Showing papers by "Wake Forest University published in 1995"

Contributions of anterior cingulate cortex to behaviour.

Abstract: Assessments of anterior cingulate cortex in experimental animals and humans have led to unifying theories of its structural organization and contributions to mammalian behaviour. The anterior cingulate cortex forms a large region around the rostrum of the corpus callosum that is termed the anterior executive region. This region has numerous projections into motor systems, however, since these projections originate from different parts of anterior cingulate cortex and because functional studies have shown that it does not have a uniform contribution to brain functions, the anterior executive region is further subdivided into ‘affect’ and ‘cognition’ components. The affect division includes areas 25, 33 and rostral area 24, and has extensive connections with the amygdala and periaqueductal grey, and parts of it project to autonomic brainstem motor nuclei. In addition to regulating autonomic and endocrine functions, it is involved in conditioned emotional learning, vocalizations associated with expressing internal states, assessments of motivational content and assigning emotional valence to internal and external stimuli, and maternal—infant interactions. The cognition division includes caudal areas 24' and 32', the cingulate motor areas in the cingulate sulcus and nociceptive cortex. The cingulate motor areas project to the spinal cord and red nucleus and have premotor functions, while the nociceptive area is engaged in both response selection and cognitively demanding information processing. The cingulate epilepsy syndrome provides important support of experimental animal and human functional imaging studies for the role of anterior cingulate cortex in movement, affect and social behaviours. Excessive cingulate activity in cases with seizures confirmed in anterior cingulate cortex with subdural electrode recordings, can impair consciousness, alter affective state and expression, and influence skeletomotor and autonomic activity. Interictally, patients with anterior cingulate cortex epilepsy often display psychopathic or sociopathic behaviours. In other clinical examples of elevated anterior cingulate cortex activity it may contribute to tics, obsessive—compulsive behaviours, and aberrent social behaviour. Conversely, reduced cingulate activity following infarcts or surgery can contribute to behavioural disorders including akinetic mutism, diminished self-awareness and depression, motor neglect and impaired motor initiation, reduced responses to pain, and aberrent social behaviour. The role of anterior cingulate cortex in pain responsiveness is suggested by cingulumotomy results and functional imaging studies during noxious somatic stimulation. The affect division of anterior cingulate cortex modulates autonomic activity and internal emotional responses, while the cognition division is engaged in response selection associated with skeletomotor activity and responses to noxious stimuli. Overall, anterior cingulate cortex appears to play a crucial role in initiation, motivation, and goal-directed behaviours. The anterior cingulate cortex is part of a larger matrix of structures that are engaged in similar functions. These structures form the rostral limbic system and include the amygdala, periaqueductal grey, ventral striatum, orbitofrontal and anterior insular cortices. The system formed by these interconnected areas assesses the motivational content of internal and external stimuli and regulates context-dependent behaviours.

Self-esteem as an interpersonal monitor: The sociometer hypothesis.

Abstract: Five studies tested hypotheses derived from the sociometer model of self-esteem according to which the self-esteem system monitors others' reactions and alerts the individual to the possibility of social exclusion Study 1 showed that the effects of events on participants' state self-esteem parallel

Short forms to assess life quality and symptom distress for urinary incontinence in women: the Incontinence Impact Questionnaire and the Urogenital Distress Inventory. Continence Program for Women Research Group.

Abstract: This article describes short form versions of the Incontinence Impact Questionnaire (IIQ) and the Urogenital Distress Inventory (UDI). These instruments assess life impact and symptom distress, respectively, of urinary incontinence and related conditions for women. All subsets regression analysis was used to find item subsets that best approximated scores of the long form versions. The approach succeeded in reducing the 30-item IIQ and the 19-item UDI to 7- and 6-item short forms, respectively. The short form versions may be more useful than the long form versions in many clinical and research applications.

