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Biomedical subjects

F M Cowan

Publications and source records attributed to F M Cowan.

At least 73 records · Page 4Linked to original sources

Detection of propan-1,2-diol in neonatal brain by in vivo proton magnetic resonance spectroscopy.

Cerebral in vivo proton magnetic resonance spectroscopy of 13 newborn infants displaying seizures and receiving phenobarbitone, in one case supplemented by phenytoin, showed signals from propan-1,2-diol (the injection vehicle for both these anticonvulsants). Subsequent in vitro spectroscopy of cerebro spinal fluid (CSF) from one of these infants also showed signals from this substance. The estimated in vivo propan-1,2-diol concentration (approximately 3 mM) was less than that measured in the CSF sample (14.4 mM). These observations suggest that propan-1,2-diol may accumulate in cerebral tissue and misidentification of its signals in both in vivo and in vitro proton spectra may confuse diagnoses of metabolic or other disorders.

Brain Chemistry↗

The role of immunoglobulin binding factors in the pathogenesis and therapy of AIDS.

The human immunodeficiency virus (HIV) gp120 and gp41 envelope proteins and Staphylococcus aureus protein A (SPA) all have Fc receptor (FcR)-like immunoglobulin binding factor (IBF) activity for the Fc constant fragments of human immunoglobulin G (IgG). Viral IBF may contribute to the pathology of HIV by jamming the network of FcR signals that control FcR-dependent immunity. Conversely, the bacterial IBF SPA has anti-retroviral activity that may involve antagonism of the immunopathological action of viral IBF, strongly suggesting IBF may act as a double-edged sword that might be turned against viral invaders.

Acquired Immunodeficiency Syndrome↗

Early detection of cerebral infarction and hypoxic ischemic encephalopathy in neonates using diffusion-weighted magnetic resonance imaging.

Twelve newborn infants with clinical evidence of hypoxic ischemic brain injury had conventional and diffusion-weighted magnetic resonance imaging (MRI) performed one to six (median two) days and 7-42 days after birth. The extent and conspicuity of the early abnormalities was greater with diffusion-weighted than with conventional imaging in each of the four infants with neonatal infarction and in four of the infants with Grades II or III hypoxic ischemic encephalopathy (HIE). No abnormality was seen with either technique in the other four infants who had Grades I or II HIE. Diffusion weighted MRI may be important for the early diagnosis and grading of infants with hypoxic ischemic brain injury.

Asphyxia Neonatorum↗

Survey of undergraduate teaching in genitourinary medicine in Britain.

OBJECTIVE: To determine whether the time allocated for undergraduate teaching of genitourinary medicine has changed since 1984 and to determine the impact of HIV/AIDS on the teaching of the specialty. METHODS: A self completion questionnaire was sent to the consultant in charge of each department of genitourinary medicine attached to a UK medical school. RESULTS: Replies were received from all twenty seven medical schools. Most schools (24/27) offer a course of lectures accompanied by clinical teaching; however, one medical school does not include teaching of genitourinary medicine in the undergraduate curriculum at all and two others are unable to offer all students clinical tuition. The mean time devoted to lectures is 6.7 hours (range 0-15 hours) made up of 4.8 hours of genitourinary medicine lectures and 1.9 hours of lectures on HIV/AIDS. The mean time allocated for clinic-based teaching of each student is 9.2 hours (range 0-27 hours). On average the time allocated for lecturing and clinical teaching of the speciality has decreased since 1984 although there is considerable variation between schools (time for clinical teaching and lecturing combined ranges from 0-41.0 hours). CONCLUSIONS: The findings of this survey suggest there is considerable variation in both the quantity and quality of undergraduate teaching of genitourinary medicine provided throughout the UK.

Acquired Immunodeficiency Syndrome↗

MRI diffusion-weighted imaging of the brain: contributions to image contrast from CSF signal reduction, use of a long echo time and diffusion effects.

The contributions of CSF signal reduction, use of a long echo time and diffusion weighting to the appearance of pulsed gradient spin echo (PGSE) images are analysed by reference to T2-weighted spin echo and T2-weighted fluid attenuated inversion recovery (FLAIR) pulse sequences. Both PGSE and T2-weighted FLAIR sequences reduce CSF signal and produce very heavy T2 weighting allowing the specific additional contribution produced by the diffusion weighting of PGSE sequences to be recognized. Considerable advantage accrues from CSF suppression with both PGSE and FLAIR sequences through reduction in partial volume effects and artefacts. The very heavy T2 weighting with both these pulse sequences highlights certain white matter tracts and provides high sensitivity to disease. The additional diffusion weighting with PGSE sequences can enhance or reduce white matter tract signals and may enhance or reduce lesion conspicuity relative to the FLAIR sequences. Many of the benefits attributed to the diffusion-weighted PGSE sequence may result from the reduction of the CSF signal and the heavy T2 weighting of the sequence without a contribution from diffusion effects. However, additional anatomical detail, sensitivity to myelination and increased lesion conspicuity may result from the diffusion weighting.

