Ovary: Immunolocalization of transforming growth factor-{beta}1 and transforming growth factor-{beta}2 in the mouse ovary during gonadotrophin-induced follicular maturation

An immunohistochemical approach was utilized to evaluate thecellular distribution of transforming growth factor-₁ (TGF₁)and transforming growth factor ₂ (TGF₂) at different stagesof follicle development in the prepubertal mouse ovary underthe following conditions: (i) after pregnant mare's serum gonadotrophin(PMSG) treatment; (ii) after PMSG and human chorionic gonadotrophin(HCG) treatment; (iii) after PMSG and HCG treatment plus mating.In the immature ovary, TGFF₁ and TGF₂ immunoreactivities arelocalized in theca and granulosa cells and in oocytes. AfterPMSG treatment, TGF₁ and TGF₂ immunoreactivities are localizedin granulosa cells; in addition, TGF₂ staining is noted in thematrix surrounding antral cells. Staining for both TGF₁ andTGF₂ drops in the theca but persists in the oocyte. PMSG plusHCG treatment results in a significant increase in TGF₁ andTGF₂ immunoreactivity in the theca and in the maintenance ofTGF₁ staining in both basal granulosa cells and cumulus cellswhereas TGF₂ immunoreactivity is essentially localized in thematrix surrounding cumulus cells. Staining for TGF₁ and TGF₂persists in the oocyte. Following PMSG plus HCG treatment andmating, TGF₁ immunoreactivity is localized in the luteal cellsof corpora lutea and TGF₂ shows a similar localization pattern.This study provides evidence that TGF₁ and TGF₂ peptides areexpressed in specific cell types during induced follicular maturationin the mouse ovary.     

Effect of dietary sodium on airways responsiveness and its importance in the epidemiology of asthma: an evaluation in three areas of northern England.

BACKGROUND--Although several investigations have shown a relationship between asthma (or its surrogate, airways responsiveness) and dietary or urinary sodium, others have not, and the matter remains controversial. This "salt effect" has been investigated during two recent epidemiological surveys of men in northern England. The first assessed the possible effect on airways responsiveness of occupational exposure to welding fumes, and the second characterised airways responsiveness in two geographically distinct residential areas. Thus, three separate study areas/populations were involved. METHODS--Investigation 1 involved 1059 shipyard workers aged 16-27 years who were exposed variously to welding fumes, and Investigation 2 involved 587 men aged 20-44 years who lived in rural West Cumbria or in urban Newcastle upon Tyne. In Investigation 1, a 24 hour urine specimen was requested from each subject with quantifiable airways responsiveness (PD20 < or = 6400 micrograms methacholine) and from an equal number of subjects without measurable airways responsiveness from the same occupational subgroup. In Investigation 2, every subject was asked to provide a 24 hour urine specimen. RESULTS--Of the men undergoing methacholine tests, satisfactory 24 hour urine specimens were obtained from 234 (22.1%) in Investigation 1 and 232 (39.5%) in Investigation 2. Analysis using multiple linear regression, multiple linear logistic regression, and multiple regression for censored data produced consistent results within each study population but conflicting results between them, such that there was no hint of a relationship between airways responsiveness and 24 hour urinary sodium excretion in the shipyard workers of Investigation 1 nor in the rural West Cumbrian population of Investigation 2, but an association was found in the urban Newcastle population of Investigation 2. All study populations were sufficiently large to demonstrate anticipated relationships between airways responsiveness and atopy, baseline FEV1, and (Newcastle only) age. CONCLUSIONS--If airways responsiveness is related to dietary sodium the relationship is not likely to be strong.     

Clinical guidelines and hospital discharges of children with acute urinary tract infections

 In order to evaluate the effect of the introduction of recent similar guidelines on the treatment of acute urinary tract infection (UTI) in children, and possible changes in its epidemiology, we analyzed the records of hospital discharge for acute UTI under the age of 15 years in England and Wales between 1979 and 1993 and in Finland between 1978 and 1994. Cases were defined by the ICD9 diagnostic codes 590.1 (acute pyelonephritis) and 599.0 (UTI, site not specified) for males and females according to three age groups (0–4, 5–9, and 10–14 years). We also compared the registry data on kidney transplants due to end-stage renal disease caused by recurrent pyelonephritis in the United Kingdom and Finland. In England the rate of attack of symptomatic UTI per 1,000 girls under 15 years increased from 0.74 (95% confidence interval 0.71–0.76) in 1987 to 1.32 (1.29–1.35) in 1993 (P<0.001, test for trend). The respective figures for Finnish girls were 1.74 (1.62–1.86) in 1987 and 1.62 (1.51–1.74) in 1993 (P=0.72). In English boys, the increase in the attack rate was from 0.38 (0.36–0.40) in 1987 to 0.70 (0.68–0.73) in 1993 (P<0.001). In Finnish boys the respective figures were 0.74 (0.66–0.82) in 1987 and 0.88 (0.80–0.97) in 1993 (P<0.02). The observed increases in the attack rates of UTI most probably relate to increased referral of acute UTI patients to hospitals for the recommended imaging studies rather than changing occurrence. Publication of guidelines for treatment of UTI in children, consolidating more-general awareness, may have contributed to this. The mean annual numbers of kidney transplants in the United Kingdom and Finland during 1989–1995 due to end-stage renal disease caused by pyelonephritis were of similar magnitude, i.e., 1.9 (1.6–2.3) transplants per million inhabitants in the United Kingdom and 2.8 (1.5–4.7) transplants per million inhabitants in Finland. The decreasing trend in these figures in both countries, although statistically significant only in the United Kingdom (P<0.05, test for trend), suggests improved long-term outcome of these patients induced by better diagnosis and treatment of pyelonephritis and the diseases related to it, such as congenital malformations. According to our data, valid clinical guidelines are effective in changing clinical practice. Received: 1 September 1997 / Revised: 29 April 1998 / Accepted: 29 April 1998     

The need to embrace molecular profiling of tumor cells in prostate and bladder cancer.

