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Biomedical subjects

M Murphy

Publications and source records attributed to M Murphy.

At least 379 records · Page 21Linked to original sources
PubMed1991

Expression of the outer capsid protein VP5 of two bluetongue viruses, and synthesis of chimeric double-shelled virus-like particles using combinations of recombinant baculoviruses.

We have previously reported the assembly of virus-like particles (VLPs), consisting of the four major structural proteins of bluetongue virus (BTV), in Spodoptera frugiperda cells coinfected with recombinant baculoviruses (French et al. (1990). J. Virol. 64, 5695-5700). In this paper we report further studies using this system to assemble heterologous VLPs containing the outer capsid proteins (VP2 and VP5) of a range of different BTV serotypes. S. frugiperda cells were coinfected with three recombinant baculoviruses; a dual recombinant expressing VP3 and VP7 (of BTV-17 and -10, respectively) in combination with a single recombinant expressing VP2 of BTV-1, -2, -10, -11, 13, or -17 and an additional single recombinant expressing VP5 of BTV-2, BTV-10, or BTV-13. The resultant VLPs were purified and analyzed by electronmicroscopy, Western immunoblotting, and hemagglutination assays to determine whether double-shelled VLPs had been assembled. In the course of these experiments the VP2 proteins of all six available serotypes were successfully incorporated into VLPs. Particles from two different combinations of chimeric VLPs (having VP2 derived from BTV-1 or that of BTV-17) were used to raise antisera in guinea pigs. Both of these sera showed high neutralizing antibody titers against live BTV, indicating that heterologous VLPs may have potential for use in anti-BTV vaccines.

Animals↗
PubMed1991

A method for the isolation of purified murine neuroepithelial cells from the developing mouse brain.

The adult mammalian central nervous system develops from the pseudostratified neuroepithelium of the neural tube. In order to study, in vitro, the differentiation of the neuroepithelial cells in detail and to identify factors that may influence this process, an uncontaminated, viable population of neuroepithelial cells, that still retains full developmental potential, is required. In this paper we describe a highly efficient method, involving differential trypsinization and micro-dissection, to cleanly separate the neuroepithelium from surrounding mesenchyme and ectoderm. The purity of isolated neuroepithelium has been assessed by monitoring for the presence of endothelial cells using an anti-endothelial antibody, MTS-12, and found to contain no significant level of contamination. Neuroepithelial cells prepared by this method have been demonstrated to divide and differentiate in tissue culture, to act as target cells for immortalization by proto-oncogenes and to differentiate into neurons in neural transplantation studies.

Animals↗
PubMed1991

Attitudes, knowledge, and training of medical residents regarding adolescent health issues.

This study examined attitudes, knowledge, and training relating to adolescent health issues, of medical residents in six different specialties who provide care to adolescents, at a southern, rural medical school without an organized curriculum in adolescent medicine. An original 18-item questionnaire was developed which examined four broad health care categories: general medicine, sexuality, high-risk behaviors, and development. Of 118 residents 91 (77%) responded. For any health care area, residents reported managing fewer than 10 adolescent patients and often fewer than 3 patients. However, they reported comfort and confidence and little desire for additional training in most of these areas. There were few differences between specialties or year of training. Almost one-half (42%) believed that pediatric care should end by age 16 years; 32% thought it should end at age 18 years. However, there was little support for pediatricians providing prenatal care to pregnant teens. These findings are useful for planning curriculum in ambulatory adolescent health and developing strategies for encouraging residents to understand and embrace the challenge of adolescent health care.

Adolescent↗
PubMed1991

Progressive platelet activation with storage: evidence for shortened survival of activated platelets after transfusion.