Nifedipine Dose-Related Increase in Mortality in Patients With Coronary Heart Disease

Abstract: Background The purpose of this study was to assess the effect of the dose of nifedipine, a dihydropyridine calcium antagonist, on the increased risk of mortality seen in the randomized secondary-prevention trials and to review the mechanisms by which this adverse effect might occur. Methods and Results We restricted the dose-response meta-analysis to the 16 randomized secondary-prevention trials of nifedipine for which mortality data were available. Recent trials of any calcium antagonist and formulation were also reviewed for information about the possible mechanisms of action that might increase mortality. Overall, the use of nifedipine was associated with a significant adverse effect on total mortality (risk ratio, 1.16, with a 95% CI of 1.01 to 1.33). This summary estimate fails to draw attention to an important dose-response relationship. For daily doses of 30 to 50, 60, and 80 mg, the risk ratios for total mortality were 1.06 (95% CI, 0.89 to 1.27), 1.18 (95% CI, 0.93 to 1.50), and 2.83 (95% CI, 1.35 to 5.93), respectively. In a formal test of dose response, the high doses of nifedipine were significantly associated with increased mortality ( P =.01). While the mechanism of this adverse effect is not known, there are several plausible explanations, including the established proischemic effect, negative inotropic effects, marked hypotension, recently reported prohemorrhagic effects attributed to antiplatelet and vasodilatory actions of calcium antagonists, and possibly proarrhythmic effects. Conclusions In patients with coronary disease, the use of short-acting nifedipine in moderate to high doses causes an increase in total mortality. Other calcium antagonists may have similar adverse effects, in particular those of the dihydropyridine type. Long-term safety data are lacking for most calcium antagonists.

The Risk of Myocardial Infarction Associated With Antihypertensive Drug Therapies

Abstract: Objective. —To assess the association between first myocardial infarction and the use of antihypertensive agents. Design and Setting. —We conducted a population-based case-control study among enrollees of the Group Health Cooperative of Puget Sound (GHC). Patients and Methods. —Cases were hypertensive patients who sustained a first fatal or nonfatal myocardial infarction from 1986 through 1993 among women and from 1989 through 1993 among men. Controls were a stratified random sample of hypertensive GHC enrollees, frequency matched to the cases on age, sex, and calendar year. All 623 cases and 2032 controls had pharmacologically treated hypertension. Data collection included a review of the ambulatory medical record and a brief telephone interview of consenting survivors. Antihypertensive therapy was assessed using the GHC's computerized pharmacy database. Results. —The first analysis included only the 335 cases and 1395 controls initially free of cardiovascular disease. Compared with users of diuretics alone, the adjusted risk ratio of myocardial infarction was increased by about 60% among users of calcium channel blockers with or without diuretics (risk ratio=1.62; 95% confidence interval [CI], 1.11 to 2.34;P=.01). The second analysis was restricted to 384 cases and 1108 controls who were taking either a calcium channel blocker or a β-blocker. Among these subjects, the use of calcium channel blockers compared with β-blockers was associated with about a 60% increase in the adjusted risk of myocardial infarction (risk ratio=1.57; 95% CI, 1.21 to 2.04;P Conclusions. —In this study of hypertensive patients, the use of short-acting calcium channel blockers, especially in high doses, was associated with an increased risk of myocardial infarction. Ongoing large-scale clinical trials will assess the effect of various antihypertensive therapies, including calcium channel blockers, on several important cardiovascular end points. Until these results are available, the findings of this study support the current guidelines from the Joint National Committee on the Detection, Evaluation and Treatment of High Blood Pressure that recommend diuretics and β-blockers as first-line agents unless contraindicated, unacceptable, or not tolerated. (JAMA. 1995;274:620-625)

SUV: Standard Uptake or Silly Useless Value?

