TGFbeta1 is implicated in regulation of ovarian function and the events of early pregnancy. We have investigated the effect of null mutation in the Tgfbeta1 gene on reproductive function in female mice. The reproductive capacity of TGFbeta1 null mutant females was severely impaired, leading to almost complete infertility. Onset of sexual maturity was delayed, after which ovarian function was disrupted, with extended ovarian cycles, irregular ovulation, and a 40% reduction in oocytes ovulated. Serum FSH and estrogen content were normal, but TGFbeta1 null mutant mice failed to display the characteristic proestrus surge in circulating LH. Ovarian hyperstimulation with exogenous gonadotropins elicited normal ovulation rates in TGFbeta1 null mutant mice. After mating with wild-type stud males, serum progesterone content was reduced by 75% associated with altered ovarian expression of mRNAs encoding steroidogenic enzymes 3beta-hydroxysteroid dehydrogenase-1 and P450 17 alpha-hydroxylase/C17-20-lyase. Embryos recovered from TGFbeta1 null mutant females were developmentally arrested in the morula stage and rarely progressed to blastocysts. Attempts to rescue embryos by exogenous progesterone administration and in vitro culture were unsuccessful, and in vitro fertilization and culture experiments demonstrated that impaired development is unlikely to result from lack of maternal tract TGFbeta1. We conclude that embryo arrest is due to developmental incompetence in oocytes developed in a TGFbeta1-deficient follicular environment. This study demonstrates that TGFbeta1 is a critical determinant of normal ovarian function, operating through regulation of LH activity and generation of oocytes competent for embryonic development and successful initiation of pregnancy.

High BP is associated with decline of renal function. Whether this is true for very old people largely is unknown. Therefore, this study assessed the effect of BP on creatinine clearance over time in very old participants. A total of 550 inhabitants (34% men) of Leiden, The Netherlands, were enrolled in a population-based study at their 85th birthday and followed until death or age 90. BP was measured twice at baseline and at age 90 yr. Creatinine clearance was estimated annually (Cockcroft-Gault formula). The mean creatinine clearance at baseline was 45.4 ml/min (SD 11.5). Systolic BP was not associated with changes in creatinine clearance during follow-up. Those with diastolic BP (DBP) <70 mmHg had an accelerated decline of creatinine clearance ( In contrast with younger populations, in the oldest individuals, the association among high BP, mortality, and renal function is not straightforward. The available data suggest that BP lowering above 80 yr does not lower overall mortality (4,5). Data on the effect of BP on morbidity such as renal function are relatively scarce in the oldest individuals (6 -8). One longitudinal report associated BP and renal function in a considerable group of very old Japanese individuals (7). In that report, high BP was related to an excess decline of serum creatinine. However, an important drawback was the use of serum creatinine for estimation of renal function. In addition, selection bias could have been induced as a result of exclusion of 40% of the participants, who did not attend the reexamination after 3 yr.Although BP lowering in individuals over 80 yr might not lower mortality, it is unknown whether a high BP might be deleterious for renal function. To investigate whether high BP still is a risk factor for decline in renal function in the oldest individuals, we prospectively studied the effect of BP on changes of creatinine clearance over time in a population-based study of the general population of the oldest individuals. Materials and Methods Study PopulationThe Leiden 85-Plus Study is a prospective, population-based study of all 85-yr-old inhabitants of Leiden, The Netherlands. The study design and characteristics of the cohort were described in detail previously (9,10). In short, between September 1997 and September 1999, all 705 members of the 1912 to 1914 birth cohort in the city of Leiden were asked to participate in the month after their 85th birthday. There were no selection criteria related to health or demographic characteristics. Participants were followed until death or the age of 90. At baseline and yearly thereafter, 85-yr-old participants were visited at their place of residence. During these visits, participants were weighed, BP was measured, a venous blood sample was drawn, an electrocardiogram was recorded, and face-to-face interviews and performance tests were conducted. Information on the medical history was obtained by standardized interviews of the participants' treating physicians. In addition, information on the use of medication was obtained from th...

SummaryIn this case report, a patient is described with an unusual cause of renal artery stenosis (RAS). The patient presented with acute anuric renal failure and hypertensive urgency, following a nephrectomy, which was complicated by massive blood loss. Because the acute renal failure was first presumed to be due to acute tubular necrosis, the diagnosis of a nearly complete iatrogenic RAS was not made until 6 weeks after surgery. The stenosis was caused by five misplaced surgical clips on the artery of the remaining kidney. The hypertension was initially treated with ACE inhibitor. Eight weeks after the initial surgery, a successful revascularisation procedure was performed, leading to the recovery of kidney function. BACKGROUND

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Following a hip replacement, a patient developed severe irreversible obstructive shock due to a fat embolism. A lung biopsy showed fat cells and bone fragments in the pulmonary capillaries.