Variation in the survival of women with breast cancer in Scotland. The Scottish Breast Cancer Focus Group and The Scottish Cancer Therapy Network

We have investigated factors influencing the survival of women with early breast cancer in Scotland. In a retrospective study, clinical, treatment and 'service' factors, e.g. surgical case load, deprivation and geographical area (health board of first treatment) were recorded from hospital records. A total of 2148 women with invasive breast cancer diagnosed in 1987 were identified from the Scottish Cancer Registry, of whom 1619 without metastases at diagnosis underwent surgery as part of their primary treatment. In a multivariate analysis, clinical factors (age, clinical stage, pathological tumour size, node status and oestrogen receptor status) all influenced survival. After allowing for these clinical factors, surgical case load and deprivation did not have statistically significant effects on survival. By contrast, health board did affect survival. This was explained in part by the selection of patients for surgery. There appeared, however, to be a residual effect that may be related to differences in the use of adjuvant systemic treatment among the different health boards. We conclude that, in Scotland, geographical variation in both surgical and non-surgical treatment has a greater effect on variability in survival for women with breast cancer than surgical case load and deprivation.     

Maternal hematologic changes during pregnancy and the effect of iron status on preterm delivery in a West Los Angeles population

This study was conducted to document the prevalence of anemia and high hematocrit during pregnancy and examine their effect on delivering preterm in a predominantly Hispanic population. The sample consisted of women receiving prenatal care from the public health clinics in the West Los Angeles from 1983 to 1986 (n = 7589). Multivariate logistic regression was used to isolate the role of anemia and high hematocrit from other factors that may influence birth outcome. The prevalence of anemia was approximately 9% at the initiation of prenatal care and at 28-32 weeks' gestation. Only anemia at 28-32 weeks was significantly associated with a preterm birth, even after adjusting for several confounders [Adjusted Odds Ratio (AOR) 1.83 95% Cl = 1.21, 2.77]. A high hematocrit that occurred in 9.6% of the population at 28-32 weeks was inversely associated with a preterm birth (AOR 0.78, 95% Cl = 0.44, 1.39). There was little differentiation of these risk factors when analyzing the etiological pathways of a preterm birth. These results indicate for the first time in a predominantly Hispanic population that despite routine iron supplementation, anemia still occurs in pregnant women and it can predict a preterm delivery.     

Gastric microbleeding following single and repeated dosing with naproxen

Our previous study provided evidence that higher serum levels of the active form of vitamin D, 1,25-dihydroxyvitamin D (1, 25-D), might possibly slow the progression of subclinical to clinically significant prostate cancer in both black and white men, especially after age 57. This paper extends the prior study by contrasting seasonal variation in 1,25-D and its precursor, 25-hydroxyvitamin D (25-D), in case and control subjects. In addition, the risk of prostate cancer is related to serum levels of vitamin D-binding protein (VDBP) and total dehydroepiandrosterone and to polymorphic variation in VDBP. The expected elevated summer levels of 25-D were seen in case and control subjects and, as expected, 1,25-D did not vary throughout the year in the control subjects. Unexpectedly, lower case levels of 1,25-D were limited largely to the summer months (P = 0.01) in both black and white cases and to cases greater than or equal to the median age of 57 years. Levels of VDBP and dehydroepiandrosterone and the frequencies of VDBP polymorphisms were similar in case and control subjects, although striking differences were seen in allelic frequencies in black and white men. These observations provide additional evidence that vitamin D metabolism may impact the risk of prostate cancer.     

Screening mammography beginning at age 40 years: a reappraisal of cost-effectiveness

BACKGROUND: Several recent studies have added significant information regarding the benefit of screening mammography, especially in the 40-49-years age group. This new information makes it important to reassess the cost-effectiveness of screening. METHODS: A Markov model was used to study the cost-effectiveness of 4 age-related screening strategies: 1) annually from ages 40-79 years; 2) annually from ages 40-64 years and biennially from ages 65-79 years; 3) annually from ages 40-49 years and biennially from ages 50-79 years; and 4) annually from ages 40-79 years in high risk women (10%) and biennially from ages 40-49 years followed by annually from ages 50 -79 years in normal risk women (90%). An additional strategy simulating hormone status and estrogen exposure was evaluated. Cost-effectiveness was expressed as marginal cost per year-life saved (MCYLS). RESULTS: The MCYLS varied from $18,800 to $16,100. For all strategies this was within the range of other generally acceptable diagnostic and therapeutic medical procedures. There was a 14% decrease in MCYLS from the least cost-effective to the most cost-effective strategy. CONCLUSIONS: Cost-effectiveness of four age-related mammographic screening strategies was evaluated. The MCYLS for all strategies was within a generally accepted range. With increasing concerns regarding the cost of health care, this information may be useful in health policy decision-making.     

