Socioecological differences in factors associated with inconsistent condom use with female sex workers and casual partners: an observational study of heterosexual men attending an anonymous HIV testing clinic in Singapore.

Sexual practices among heterosexual men may differ between female sex workers (FSWs) and casual partners. We surveyed 203 heterosexual men and investigated the attributes associated with inconsistent condom use among them. Lower educational attainment was positively associated with inconsistent condom use with FSWs (adjusted prevalence ratio (aPR) 2.63; P = 0.018) and casual partners (aPR 1.55; P = 0.022), whereas early age of sexual debut (aPR 3.00; P = 0.012) and alcohol use during sex (aPR 7.95; P < 0.001) were positively associated with inconsistent condom use with FSWs. Socioecological factors may explain such differences.

Appetite-suppressing effects of urocortin, a CRF-related neuropeptide.

The neuropeptide corticotropin-releasing factor (CRF) is well known to act on the central nervous system in ways that mimic stress and result in decreases in exploration, increases in sympathetic activity, decreases in parasympathetic outflow, and decreases in appetitive behavior. Urocortin, a neuropeptide related to CRF, binds with high affinity to the CRF2 receptor, is more potent than CRF in suppressing appetite, but is less potent than CRF in producing anxiety-like effects and activation. Doses as low as 10 nanograms injected intracerebroventricularly were effective in decreasing food intake in food-deprived and free-feeding rats. These results suggest that urocortin may be an endogenous CRF-like factor in the brain responsible for the effects of stress on appetite.

Quality improvement: experience of a sexually transmitted infection clinic in Singapore.

SUMMARY: Over the past two years, the Department of Sexually Transmitted Infection Control Clinic (DSC) in Singapore has embarked on a programme to review and enhance its quality improvement programmes. A thorough review of its day-to-day operations was conducted, infection control processes and standard operating procedures. It capitalized on its use of computerized medical records to improve documentation and patient screening. DSC introduced risk-management protocols and revised patient, staff and workplace safety guidelines. These measures have resulted in benefits such as reduced prescription errors, fewer patient complaints and active clinical practice improvement programmes. In January 2008, DSC, along with its parent hospital the National Skin Centre, became the first ambulatory health-care facility in Singapore, and also among the first few outside the United States to be accredited by the Joint Commission International.

Isolation and genetic analysis of Saccharomyces cerevisiae mutants supersensitive to G1 arrest by a factor and alpha factor pheromones.

Eight independently isolated mutants which are supersensitive (Sst-) to the G1 arrest induced by the tridecapeptide pheromone alpha factor were identified by screening mutagenized Saccharomyces cerevisiae MATa cells on solid medium for increased growth inhibition by alpha factor. These mutants carried lesions in two complementation groups, sst1 and sst2. Mutations at the sst1 locus were mating type specific: MATa sst1 cells were supersensitive to alpha factor, but MAT alpha sst1 cells were not supersensitive to a factor. In contrast, mutations at the sst2 locus conferred supersensitivity to the pheromones of the opposite mating type on both MATa and MAT alpha cells. Even in the absence of added alpha pheromone, about 10% of the cells in exponentially growing cultures of MATa strains carrying any of three different alleles of sst2 (including the ochre mutation sst2-4) had the aberrant morphology ("shmoo" shape) that normally develops only after MATa cells are exposed to alpha factor. This "self-shmooing" phenotype was genetically linked to the sst2 mutations, although the leakiest allele isolated (sst2-3) did not display this characteristic. Normal MATa/MAT alpha diploids do not respond to pheromones; diploids homozygous for an sst2 mutation (MATa/MAT alpha sst2-1/sst2-1) were still insensitive to alpha factor. The sst1 gene was mapped to within 6.9 centimorgans of his6 on chromosome IX. The sst2 gene was unlinked to sst1, was not centromere linked, and was shown to be neither linked to nor centromere distal to MAT on the right arm of chromosome III.

Physiological characterization of Saccharomyces cerevisiae mutants supersensitive to G1 arrest by a factor and alpha factor pheromones.

