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Biomedical subjects

L Young

Publications and source records attributed to L Young.

At least 109 records · Page 6Linked to original sources

Clinical characteristics and management of acute stroke in patients with atrial fibrillation admitted to US university hospitals.

UNLABELLED: The optimal evaluation and management of patients with atrial fibrillation who suffer an acute ischemic stroke remains controversial. METHODS: Medical records of 171 consecutive patients with atrial fibrillation and acute stroke at six U.S. university hospitals were reviewed. Data collected included the use of antithrombotic therapy, brain and cardiac imaging, bleeding complications, stroke risk factors, and contraindications to anticoagulation. RESULTS: Mean age was 75.4 years. Cardiovascular risk factors associated with increased stroke risk were present in 87%; 35% had at least one contraindication to anticoagulation. Half of the patients with stroke risk factors and no contraindications to anticoagulation were not receiving any antithrombotic therapy at the time of admission. Of the 22 patients who were treated with warfarin, and had INR values on admission, 16 had levels of < 2.0; only six had INR values between 2.0 and 3.0. Transthoracic echocardiography was performed in 107 patients (63%); intracardiac thrombi were visualized in only 5%. Initial brain imaging revealed hemorrhagic transformation in nine. Heparin was used in 93 patients (54%), usually within 48 hours of stroke onset. Patients who received delayed heparin typically did not have repeat brain imaging prior to starting heparin. One patient had a delayed symptomatic cerebral hemorrhage. Of the survivors, 47% were discharged and treated with warfarin (or warfarin plus aspirin), 28% with ASA, 7% with other antithrombotic therapies, and 18% with no antithrombotic therapy. CONCLUSION: Antithrombotic therapy was underutilized and inadequately monitored in atrial fibrillation patients prior to stroke onset. After hospital admission, a wide range of diagnostic and management strategies, which often did not follow current recommendations, were employed.

Acute Disease↗

Central oxytocin and reproductive behaviours.

Oxytocin is a neurohypophyseal hormone that has long been associated with uterine contraction during parturition and milk ejection during nursing. Recent studies have suggested that oxytocin is also a neurotransmitter that has central effects important for reproduction, including the initiation of parental and sexual behaviours. This review describes oxytocin pathways in the brain and examines their regulation by gonadal steroids. Brain oxytocin receptors are remarkable for their plasticity and for striking species differences in their distribution. The molecular characterization of this receptor has provided several clues to the regulation of its expression. Comparative and transgenic studies suggest that central oxytocin release may influence reproductive behaviours, but the importance of these central effects depends on the pattern of expression of the receptor--a pattern that is species-specific.

Animals↗

Cardiopulmonary effects of carfentanil in dama gazelles (Gazella dama).

Sixteen (10 female, six male) captive-born dama gazelles (Gazella dama) weighing 48 +/- 10 kg (mean +/- SD) were used to evaluate the cardiopulmonary effects of i.m. carfentanil and to validate the use of pulse oximetry in immobilized gazelles. Carfentanil (18.4 +/- 2.2 micrograms/kg i.m.) produced rapid induction (6 +/- 3 min), moderate muscle relaxation, and a significant (P < 0.05) decrease in heart rate (87 +/- 12 beats/min) beginning 5 min following induction and continuing throughout the immobilization period. A decrease in respiratory rates began 15 min following induction (11 +/- 4 breaths/min). Systemic hypertension was present throughout the immobilization period. Arterial blood gas analysis, performed at 10, 20, and 30 min after induction, showed PaCO2 and PaO2 values within normal limits. Arterial blood oxygen saturation (SaO2) was < 95% 10 min after induction. Relative arterial oxygen saturation (SpO2) values indicated by pulse oximetry were generally lower than SaO2 values but reliably demonstrated trends in arterial oxygen saturation as confirmed by arterial blood gas analysis. Periods of hypoxemia were usually indicated by the pulse oximeter reading and confirmed by SaO2 measurements. There was an increase in creatine phosphokinase values (88 +/- 53 U/L to 109 +/- 48 U/L) at 30 min postimmobilization. Naltrexone reversal (1.8 +/- 0.3 mg/kg, half i.v. and half s.c.) was rapid and uneventful, and time to standing was 2 +/- 1 min.