Brain↗

MRI: early onset of changes in Wallerian degeneration.

T2-weighted spin echo scans were performed on a neonate and two adults aged 42 and 60 years within 2 weeks of the onset of infarction in the frontoparietal region of the brain. Areas of increased signal intensity were observed in the anterior and posterior limbs of the internal capsule in the infant and in the posterior limbs of the internal capsules in the adults. Although these signal changes were typical of the chronic phase of Wallerian degeneration, their onset was much earlier than the 10-14 weeks previously described for this stage in adults. The low level of myelination of white matter tracts at birth, and the relatively sparse myelination of the parietopontine tract may account for the rapid onset of changes in these patients which more closely follows the time course described pathologically for Wallerian degeneration in unmyelinated fibres.

Adult↗

HIV testing and assessment of risk of other sexually transmitted diseases.

The risk factors for infection with the human immunodeficiency virus (HIV) were assessed in individuals attending two different HIV antibody testing clinics: Genitourinary Medicine (GUM) and an HIV counselling and screening clinic (CSC) The risk of acquiring other sexually transmissible infections (STD) was also assessed, and all patients were offered STD screening. Fewer STDs were found in CSC patients than in GUM patients, but the results highlight the need to be aware of the possibility of other STDs whenever and wherever HIV antibody testing is undertaken.

Adolescent↗

Athetoid cerebral palsy with cysts in the putamen after hypoxic-ischaemic encephalopathy.

Three cases of athetoid cerebral palsy after hypoxic-ischaemic encephalopathy (HIE) are reported. All three neonates had haemorrhagic lesions in the basal ganglia and thalami on magnetic resonance imaging (MRI). Prior cranial ultrasound had detected the lesions in only two cases. In all three children athetoid movements began within the first year of life. Follow up MRI scans showed bilateral symmetrical cystic lesions in the posterior putamen. Although haemorrhagic lesions within the basal ganglia are a common MRI finding in neonates with HIE, few of these babies develop athetoid cerebral palsy. We believe this to be the first report of discrete cystic lesions found in the basal ganglia of children with athetoid cerebral palsy.

Basal Ganglia Diseases↗

Effect of sulfur exposure on protease activity in human peripheral blood lymphocytes.

Sulfur mustard is a chemical warfare blistering agent for which neither the mechanism of action nor an antidote is known. Papirmeister et al. (1985) have postulated a biochemical hypothesis for mustard-induced cutaneous injury involving a sequelae of DNA alkylation, metabolic disruption and activation of protease. Human peripheral blood lymphocytes in cell cultures were employed as an in vitro model for alkylating agent toxicity. A chromogenic peptide substrate assay was used for detection of protease in lymphocytes treated with sulfur mustard or chloroethyl ethyl sulfide. Exposure of human peripheral blood lymphocytes from normal donors to these alkylating agents resulted in an increase in cell associated protease activity. This increase in protease activity may contribute to the pathology or act as an indicator to predict methods of therapeutic intervention for sulfur mustard toxicity.

Alkylating Agents↗

Dissociation between the secretion and renal action of endogenous atrial natriuretic peptide in the syndrome of inappropriate antidiuresis.

A patient is described with the syndrome of inappropriate antidiuresis (SIAD) and renal sodium retention secondary to a lymphoma. The basal atrial natriuretic peptide (ANP) level and the ANP response to volume expansion were normal (age adjusted) but the natriuretic effect of ANP was attenuated by an unidentified factor. The case emphasizes the dominance of circulating volume over plasma tonicity in the regulation of ANP secretion.

Aged↗

Use of zidovudine for drug misusers infected with human immunodeficiency virus.