Saccharomyces cerevisiae MATa cells carrying mutations in either sst1 or sst2 are supersensitive to the G1 arrest induced by alpha factor pheromone. When sst1 mutants were mixed with normal SST+ cells, the entire population recovered together from alpha factor arrest, suggesting that SST+ cells helped sst1 mutants to recover. Complementation tests and linkage analysis showed that sst1 and bar1, a mutation which eliminates the ability of MATa cells to act as a "barrier" to the diffusion of alpha factor, were lesions in the same genes. These findings suggest that sst1 mutants, are defective in recovery from alpha factor arrest because they are unable to degrade the pheromone. In contrast, recovery of sst2 mutants was not potentiated by the presence of SST+ cells in mixing experiments. When either normal MATa cells or mutant cells carrying defects in sst1 or sst2 were exposed to alpha factor for 1 h and then washed free of the pheromone, the sst2 cells subsequently remained arrested in the absence of alpha factor for a much longer time than SST+ or sst1 cells. These observations suggest that the defect in sst2 mutants is intrinsic to the cell and is involved in the mechanism of alpha factor action at some step after the initial interaction of the pheromone with the cell. The presence of an sst2 mutation appears to cause a growth debility, since repeated serial subculture of haploid sst2-1 strains led to the accumulation of faster-growing revertants that were pheromone resistant and were mating defective ("sterile").

An epidemiological and knowledge, attitudes, beliefs and practices study of sexually transmitted infections in older men.

INTRODUCTION: This study was conducted to determine the disease patterns of sexually transmitted infections (STI) in older men, as well as to gather information on their knowledge, attitudes, beliefs and sexual practices. METHODS: A prospective study was carried out from January to June 2005 in men aged 50 years or older who attended the Department of STI Control clinic. RESULTS: There were 104 men enrolled. The majority (92.3 percent) were Chinese, and 62.5 percent were aged between 50 and 59 years, 25.9 percent between 60 and 69 years, and 11.5 percent aged 70 years or older. The patients were predominantly heterosexual, and had fairly low levels of education--85.6 percent of the patients had received primary or secondary school level of education. Majority (79.8 percent) of the men had been sexually active in the preceding six months, and 37.3 percent had paid sex during that time. 29.8 percent of men reported having taken drugs such as sildenafil (Viagra, Pfizer, New York, NY, USA) or similar drugs such as vardenafil (Levitra, Bayer, Wuppertal, Germany) or tadalafil (Cialis, Eli Lilly, Indianapolis, IN, USA). 56.7 percent of the men had active infections, with non-gonococcal urethritis (15.4 percent), genital warts (12.5 percent) and gonorrhoea (10.6 percent) being the commonest. Generally, condom usage was accepted as an effective way to prevent transmission of STI. However, many of the men surveyed felt that condom usage reduced their sexual pleasure, and 38.5 percent felt that condoms were inconvenient. There were also areas of human immunodeficiency virus (HIV) knowledge that were lacking. Most patients listed the media as their main source of knowledge about STI and HIV. CONCLUSION: Older males attending the clinic remain at significant risk of STI and targeted educational efforts are warranted.

Comparison of dobutamine echocardiography and positron emission tomography in patients with chronic ischemic left ventricular dysfunction.

OBJECTIVES: The aim of this study was to correlate dobutamine-induced contractile reserve as detected by echocardiography with findings on positron emission tomography in patients with chronic ischemic left ventricular dysfunction. BACKGROUND: Contractile reserve induced by low dose dobutamine infusion has been proposed as a marker of myocardial viability. METHODS: Sixty patients with stable coronary artery disease and left ventricular dysfunction (mean ejection fraction [+/- SD] 29 +/- 10%) underwent transthoracic echocardiography with dobutamine infusion (up to 10 micrograms/kg body weight per min) and positron emission tomography with nitrogen-13 ammonia and fluorine-18 (F-18) fluorodeoxyglucose as a perfusion and a metabolic tracer, respectively. Regional wall motion, perfusion and metabolism were analyzed semiquantitatively by using a 16-segment model. Segments with F-18 fluorodeoxyglucose uptake > 50% were considered viable on positron emission tomography. RESULTS: After dobutamine infusion, hemodynamic variables changed significantly, and myocardial ischemia was evident in 17 patients. All 60 patients had dysfunctional myocardium considered viable on positron emission tomography (8 +/- 4 segments/patient), whereas 52 patients had dysfunctional myocardium with contractile enhancement by dobutamine echocardiography (4 +/- 2 segments/patient, p = 0.01). The extent of dysfunctional myocardium with contractile reserve appeared to correlate less closely with the total extent of viable dysfunctional myocardium identified by positron emission tomography than with the number of such segments associated with a pattern of perfusion-metabolism mismatch. CONCLUSIONS: In patients with chronic ischemic left ventricular dysfunction, echocardiography can be used to identify enhancement in the contractile function of viable dysfunctional myocardium after infusion of low dose dobutamine. In this study, the presence and extent of such enhancement were relatively less than the values obtained from positron emission tomography.