Analgesics, Opioid↗

Multidisciplinary approach to management of a hereditary neurodegenerative disorder: Huntington disease.

Huntington Disease is a well known autosomal dominant inherited disease resulting in emotional problems, abnormalities of movement, and eventually dementia. It stands out as one of the most devastating illnesses, not only for its neurodegenerative progression but also for its impact on families. Care often becomes fragmented due to the person's response to symptoms and/or family breakdown. The successful interaction of health care disciplines working with Huntington Disease in our centers, namely, the family physicians, nursing, Genetics, Neurology, Psychiatry, Social Work, and Long Term Care has resulted in a comprehensive program of care for our patients and their families. This article will describe the history, structure and interaction of the multidisciplinary group. It will describe the difficulties we have overcome and offer suggestions for the implementation of similar programs for the care of people with other disorders.

Humans↗

Catalysis by entropic guidance from enzymes.

Certain features underlying enzymatic catalysis, such as energetic stabilization from binding interactions or proximity and orientation of chemical groups, are evident in the equilibrium-averaged structure of an enzymatic complex determined by crystallography or NMR. Transient features are not apparent from an average structure. Here, we report on a catalytically relevant property of an enzymatic complex revealed by thermal fluctuations from a molecular dynamics study. The conformational fluctuations of the cofactor NADH are altered by binding the enzyme lactate dehydrogenase (LDH) compared to those of free NADH; thermal motions give rise to structures similar to that of the putative transition state. The alteration is stereospecific, in agreement with measured changes in vibrational spectra, and leads to an understanding of the correlation, established some time ago by crystallography and NMR, between the nicotinamide glycosidic bond torsion angle (anti/syn) and the stereospecificity of hydride transfer. These results suggest that one catalytic role of the enzyme is to funnel the population of NADH conformers to the transition state and reduce the entropic barrier to activation. The specific motions in an enzyme complex that might function to enhance transition state formation are described.

Animals↗

Cardiac Na+ pump current-voltage relationships at various transmembrane gradients of the pumped cations.

Thermodynamic considerations predict changes of the Na+ pump current (Ip)-voltage (V) relationship of animal cells upon variations of the electrochemical gradients against which cations must be pumped. Experimental data in support of the predictions are sparse. Therefore, the effect on the Ip-V relationship of various electrochemical gradients for pumped Na+ and Cs+ was studied at constant deltaGATP (approximately -39kJ/mol in cardioballs from sheep Purkinje fibres. Control of the subsarcolemmal ionic concentrations during whole-cell recording was ensured by activation of Ip below its half maximal activity or by measuring the initial Ip following reactivation of the Na+/K+ pump. With gradients close to physiological conditions Ip was outward over the entire voltage range and the Ip-V relationship showed a maximum near zero potential. Steepening the ionic gradients diminished the Ip amplitude and outward pump current was no longer detectable between -65 mV and -110 mV. Flattened ionic gradients increased the Ip amplitude and shifted apparently the reversal potential Erev to more negative values. These changes are in line with theoretical considerations. The measured Ip-V relationships were fitted by curves computed on the basis of a simplified Post-Albers scheme of Na+/Cs+ pumping. The increased Ip amplitude at flat ionic gradients was due to a decrease of [Cs+]o for half maximal Ip activation. The maximal Ip amplitude remained unaffected

Animals↗

Molecular cloning and disease association of hepatitis G virus: a transfusion-transmissible agent.

