Role of HERG-like K(+) currents in opossum esophageal circular smooth muscle.

An inwardly rectifying K(+) conductance closely resembling the human ether-a-go-go-related gene (HERG) current was identified in single smooth muscle cells of opossum esophageal circular muscle. When cells were voltage clamped at 0 mV, in isotonic K(+) solution (140 mM), step hyperpolarizations to -120 mV in 10-mV increments resulted in large inward currents that activated rapidly and then declined slowly (inactivated) during the test pulse in a time- and voltage- dependent fashion. The HERG K(+) channel blockers E-4031 (1 microM), cisapride (1 microM), and La(3+) (100 microM) strongly inhibited these currents as did millimolar concentrations of Ba(2+).

Conceptualization of the liability for schizophrenia: clinical implications.

Historically, the Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic criteria for schizophrenia have emphasized several features, including symptoms of psychosis, a dissociation of symptoms from their etiology, a reliance on clinical symptoms, and a categorical approach to classifying the disorder. Although these emphases are quite useful, they have limitations. We review these here, and stress the importance of incorporating recent data on the genetic /biological and neurodevelopmental origins of schizophrenia into current conceptions of the disorder.

Neuronal NOS provides nitrergic inhibitory neurotransmitter in mouse lower esophageal sphincter.

To identify the enzymatic source of nitric oxide (NO) in the lower esophageal sphincter (LES), studies were performed in wild-type and genetically engineered endothelial nitric oxide synthase [eNOS(-)] and neuronal NOS [nNOS(-)] mice. Under nonadrenergic noncholinergic (NANC) conditions, LES ring preparations developed spontaneous tone in all animals. In the wild-type mice, electrical field stimulation produced frequency-dependent intrastimulus relaxation and a poststimulus rebound contraction.

The effect of therapeutic drugs and other pharmacologic agents on activity of porphobilinogen deaminase, the enzyme that is deficient in intermittent acute porphyria.

Drugs and toxins precipitate life-threatening acute attacks in patients with intermittent acute porphyria. These materials may act by directly inhibiting enzyme activity, thus further reducing porphobilinogen (PBG) deaminase activity below the ca. 50% level that results from the gene defect.

Quantitative volumetric MRI study of the cerebellum and vermis in schizophrenia: clinical and cognitive correlates.

Objective: Recent evidence suggests that the cerebellum may play a role in higher cognitive functions and, therefore, may play an important role in schizophrenia.

Method: The authors used magnetic resonance imaging to measure cerebellum and vermis volume in 15 patients with schizophrenia and 15 normal comparison subjects.

Results: They found that 1) vermis volume was greater in patients with schizophrenia than in normal subjects, 2) greater vermis white matter volume in the patients with schizophrenia significantly correlated with severity of positive symptoms and thought disorder and with impairment in verbal logical memory, and 3) patients with schizophrenia showed a trend for more cerebellar hemispheric volume asymmetry (left greater than right).

Urodynamic characterization of nonobstructive voiding dysfunction in symptomatic elderly men.

Purpose: The pathogenesis of lower urinary tract symptoms in men without bladder outlet obstruction has not been well characterized. Therefore, we defined the urodynamic abnormalities associated with symptomatic nonobstructive voiding dysfunction, and determined the relationship between age and type of dysfunction.

Materials And Methods: Video urodynamic studies of symptomatic men without outlet obstruction were examined.

Collagen-bound von Willebrand factor has reduced affinity for factor VIII.

von Willebrand factor (vWf) is a multimeric adhesive glycoprotein that serves as a carrier for factor VIII in plasma. Although each vWf subunit displays a high affinity binding site for factor VIII in vitro, in plasma, only 2% of the vWf sites for factor VIII are occupied. We investigated whether interaction of plasma proteins with vWf or adhesion of vWf to collagen may alter the affinity or availability of factor VIII-binding sites on vWf.

Temporal discrimination learning in severe amnesic patients reveals an alteration in the timing of eyeblink conditioned responses.

This study investigated whether the hippocampal system plays a modulatory role in the timing of conditioned responses (CRs) in eyeblink classical conditioning. Seven bitemporal amnesic patients and 7 controls were randomly presented 2 tone conditioned stimuli (CSs) that were individually paired with two different interstimulus intervals (ISIs) in a delay conditioning task. It was found that amnesic patients' CRs occurred significantly earlier than control participants' CRs at the longer ISI.