Specialized transduction by bacteriophage P22 in Salmonella typhimurium: genetic and physical structure of the transducing genomes and the prophage attachment site.

P22pro-1 and P22pro-3 are specialized transducing derivatives of phage P22 that carry the proA and proB genes of Salmonella typhimurium. These genes lie immediately adjacent to the prophage attachment site on the bacterial chromosome. By examining DNA heteroduplexes in the electron microscope, we found that DNA molecules from P22pro-1 and P22pro-3 each contain a substitution which adds length to the composite genome making the intracellular replicated genome too long to fit into a single phage particle. In this respect, and in many of their biological properties, the proline-transducing phages resemble P22Tc-10, another specialized transducing phage with an oversize, intracellular replicated genome which carries a tetracycline-resistance determinant from an R-factor.--Unlike P22Tc-10, however, P22pro-1 and P22pro-3 fail to integrate normally during lysogenizing infections, even when provided with all known integration functions. These results suggest that the proline substitutions have created a defect in the phage attachment site and suggest that the Campbell model for the formation of specialized transducing phages is applicable to phage P22 with the additional feature that oversize genomes can be produced and propagated.--A physical and genetic map of the P22 genome near the prophage attachment site was constructed which shows that the insertion from the R-factor in P22Tc-10 is not at the attachment site: it is therefore unlikely that P22Tc-10 was formed in an abnormal prophage excision event as envisioned in the Campbell model, but was instead the result of a direct translocation from the R-plasmid to P22.

Spatially and temporally differentiated patterns of c-fos expression in brainstem catecholaminergic cell groups induced by cardiovascular challenges in the rat.

Brainstem catecholaminergic neurons have been implicated as mediating adaptive autonomic and neuroendocrine responses to cardiovascular challenges. To clarify the nature of this involvement, immuno- and hybridization histochemical methods were used to follow c-fos expression in these neurons in response to acute stimuli that differentially affect blood pressure and volume. From low basal levels, hypotensive hemorrhage (15%) provoked a progressive increase in the number and distribution of Fos-immunoreactive (ir) nuclei in the nucleus of the solitary tract (NTS), the A1 and C1 cell groups of the ventrolateral medulla, and in the pontine A5, locus coeruleus, and lateral parabrachial cell groups peaking at 2.0-2.5 hours after the challenge. Fos-ir ventrolateral medullary neurons, subsets of which were identified as projecting to the paraventricular hypothalamic nucleus or spinal cord, were predominantly aminergic, whereas most of those in the NTS were not. Infusion of an angiotensin II antagonist blunted hemorrhage-induced Fos expression in the area postrema, and attenuated that seen elsewhere in the medulla and pons. Nitroprusside-induced isovolemic hypotension yielded a pattern of c-fos induction similar to that seen following hemorrhage, except in the area postrema and the A1 cell group, where the response was muted or lacking. Phenylephrine-induced hypertension stimulated a restricted pattern of c-fos expression, largely limited to induced hypertension stimulated a restricted pattern of c-fos expression, largely limited to non-aminergic neurons, whose distribution in the NTS conformed to the termination patterns of primary baroreceptor afferents, and in the ventrolateral medulla overlapped in part with those of vagal cardiomotor and depressor neurons. These findings underscore the importance of brainstem catecholaminergic neurons in effecting integrated homeostatic responses to cardiovascular challenges and their ability to responding strategically to specific modalities of cardiovascular information. They also foster testable predictions as to effector neuron populations that might be recruited to respond to perturbations in individual circulatory parameters.

A1 catecholamine cell group: fine structure and synaptic input from the nucleus of the solitary tract.

