All men with vasculogenic erectile dysfunction require a cardiovascular workup.

An association between erectile dysfunction and cardiovascular disease has long been recognized, and studies suggest that erectile dysfunction is an independent marker of cardiovascular disease risk. Therefore, assessment and management of erectile dysfunction may help identify and reduce the risk of future cardiovascular events, particularly in younger men. The initial erectile dysfunction evaluation should distinguish between predominantly vasculogenic erectile dysfunction and erectile dysfunction of other etiologies. For men believed to have predominantly vasculogenic erectile dysfunction, we recommend that initial cardiovascular risk stratification be based on the Framingham Risk Score. Management of men with erectile dysfunction who are at low risk for cardiovascular disease should focus on risk-factor control; men at high risk, including those with cardiovascular symptoms, should be referred to a cardiologist. Intermediate-risk men should undergo noninvasive evaluation for subclinical atherosclerosis. A growing body of evidence supports the use of emerging prognostic markers to further understand cardiovascular risk in men with erectile dysfunction, but few markers have been prospectively evaluated in this population. In conclusion, we support cardiovascular risk stratification and risk-factor management in all men with vasculogenic erectile dysfunction.

Thiol-reactive agents biphasically regulate inositol 1,4,5-trisphosphate binding and Ca(2+) release activities in bovine adrenal cortex microsomes.

Within all endocrine cells, the inositol 1,4,5-trisphosphate (InsP(3)) receptor plays an important role in regulation of the intracellular Ca(2+) concentration. In the present study we showed that a single short-term treatment with either N-ethylmaleimide (known to decrease InsP(3) receptor activity) or thimerosal (known to increase InsP(3) receptor activity) caused time-dependent biphasic effects on the InsP(3) binding activity of bovine adrenal cortex microsomes. The early potentiating effect of thiol-reactive agents translated into a 2-fold increase in binding affinity and Ca(2+) release efficiency. The late dampening effect of thiol-reactive agents translated into a continuous reduction of the maximal binding capacity of the microsomes with a concomitant decrease in Ca(2+) release efficiency. Under these conditions, Western blot analyses demonstrated that the level of InsP(3) receptor protein was not modified. Sequential treatments with thimerosal and the reducing agent dithiothreitol showed that the InsP(3) receptor can readily oscillate between high and low affinity states that are related to its alkylation state. Our results suggest a common mode of action of thiol-reactive agents on the InsP(3) receptor. These results also support the contention that cellular mechanisms of thiol group modification could play important roles in regulation of the intracellular Ca(2+) concentration.

Use of preventive care services, beneficiary characteristics, and Medicare HMO performance.

Medicare health maintenance organization (HMO) enrollees use more preventive care services than their fee-for-service (FFS) counterparts. This may be because those who enroll in HMOs have characteristics that make them more disposed to use preventive care. To investigate this possibility, we examined the use of four preventive care services by respondents to the 1996 Medicare Current Beneficiary Survey (MCBS). Unadjusted preventive care use rates for HMO enrollees were slightly higher than rates for non-HMO enrollees with private supplemental insurance. However, after adjusting for enrollee characteristics (sociodemographics, health behaviors, health status, and functioning) we found that preventive care use rates for HMO enrollees were substantially higher--consistent with HMO enrollees being less disposed to use preventive care. In comparing preventive care service rates across groups, managers and policymakers may want to consider taking into account beneficiary characteristics that are correlated with the disposition to use preventive care.

Different populations of inositol 1,4,5-trisphosphate receptors expressed in the bovine adrenal cortex.

The inositol 1,4,5-trisphosphate (InsP3) receptor forms a tetrameric channel responsible for the release of Ca2+ from intracellular stores. In the present study we showed that the experimental approach used to separate bound and free ligands may discriminate between two populations of InsP3 binding sites in bovine adrenal cortex microsomes. A large population of low affinity sites and a small population of high affinity sites were detected with centrifugation and filtration approaches, respectively. Both populations were found in the supernatant and the cytoskeleton fractions of Triton X-100 solubilized microsomes. After treatment of microsomes with thimerosal, an alkylating reagent known to increase InsP3 receptor affinity, the filtration and the centrifugation approaches yielded identical results. With selective anti-InsP3 receptor antibodies, we showed that types 1, 2 and 3 InsP3 receptors are present in intact microsomes and in the cytoskeleton fraction. Binding studies on immunoprecipitated receptors revealed that anti-type 1 antibody recognizes a large population of low affinity sites whereas anti-type 2 antibody recognizes a small population of high affinity sites. Our results indicate that the three types of InsP3 receptors are expressed at different levels in the bovine adrenal cortex. The presence of different types of InsP3 receptors with different ligand binding affinities and their association with the cytoskeleton offer a convenient way for the cell to simultaneously regulate its intracellular Ca2+ concentration and reorganize the spatial distribution of its Ca2+ stores.