Abstract: Quantification has always held a pervasive allure for nuclear medicine. There is a sense that anything that can be quantified should be. Once we have the numbers in hand, there is a mysterious tendency to accord them special value. Why this should be the case is unclear. Perhaps it is because of the functional nature of nuclear medicine studies, which seem as if they should be quantified. Perhaps it is because it is so easy to extract numbers from our studies. Whatever the cause, the phenomenon has been particularly strong in PET, in which we hear at every turn that PET is {open_quotes}quantitative.{close_quotes} DiChiro and Brooks commented on this phenomenon years ago, noting that, in many applications, subjective interpretation of PET images is actually superior to the use of quantitative data. Undaunted, however, the field has continued to lean heavily toward numbers as the final arbiter of correctness. 15 refs., 2 tabs.

Developing motor neurons rescued from programmed and axotomy-induced cell death by GDNF

Abstract: DURING normal development of the vertebrate nervous system, large numbers of neurons in the central and peripheral nervous system undergo naturally occurring cell death1. For example, about half of all spinal motor neurons die over a period of a few days in developing avian, rat and mouse embryos1. Previous studies have shown that extracts from muscle and brain, secreted factors from glia, as well as several growth factors and neurotrophic agents, including muscle-derived factors, can promote the survival of developing motor neurons in vitro and in vivo2–15. But because neurotrophins and other known trophic agents administered alone or in combination are insufficient to rescue all developing motor neurons from cell death8, other neurotrophic molecules are probably essential for the survival and differentiation of motor neurons. Here we report that glial-cell-line-derived neurotrophic factor (GDNF), a potent neurotrophic factor that enhances survival of mammalian midbrain dopaminergic neurons16,17, rescues developing avian motor neurons from natural programmed cell death in vivo and promotes the survival of enriched populations of cultured motor neurons. Furthermore, treatment with this agent in vivo also prevents the induced death and atrophy of both avian and mouse spinal motor neurons following peripheral axotomy.

Human cingulate cortex: Surface features, flat maps, and cytoarchitecture

Abstract: The surface morphology land cytoarchitecture of human cingulate cortex was evaluated in the brains of 27 neurologically intact individuals. Variations in surface features included a single cingulate sulcus (CS) with or without segmentation or double parallel sulci with or without segmentation. The single CS was deeper (9.7 ± 0.81 mm) than in cases with double parallel sulci (7.5 ± 0.48 mm). There were dimples parallel to the CS in anterior cingulate cortex (ACC) and anastomoses between the CS and the superior CS. Flat maps of the medial cortical surface were made in a two-stage reconstruction process and used to plot areas. The ACC is agranular and has a prominent layer V. Areas 33 and 25 have poor laminar differentiation, and there are three parts of area 24: area 24a adjacent to area 33 and partially within the callosal sulcus has homogeneous layers II and III, area 24b on the gyral surface has the most prominent layer Va of any cingulate area and distinct layers IIIa-b and IIIc, and area 24c in the ventral bank of the CS has thin layers II–III and no differentiation of layer V. There are four caudal divisions of area 24. Areas 24a′ and 24b′ have a thinner layer Va and layer III is thicker and less dense than in areas 24a and 24b. Area 24c′ is caudal to area 24c and has densely packed, large pyramids throughout layer V. Area 24c'g is caudal to area 24c′ and has the largest layer Vb pyramidal neurons in cingulate cortex. Area 32 is a cingulofrontal transition cortex with large layer IIIc pyramidal neurons and a dysgranular layer IV. Area 32′ is caudal to area 32 and has an indistinct layer IV, larger layer IIIc pyramids, and fewer neurons in layer Va. Posterior cingulate cortex has medial and lateral parts of area 29, a dysgranular area 30, and three divisions of area 23: area 23a has a thin layer IIIc and moderate-sized pyramids in layer Va, area 23b has large and prominent pyramids in layers IIIc and Va, and area 23c has the thinnest layers V and VI in cingulate cortex. Area 31 is the cinguloparietal transition area in the parasplenial lobules and has very large layer IIIc pyramids. Finally, variations in architecture between cases were assessed in neuron perikarya counts in area 23a. There was an age-related decrease in neuron density in layer IV (r = −0.63; ages 45–102), but not in other layers. These observations provide structural underpinnings for interpreting functional imaging studies of the human medial surface. © 1995 Wiley-Liss, Inc.