Platelets are known to become activated during storage, but it is unclear whether such activation affects recovery or survival after platelet concentrate (PC) transfusion. With the use of flow cytometry to determine the percentage of platelets expressing the alpha-granule membrane protein 140 (GMP-140), a known adhesive ligand appearing on the platelet surface after activation, several studies were conducted. These investigations evaluated 1) the occurrence of significant platelet activation over time in PCs (n = 46) stored under standard blood bank conditions; 2) the correlation between platelet activation and platelet recovery in normal subjects after PC storage (n = 12), as assessed by the recovery of Indium-labeled platelets; and 3) the recovery of activated and unactivated platelets in thrombocytopenic cancer patients transfused with standard PCs (n = 11). It was determined 1) that an increasing duration of storage of PC was associated with increasing platelet activation as measured by the percentage of platelets expressing GMP-140, progressing from a mean of 4 +/- 2 percent (SD) on the day of collection to a mean of 25 +/- 8 percent by 5 days of storage: 2) that, in normal subjects, posttransfusion recovery of autologous platelets stored for 2 to 4 days and then labeled with In111 was inversely correlated with the percentage of activated platelets in the transfused PC (r = -0.55, p = 0.05); and 3) that, when thrombocytopenic patients were transfused with standard PCs, the recovery of the activated platelets in the transfused PCs averaged only 38 +/- 15 percent of the number predicted by the absolute platelet increment.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1991

Household modelling and forecasting--dynamic approaches with use of linked census data.

The author proposes improved methods of household modeling, using dynamic models rather than the headship rate method. "Reasons are discussed why this method has been criticised in recent years.... The advantages of dynamic models are discussed, and a number of alternative dynamic models of household formation and dissolution are presented. The data source used is the Office of Population Censuses and Surveys 1% longitudinal study, which contains linked information on 500,000 people in the 1971 and 1981 England and Wales Censuses of Population."

Developed Countries↗
PubMed1991

A prospective analysis of injury severity among helmeted and nonhelmeted bicyclists involved in collisions with motor vehicles.

To evaluate the impact of helmet use on injury severity, patient information was prospectively obtained for all bicyclists involved in collisions with motor vehicles seen at a level-I trauma center from January 1986 to January 1989. Two hundred ninety-eight patients were evaluated; in 284 (95.3%, study group) cases there was documentation of helmet use or nonuse. One hundred sixteen patients (40.9%) wore helmets and 168 (59.1%) did not. One hundred ninety-nine patients (70.1%) had an ISS less than 15, while 85 (29.9%) were severely injured (ISS greater than 15). Only 5.2% of helmet users (6/116) had an ISS greater than 15 compared with 47.0% (79/168) of nonusers (p less than 0.0001). The mean ISS for helmet users was 3.8 compared with 18.0 for nonusers (p less than 0.0001). Mortality was higher for nonusers (10/168, 6.0%) than for helmet users (1/116, 0.9%; p less than 0.025). A striking finding was noted when the group of patients without major head injuries (246) was analyzed separately. Helmet users in this group still had a much lower mean ISS (3.6 vs. 12.9, p less than 0.001) and were much less likely to have an ISS greater than 15 (4.4% vs. 32.1%, p less than 0.0001) than were nonusers. In this group, 42 of 47 patients with an ISS greater than 15 (89.4%) were not wearing helmets. We conclude that helmet nonuse is strongly associated with severe injuries in this study population. This is true even when the patients without major head injuries are analyzed as a group; a finding to our knowledge not previously described.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Traffic↗
PubMed1991

Does flexibility at mealtimes disturb blood glucose control on a multiple insulin injection regimen?

Randomized crossover studies of a half-sized lunch with reduced insulin dose in 21 patients, and a delayed (by 2 h) evening meal in 22 patients, compared with normal meals, were performed in Type 1 diabetic patients. The aim was to examine whether the size and timing of meals can be varied in patients on multiple injection regimens without disturbance of blood glucose control. All patients had previously had their control optimized on multiple injection therapy using a pen-injector. The studies were carried out at home on 6 days (3 changed meals, 3 control) over 2 months, and as 8- and 7-h metabolic profiles (1 study day, 1 control) in an investigation unit. A halved calorie lunch with half the usual insulin dose resulted in equivalent blood glucose control on the study day (area under curve: changed meal 40.0 +/- 3.4 vs control meal 40.3 +/- 3.5 mmol l-1 h for the 5-h period after the meal). Ketone body levels were also unchanged. The late evening meal shifted the post-prandial blood glucose concentration accordingly, but the excursion was not different in extent from the control day (24.8 +/- 1.9 vs 21.0 +/- 1.7 mmol l-1 h). A small excursion of 3-hydroxybutyrate levels before the delayed meal (to 187 +/- 48 mumol l-1) was quickly corrected on eating. Hypoglycaemia was not different in frequency on the changed meal days. Thus no problems of clinical significance were observed when some flexibility in meal size and timing was allowed.

