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Biomedical subjects

M Thomson

Publications and source records attributed to M Thomson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Geographical perspectives on bednet use and malaria transmission in The Gambia, West Africa.

Insecticide-impregnated bednets are now widely accepted as an important tool in reducing malaria-related deaths in children in Africa. Defining the circumstances in which net treatment programmes are likely to be effective is essential to a rational development of this control strategy. In The Gambia a National Impregnated Bednet Programme was introduced into the primary health care system in 1992. Prior to its introduction baseline epidemiological and entomological studies were conducted throughout the country. These studies showed that in areas where mosquito biting nuisance was high, people protected themselves with bednets and that where mosquito densities (and therefore bednet usage) was low malaria prevalence rates were relatively high. Since the national programme is designed to assist only those people who already own a bednet (by providing the insecticide) an understanding of the factors which determine bednet ownership is needed to help evaluate the programme's effectiveness and provide guidelines for increasing bednet usage. Village scale bednet usage rates and malaria prevalence rates obtained from the baseline survey were correlated with certain geographical variables: dominant ethnic group, area, habitat, distance from the River Gambia and distance from the 'bluffline' (the interface between the sandstone soils and alluvial soils which border the river system). In a multiple regression analysis, bednet usage was independently associated with area (P < 0.001), ethnic group (P = 0.010), habitat (P = 0.006) and distance from the river (P = 0.013). A negative association of bednet usage with malaria prevalence persisted after allowing for the other variables. Malaria prevalence was not independently associated with area, ethnic group, habitat or distance from the river. Our analysis showed that the impregnated bednet programme is likely to be most effective in villages which are sited near to or on the alluvial soils in the middle and lower river zones. These villages, which were originally settled for easy access to the river (for transport) and its swampy margins (for rice production) are within the flight distance of mosquitoes that have their breeding sites on the poorly drained alluvial soils. Variation in malaria prevalence rates (after bednet usage has been taken into account) may be related to factors such as poverty and access to health care, and/or to localized differences in the ecology of The Gambia, which determine the duration and intensity of transmission. If the National Bednet Programme is to be effective throughout The Gambia it is vital to develop promotional activities which will encourage bednet usage in areas where nuisance biting by mosquitoes is low.

Animals↗
PubMed1996

Histopathological effects of garlic on liver and lung of rats.

The comparative toxic effects of oral and intraperitoneal administration of garlic extracts on lung and liver tissue of rats were studied. Administration of low doses of garlic (50 mg/kg) to rats either orally or intraperitoneally had little effect on lung and liver tissues as compared to control animals. In contrast, administration of high doses of garlic (500 mg/kg) resulted in profound changes in lung and liver tissues of rats. Intraperitoneal administration of the high dose of garlic was more damaging to lung and liver tissue of rats than oral administration.

Administration, Oral↗
PubMed1996

An evaluation of garlic and onion as antithrombotic agents.

Garlic (Allium sativum) and onion (Allium cepa) have been evaluated as possible antithrombotic agents. Rats were given aqueous extracts of garlic and onion, orally or intraperitoneally, daily for a period of 4 weeks after which the rats were sacrificed. The blood was collected from the heart without anticoagulant and the serum was prepared. The level of thromboxane B2 (TXB2) in the serum was measured by radioimmunoassay. TXB2 levels in serum of rats treated with the low dose of aqueous extract of garlic (50 mg/kg) was significantly inhibited regardless of the mode of administration (orally or intraperitoneally). At the high dose of garlic and onion (500 mg/kg), a further decrease of TXB2 levels in the serum of the rats was observed. Boiled garlic and onion at high concentration (500 mg/ kg) had very little effect on TXB2 synthesis. This shows that garlic and onion should be consumed in a raw rather than cooked form in order to achieve a beneficial effect. Boiling of these plants may cause the decomposition of the potential antithrombotic ingredient present in these herbs. Garlic was found to be more potent than onion in lowering the TXB2 levels. A high dose of garlic and onion produces toxicity in the rats (unpublished observation). These results show that garlic and onion can be taken frequently in low doses without any side effects, and can still produce a significant antithrombotic effect.