Preembedding immunoperoxidase staining methods were used to characterize tyrosine hydroxylase-immunoreactive (TH-ir) elements in the caudal ventrolateral medulla, and to determine the extent to which neurons of the A1 cell group are directly innervated by projections of the nucleus of the solitary tract (NTS). TH-ir neurons in the A1 region were medium-sized and multipolar. They possessed rounded nuclei with infrequent invaginations, well-developed Golgi apparati, high cytoplasmic densities of mitochondria, and a low to moderate tendency for rough endoplasmic reticulum (RER) to align in parallel stacks. A1 cell bodies were commonly juxtaposed to TH-positive and TH-negative neurons, myelinated profiles, glia and/or vascular elements, but close membrane appositions were only seen with glial elements. Synaptic input to A1 neurons was predominantly asymmetric, provided virtually exclusively by non-TH-ir terminals, and directed principally to dendritic shafts; A1 somata are relatively sparsely innervated. In a second experiment, silver-intensified immunogold localization of TH-ir was combined with immunoperoxidase labeling for anterogradely transported Phaseolus vulgaris-leucoagglutinin (PHA-L), following tracer injections in the caudal aspect of the medial division of the NTS. These experiments revealed a small proportion of PHA-L-labeled axon terminals that made asymmetric contacts with dendritic shafts of TH-ir neurons. These results suggest that the fine structure and synaptic input of A1 neurons are somewhat distinct from that of rostrally situated C1 catecholamine cells. In addition, while they document a direct NTS-A1 projection that may participate in the interoceptive control of vasopressin secretion, the bulk of ventrolaterally directed projections from the caudomedial NTS contact noncatecholaminergic elements in the A1 region, some of which may correspond to so-called depressor neurons implicated in the baroreflex control of sympathetic outflow and vasopressin secretion.

Fine structure and plasticity of barosensitive neurons in the nucleus of solitary tract.

Intravenous phenylephrine (PE) activates neurons in the nucleus of the solitary tract (NTS) whose distribution conforms to those of central projections of the carotid sinus and aortic depressor nerves. This was exploited to permit fine structural characterization of cells presumed to compose the first station in the processing of arterial baroreceptor input, and their responses to stimulation. Rats were perfused at varying intervals after PE injection, and sections through the baroreceptor afferent zone of the NTS prepared for preembedding immunolocalization of Fos-immunoreactivity. Labeled neurons composed a continuous strip extending from the dorsal part of the commissural NTS (NTScom) to the dorsal subnucleus at the level of the area postrema (NTSap). PE-sensitive neurons in these regions were medium-sized, round to ovoid in shape, with scant cytoplasm and an unremarkable complement of organelles. Distinctive features included extensively invaginated nuclei and well-developed Golgi apparati; Fos-ir cells in the NTSap were distinguished from those in NTScom by virtue of better-developed rough endoplasmic reticulum and Golgi, and less convoluted nuclei. Proximal synaptic input to PE-sensitive neurons was sparse and was provided by terminals containing predominantly small, clear synaptic vesicles that formed mainly symmetric junctions with somata and primary dendrites. Prolonged stimulation was accompanied by accentuation of nuclear invaginations, marked accumulation of heterochromatin at their apices, and evidence of enhanced Golgi activity (vesicular budding). These may represent adaptations to facilitate changes in gene expression, to maintain neurotransmitter availability, or both, in the face of a persistent hypertensive challenge.

Distribution of mRNAs encoding CRF receptors in brain and pituitary of rat and mouse.

Two G protein-coupled receptors have been identified that bind corticotropin-releasing factor (CRF) and urocortin (UCN) with high affinity. Hybridization histochemical methods were used to shed light on controversies concerning their localization in rat brain, and to provide normative distributional data in mouse, the standard model for genetic manipulation in mammals. The distribution of CRF-R1 mRNA in mouse was found to be fundamentally similar to that in rat, with expression predominating in the cerebral cortex, sensory relay nuclei, and in the cerebellum and its major afferents. Pronounced species differences in distribution were few, although more subtle variations in the relative strength of R1 expression were seen in several forebrain regions. CRF-R2 mRNA displayed comparable expression in rat and mouse brain, distinct from, and more restricted than that of CRF-R1. Major neuronal sites of CRF-R2 expression included aspects of the olfactory bulb, lateral septal nucleus, bed nucleus of the stria terminalis, ventromedial hypothalamic nucleus, medial and posterior cortical nuclei of the amygdala, ventral hippocampus, mesencephalic raphe nuclei, and novel localizations in the nucleus of the solitary tract and area postrema. Several sites of expression in the limbic forebrain were found to overlap partially with ones of androgen receptor expression. In pituitary, rat and mouse displayed CRF-R1 mRNA signal continuously over the intermediate lobe and over a subset of cells in the anterior lobe, whereas CRF-R2 transcripts were expressed mainly in the posterior lobe. The distinctive expression pattern of CRF-R2 mRNA identifies additional putative central sites of action for CRF and/or UCN. Constitutive expression of CRF-R2 mRNA in the nucleus of the solitary tract, and stress-inducible expression of CRF-R1 transcripts in the paraventricular nucleus may provide a basis for understanding documented effects of CRF-related peptides at a loci shown previously to lack a capacity for CRF-R expression or CRF binding. Other such "mismatches" remain to be reconciled.