Adult↗
PubMed1991

Is oral contraceptive use still associated with an increased risk of fatal myocardial infarction? Report of a case-control study.

OBJECTIVE: To investigate the association between fatal myocardial infarction and use of modern low-dose oral contraceptives. DESIGN: A case-control study. SETTING: General practices throughout England and Wales. SUBJECTS: 161 women aged under 40 dying from myocardial infarction during 1986-1988. Living controls (2 per case), matched for age and marital status, were chosen from general practice lists. Information was collected during structured interviews with general practitioners, and from postal questionnaires sent to surviving partners of the cases and to control women. MAIN OUTCOME MEASURES: Mortality from myocardial infarction in relation to many risk factors, notably oral contraception, as measured by relative risk. RESULTS: After allowing for the confounding effects of medical risk factors and for surgical sterilization, the overall relative risk associated with both current and past use of oral contraceptives was estimated to be 1.9 (95% CI 0.7 to 4.9, and 1.0 to 3.5 respectively). The relative risk associated with current use of preparations containing 50 micrograms of oestrogen, however, was estimated to be 4.2 (0.5 to 39.2). At least some of the relative risk associated with oral contraceptive use is likely to be attributable to the confounding effect of cigarette smoking, but it is impossible to estimate how much from the available data. CONCLUSIONS: If there was an increased risk of fatal myocardial infarction associated with oral contraceptive use in 1986-1988 it is likely to have been less than two-fold; in this study risks were slightly, but not significantly, elevated with both current and previous use. It may be that any increase in risk is associated solely with the older combined preparations containing 50 micrograms of oestrogen.

Adult↗
PubMed1991

Potential clinical use of an adrenergic/cholinergic agent (HP 128) in the treatment of Alzheimer's disease.

A novel compound designated HP 128, which manifests adrenergic and cholinergic properties, was administered for 10 days to patients with Alzheimer's disease in a double-blind, placebo-controlled trial. All patients who entered the trial had previously failed to respond to a structurally related cholinesterase inhibitor without adrenergic properties (HP 029). The primary purpose of the study was to assess the safety and tolerance of HP 128. Efficacy measures were obtained to generate hypotheses for possible future studies. In the dosage range examined, HP 128 was safe and well tolerated. Effects on clinical measures of dementia severity were equivocal.

Aged↗
PubMed1991

Cholinesterase inhibition in the scopolamine model of dementia.

Scopolamine produces a satisfactory model of the attentional and secondary memory deficits seen in Alzheimer's disease (AD) that can be used to screen compounds for potential therapeutic usefulness. Physostigmine, which is known to enhance memory in AD, produced marked and widespread antagonism of the scopolamine-induced impairments, indicating the sensitivity of the model and establishing its relevance for the clinical situation. HP 029, a novel anticholinesterase, also exhibited widespread potency in the model, and in an international trial with patients with AD, it subsequently showed improvement on similar measures, demonstrating the predictive use of the scopolamine model.

Alzheimer Disease↗
PubMed1991

Fournier's gangrene of scrotum in a patient with AIDS.

Fournier's gangrene of the scrotum, a form of necrotising fasciitis, is a rare but potentially fatal disorder. Predisposing conditions include chronic alcoholism and diabetes mellitus, possibly as a result of impaired immunity. Fournier's syndrome, occurring in a patient with AIDS, is described.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Pathophysiology of inner ear fluid imbalance.