Pravastatin, lipids, and atherosclerosis in the carotid arteries (PLAC-II)

Abstract: We randomized 151 coronary patients to placebo or pravastatin and treated them for 3 years. B-mode ultrasound quantification of carotid artery intimal-medial thickness (IMT) was obtained at baseline and sequentially during this period. The primary outcome was the change in the mean of the maximal IMT measurements across time. Effects on individual carotid artery segments (common, bifurcation, and internal carotid) and on clinical events were also investigated. Plasma concentrations of total cholesterol were lower with active treatment than with placebo (4.80 vs 6.07 mmol/L [186 vs 235 mg/dl], respectively) as were concentrations of low-density lipoprotein cholesterol (3.11 vs 4.30 mmol/L [120 vs 167 mg/dl], respectively). Plasma concentrations of high-density lipoprotein2 cholesterol were higher with active treatment (0.16 vs 0.14 mmol/L [6.1 vs 5.5 mg/dl], respectively). Active treatment resulted in a nonsignificant 12% reduction in progression of the mean-maximum IMT (from 0.068 to 0.059 mm/year) and a statistically significant 35% reduction in IMT progression in the common carotid. Active treatment was also associated with a reduction in fatal and nonfatal coronary events [corrected] (p = 0.09) and of any fatal event plus nonfatal myocardial infarction (p = 0.04).

Non–Insulin-Dependent Diabetes Mellitus and Fasting Glucose and Insulin Concentrations Are Associated With Arterial Stiffness Indexes: The ARIC Study

Abstract: Background Cardiovascular diseases are the most common cause of disability and death among subjects with non–insulin-dependent diabetes mellitus (NIDDM). The atherosclerotic process begins during the prediabetic phase characterized by impaired glucose tolerance, hyperinsulinemia, and insulin resistance. In vitro studies have suggested that glucose and insulin can substantially alter the structure and function of the arterial wall and affect the development of atherosclerosis. Methods and Results We performed a cross-sectional study of the relation of arterial stiffness indexes with glucose tolerance and serum insulin concentrations. Several indexes of common carotid artery stiffness were assessed with noninvasive ultrasound methods in a biracial sample of 4701 men and women 45 to 64 years of age in the Atherosclerosis Risk in Communities (ARIC) Study. Arterial compliance (AC), stiffness index (SI), pressure-strain elastic modulus (Ep), and Young’s elastic modulus (YEM) were calculated. YEM includes wall (...

Epidural clonidine analgesia for intractable cancer pain

Abstract: Although the vast majority of patients with cancer pain receive effective analgesia from standard therapy, a few patients, particularly those with neuropathic pain, continue to experience severe pain despite large doses of systemic or intraspinal opioids. Animal studies suggest intraspinal alpha 2-adrenergic agonists may be effective in such cases. Eighty-five patients with severe cancer pain despite large doses of opioids or with therapy-limiting side effects from opioids were randomized to receive, in a double-blind manner, 30 micrograms/h epidural clonidine or placebo for 14 days, together with rescue epidural morphine. Pain was assessed by visual analog score (VAS), McGill Pain Questionnaire, and daily epidural morphine use. Success was defined as a decrease in either morphine use of VAS pain, with the alternative variable either decreasing or remaining constant. Blood pressure, heart rate, and degree of nausea and sedation were monitored. Successful analgesia was more common with epidural clonidine (45%) than with placebo (21%). This was particularly prominent in those with neuropathic pain (56% vs. 5%). Pain scores were lower at the end of the treatment period in patients with neuropathic pain treated with clonidine rather than placebo, whereas morphine use was unaffected. Clonidine, but not placebo, decreased blood pressure and heart rate. Hypotension was considered a serious complication in 2 patients receiving clonidine and in 1 patient receiving placebo. This study confirms the findings from previous animal studies which showed the effective, potent analgesic properties of intraspinal alpha 2-adrenergic agonists and suggests that epidural clonidine may provide effective relief for intractable cancer pain, particular of the neuropathic type.