Automated detection of the factor V Leiden mutation using the LCx microparticle enzyme immunoassay.

The factor V Leiden mutation, a G-->A transition at position 1691 in exon 10 of the gene that codes for factor V, produces an Arg506Gln substitution and is the most common genetic risk factor for venous thrombosis. We have developed a rapid, sensitive, and specific method to detect the factor V Leiden mutation in genomic DNA from whole blood by PCR amplification and microparticle enzyme immunoassay detection using the Abbott LCx instrument. We compared this automated method with the standard procedure using restriction endonuclease digestion of PCR products followed by gel electrophoresis in blinded experiments.

Fetal alcohol effects in alcoholic veteran patients.

Fetal alcohol syndrome is often associated with severe physical and neuropsychiatric maldevelopment. On the other hand, some offspring of women who drank during pregnancy appear to be affected in minimal ways and function relatively well within society. We questioned whether this effect of prenatal alcohol in the adult is generally minimal.

The maximum watts factor as a measure of detrusor contractility independent of outlet resistance.

The maximum watts factor (WFmax) is often used to characterize detrusor contractility. It was recently shown that the WFmax may increase in some patients with chronic outlet obstruction. It is, however, unclear whether this increase reflects a dependence of the WFmax on the degree of outlet obstruction or whether it represents a true increase in detrusor contractility secondary to chronic outlet obstruction.

Co-occurrence of abuse of different drugs in men: the role of drug-specific and shared vulnerabilities.

Background: Previous research has demonstrated genetic and environmental influences on abuse of individual substances, but there is less known about how these factors may influence the co-occurrence of abuse of different illicit drugs.

Methods: We studied 3372 male twin pairs from the Vietnam Era Twin Registry. They were interviewed using the Diagnostic Interview Schedule, Version III, Revised to investigate the extent to which the abuse of different categories of drugs occurs together within an individual, as well as the possibility that genetic and environmental factors are responsible for observed co-occurrence.

Critical limits (alert values) for physician notification: universal or medical center specific limits?

The concept of critical limits (alert values), defined as an imminent life threatening laboratory result requiring immediate physician notification, has been widely adopted as a standard of good laboratory practice. Although virtually all laboratories have tests with critical limits, surveys have shown that there is no universal alert value list. Recently, nine VA medical centers in the New England region, which now constitute one consolidated entity, were surveyed with the objective of summarizing critical limits.

Differences in contractile protein content and isoforms in phasic and tonic smooth muscles.

The basis of tonic vs. phasic contractile phenotypes of visceral smooth muscles is poorly understood. We used gel electrophoresis and quantitative scanning densitometry to measure the content and isoform composition of contractile proteins in opossum lower esophageal sphincter (LES), to represent tonic muscle, and circular muscle of the esophageal body (EB), to represent phasic smooth muscle.

Negative, positive, and disorganized symptom dimensions in schizophrenia, major depression, and bipolar disorder.

We compared the factor structure of positive and negative symptoms in schizophrenia (N = 214), major depression (N = 97), and bipolar disorder (N = 58) to determine whether schizophrenia factors would generalize to mood disorders. A study of schizophrenia and mood disorders identified patients whose symptoms were evaluated with the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms. We conducted principal component analyses with orthogonal rotation on the global ratings.

Nitric oxide suppresses a Ca(2+)-stimulated Cl- current in smooth muscle cells of opossum esophagus.

Nitric oxide (NO) hyperpolarizes visceral smooth muscles. Using the patch-clamp technique, we investigated the possibility that NO-mediated hyperpolarization in the circular muscle of opossum esophagus results from the suppression of a Ca(2+)-stimulated Cl- current. Smooth muscle cells were dissociated from the circular layer and bathed in high-K+ Ca(2+)-EGTA-buffered solution.

Impact of injection rate on the Thrombolysis in Myocardial Infarction (TIMI) trial frame count.

A mechanical injection was used to determine the impact of injection rate on the TIMI frame count. The 1.0-ml/s increase in hand injection rates from the 10th to 90th percentiles for angiographers is associated with a minor decrease of <2 frames that is <7% of the corrected TIMI frame count.

Using a computerized sign-out program to improve continuity of inpatient care and prevent adverse events.

