Incidence of end-stage renal disease in medically treated patients with severe bilateral atherosclerotic renovascular disease

Incidence of end-stage renal disease in medically treated patients with severe bilateral atherosclerotic renovascular disease. Atherosclerotic renovascular disease is an important cause of end-stage renal disease (ESRD). The exact incidence of ESRD and the rate of decline in glomerular filtration rate (GFR) in patients with this condition is unknown. We report the mortality, the rate of decline in renal function, and incidence of ESRD in 51 patients with bilateral atherosclerotic renovascular disease followed-up for a median period of 52 months. None of these patients had undergone any surgical or radiological intervention. Renal function was determined by serial measurements of serum creatinine. Bilateral atherosclerotic renovascular disease was associated with a high mortality rate; the crude mortality rate at 60 months was 45%. Assessment of renal function showed impaired renal function at time of angiography and a nonuniform and variable decline in renal function during the period of observation. The median GFR decreased from 39 mL/min (range, 15 to 80 mL/min) at time of angiography to 31 mL/min (range, 10 to 70 mL/min) and 24 mL/min (range, 10 to 40 mL/min) at 24 and 60 months, respectively (P < 0.05). The calculated mean rate of decline in GFR for all patients was 4 mL/min/yr (range, 1 to 16 mL/min/yr). Over the 5 years, there was a progressive increase in the incidence of ESRD. Of the original 51 patients who underwent angiography, six patients reached ESRD. The crude incidence of ESRD was, therefore, 12%. Patients who reached ESRD were characterized by advanced azotemia at the time of angiography (median GFR, 25 mL/min) and a rapid decline in GFR (8 mL/min) compared with patients who did not reach ESRD during the observation period (median GFR, 43 mL/min and an average rate of decline GFR of 3 mL/min).     

Use of a food frequency questionnaire in American Indian and Caucasian pregnant women: a validation study

Background  

Food frequency questionnaires (FFQs) have been validated in pregnant women, but few studies have focused specifically on low-income women and minorities. The purpose of this study was to examine the validity of the Harvard Service FFQ (HSFFQ) among low-income American Indian and Caucasian pregnant women.     

Corneal asphericity and apical curvature in children: a cross-sectional and longitudinal evaluation

PURPOSE: The contour of the human cornea is closely modeled by a conic section, which is fully described by asphericity (Q) and apical radius of curvature (r(o)). The relationship between corneal shape and other ocular dimensions in children, including anterior and vitreous chamber depths, axial length, and spherical equivalent refractive error, was investigated. METHODS: Corneal asphericity and r(o) were calculated by using corneal topography data on 643 children (72 myopes, 370 emmetropes, and 201 hyperopes), ages 6 to 15 years, who participated in the Orinda Longitudinal Study of Myopia (OLSM) during 1991. Measurements from a younger subset of these children, including 8 myopes, 92 emmetropes, and 75 hyperopes, ages 6 to 9 years in 1991, were compared to 1996 data for longitudinal analysis. RESULTS: Mean +/- SD Q of the 1991 study sample was -0.346 +/- 0.101, representing a prolate corneal shape. Almost all (99.7%) of the corneas examined were prolate. Corneal asphericity was less prolate among myopes than in emmetropes and hyperopes (P = 0.010). Less prolate corneas were related to deeper anterior chamber depths among emmetropes (r = 0.324, P < 0.0001) and hyperopes (r = 0.275, P < 0.0001), but not among myopes (r = 0.230, P = 0.0515). Flatter values of r(o) were related to longer vitreous chamber depth (r = 0.607, P < 0.0001) and axial length (r = 0.606, P < 0.0001) in all refractive error groups. Initial corneal shape was unrelated to change in refractive error over a 5-year period. CONCLUSIONS: Most corneas examined in this study were prolate in contour. Deeper anterior chamber depths were related to less prolate corneas among emmetropes and hyperopes, which is probably the result of mechanical influences on the peripheral cornea as the anterior chamber elongates during ocular growth. Longitudinal results suggest initial corneal shape is of little or no value in predicting refractive error progression.     

Angiotensin II inhibition reduces stress sensitivity of hypothalamo-pituitary-adrenal axis in spontaneously hypertensive rats

Angiotensin II type 1 (AT(1)) receptors are expressed within organs of the hypothalamo-pituitary-adrenal (HPA) axis and seem to be important for its stress responsiveness. Secretion of CRH, ACTH, and corticosterone (CORT) is increased by stimulation of AT(1) receptors. In the present study, we tested whether a blockade of the angiotensin II system attenuates the HPA axis reactivity in spontaneously hypertensive rats. Spontaneously hypertensive rats were treated with candesartan (2 mg/kg), ramipril (1 mg/kg), or mibefradil (12 mg/kg) for 5 wk. In addition to baseline levels, CORT and ACTH responses to injection of CRH (100 microg/kg) were monitored over 4 h. mRNA of CRH, proopiomelanocortin, AT(1A), AT(1B), and AT(2) receptors was quantified by real-time PCR. All treatments induced equivalent reductions of blood pressure and had no effect on baseline levels of CORT and ACTH. However, both candesartan and ramipril significantly reduced CRH-stimulated plasma levels of ACTH (-26 and -15%) and CORT (-36 and -18%) and lowered hypothalamic CRH mRNA (-25 and -29%). Mibefradil did not affect any of these parameters. Gene expression of AT(1A), AT(1B), and AT(2) receptors within the HPA axis was not altered by any drug. We show for the first time that antihypertensive treatment by inhibition of AT(1) receptors or angiotensin-converting enzyme attenuates HPA axis reactivity independently of blood pressure reduction. This action is solely evident after CRH stimulation but not under baseline conditions. Both a reduced pituitary sensitivity to CRH and a down-regulation of hypothalamic CRH expression have the potential to reduce HPA axis activity during chronic AT(1) blockade or angiotensin-converting enzyme inhibition.     

The inositol monophosphatase inhibitor L-690,330 affects pilocarpine-behavior and the forced swim test

Rationale

Lithium has been a standard pharmacological treatment for bipolar disorder over the last 60 years; however, the molecular targets through which lithium exerts its therapeutic effects are still not defined. Attenuation of the phosphatidylinositol signal transduction pathway as a consequence of inhibition of inositol monophosphatase (IMPase) has been proposed as one of the possible mechanisms for lithium-induced mood stabilization.

Objectives

The objective was to study the behavioral effect of the specific competitive IMPase inhibitor L-690,330 in mice in the lithium-sensitive pilocarpine-induced seizures paradigm and the forced swim test (FST).

Methods

The inhibitor was administered intracerebroventricularly in liposomes.

Results

L-690,330 increased the sensitivity to subconvulsive doses of pilocarpine and decreased immobility time in the FST.

Conclusions

It is possible that the behavioral effects of lithium in the pilocarpine-induced seizures and in the FST are mediated through the inhibition of IMPase, but reversal of the inhibitor’s effect with intracerebroventricular inositol would be an important further step in proof.