Method and system for producing interactive three-dimensional renderings of selected body organs having hollow lumens to enable simulated movement through the lumen

Abstract: A method and system are provided for effecting interactive, three-dimensional renderings of selected body organs for purposes of medical observation and diagnosis. A series of CT images of the selected body organs are acquired. The series of CT images is stacked to form a three-dimensional volume file. To facilitate interactive three-dimensional rendering, the three-dimensional volume file may be subjected to an optional dataset reduction procedure to reduce pixel resolution and/or to divide the three-dimensional volume file into selected subvolumes. From a selected volume or subvolume, the image of a selected body organ is segmented or isolated. A wireframe model of the segmented organ image is then generated to enable interactive, three-dimensional rendering of the selected organ.

In vitro autoradiography of receptor-activated G proteins in rat brain by agonist-stimulated guanylyl 5'-[gamma-[35S]thio]-triphosphate binding.

Abstract: Agonists stimulate guanylyl 5'-[gamma-[35S]thio]-triphosphate (GTP[gamma-35S]) binding to receptor-coupled guanine nucleotide binding protein (G proteins) in cell membranes as revealed in the presence of excess GDP. We now report that this reaction can be used to neuroanatomically localize receptor-activated G proteins in brain sections by in vitro autoradiography of GTP[gamma-35S] binding. Using the mu opioid-selective peptide [D-Ala2,N-MePhe4,Gly5-ol]enkephalin (DAMGO) as an agonist in rat brain sections and isolated thalamic membranes, agonist stimulation of GTP[gamma-35S] binding required the presence of excess GDP (1-2 mM GDP in sections vs. 10-30 microM GDP in membranes) to decrease basal G-protein activity and reveal agonist-stimulated GTP[gamma-35S] binding. Similar concentrations of DAMGO were required to stimulate GTP[gamma-35S] binding in sections and membranes. To demonstrate the general applicability of the technique, agonist-stimulated GTP[gamma-35S] binding in tissue sections was assessed with agonists for the mu opioid (DAMGO), cannabinoid (WIN 55212-2), and gamma-aminobutyric acid type B (baclofen) receptors. For opioid and cannabinoid receptors, agonist stimulation of GTP[gamma-35S] binding was blocked by incubation with agonists in the presence of the appropriate antagonists (naloxone for mu opioid and SR-141716A for cannabinoid), thus demonstrating that the effect was specifically receptor mediated. The anatomical distribution of agonist-stimulated GTP[gamma-35S] binding qualitatively paralleled receptor distribution as determined by receptor binding autoradiography. However, quantitative differences suggest that variations in coupling efficiency may exist between different receptors in various brain regions. This technique provides a method of functional neuroanatomy that identifies changes in the activation of G proteins by specific receptors.

Minimal-access surgery for staging of malignant melanoma.

Abstract: Objective: To develop a simple, minimally invasive technique of determining whether regional node metastasis has occurred in patients with melanoma. Setting: Teaching hospital tertiary care and private practice settings. Patients: Between February 1993 and October 1994, 121 patients with invasive malignant melanoma and clinically negative lymph nodes were enrolled in this clinical trial. Design: Consecutive sample clinical trial. Within 24 hours prior to lymph node resection, a radioactive tracer was injected into the dermis around the site of the primary melanoma. Forty-four patients also had blue dye injected immediately prior to surgical resection. Measurement of radioactivity in the lymph nodes and surgical localization were made using a handheld gamma detector. Radiolabeled nodes were selectively removed with the least dissection possible. In patients with pathologically positive radiolabeled nodes, regional lymphadenectomy was performed. Outcome Measures: Successful identification of radiolabeled sentinel lymph nodes, correlation of radiolabeling with injection of blue dye, and regional node recurrence rate. Results: Surgeons successfully resected the radiolabeled sentinel lymph nodes in 118 (98%) of 121 patients. One hundred percent of blue-stained lymph nodes were successfully radiolabeled. Fifteen patients had pathologically positive sentinel lymph nodes. In 10 patients, the sentinel node was the only node with metastasis. Two systemic and one regional node recurrences occurred during a mean follow-up of 220 days. Conclusions: Selective gamma probe—guided resection of the radiolabeled sentinel lymph node is possible in over 95% of patients with melanoma. This technique offers a simple and reliable method of staging of regional lymph nodes in these patients without performing a regional lymphadenectomy. (Arch Surg. 1995;130:654-658)

