elevated CA19-9. CONCLUSIONS: Serum OPN may have utility as a diagnostic marker in patients with pancreatic cancer.     

Approval summary: Docetaxel in combination with prednisone for the treatment of androgen-independent hormone-refractory prostate cancer.

PURPOSE: Docetaxel, a taxane previously approved for the treatment of breast cancer and non-small cell lung cancer, was approved by the United States Food and Drug Administration on May 19, 2004 for use in combination with prednisone for the treatment of metastatic androgen-independent (hormone-refractory) prostate cancer. The purpose of this summary is to review the database supporting this approval. EXPERIMENTAL DESIGN: In a randomized, global study enrolling 1,006 patients, two schedules of docetaxel were compared with mitoxantrone + prednisone as follows: MTZ q 3w, mitoxantrone 12 mg/m2 every 21 days + prednisone 5 mg twice a day for a total of 10 cycles; TXT q 3w, docetaxel 75 mg/m2 every 21 days + prednisone 5 mg twice a day for a total of 10 cycles; and TXT qw, docetaxel 30 mg/m2 days 1, 8, 15, 22, and 29 every 6 weeks + prednisone 5 mg twice a day for a total of 5 cycles. RESULTS: There was a statistically significant overall survival advantage shown for the TXT q 3w arm over MTZ q 3w (median survival 18.9 months versus 16.5 months, P = 0.0094). No overall survival advantage was shown for TXT qw compared with MTZ q 3w. The most commonly occurring adverse events included anemia, neutropenia, infection, nausea, sensory neuropathy, fluid retention, alopecia, nail changes, diarrhea, and fatigue. CONCLUSIONS: This report describes the Food and Drug Administration review supporting this first approval of a combination therapy for hormone-refractory prostate cancer based on demonstration of a survival benefit.