An RNA virus, designated hepatitis G virus (HGV), was identified from the plasma of a patient with chronic hepatitis. Extension from an immunoreactive complementary DNA clone yielded the entire genome (9392 nucleotides) encoding a polyprotein of 2873 amino acids. The virus is closely related to GB virus C (GBV-C) and distantly related to hepatitis C virus, GBV-A, and GBV-B. HGV was associated with acute and chronic hepatitis. Persistent viremia was detected for up to 9 years in patients with hepatitis. The virus is transfusion-transmissible. It has a global distribution and is present within the volunteer blood donor population in the United States.

Acute Disease↗

The behavioural and neurochemical profile of the putative dopamine D3 receptor agonist, (+)-PD 128907, in the rat.

The functional relevance of the dopamine D3 receptor is still unresolved, largely because of the absence of selective D3 receptor ligands. In the present study we have examined the in vivo profile of (+)-PD 128907, a potent and functionally selective D3 receptor agonist. Low doses of (+)-PD 128907 reduced spontaneous locomotor activity in the rat (ED50 = 13 +/- 3 micrograms/kg, s.c.) a response which was comparable with the non-selective D2,3 receptor agonist apomorphine (ED50 = 13 +/- 1.6 micrograms/kg, s.c.). In addition (+)-PD 128907 impaired prepulse inhibition of the acoustic startle response, with significant effects observed at doses of 30 micrograms/kg when appropriate prepulse intensities were used. Higher doses reversed gamma-butyrolactone-induced catecholamine synthesis (ED50 = 95 +/- 22 and 207 +/- 37 micrograms/kg in accumbens and striatum respectively) and induced yawning (100-300 micrograms/kg), penile grooming (30-1000 micrograms/kg) and sniffing (> or = 300 micrograms/kg) although doses 3- to 10-fold greater than apomorphine were required to produce maximal effects. In contrast to apomorphine, however, (+)-PD 128907 failed to induce intense stereotyped licking and biting in the rat. In view of the potency and selectivity of (+)-PD 128907 for the D3 receptor, a role in the control of locomotor activity is suggested. In addition, the observation that (+)-PD 128907 disrupts prepulse inhibition, a phenomenon which is also impaired in schizophrenic subjects, may indicate the pathological importance of this receptor subtype.

4-Butyrolactone↗

Human papillomavirus infection and risk of progression of epithelial abnormalities of the cervix.

The polymerase chain reaction has been used to determine the presence of human papillomavirus (HPV) 16 and HPV 18 DNA sequences in archival histological material removed from a cohort of untreated women with cervical epithelial abnormalities. The detection of HPV 16 or HPV 18 DNA sequences in the initial biopsy specimen was associated with a significantly increased risk of subsequent disease progression.

Cervix Uteri↗

Pregnancy and warm autoantibodies: a case report.

The presence of the maternal warm antibody in pregnancy should not be ignored. As there is risk of both maternal and fetal anemia, both patients need to be followed for the development of such. Serial complete blood counts in the mother and treatment if significant fetal anemia develops should be considered. Serial amniocentesis and nonstress testing should be part of any management plan in the presence of a maternal warm antibody.

Adult↗

A noncovalent complex vaccine prepared with detoxified Escherichia coli J5 (Rc chemotype) lipopolysaccharide and Neisseria meningitidis Group B outer membrane protein produces protective antibodies against gram-negative bacteremia.

Earlier studies showed that purified IgG from sera of rabbits immunized with a boiled Escherichia coli J5 (Rc chemotype) whole cell vaccine protected neutropenic rats against gram-negative bacterial sepsis. In the present study, de-O-acylated J5 lipopolysaccharide (J5 DLPS) as a noncovalent complex with Neisseria meningitidis group B outer membrane protein (GBOMP) elicited anti-J5 LPS antibodies in rabbits. IgG prepared from immune rabbit sera protected neutropenic rats against lethal challenge with Pseudomonas aeruginosa 12:4:4 (Fisher Devlin immunotype 6). Sixteen of 26 rats treated with the postimmune serum IgG were protected compared with none of 20 rats treated with the control rabbit serum IgG (P < .001). In vitro binding studies showed binding of anti-J5 IgG to several gram-negative bacteria. These results indicate that a subunit vaccine made of J5 DLPS as a noncovalent complex with GBOMP may protect against gram-negative bacteremia.