Users' Guides to the Medical Literature: VIII. How to Use Clinical Practice Guidelines A. Are the Recommendations Valid?

Abstract: CLINICAL SCENARIO You are relieved to find that the last patient in your busy primary care clinic is a previously well 48-year-old woman with acute dysuria. There has been no polydipsia, fever, or hematuria; the physical examination reveals suprapubic tenderness; and urinalysis shows pyuria but no casts. You arrange cultures and antibiotic treatment for a lower urinary tract infection. On her way out the door, your patient observes that her friend has just started taking "female hormones," and she wonders whether she should too. Her menstrual periods stopped 6 months ago and she has never had cervical, ovarian, uterine, breast, or cardiovascular problems, but her mother had a mastectomy at age 57 for postmenopausal breast cancer. You give the same general advice you have offered similar patients in the past, but suggest that the matter be discussed at greater length when she returns after completing the antibiotic treatment. Later, as

Association of Coronary Disease With Segment-Specific Intimal-Medial Thickening of the Extracranial Carotid Artery

Abstract: Background Several investigators have evaluated relations between risk factors and intimal-medial thickness (IMT) of the extracranial carotid arteries and between IMT and clinical cardiovascular disease. Different indexes of IMT have been used as referents. We compared the strength of association of various IMT measurements with coronary artery disease as measured at coronary angiography. Methods and Results We quantified the mean of the IMT for 12 sites of the extracranial carotid arteries (common carotid, bifurcation, internal carotid, near and far walls, and left and right sides [mean aggregate]) as well as for various combinations of sites (eg, segment-specific means, far walls only, maximum of any site) in 270 patients with or free of coronary artery disease. Models including age and all the indexes of IMT identified the mean aggregate as the only variable independently associated with the status of coronary atherosclerosis for the group as a whole. Next most strongly correlated was the mean common p...

Rescue of adult mouse motoneurons from injury-induced cell death by glial cell line-derived neurotrophic factor.

Abstract: Glial cell line-derived neurotrophic factor (GDNF) has been shown to rescue developing motoneurons in vivo and in vitro from both naturally occurring and axotomy-induced cell death. To test whether GDNF has trophic effects on adult motoneurons, we used a mouse model of injury-induced adult motoneuron degeneration. Injuring adult motoneuron axons at the exit point of the nerve from the spinal cord (avulsion) resulted in a 70% loss of motoneurons by 3 weeks following surgery and a complete loss by 6 weeks. Half of the loss was prevented by GDNF treatment. GDNF also induced an increase (hypertrophy) in the size of surviving motoneurons. These data provide strong evidence that the survival of injured adult mammalian motoneurons can be promoted by a known neurotrophic factor, suggesting the potential use of GDNF in therapeutic approaches to adult-onset motoneuron diseases such as amyotrophic lateral sclerosis.

Sustaining interventions in community systems: on the relationship between researchers and communities.

Abstract: Important goals of research-based community interventions include the long-term maintenance of effects and fostering of collaboration between researchers and community leaders. This article reviews the challenges associated with transferring innovations to community systems, changing program delivery from an experimental context controlled by researchers to program delivery controlled by community organizations, and sustaining long-term effects of interventions. It is suggested that researchers who develop and implement community interventions in diverse health areas need to confront several issues: (a) fostering effective long-term relationships between researchers and the communities they study and in which they intervene and (b) designing and implementing interventions that are useful to community systems after the formal phase of research ends.