"Economy class" stroke syndrome?

The authors report three cases of ischemic stroke in young adults that occurred during or after an airplane flight. Workup was negative for any cause of stroke other than the presence of a patent foramen ovale (PFO). There is an increasing awareness of deep vein thrombosis and pulmonary embolism occurring in relation to long flights. Individuals with a PFO under these circumstances may be vulnerable to stroke from paradoxic embolism. "Economy class" stroke syndrome may be underdiagnosed and is an eminently preventable cause of stroke.

Hemodynamic regulation of tyrosine hydroxylase messenger RNA in medullary catecholamine neurons: a c-fos-guided hybridization histochemical study.

Medullary catecholamine cell groups are involved in multiple modes of cardiovascular regulation and display indices of functional activation, including widespread c-fos expression, in response to hypotensive hemorrhage. Assessments of the impact of such challenges on transmitter-related gene expression are complicated by the biochemical and connectional heterogeneity that characterize these cell groups. Quantitative hybridization histochemical methods were used to follow the effects of 15% hemorrhage on levels of messenger RNA encoding tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, in medullary aminergic neurons; concurrent staining for nuclear Fos-immunoreactivity permitted comparisons between cells that ostensibly were and were not targeted by the challenge. Increased levels of tyrosine hydroxylase messenger RNA were detected in Fos-immunoreactive neurons in all cell groups examined. Mean maximal increases ranged between 133 and 192% of control values, and were attained within 0.5-1 h post-hemorrhage in noradrenergic (A1 and A2) cell groups, and at 2 h in adrenergic ones (C1, C2, and C2d or dorsal strip). By 4 h after the challenge, tyrosine hydroxylase messenger RNA levels in Fos-immunoreactive neurons in all cell groups had returned to control values. By contrast, tyrosine hydroxylase messenger RNA in non-Fos-immunoreactive cells either did not change significantly over the course of the experiment (C2 and C2d), or showed a rapid and transient increase, whose magnitude tended to be less than that seen in Fos-immunoreactive cells. c-fos messenger RNA was prominently induced in catecholaminergic neurons in each of the medullary cell groups examined at 0.5 h after hemorrhage, suggesting that the early tyrosine hydroxylase messenger RNA response to hemorrhage in non-Fos-immunoreactive cells preceded the capacity of responsive neurons to manifest detectable Fos protein expression. These findings indicate that hemorrhage up-regulates tyrosine hydroxylase messenger RNA levels in medullary catecholaminergic cell groups which have access to adaptive neuroendocrine and/or autonomic control systems. The approach employed here should prove of general utility in assessing the impact of environmental events on messenger RNA expression in connectionally heterogeneous cell groups that share a common biochemical phenotype.

Paradoxical activational effects of a corticotropin-releasing factor-binding protein "ligand inhibitor" in rat brain.