The use of zidovudine in drug misusers, especially current drug misusers, has not been extensively studied. Since periods of abstinence may be interspersed with drug misuse, it is necessary to establish the safety of zidovudine in injection drug misuse-related human immunodeficiency virus (HIV) infection under a variety of conditions. HIV serology became available in October 1985 and we have now examined medically 289 HIV seropositive patients, 85% of whom acquired their infection via injection drug misuse. Since March 1987 we have treated 40 individuals with zidovudine, 25 of whom were former or current injection drug misusers and one who was a heterosexual contact of a drug misuser. Eighteen patients were taking various types of opiates. Six of this latter group injected either occasionally or regularly whilst taking zidovudine. There were no adverse clinical events associated with zidovudine treatment and continued opiate drug misuse whether by mouth or by injection. Although defaults from clinic visits were a problem, these defaults were not associated with any particular form of drug misuse. Compliance with zidovudine therapy as judged by change in the mean corpuscular volume was no different for the various risk groups. In our experience it is possible to treat safely current and former drug misusers with zidovudine.

Acquired Immunodeficiency Syndrome↗

Cranial blood flow and blood pressure changes during sleep in the human neonate.

The purpose of this study was to evaluate the relation between cranial blood flow (CBF) and arterial blood pressure (BP) in the human newborn. In 29 healthy term neonates simultaneous measurements of CBF using jugular venous occlusion plethysmography and BP using the neonatal Dinamap 847 were performed during active sleep (AS) and quiet sleep (QS) at least 1 h from th end of the last feed. In AS as compared to QS there was significant rise in CBF (P less than 0.001), mean arterial (P less than 0.001), systolic (P less than 0.001), diastolic (P less than 0.005) and pulse pressure (P less than 0.027). There was a significant correlation between change in the mean arterial pressure (MAP) and change in CBF (r=0.37, P less than 0.05). No correlation, however, was found between changes in CBF and changes in systolic, diastolic or pulse pressures.

Blood Pressure↗

Inhibition of rat adenocarcinoma metastases by "Staphylococcus aureus" protein A.

Fischer F 344/CRBL female rats were injected intravenously with 10(6) syngeneic 13,762 adenocarcinoma cells, and daily doses of either 10 micrograms, 100 micrograms or 1 mg Staphylococcus aureus protein A were administered intraperitoneally on days 1 through 11. The animals were sacrificed on day 12, their lungs infused with Bouin's solution, and lung metastases counted. A significant reduction in the number of visible metastatic nodules was observed in the animals given 100 micrograms and 1 mg of Staphylococcus aureus protein A daily.

Adenocarcinoma↗

Fc receptor mediated immune regulation and gene expression.

Exogenous Fc receptors (FcR) have been demonstrated to either augment or inhibit endogenous FcR mediated immunity, immune regulation and gene expression. Other immune regulatory or modulator molecules, such as the H2 histocompatibility antigens, interferon, transfer factor and leukocyte chalones might involve association with or alter the synthesis or status of FcR, thus effecting regulation of immunity and/or gene expression. FcR provide a unique opportunity for eliciting the mechanisms and perhaps altering the immunity and/or gene expression which influence immune regulation, cellular differentiation, viral replication and malignant transformation.

Animals↗

Neutralization of immune complex inhibition of antibody dependent cellular cytotoxicity in vitro by Staphylococcus-aureus protein A.

Staphylococcus-aureus protein A (SPA) incubated with sera containing immune complexes and effector cells increases antibody dependent cellular cytotoxicity (ADCC)and rosette formation. The enhanced ADCC and rosetting is due to SPA functioning as an IgG Fc cellular receptor. SPA binds to the Fc portion of Igg and has much greater affinity for immune complexes than free IgG. SPA bound immune complexes are blocked from attaching to the Fc cellular receptors via a competitive inhibition which neutralizes the inhibitory effect of these complexes on ADCC and rosette formation.

Animals↗

Augmentation and inhibition of delayed hypersensitivity by Staphylococcus aureus protein A.

The injection of Staphylococcus-aureus protein A into mice, previously exposed to an antigen (sheep red blood cells), is capable of augmenting or inhibiting a primary delayed hypersensitivity (DH) response. SPA enhances DH response to SRBC when given with a greater than optimal sensitizing dose of the antigen. At antigen doses optimal for eliciting DH to SRBC, SPA inhibited DH. A proposed mechanism for the action of Staphylococcus-aureus protein A is based upon the ability of the protein to function as a Fc cellular receptor, thus neutralizing the effect of antigen-antibody immune complexes on DH. The binding of protein A to the Fc portion of antigen-antibody immune complexes effectively prevents subsequent binding of these complexes to Fc cellular receptors, thus eliminating their participation as co-factors in inter-cellular immunological communication. The ability of protein A to both augment and inhibit DH suggests a role for relative concentrations of serum factors and/or cellular receptors in the regulation of a primary DH response.

Animals↗