Distinct morphological and mito-inhibitory effects induced by TGF-beta 1, HGF and EGF on mouse, rat and human hepatocytes

TGF-beta 1 is known as a potent inhibitor of proliferation of rat and human hepatocytes. In this study we show that the effects of TGF-beta 1 are quite different on mouse hepatocytes. In rat and human hepatocytes, TGF-beta 1 inhibited DNA synthesis and also inhibited the morphological changes induced by growth factors in rat and human hepatocytes. In contrast, addition of TGF-beta 1 to mouse hepatocytes resulted in pronounced alterations in morphology of these cells. These changes were similar to those induced by HGF and EGF. The induction of structural changes by TGF-beta 1 was noted only in mouse hepatocytes. Mouse hepatocytes were also much more resistant to the mito-inhibitory effect of TGF-beta 1. These findings suggest profound differences in hepatocyte growth regulation between these species and may relate to observed differences in susceptibility to carcinogenesis.     

An empirical real-time approximation of waiting time distributionin MMPP(2)/D/1

We propose a simple, empirical real-time approximation method for calculating the waiting time distribution for the MMPP(2)/D/1 system. Our approach is based on approximation using a two-term exponential function. We match the poles, the residue for the asymptotic constant, and the mean waiting time between the Laplace transforms of the exact distribution and the approximate distribution. Numerical examples show that our method yields quite accurate results over a wide range. The result can be adopted in evaluating asynchronous transfer mode (ATM) multiplexers for real-time ATM traffic control     

Activity-dependent regulation of NMDAR1 immunoreactivity in the developing visual cortex

NMDA receptors have been implicated in activity-dependent synaptic plasticity in the developing visual cortex. We examined the distribution of immunocytochemically detectable NMDAR1 in visual cortex of cats and ferrets from late embryonic ages to adulthood. Cortical neurons are initially highly immunostained. This level declines gradually over development, with the notable exception of cortical layers 2/3, where levels of NMDAR1 immunostaining remain high into adulthood. Within layer 4, the decline in NMDAR1 immunostaining to adult levels coincides with the completion of ocular dominance column formation and the end of the critical period for layer 4. To determine whether NMDAR1 immunoreactivity is regulated by retinal activity, animals were dark-reared or retinal activity was completely blocked in one eye with tetrodotoxin (TTX). Dark-rearing does not cause detectable changes in NMDAR1 immunoreactivity. However, 2 weeks of monocular TTX administration decreases NMDAR1 immunoreactivity in layer 4 of the columns of the blocked eye. Thus, high levels of NMDAR1 immunostaining within the visual cortex are temporally correlated with ocular dominance column formation and developmental plasticity; the persistence of staining in layers 2/3 also correlates with the physiological plasticity present in these layers in the adult. In addition, visual experience is not required for the developmental changes in the laminar pattern of NMDAR1 levels, but the presence of high levels of NMDAR1 in layer 4 during the critical period does require retinal activity. These observations are consistent with a central role for NMDA receptors in promoting and ultimately limiting synaptic rearrangements in the developing neocortex.     

Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts

NIH 3T3 fibroblasts stably transformed with a constitutively active isoform of p21(Ras), H-RasV12 (v-H-Ras or EJ-Ras), produced large amounts of the reactive oxygen species superoxide (.O2-). .O2- production was suppressed by the expression of dominant negative isoforms of Ras or Rac1, as well as by treatment with a farnesyltransferase inhibitor or with diphenylene iodonium, a flavoprotein inhibitor. The mitogenic activity of cells expressing H-RasV12 was inhibited by treatment with the chemical antioxidant N-acetyl-L-cysteine. Mitogen-activated protein kinase (MAPK) activity was decreased and c-Jun N-terminal kinase (JNK) was not activated in H-RasV12-transformed cells. Thus, H-RasV12-induced transformation can lead to the production of .O2- through one or more pathways involving a flavoprotein and Rac1. The implication of a reactive oxygen species, probably .O2-, as a mediator of Ras-induced cell cycle progression independent of MAPK and JNK suggests a possible mechanism for the effects of antioxidants against Ras-induced cellular transformation.     

Pancreaticoduodenectomy for benign disease

BACKGROUND: Surgeons are often called upon to perform pancreaticoduodenectomy for either suspicion of malignancy or symptoms due to benign disease. Perioperative morbidity and mortality following pancreaticoduodenectomy have decreased markedly over the last 2 decades. In response, many surgical centers advocate expanding the indications for pancreaticoduodenectomy to include lesions other than periampullary carcinoma. PATIENTS AND METHODS: A retrospective review of medical records for 108 patients undergoing pancreaticoduodenectomy for benign disease at The Johns Hopkins Medical Institutions over 100 months was completed. The subset of patients with a histopathologic diagnosis of chronic pancreatitis was identified and compared with patients undergoing pancreaticoduodenectomy for other benign conditions. RESULTS: The mortality rate for the present series was less than 1%. Perioperative complications, the majority of which were self-limited, occurred in 51% of patients. The most common complication was delayed gastric emptying. Pancreatic anastamotic leak occurred in 18% of patients and developed significantly more frequently in patients with benign diseases other than chronic pancreatitis (31% versus 8%, P < 0.05). CONCLUSION: Among appropriately selected patients, the rates of perioperative mortality and serious morbidity are low, and concerns about mortality and morbidity should not prevent an aggressive approach to surgical resection in patients with benign disease.