Maintenance of homeostasis of inner ear fluids and biochemical integrity of inner ear tissue are essential for proper functioning of the auditory and vestibular end organs. Although various regulatory mechanisms exist in a different portion of the labyrinth, the inner ear is known to respond to systemic challenges. The association of Meniere's syndrome with an imbalance of inner ear fluid homeostasis has been hypothesized for the past century. Among many factors, the effects of hormonal imbalance on inner ear fluid composition and inner ear function have however scarcely been studied. The purpose of this study was to explore the relationship between the autonomic nervous system and inner ear function and possible mechanisms of functional disturbances in an experimental condition. An infusion of supraphysiologic amounts of epinephrine, a stress related hormone, resulted in an elevation of osmolality in serum and perilymph. Furthermore, the infusion of epinephrine resulted in elevation of threshold, prolongation of latency, and depression of amplitude in the compound action potential of the auditory nerve. These findings were most marked at high frequencies. We hypothesized that the epinephrine-induced hearing loss was brought about by an increase in perilymphatic osmolality, as well as by the ionic imbalance caused by the osmotic gradient. Since emotional stress has been implicated as a mechanism of inducing a Meniere's attack, evaluation of the relationship between the autonomic system and cochlear function may contribute to the understanding of possible mechanisms of inner ear dysfunction caused by hormonal imbalances.

Animals↗
PubMed1991

Somatisation disorder in a British teaching hospital.

We describe 33 patients (31 women, 2 men; mean age 47 years) who satisfied research criteria for somatization disorder (SD), a disorder characterised by persistent or recurrent unexplained somatic symptoms beginning before the age of 30. The mean duration of symptoms was 30 years (range 12-57). Twenty patients had co-existing physical disease: seven (21%) had histories of chronic physical disease in childhood, whereas in 13 (39%) the physical disorders began in adult life, after many years of somatic complaints, and were largely coincidental. All had been repeatedly investigated for their symptoms. Twenty-one patients (64%) were receiving medication for spurious physical disorders, most commonly 'angina' and 'asthma'. Hysterectomies had been performed in 16 (52%) of the 31 women at a mean age of 37 years, but pathology was detected in only two. Twenty-nine patients (88%) had received previous treatment for psychiatric illness, and 20 (61%) were receiving invalidity benefits. British psychiatrists do not usually diagnose SD, but focus selectively on symptoms that suggest more familiar psychiatric syndromes. Similarly, medical specialists often diagnose 'functional syndromes' affecting the system that interests them. Over time these patients acquire spurious organic diagnoses and develop physical disorders that make the assessment of new symptoms more difficult. Disability is invariably in excess of what might be predicted from physical findings. We conclude that a diagnosis of SD draws attention to a group of patients who are chronically ill and unresponsive to conventional medical and psychiatric treatment. They use a lot of resources to little avail and thus merit more research.

Adult↗
PubMed1991

Clinical signs, laboratory changes and toxicokinetics of brodifacoum in the horse.

Six horses gavaged with a commercial brodifacoum (BDF)-containing bait (Talone) at a dosage of 0.125 mg of BDF/kg of body weight showed weight loss, severe hypocoagulability and hemogram alterations. Four of the horses became depressed and anorectic; one required vitamin K1 therapy. Increases in clotting times were observed at 24 h in the partial thromboplastin time (PTT) followed by the thrombotest (TBT) and one-stage prothrombin time (PT) at 48 h. Elevated mean PTT, PT and TBT were observed from days 4 to 8 (p less than 0.05) with levels returning to pretreatment levels by day 12. Maximum prolongation was a fourfold increase in PTT (day 4), a 2.5-fold increase in TBT (day 6) and a twofold increase in PT (day 6). Thrombin clotting times remained unchanged. In two horses prolongation in clotting time did not normalize until day 23. The mean hematocrit (0.38 +/- 0.01 L/L) was decreased (p less than 0.05) from day 8 (0.33 +/- 0.02 L/L) to day 14 (0.33 +/- 0.01 L/L). The hemoglobin concentration and erythrocyte numbers were decreased (p less than 0.05) from day 6 (20.1%, 17.6% respectively) to day 14 (22%, 20% respectively). Platelet counts decreased on day 6 (17.2%) to nine (14.6%). No other significant changes were observed in routine hematological and serum biochemical parameters. Peak plasma concentrations of BDF occurred 2 to 3 h after oral administration; two horses had detectable levels of BDF at nine days. Pharmacokinetic evaluation indicated that BDF has a half-life of 1.22 +/- 0.22 days, a body clearance of 1073.1 +/- 53.21 mL/kg/day, a volume of distribution of 1853.7 +/- 26.41 ng-day/mL and closely approximates a one-compartment model in the elimination phase.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Hydroxycoumarins↗
PubMed1991