Absence of correlation between amobarbital distribution as assessed with SPECT brain perfusion imaging and behavioral manifestations during the intracarotid amobarbital procedure (Wada test).

1. The IAP is used presurgically in patients with temporal lobe epilepsy to predict the effects on LTM and language of the planned temporal lobectomy. This prognosis presumes that a similar pattern of perfusion will result in anesthesia of the same cerebral regions in most patients. 2. Coinjection of Tc-99m HMPAO with the barbiturate during the IAP has been used to ascertain whether this actually is true, with variable results. Moreover, most studies document only unilateral IAPs and do not report on behavioral performance. 3. The authors coinjected Tc-99m HMPAO and amobarbital in 33 IAPs from 18 patients (15 injected bilaterally, 3 unilaterally) to clarify this and to evaluate the relationship of the perfusion pattern to behavioral performance; SPECT results were also compared to angiographic evaluation obtained at the time of catheter placement. 4. SPECT perfusion data was rated for presence/absence and intensity of perfusion to the ACA, MCA, PCA territories and to H, i or c to the injection site. V, STM and LTM were graded according to a standardized protocol. 5. MCAi was perfused in 100% of cases, ACAi in 91%, PCAi in 21% and Hi in only 6%. Cross-over flow was shown in 9 studies; 50% of the patients in whom both sides were injected (on different days) had crossover, involving the ACAc territory in 80% of cases. As expected, injection on the non-ES was associated with a significantly worse LTM performance than on the ES (p = 0.006). There was no relationship between the perfusion pattern and the V level of the patients (a potential confounding variable in memory/language evaluation) during IAP, nor between perfusion pattern and LTM. STM was significantly adversely affected by the presence of crossover perfusion. Angiography in general overestimated the extent of cerebral perfusion demonstrated by SPECT, most probably because of the markedly different injection conditions. 6. Despite the best efforts to standardize injections, the perfusion pattern has been mostly unpredictable in the patients. Moreover, it has little bearing on their behavioral performance, except for the prediction of poor STM performance (the clinical implications of this remaining dubious). Marked LTM alterations after non-ES injections confirm remote hippocampal effects in the presence of only rare direct perfusion of that region. Tc-99m HMPAO/Amobarbital coinjection was unhelpful from a clinical perspective, most probably because a large part of the effects of amobarbital arise from deafferentation of regions not directly perfused by the anesthetic agent.

Progesterone increases levels of mu-opioid receptor mRNA in the preoptic area and arcuate nucleus of ovariectomized, estradiol-treated female rats.

Estradiol (E2) and progesterone (P) play different roles in generating the preovulatory surge release of luteinizing hormone-releasing hormone (LH-RH) and luteinizing hormone (LH). Results of our previous studies suggest that at least some of these steroid-specific effects may be mediated by beta-endorphinergic neurons. However, it is also possible that E2 and P differentially regulate responsiveness to opioids by altering mu-opioid receptor gene expression. To test this hypothesis, we used quantitative in situ hybridization histochemistry (ISHH) to measure the effects of E2 and P on mu-opioid receptor mRNA levels in cells of the preoptic area (POA) and arcuate nucleus (Arc). We examined several groups of animals in the morning and afternoon on the day of LH surge release: (1) 1-week ovariectomized (OVX) rats with or without E2 treatment sacrificed between 09:00 and 09:30 h (48 h after E2 capsules inserted); (2) OVX with or without E2 treatment sacrificed between 15:30 and 16:00 h; and (3) OVX with both E2 and P treatment sacrificed between 15:30 and 16:00 h (approximately 54 h after E2 and 6 h after P administration). We found that E2 had no effect on morning or afternoon levels of mu-opioid receptor mRNA levels in either the POA or Arc. In contrast, P treatment increased afternoon levels of mu-opioid receptor mRNA in both regions. These findings indicate that differential effects of E2 and P on LH-RH release may be mediated by steroid-specific effects on mu-opioid receptor gene expression in neurons of the POA and/or Arc.