Animals↗

Molecular cloning and characterization of HE1, a major secretory protein of the human epididymis.

The cDNA sequence of HE1, a novel human epididymal gene product isolated by differential screening, predicts an abundant, small secretory glycopeptide. HE1 is encoded by a single copy gene and seems to be well conserved among mammals. The predicted HE1 peptide is identical to that of EPI-1, the chimpanzee homologous gene product, and to ESP14.6, the macaque homologous product. Its tentative N-terminus also shows similarity to that of a major porcine epididymal sperm-associated glycopeptide. Northern blot analysis of various bovine and rat tissues indicated that their HE1-homologous gene products showed highly increased expression in the epididymis, suggesting that the tissue distribution observed in humans is also conserved. With use of antipeptide antibodies, HE1-related antigen was shown by immunohistochemical methods to be present within the epithelium and lumen of the human corpus epididymidis. High amounts were also present in the lumen of the cauda epididymidis and deferent duct. Moreover, HE1 seemed to be associated with epididymal spermatozoa, and association with ejaculated spermatozoa remained doubtful. With Western blotting, an antiserum raised against the synthetic HE1 epitope specifically cross-reacted with proteins of human seminal plasma in the range of 25-27 kDa. An antiserum raised against chimpanzee EPI-1 recognized human seminal plasma antigens of the same apparent molecular size.

Amino Acid Sequence↗

Alveolar type II cell growth on a pulmonary endothelial extracellular matrix.

Most of the alveolar epithelium overlies a fused basement membrane produced by epithelial and endothelial cells. To determine how this type of matrix influences type II cell growth and function, we studied the effects of culturing isolated rat alveolar type II cells on an extracellular matrix (ECM) freshly produced by pulmonary vascular endothelial cells grown 5 days in culture. Type II cells from the same rats were cultured on plastic or Matrigel for comparison. A large increase in mitotic activity was seen in type II cells grown on the endothelial ECM at 2 days only; thereafter cells spread rapidly to confluence and lost their lamellar bodies. Cells grown on Matrigel remained cuboidal with lamellar bodies but grew more slowly, as judged by [3H]thymidine uptake and cell numbers. Incorporation of labeled choline into disaturated phosphatidylcholine (DSPC) was used as a marker of surfactant synthesis. After the rapid, brief burst of proliferation, type II cells on endothelial ECM showed a sudden decline in DSPC-DNA by day 4 compared with cells grown on matrigel. Binding of the lectin Bauhinia purpurea (BPA) indicated that after a phase of division, cells on endothelial ECM developed as type I epithelium by 4 days of culture, when > 70% of cells stained positively for BPA binding, whereas few cuboidal cells on Matrigel were stained. The results indicate that type II cells respond briefly to growth factors in pulmonary endothelial ECM; then this type of matrix promotes cell spreading with loss of type II function as cells subsequently resemble type I epithelium.

Animals↗

d-fenfluramine treatment of binge eating disorder.

OBJECTIVE: The purpose of this study was to assess the efficacy of the appetite suppressant d-fenfluramine in the treatment of binge eating disorder. METHOD: The authors conducted an 8-week double-blind, placebo-controlled clinical trial of the drug with 28 severely obese female patients meeting full criteria for binge eating disorder. The primary outcome measure was number of binges per week, as recorded in binge diaries and reviewed weekly with the principal investigators. RESULTS: Random effects linear regression analysis showed that the rate of binge eating in the d-fenfluramine group fell three times more rapidly than that in the placebo group, a result that was both clinically and statistically significant. At 4-month follow-up the binge frequency of the d-fenfluramine group had increased to pretreatment levels and no longer differed from that of the placebo group. CONCLUSIONS: d-Fenfluramine reduced the frequency of binge eating by obese women with binge eating disorder.

Appetite Depressants↗