Allium↗
PubMed1996

A locus for bipolar affective disorder on chromosome 4p.

The main clinical feature of bipolar affective disorder is a change of mood to depression or elation. Unipolar disorder, also termed major depressive disorder, describes the occurrence of depression alone without episodes of elevated mood. Little is understood about the underlying causes of these common and severe illnesses which have estimated lifetime prevalences in the region of 0.8% for bipolar and 6% for unipolar disorder. Strong support for a genetic aetiology is found in the familial nature of the condition, the increased concordance of monozygotic over dizygotic twins and adoption studies showing increased rates of illness in children of affected parents. However, linkage studies have met with mixed success. An initial report of linkage on the short arm of chromosome 11 (ref. 4) was revised and remains unreplicated. Reports proposing cosegregation of genes found on the X chromosome with bipolar illness have not been supported by others. More recently bipolar disorder has been reported to be linked with markers on chromosomes 18, 21, 16 and a region on the X chromosome different from those previously suggested. We have carried out a linkage study in twelve bipolar families. In a single family a genome search employing 193 markers indicated linkage on chromosome 4p where the marker D4S394 generated a two-point lod score of 4.1 under a dominant model of inheritance. Three point analyses with neighbouring markers gave a maximum lod score of 4.8. Eleven other bipolar families were typed using D4S394 and in all families combined there was evidence of linkage with heterogeneity with a maximum two-point lod score of 4.1 (theta = 0, alpha = 0.35).

Bipolar Disorder↗
PubMed1996

Relationship of cues to assessed infant pain level.

Cues that 46 pediatric nurses with a BS in Nursing reported as key to their pain assessments of 88 videotaped infants, ages 0 to 12 months, are identified. Frequencies with which these cues were used for infants of different ages and the relationships between key cues and assessed levels of pain are described. Greater pain was strongly associated with tears, stiff posture, guarding, and fisting. Greater pain was moderately associated with inadequate type or dosage of analgesia, more recent surgery, inconsolability, difficult to distract, does not focus on surroundings, frown, grimace, wrinkled face, flushed face, pain cry, and increased arousal in response to touch of sore area. Internurse variability in cue use was sizable. Most of the often-used cues had weak or no association with assessed pain level. Only consolability, pain cry, grimace, and stiff posture were frequently used and correlated > .51 with assessed level of pain.

Clinical Nursing Research↗
PubMed1996

Epidural analgesia in Scotland: a survey of extradural opioid practice.

A postal survey of all Consultant Anaesthetists working within Scotland was conducted to establish the current state of epidural analgesia and the level of post-operative care for patients after epidural opioid administration. Of those consultants using epidurals for post-operative analgesia, 89% use extradural opioids, and the lipid soluble opioids diamorphine and fentanyl by an infusion technique were the most popular. For analgesia in labour the use of extradural opioids drops to 41% with fentanyl by bolus the commonest drug and method of administration. Monitoring requirements after extradural opioids are variable with more than half of consultants satisfied with intermittent observational measurements. Sixty-nine per cent of consultants frequently send their patients to a high dependency unit following epidural opioid administration. Additional administration of opioids on an ordinary ward setting is considered inappropriate by over half of the consultants replying. There is considerable variability amongst anaesthetists as to how patients receiving epidural opioids should be monitored and National Recommendations are required to stop the present confusion.

Analgesia, Epidural↗
PubMed1995

Skeletal abnormalities in Rett syndrome: increasing evidence for dysmorphogenetic defects.