The corticotropin-releasing factor-binding protein is distinct from known corticotropin-releasing factor receptors, but can bind the peptide and neutralize its biological actions. Recent interest has centered about the therapeutic potential of "ligand inhibitors" of binding protein action, synthetic corticotropin-releasing factor fragments which are inactive at corticotropin-releasing factor receptors, but can displace the peptide from the binding protein, thereby increasing levels of free corticotropin-releasing factor. To identify sites of action of such ligands, the distribution of Fos expression seen following intracerebroventricular administration of rat/human corticotropin-releasing factor(6-33) (5-50 microg) was charted in relation to corticotropin-releasing factor-binding protein and receptor expression. It was expected that Fos induction would mimic aspects of the distribution of the two known corticotropin-releasing factor receptors, but the far greater correspondence was seen with that of the binding protein itself. This included neurons in the isocortex, the olfactory system, amygdala and a number of discrete brainstem cell groups; many Fos-immunoreactive neurons in each were found to co-express corticotropin-releasing factor-binding protein messenger RNA. Subsets of activated neurons co-expressed Type 1 corticotropin-releasing factor receptor messenger RNA, though these were largely limited to cell groups that also express the corticotropin-releasing factor-binding protein, and where binding protein immunoreactivity and Type 1 receptor transcripts were found to co-exist. Responsive neurons displaying Type 2 corticotropin-releasing factor receptor message were seen reliably only in the lateral septal nucleus. These findings support only a limited capacity of the ligand inhibitor to activate neurons bearing corticotropin-releasing factor receptors. The more pervasive activation seen among neurons that express the corticotropin-releasing factor-binding protein may be indicative of an unexpected role for this protein in signaling by corticotropin-releasing factor-related peptides.

Effects of selective sinoaortic denervations on phenylephrine-induced activational responses in the nucleus of the solitary tract.

Intravenous administration of phenylephrine provokes a pattern of cellular activation in the nucleus of the solitary tract that resembles the central distributions of primary baroreceptor afferents supplied by the carotid sinus and aortic depressor nerves. Transganglionic transport and denervation methods were used in an experimental setting to test the dependence of phenylephrine-induced Fos immunoreactivity on the integrity of buffer nerve afferents, and to identify the subregions of the nucleus of the solitary tract supplied by each. Cholera toxin B-horseradish peroxidase injections into either or both nerves revealed terminal labeling concentrated in, but not restricted to, the dorsal commissural part of the nucleus of the solitary tract at the level of the apex of calamus scriptorius, and extending into the dorsal subnucleus at the level of the area postrema. Preferential ramifications of carotid sinus and aortic depressor nerve afferents at the levels of the commissural part of the nucleus and the area postrema, respectively, were reflected in the extent to which labeled fibers comingled with neurons exhibiting phenylephrine-induced Fos in dual labeling experiments. Complete sinoaortic denervation reduced by 90% the number of neurons exhibiting drug-induced Fos expression. Selective carotid and aortic sinus denervations effected partial reductions manifest preferentially in the caudal and rostral foci of the distribution, respectively. Reduced activational responses at the level of the area postrema of aortic sinus-denervated rats were accompanied by a reduction in cellular nicotinamide adenine dinucleotide phosphate-diaphorase activity in this region. Animals killed 30 days after complete sinoaortic denervation displayed no evidence of recovery of phenylephrine-induced Fos, while the strength and distribution of the response in rats that received selective carotid sinus denervation were indistinguishable from those seen in controls. These findings (i) support the dependence of phenylephrine-induced Fos expression on the integrity of carotid sinus and aortic depressor nerve afferents, (ii) provide anatomical and functional evidence that the two buffer nerves distribute differentially within the nucleus of the solitary tract, and (iii) implicate central reorganization as a likely basis for functional recovery of baroreflex mechanisms following partial sinoaortic denervation.

Effects of [Sar1, Ile8]-angiotensin II on rostral ventrolateral medulla neurons and blood pressure in spontaneously hypertensive rats.

The present study was an attempt to determine the influence of brain angiotensin II, the activity of which is known to be higher in spontaneously hypertensive rat, on the spontaneous activity of the cardiovascular neurons in the rostral ventrolateral medulla of the spontaneously hypertensive rat. Both the spontaneous activity of the spinal projecting rostral ventrolateral medulla cardiovascular neurons and the arterial blood pressure were simultaneously measured in the pentobarbital-anesthetized spontaneously hypertensive rat and its normotensive control, the Wistar Kyoto rat, following microinjection to rostral ventrolateral medulla of an angiotensin II antagonist, [Sar1, Ile8]-angiotensin II (sarile). A microinjection method was developed that enabled us to perform extracellular recording of the rostral ventrolateral medulla cardiovascular neurons during the microinjection of drug to the vicinity of the neuron. It was found that sarile reduced both the arterial blood pressure and firing rate of some rostral ventrolateral medulla cardiovascular neurons dose-dependently. The effects of sarile were significantly greater in spontaneously hypertensive rat than in the Wistar Kyoto rat. The present findings indicate that the rostral ventrolateral medulla cardiovascular neurons of spontaneously hypertensive rat exhibit an augmented sensitivity to endogenous brain angiotensin II. Such an increase in sensitivity to brain angiotensin II in the spontaneously hypertensive rat may contribute to the enhanced spontaneous activities of rostral ventrolateral medulla cardiovascular neurons, as in the sarile responsive single discharge units, even in the resting or prestimulation state. This interaction of brain angiotensin II and rostral ventrolateral medulla cardiovascular neurons is likely to be contributory to the genesis of hypertension in this strain of rats.