PURPOSE: Current treatment strategies for urological cancer are still based on empirical formulae as opposed to treatment tailored for each cancer patient. To individualize treatment, the multiple molecular abnormalities within tumor cell populations needs to be mapped out. The aim of this article is to explain molecular profiling (MP) and its associated techniques so that the process is not purely seen as a research tool but as a future adjunctive measure in patient diagnosis and treatment. EXPERIMENTAL DESIGN: A Medline search of publications relating to MP of prostate and bladder cancer was carried out. A review article was written combining the relevant published literature along with the clinical and scientific experience of both centers. RESULTS: The advent of MP now provides a strategy by which these molecular abnormalities can be assessed. As well as being of diagnostic and prognostic use, these molecular profiles will identify putative molecular abnormalities within tumor cells that may be appropriate for therapeutic modulation. CONCLUSIONS: In prostate and bladder cancer, mapping out the molecular abnormalities could be translated into a valuable tool to help solve difficult issues regarding patient management decisions.     

Identification of High-Risk Groups among Node-Positive Patients with Stage IB and IIA Cervical Carcinoma

The purpose of the present study was to identify a subset of high-risk patients among surgically treated node-positive patients with stage IB and IIA cervical carcinoma. From 1982 through 1991, 334 patients underwent radical hysterectomy for FIGO stage IB and IIA cervical carcinoma. In 68 patients pathological analysis of the surgical specimen revealed positive pelvic nodes. In this group, a Cox proportional hazard analysis was performed to examine the prognostic significance of clinicopathological variables. Only for adenocarcinoma (P= 0.002) and parametrium infiltration (P= 0.003) was evidence of an association with prognosis found. Based on these two factors, patients with positive pelvic nodes were categorized into a low-risk group (squamous cell carcinoma without parametrium infiltration,N= 33) and a high-risk group (squamous cell carcinoma with parametrium infiltration or adenocarcinoma,N= 34). The 5-year disease-specific survival in the low-risk group was 94% compared with 60% in the high-risk group (P= 0.003). For patients in the high-risk group, there is an urgent need for alternative adjuvant treatment to improve outcome.     

CD44 variant expression and estrogen receptor status in breast cancer

To understand the relationship between CD44 gene expressionand an established variable associated with aggressive behaviourin human breast cancer, we have studied apanel of 6 breast cell lines and 40breast tumors selected primarily on the basis ofestrogen receptor (ER) status. CD44s (standard form) mRNAwas assessed by semi-quantitative RT-PCR, and CD44 variantsincorporating exon v7 or v10 were studied byRT-PCR and Southern blot. While CD44 expression wasnot influenced by estrogen in ER+ve MCF-7 cells,CD44s expression was slightly higher (up to 2fold) in ER–ve cells but there was amarked decrease in the range of CD44 variantsincorporating exons v7 or v10. In microdissected tumors,the levels of CD44s showed no correlation withER status but the pattern of expression oflarger forms of CD44 incorporating variant exons v7and v10 was significantly different (p=0.005and p=0.015, respectively) between ER+ve andER–ve tumors, reflecting the pattern seen in thecell lines. These findings suggest that the profileof CD44 expression in breast cancer may reflectcellular differentiation as indicated by the ER phenotype.The influence of these differences in CD44 expressionon the increased metastatic potential of ER negativebreast cancer remains to be determined.     

Prolonged pregnancy: evaluating gestation-specific risks of fetal and infant mortality

Objective To evaluate gestation-specific risks of stillbirth, neonatal and post-neonatal mortality.
Design Retrospective analysis of 171,527 notified births (1989–1991) and subsequent infant survival at one year, from community child health records.
Setting Notifications from maternity units in the North East Thames Region, London.
Main outcome measures The incidence of births, stillbirths, neonatal and post-neonatal deaths at each gestation after 28 completed weeks. Mortality rates per 1000 total or live births and per 1000 ongoing pregnancies at each gestation were calculated.
Results The rates of stillbirth at term (2.3 per 1000 total births) and post-term (1.9 per 1000 total births) were similar. When calculated per 1000 ongoing pregnancies, the rate of stillbirth increased six-fold from 0.35 per 1000 ongoing pregnancies at 37 weeks to 2.12 per 1000 ongoing pregnancies at 43 weeks of gestation. Neonatal and post-neonatal mortality rates fell significantly with advancing gestation, from 15 1.4 and 31.7 per 1000 live births at 28 weeks, to reach a nadir at 41 weeks of gestation (0.7 and 1.3 per 1000 live births, respectively), increasing thereafter in prolonged gestation to 1.6 and 2.1 per 1000 live births at 43 weeks of gestation. When calculated per 1000 ongoing pregnancies, the overall risk of pregnancy loss (stillbirth + infant mortality) increased eight-fold from 0.7 per 1000 ongoing pregnancies at 37 weeks to 5.8 per 1000 ongoing pregnancies at 43 weeks of gestation.
Conclusion The risks of prolonged gestation on pregnancy are better reflected by calculating fetal and infant losses per 1000 ongoing pregnancies. There is a significant increase in the risk of stillbirth, neonatal and post-neonatal mortality in prolonged pregnancy. This study provides accurate data on gestation-specific risks of pregnancy loss, enabling pregnant women and their carers to judge the appropriateness of obstetric intervention.