The Outsourcing of Information Services: Transforming the Nature of Business in the Information Industry:

Abstract: The structure of the decision faced by a firm to outsource or to retain information services is developed in this paper Theory regarding the decision structure is discussed and the results of in-depth interviews with a variety of chief information officers presented Specifically, the forces that drive the outsourcing decision are identified, the incentives and disincentives of outsourcing relationships being addressed in detail A framework for contemplating the outsourcing option is presented, followed by recommendations on managing relationships with outsourcing vendors

Determination of left ventricular chamber stiffness from the time for deceleration of early left ventricular filling.

Abstract: Background A noninvasive measure of left ventricular (LV) chamber stiffness (KLV) would be clinically useful. Our theoretical analysis predicts that KLV can be calculated from the time for deceleration of LV early filling (tdec) by \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[K\_{LV}{=}\frac{{\rho}\ {\cdot}\ L}{A}\ {\cdot}\ (\frac{{\pi}}{2}\ {\cdot}\ \frac{1}{t\_{dec}})^{2}\] \end{document} where ρ=density of blood, L=effective mitral length, and A=mitral area. Methods and Results We tested this hypothesis in eight conscious dogs instrumented for measurement of LV pressure (P) with use of a micromanometer and volume (V) with use of sonomicrometers. KLV was determined as the slope of the late diastolic portion of the LV P-V loop. KLV was varied from 0.99±0.35 to 2.58±0.92 mm Hg/mL with use of three graded doses of phenylephrine. We assumed that ρ=1.0 and that L/A=3.4. Thus, we predicted that KLV=(0.08/tdec)[2][1] . The LV filling pattern was determined from the derivative of LV volume (dV/dt). tdec was measured from peak early filling to the end of early filling. Predicted KLV and actual KLV were closely correlated ( r =.94, SEE=0.06 mm Hg/mL, P <.05). The regression line was close to the line of identity (slope=0.95, intercept=0.13 mm Hg/mL). Dobutamine did not alter the relation between tdec and KLV. tdec determined from the mitral valve flow velocity measured with Doppler echocardiography correlated well with that measured by dV/dt ( r =.89, P <.01) but was 0.02 seconds longer. KLV-calculated tdec from the corrected Doppler tdec provided a good estimate of measured KLV ( r =.75, SEE=0.5 mm Hg/mL, P <.01). Conclusions LV chamber stiffness can be determined from the time for deceleration of LV early filling, which can be measured noninvasively. [1]: #ref-2

Reduction in cardiovascular events during pravastatin therapy. Pooled analysis of clinical events of the Pravastatin Atherosclerosis Intervention Program

Abstract: Background It has been documented that the HMG coenzyme A reductase inhibitors, or statins, can decrease cardiovascular events and mortality in patients with clinical coronary disease and moderately to severely elevated lipid levels. Additional data are required to demonstrate a reduction of vascular events in coronary patients with less than severely elevated lipid levels and in subgroups of this population. Methods and Results Clinical data from four atherosclerosis regression trials that evaluated pravastatin were pooled for a predetermined analysis of the effect of that agent on the risk of coronary events. All trials were double-masked, placebo-controlled designs that used pravastatin as monotherapy for 2 to 3 years. The 1891 participants in the trials had evidence of atherosclerosis and mildly to moderately elevated lipid levels. For fatal or nonfatal myocardial infarction, there was a 62% reduction in events attributable to pravastatin (P=.001). This effect was evident in younger and older patients...

Cloning and molecular characterization of the ontogeny of a rat ileal sodium-dependent bile acid transporter.