Effects of Angiotensin II on the Spontaneous Activity of Rostral Ventrolateral Medullary Cardiovascular Neurons and Blood Pressure in Spontaneously Hypertensive Rats.

The interactive role of rostral ventrolateral medulla (RVL) cardiovascular neurons and brain angiotensin II (Ang II) in regulating the arterial blood pressure was examined by recording simultaneously the spontaneous activity of these spinal projecting neurons and the arterial blood pressure in the pentobarbital-anesthetized spontaneously hypertensive rat (SHR) and its normotensive control, the Wistar Kyoto rat (WKY). It was found that Ang II elicited dose-dependent excitatory responses in a subpopulation of RVL cardiovascular neurons, followed by a subsequent increase in blood pressure. These effects of Ang II were significantly greater in SHR than in WKY. The effects were attenuated or abolished by co-administration of Ang II antagonist, [Sar(1), Ile(8)]-Ang II to RVL using bilateral microinjection attenuated the blood pressure effects of intracerebroventricularly administered Ang II by as much as 70%. These results indicated that spinal projecting RVL cardiovascular neurons are important in mediating the pressor action of Ang II. The enhanced sensitivity and responsiveness of RVL cardiovascular neurons to Ang II may be pertinent to the genesis of hypertension in adult SHR. Copyright 1996 S. Karger AG, Basel

Prediction of outcome after revascularization in patients with poor left ventricular function.

BACKGROUND: In patients with poor left ventricular function, the determinants of outcome after revascularization are unknown. METHODS: We studied prospectively 57 patients with stable coronary artery disease and poor left ventricular function (left ventricular ejection fraction, 0.28 +/- 0.04) who underwent coronary artery bypass grafting. Clinical variables were assessed as predictors of outcome in all patients, and preoperative stress thallium-201 scintigraphic data were analysed in 37 patients. RESULTS: The operative mortality was 1.7%. At 12 months after operation, 46 of the 49 survivors were angina-free and 35 had fewer heart failure symptoms, but postoperative left ventricular ejection fraction (0.30 +/- 0.09) did not change significantly. Eighteen survivors had left ventricular ejection fraction improved by 0.05 or more (0.30 +/- 0.03 preoperatively, 0.40 +/- 0.05 postoperatively; p = 0.0001). The adjusted odds ratio of large reversible thallium-201 defects in predicting such outcome was 15 (95% confidence interval, 1.6 to 140), whereas other clinical variables had no predictive value. The transplantation-free 5-year survival was 73%. CONCLUSIONS: In patients with poor left ventricular function, surgical revascularization can be performed safely, with good symptomatic relief and long-term survival. One-year survival and improvement in left ventricular function is better in patients with large reversible defects on preoperative stress thallium-201 scintigraphy.

Responses of cardiovascular neurons in the rostral ventrolateral medulla of the normotensive Wistar Kyoto and spontaneously hypertensive rats to iontophoretic application of angiotensin II.

In female pentobarbital-anesthetized Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), changes in spontaneous discharges of cardiovascular neurons in the rostral ventrolateral medulla (RVL) in response to iontophoretic application of angiotensin II (Ang II) were studied and compared. It was found that iontophoretic application of Ang II to RVL increased the spontaneous neuronal activities of 30% of the cardiovascular neurons in both types of rats and that the increase was significantly greater in SHR than in WKY. In both types of rats, there was an increase in arterial blood pressure in response to iontophoretic release of Ang II to RVL. The pressor response was accompanied by tachycardia, which was significantly greater in SHR than in WKY. The present study provides evidence that Ang II acts directly on cardiovascular neurons in RVL, and in SHR, an enhanced sensitivity and responsiveness of the RVL cardiovascular neurons to Ang II may augment the sympathetic outflow from RVL and contribute to the genesis of hypertension.