Background: Many medical injuries are preventable, but there are few reported successful strategies to prevent such injuries. Previous work identified coverage by house staff not primarily responsible for the patient (cross-coverage) as a significant correlate of risk for preventable adverse events. A four-month intervention--computerized sign-outs--was introduced in 1993 in an urban teaching hospital to improve continuity of care during cross-coverage and thereby reduce risk for preventable adverse events.

Vibration-induced postural posteffects.

It generally is known that vibration of various muscles in free-standing subjects evokes a spatially oriented postural response. Furthermore, it recently has been shown that when a vibratory stimulus is terminated, a powerful involuntary contraction of the previously vibrated muscle often occurs that, under the isotonic condition, is accompanied by movement of a limb. The aim of this study was to explore effects of a low-amplitude mechanical vibration, applied in a seated position, on the standing posture.

Antiarrhythmic actions of intravenous ibutilide compared with procainamide during human atrial flutter and fibrillation: electrophysiological determinants of enhanced conversion efficacy.

Background: The selective class III antiarrhythmic agent ibutilide prolongs action potential duration and terminates atrial flutter (AFL) and fibrillation (AF), but the mechanism of its antiarrhythmic efficacy in humans has not been fully characterized. This study compared the antiarrhythmic effects of ibutilide with the class IA agent procainamide in humans during AFL and AF. Antiarrhythmic drug actions and electrophysiological characteristics of AFL and AF that enhanced pharmacological termination were investigated.

Identification and functional assay of an extracellular calcium-sensing receptor in Necturus gastric mucosa.

In mammals and amphibians, increases in extracellular Ca2+ can activate bicarbonate secretion and other protective functions of gastric mucosa. We hypothesized that the recently cloned extracellular Ca(2+)-sensing receptor (CaR) is functioning in the gastric mucosa. In Necturus maculosus gastric mucosa, reverse transcription-polymerase chain reaction using primers based on previously cloned CaR sequences amplified a 326-bp DNA fragment that had 84% nucleotide sequence identity with the rat kidney CaR.

Acute hemodynamic effects of intravenous ibutilide in patients with or without reduced left ventricular function.

Many antiarrhythmic agents have adverse hemodynamic effects which limit their use in patients with impaired ventricular function or during tachyarrhythmias. Ibutilide is an intravenous, selective class III antiarrhythmic agent that is effective for conversion of atrial fibrillation or flutter. This multicenter, randomized, placebo-controlled, dose-ranging study evaluated the effects of intravenous ibutilide on hemodynamic parameters during invasive monitoring in 47 patients with or without reduced left ventricular ejection fraction (LVEF) > 35% or < or = 35%.

Tyrosine phosphorylation in contraction of opossum esophageal longitudinal muscle in response to SNP.

Sodium nitroprusside (SNP) has been shown to elicit a guanosine 3',5'-cyclic monophosphate (cGMP)-mediated, indomethacin-sensitive contraction of the opossum esophageal longitudinal muscle. We examined the role of tyrosine phosphorylation in the signal transduction pathway of contractions induced by SNP and cGMP in longitudinal muscle strips in vitro. Force of isometric contractions was expressed as the percentage of responses to KCl (73 mM).

Urodynamic risk factors for renal dysfunction in men with obstructive and nonobstructive voiding dysfunction.

Purpose: Urodynamic investigation of men with lower urinary tract symptoms, usually attributed to benign prostatic hyperplasia, often reveals bladder outlet obstruction, detrusor instability and/or diminished vesical compliance. We investigated whether these urodynamic abnormalities alone or in combination contribute to renal dysfunction.

Materials And Methods: A total of 161 men with lower urinary tract symptoms was evaluated by urodynamics, and outlet obstruction, detrusor instability and decreased compliance (30 ml.

Outcomes of acute myocardial infarction in the Department of Veterans Affairs: does regionalization of health care work?

Objectives: This study examines the association between the regional availability of cardiac technology and outcomes of care for patients admitted to Department of Veterans Affairs (VA) hospitals. Patients using the VA regional medical system initially are admitted to a hospital with or without the on-site availability of technology-intensive cardiac services.

Methods: The authors identified male veterans (n = 24,229) discharged from VA hospitals with a primary diagnosis of acute myocardial infarction (AMI) from January 1, 1988 through December 31, 1990.