Abstract: Sodium-dependent bile acid transport in the rat ileum is abruptly expressed at weaning. Degenerate oligonucleotides, based on amino acid sequence identities between the rat liver and hamster ileal transporters, were used to amplify a rat ileal probe. A 1.2-kb cDNA clone, which contains the full coding region (348 amino acids, 38 kD), was isolated by hybridization screening. In vitro translation yielded a 38-kD protein which glycosylated to 48 kD. Sodium-dependent uptake of taurocholate was observed in oocytes injected with cRNA. Northern blot analysis revealed a 5.0-kb mRNA in ileum, kidney, and cecum. A 48-kD protein was detected in ileal brush border membranes and localized to the apical border of villus ileal enterocytes. mRNA and protein expression, which were negligible before weaning, increased dramatically at weaning. Nuclear transcription rates for the transporter increased 15-fold between postnatal days 7 and 28. The apparent molecular weight of the transporter also increased between days 19 and 28. In summary, the developmental regulation of the rat ileal sodium-dependent bile acid cotransporter is characterized by transcriptionally regulated increases in mRNA and protein levels at the time of weaning with changes in apparent molecular weight of the protein after weaning.

Phase I Safety Assessment of Intrathecal Neostigmine Methylsulfate in Humans

Abstract: Background In dogs, sheep, and rats, spinal neostigmine produces analgesia alone and enhances analgesia from alpha 2-adrenergic agonists. This study assesses side effects and analgesia from intrathecal neostigmine in healthy volunteers. Methods After institutional review board approval and informed consent, 28 healthy volunteers were studied. The first 14 volunteers received neostigmine (50-750 micrograms) through a #19.5 spinal needle followed by insertion of a spinal catheter. The remaining 14 volunteers received neostigmine through a #25 or #27 spinal needle without a catheter. Safety measurements included blood pressure, heart rate, oxyhemoglobin saturation, end-tidal carbon dioxide, neurologic evaluation, and computer tests of vigilance and memory. Analgesia in response to ice water immersion was measured. Results Neostigmine (50 micrograms) through the #19.5 needle did not affect any measured variable. Neostigmine (150 micrograms) caused mild nausea, and 500-750 micrograms caused severe nausea and vomiting. Neostigmine (150-750 micrograms) produced subjective leg weakness, decreased deep tendon reflexes, and sedation. The 750-micrograms dose was associated with anxiety, increased blood pressure and heart rate, and decreased end-tidal carbon dioxide. Neostigmine (100-200 micrograms) in saline, injected through a #25 or #27 needle, caused protracted, severe nausea, and vomiting. This did not occur when dextrose was added to neostigmine. Neostigmine by either method of administration reduced visual analog pain scores to immersion of the foot in ice water. Conclusions The incidence and severity of these adverse events from intrathecal neostigmine appears to be affected by dose, method of administration, and baricity of solution. These effects in humans are consistent with studies in animals. Because no unexpected or dangerous side effects occurred, cautious examination of intrathecal neostigmine alone and in combination with other agents for analgesia is warranted.

Sodium nitroprusside: twenty years and counting.

Abstract: Summary SNP remains an effective, reliable, and commonly used drug for the rapid reduction of significant arte- rial hypertension regardless of the etiology, for after- load reduction in the face of low CO when blood volume is normal or increased, and for intraoperative induced hypotension. After establishing indwelling arterial monitoring, an initial infusion rate of 0.3-0.5 pg * kg-’ . min -’ is be f: un with titration as needed up to 2.0 p.g * kg-’ * min- . Higher rates for brief periods of time (10 min) are acceptable. The use of alternative drugs to reduce the dose or shorten the duration of infusion should be considered when the 2.0 pg * kg-’ * mine1 range is exceeded (Table 1). SNP should not be used by individuals unfamiliar with its potency and metabolic pathways, as the many reports of adverse reactions testify. Careful attention to infusion rates, particularly in patients at risk for depleted thiosulfate stores, is mandatory, and the use of other drugs in conjunction with or instead of SNP should always be considered. As with many therapeu- tic interventions, SNP requires careful administration to appropriately selected patients by a clinician who knows its inherent hazards. Despite its toxicity, SNP is popular because it often the most (in some cases, the only) effective drug in some difficult clinical circumstances.