The presence of metatarsal and metacarpal abnormalities in some individuals has raised the possibility that Rett syndrome is, in fact, a multiple congenital abnormalities/mental retardation (MCA/MR) syndrome. We have conducted radiological examination of 17 cases of Rett syndrome in Western Australia. Short fourth and/or fifth metatarsals were identified in 65% of cases and short fourth and/or fifth metacarpals in 57%. Metatarsal (P = 0.045) and metacarpal (P = 0.006) shortness were significantly more common in girls 14 years or older. Negative ulnar variance (found in 79% of cases) appeared to be independent of age. Reduced bone density in the hands was found in 86% of cases. A nationwide study using the Australian Rett Syndrome Database is planned to follow up these findings and compare them with findings from a control group. The confirmation of these abnormalities in a high proportion of cases may provide morphologic markers to assist in the diagnosis of Rett syndrome and perhaps provide a further avenue of research into the pathogenesis of this disorder.

Abnormalities, Multiple↗
PubMed1995

GTP-binding proteins in adrenocortical mitochondria.

We have identified two GTP-binding proteins in mitochondria from bovine adrenal cortex (fasciculata). Sub-mitochondrial particles were fractionated into inner membrane, contact point and outer membrane vesicles on sucrose density gradients. These sub-mitochondrial fractions were identified by the presence of enzyme markers and electron microscopy. Photoaffinity labelling with [gamma-32P]GTP identified a 45 kDa GTP-binding protein in outer mitochondrial membranes and a 19 kDa protein in the contact points. The molecular weight of 45 kDa and requirement for Mg2+ ions raise the possibility that this protein is an alpha subunit of a heterotrimeric GTP-binding protein or a novel GTP-binding protein. The specificity of nucleotide binding, the requirement for low concentrations of Mg2+ (0.1 mM) and molecular weight of 19 kDa suggest that this protein is a typical member of the so-called small GTP-binding protein family. The location of 45 kDa in the outer membrane and that of 19 kDa in the contact points suggest roles for these proteins in the interaction with the extramitochondrial environment and in the regulation of mitochondrial membranes, respectively.

Adrenal Cortex↗
PubMed1995

Consumption of a garlic clove a day could be beneficial in preventing thrombosis.

The effect of the consumption of a fresh clove of garlic on platelet thromboxane production was examined. A group of male volunteers in the age range 40-50 years participated in the study. Each volunteer consumed one clove (approximately 3 g) of fresh garlic daily for a period of 16 weeks. Each participant served as his own control. Thromboxane B2 (TXB2, a stable metabolite of thromboxane A2), cholesterol and glucose were determined in serum obtained after blood clotting. After 26 weeks of garlic consumption, there was an approximately 20% reduction of serum cholesterol and about 80% reduction in serum thromboxane. No change in the level of serum glucose was observed. Thus, it appears that small amounts of fresh garlic consumed over a long period of time may be beneficial in the prevention of thrombosis.

Adult↗
PubMed1995

An autoregulated dual-function antitat gene for human immunodeficiency virus type 1 gene therapy.

One approach to gene therapy for AIDS is to block the replication of human immunodeficiency virus type 1 (HIV-1) by inhibiting that tat gene, whose product activates the expression of all HIV-1 genes. To accomplish this, we constructed an antitat gene expressing an RNA with dual (polymeric TAR and antisense-tat) function in an attempt to both sequester Tat protein and block its translation from mRNA. A minigene consisting of the antitat gene driven by the HIV-1 long terminal repeat was inserted into a double-copy retrovirus vector, such that antitat expression would be upregulated only in HIV-1-infected cells. After transduction of a T-lymphocytic cell line (Molt-3) the antitat gene inhibited HIV-1 replication. This inhibition was inversely correlated with the virus infections dose. Virus replication was also inhibited for 5 months in two different T-cell lines after they had been infected at a high multiplicity of infection, suggesting that the antitat gene may be effective over long periods. Importantly, antitat blocked the replication and the cytopathic effect of HIV-1 in human peripheral blood mononuclear cells and led to as much as 4,000-fold inhibition of the replication of an HIV-1 field isolate as well as HIV-1 prototypes maintained in culture. These results suggest that antitat gene therapy has potential use for blocking HIV-1 replication in infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Prescribing benzodiazepines for noninstitutionalized elderly.