Patient preferences regarding educational pamphlets in the family practice center.

Educational pamphlets are widely used in family practice offices despite few studies on patient attitudes toward this educational technique. The purpose of this study was to: 1) determine how frequently patients perceive that pamphlets are used and how often they are desired; 2) determine what is usually done with pamphlets; and 3) determine patient preferences regarding requesting pamphlets, location of unsolicited pamphlets, techniques of getting pamphlets, and style of pamphlets. In this survey of 360 patients, 90% reported wanting a pamphlet at some or all of their office visits. Overall, 67% reported reading or looking through and saving pamphlets received, 30% read or looked through them and then threw them away, and only 2% threw them away without review. Only 11% of males and 26% of females reported ever asking a doctor for pamphlets. Some conclusions are that: 1) more patients desire pamphlets than are receiving them; 2) most patients do save pamphlets; and 3) patients need encouragement and permission to ask for pamphlets.

Adolescent↗
PubMed1990

Effects of propylene glycol-containing diets on acetaminophen-induced methemoglobinemia in cats.

Soft-moist cat foods contain 7 to 13% propylene glycol (PG) on a dry-weight basis. These diets induce Heinz body formation in feline RBC. In this study, we evaluated cats on a control diet and on a commercial diet containing 8.3% PG. All cats on the PG diet developed an increase in the number of circulating Heinz bodies. We then administered acetaminophen to cats on each diet to determine whether RBC from cats on PG diets were more susceptible to oxidant stress. Methemoglobin concentrations were significantly greater in cats in PG diets after acetaminophen administration. These data indicate that RBC from cats fed PG diets are more susceptible to oxidative stress.

Acetaminophen↗
PubMed1990

Decreased level of T cell receptor expression by Down syndrome (trisomy 21) thymocytes.

Individuals with Down syndrome (DS) have an enhanced susceptibility to viral and bacterial infections. Previous studies by our laboratory demonstrated alterations in the proportions of peripheral T cell subpopulations and decreased proliferative, interleukin-2, and antibody responses to viral and bacterial antigens in DS. These data suggested that DS lymphocytes have a diminished ability to recognize and respond to specific antigen. It has been proposed that the abnormalities in T cell function in DS may be a result of aberrant T cell maturation within the DS thymus. Therefore, we examined by immunofluorescence and flow cytometry the cell surface expression of the alpha,beta chains of the T cell receptor (TCR alpha,beta) and the associated CD3 molecule on thymocytes from 10 DS and 27 control children. A significantly smaller proportion of cells expressing high levels of TCR alpha,beta was observed in DS thymuses compared to controls (17.0% vs. 34.3%, respectively; P less than 0.01). A similar observation was made for CD3, a molecule responsible for signal transduction through the TCR, where a lower proportion of cells expressing high levels of CD3 was found in DS compared to controls (18.4% vs. 43.3%, respectively; P less than 0.001). These data are evidence for aberrant T cell maturation in DS. In addition, our findings of decreased acquisition of high levels of the molecules which are critical for antigen-specific recognition by T cells suggest a possible mechanism for the decreased T cell function found in individuals with DS.

Antigens, CD↗