OBJECTIVE: To describe benzodiazepine prescribing for elderly people living in the community in British Columbia, and to compare such prescribing with an indicator of current guidelines. DESIGN: Descriptive analysis of pharmacy billing data. SETTING: Province of British Columbia. PARTICIPANTS: All elderly persons (age 65 and older) dispensed benzodiazepines by community pharmacies in British Columbia during 1990. MAIN OUTCOME MEASURE: Potentially inappropriate prescriptions were defined by a maximum 2-month limit of 20 diazepam equivalents daily, as determined by the BC Drug Usage Review Program in consultation with experts in the field. Physicians' rates of potentially inappropriate prescribing were determined per 100 benzodiazepine prescriptions written. RESULTS: Almost 24% of elderly people in British Columbia were prescribed benzodiazepines at least once during 1990. Of these, 17.1% were given potentially inappropriate prescriptions. Physicians who prescribed benzodiazepines most frequently had the highest rates of potentially inappropriate prescriptions. CONCLUSION: Prescribing practice does not correspond with our indicator of current guidelines.

Age Factors↗
PubMed1994

Efflux of RNA from resealed nuclear envelope ghosts.

mRNA translocation across the nuclear envelope and the appropriate signal-receptor interactions have been studied using resealed rat liver nuclear envelope ghosts (RNEG). We compared export kinetics of nonadenylated (tRNAs, histone-2 poly(A)- mRNA), and adenylated RNAs (poly(A)+ tRNAs, synthetic histone-2 poly(A) +mRNA, albumin mRNA, beta-globin poly(A) +mRNA and a total poly(A) + mRNA extract from rat liver cells). ATP-dependent export of mRNAs and of total poly(A)+ RNA was prevented by inhibitors of a nuclear envelope NTPase. All adenylated RNA species competed with each other for export, but nonadenylated RNAs did not. This indicates the existence of different translocation mechanisms for different RNA species with their appropriate nuclear envelope associated RNA receptors involved in export. The attachment of a poly(A)250 sequence at the 3'-end of tRNA or histone messenger masks the intrinsic RNA export signal of nonadenylated RNAs and results in efflux comparable to that of beta-globin poly(A)+ mRNA. The attachment on oligo(A)5 does not have any comparable effect of nonadenylated RNA translocation. Export of all polyadenylated RNAs from RNEGs is blocked by a monoclonal antibody, which is directed against an intranuclear envelope poly(A) binding protein. The results suggest that the pore complexes do not select RNAs for export to the cytoplasm and are therefore not responsible for nuclear restriction of mRNA precursors.

Adenosine Triphosphate↗
PubMed1994

A Rev-inducible mutant gag gene stably transferred into T lymphocytes: an approach to gene therapy against human immunodeficiency virus type 1 infection.

One strategy for somatic gene therapy for human immunodeficiency virus type 1 (HIV-1) infection is based on the regulated expression of dominant negative mutants of the HIV-1 gag gene. To limit expression of the mutant Gag polypeptide to HIV-1-infected cells, we have constructed a replication-defective retroviral vector that contains a Rev-responsive element. By using this construct we have obviated problems that can be associated with constitutive expression of an exogenous gene, an important step toward developing a human therapy. In uncloned T lymphocytes infected (transduced) with this retroviral construct, HIV-1 replication was inhibited by 94% with a concomitant decrease in the cytopathic effects of the virus. In addition, simian immunodeficiency virus (SIV) replication was also shown to be significantly inhibited, suggesting that this mutant Gag protein may have antiviral efficacy against a broad range of primate lentiviruses and that an SIV/macaque model can be used for further in vivo studies. These results have important implications in assessing the potential of somatic gene therapy in the treatment of HIV-1 infection.

Amino Acid Sequence↗
PubMed1994

Common sequence elements in structurally unrelated genomes of defective interfering Semliki Forest virus.

The polymerase chain reaction was used to amplify defective interfering (DI) Semliki Forest virus (SFV) genomes from tissue culture preparations which had in vitro interfering and in vivo mouse-protecting activity. The products were molecularly cloned and sequenced (pSFVDI-6, 2146 nt and pSFVDI-19, 1244 nt). Comparison with the sequence of the SFV genome showed that both were derived from three noncontiguous regions: the 5' terminus including the start of the nsP1 coding region, part of the nsP2 coding region, and the 3' untranslated region. Both clones possessed open reading frames, including one with the potential of encoding truncated versions of nsP1. Transcribed RNAs from pSFVDI-6 and pSFVDI-19 were translated in an in vitro system in polypeptides of M(r) 27,000 and 25,000, respectively. Although pSFVDI-6 and pSFVDI-19 did not possess the rearranged sequences or extensive repeat regions of previously cloned DI SFV genomes (Lehtovaara et al., Proc. Natl. Acad. Sci. USA 78, 5353-5357, 1981; Lehtovaara et al., J. Mol. Biol. 156, 731-748, 1982), they were derived from similar regions of the SFV genome, suggesting a common sequence requirement for DI SFV particles.

Animals↗
PubMed1994

Endocytosis, partial degradation and release of heparan sulfate by elicited mouse peritoneal macrophages.

Interactions between glycosaminoglycans (GAGs) and low density lipoprotein (LDL) are thought to influence the progression of atherogenesis. In an effort to gauge whether macrophages mediate GAG-LDL interaction by GAG modification, we have investigated the endocytosis, degradation and retro-endocytosis of the GAG heparan sulfate (HS) by mouse peritoneal macrophages. Radiolabelled HS was produced by derivatization with sulfosuccinimidyl-3-(4-hydroxyphenyl) propionate and radio-iodination by the chloramine T method. The amount of 125I-HS internalized by cultures of thioglycollate-elicited macrophages rose over a 24 h time period in proportion to the amount of tracer added to the wells (2-2500 ng ml-1). Analysis of GAG molecular weight was performed using gel filtration chromatography and polyacrylamide gel electrophoresis. After a 24 h pulse period, the 125I-HS in the intracellular fraction of the cultured cells was of smaller molecular weight than for control material. During a 24 h cold chase, fragments of 125I-HS were released into the medium. These fragments had lower affinity for Polybrene-Sepharose but did not appear significantly N-desulfated as determined by low pH nitrous acid treatment. The NADPH oxidase inhibitor diphenylene iodonium, although minimizing basal and phorbol ester-triggered radical output, did not inhibit 125I-HS depolymerization. These data indicate that elicited macrophages can interact with and reduce the polymer length of HS without extensively desulfating the molecule. They are consistent with a mechanism by which the macrophage internalizes and partially degrades HS by endoglucuronidase activity rather than NADPH oxidase-generated free radicals, followed by release of the products into the extracellular milieu.

Animals↗
PubMed1994

After Re S.

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Cesarean Section↗
PubMed1994

The influence of nasal obstruction and its relief on oxygen saturation during sleep and the early postoperative period.

Nasal obstruction causes abnormal breathing patterns during sleep which often result in hypoxaemia. We studied the effect of nasal obstruction on arterial oxygen saturation in 20 healthy patients undergoing elective surgery which required bilateral nasal packing. Ten patients were subject to complete nasal obstruction while the remaining half had the obstruction relieved by the insertion of nasal cannulae. We found that nasal obstruction did not have any detrimental effect on the already low incidence of oxygen desaturation. There was no effect of the cannulae on the degree or frequency of hypoxaemia, although they did appear to improve the quality of sleep during the first postoperative night. They were more comfortable by day than simple packing alone and no adverse effects were observed.

Adolescent↗