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Biomedical subjects

R J Wilson

Publications and source records attributed to R J Wilson.

At least 73 records · Page 4Linked to original sources

Pre-emptive analgesia from intravenous administration of opioids. No effect with alfentanil.

Forty patients undergoing total abdominal hysterectomy were randomly allocated to receive either 40 micrograms.kg-1 of alfentanil on induction of anaesthesia or 40 micrograms.kg-1 of alfentanil after the skin incision. Postoperative pain relief was provided with morphine from a patient-controlled analgesia system. The amount of morphine consumed in the operating theatre, while in recovery and for the first 24 h postoperatively was recorded. Pain scores were assessed at 24 h using a visual analogue scale. There were no differences found between the two groups for morphine consumption but the 'pre-emptive' group had significantly higher pain scores at rest. We conclude that there is no clinically useful pre-emptive analgesic effect with this dose of alfentanil and that therefore systemic opioid premedication is unlikely to decrease postoperative analgesic requirements through the mechanism of pre-emptive analgesia.

Adult↗

Incidence rates of leprosy in Karonga District, northern Malawi: patterns by age, sex, BCG status and classification.

This paper describes incidence rates by age, sex, prior BCG status and classification in Karonga District, northern Malawi. New cases (489) were identified among 83,500 individuals followed for an average of 5 years (1.12 cases per 1000 person years). Only 29 (6%) of the incident cases were multibacillary. Incidence rates generally were higher among females than males, and increased steadily with age. Although the highest incidence rates of disease were recorded among young adults without BCG scars (males 15-19; females 20-24), these peaks were less dramatic than those reported among young adults in The Philippines and Norway. In the absence of historical data and data on infection status, it is not possible to assess to what extent these peaks may reflect either greater exposure or greater susceptibility to disease among adolescents or young adults. The incidence rates of leprosy among individuals with a prior recorded BCG scar were approximately half those of individuals lacking a scar, at all ages. Since BCG had been introduced into this population only during the 1970s, this provides strong evidence for the effectiveness of BCG when given to adults. It was estimated that past vaccination of approximately 40% of the district population had reduced the overall incidence rate of leprosy by 18%, and that this impact would increase with aging of the vaccinated cohorts. A retrospective examination of the detailed records of initial examinations revealed that 62 (13%) of the incidence cases were recorded as having skin hypopigmentation or blemishes, at the site of subsequent confirmed leprosy lesions, several months or years before they were suspected of having leprosy. The nonspecificity of these lesions, some of which were probably attributable to Mycobacterium leprae infection, highlights the difficulty of diagnosing leprosy in its earliest forms.

Adolescent↗

Sequence and organization of large subunit rRNA genes from the extrachromosomal 35 kb circular DNA of the malaria parasite Plasmodium falciparum.

The malaria parasite Plasmodium falciparum carries an extrachromosomal 35 kb circular DNA molecule of unknown provenance. A striking feature of the circle is a palindromic sequence of genes for subunit rRNAs and several tRNAs, spanning ca. 10.5 kb. The palindrome has an intriguing resemblance to the inverted repeat of plastid genomes, and the sequence and putative secondary structure of the malarial large subunit (LSU) rRNA described in this report were used as the basis of a phylogenetic study. The malarial rRNA was found to be highly divergent in comparison with a selected group of chloroplast LSU rRNAs but was more closely related to them than to mitochondrial LSU rRNA genes.

Animals↗

Actin in the merozoite of the malaria parasite, Plasmodium falciparum.

Merozoites of the human malaria parasite, Plasmodium falciparum, when treated with cytochalasin B, will attach irreversibly to red cells with formation of a vestigial internal (parasitophorous) vacuole, but they are inhibited from moving into the cell. The existence of an actin-based motile mechanism is implied. Immunoblotting, peptide mapping and the DNase inhibition assay have been used to show that the merozoite contains actin. It makes up an estimated 0.3% of the total parasite protein and is partitioned in the ratio of about 1:2 between the cytosolic and particulate protein fractions. In the former it is unpolymerised and in the latter filamentous. Most of the anti-actin-reactive protein in the soluble fraction and about 20% of that in the pellet has an apparent molecular weight of 55,000 and reacts with an anti-ubiquitin antibody; it is thus evidently ubiquitinyl actin, or arthrin, which has so far been detected only in insect flight muscle.

Actins↗

Uniparental inheritance of the mitochondrial gene cytochrome b in Plasmodium falciparum.

The inheritance of an extrachromosomal 6-kb element has been examined in the human malaria parasite Plasmodium falciparum. A single base pair difference in the cytochrome b gene from the 6-kb element of two different cloned lines of the parasite was identified, and used as a marker in a cross in the mosquito stage of the life cycle. Analysis of 59 individual hybrid oocysts resulting from this cross clearly demonstrated that inheritance of the cytochrome b gene was uniparental. This observation makes it possible to investigate the inheritance and evolution of cytoplasmic traits, including certain forms of drug resistance, in natural populations of this parasite.

Animals↗

Glycemic control and development of retinopathy in youth-onset insulin-dependent diabetes mellitus. Results of a 12-year longitudinal study.

BACKGROUND: In 1979, the authors began a prospective study of the natural history of retinopathy in youth-onset insulin-dependent diabetes mellitus (IDDM). Their major goal was to determine if there was an association between glycemic control and the development and progression of retinopathy. METHODS: The study consisted of 420 individuals with IDDM (onset younger than 20 years of age) and no retinopathy at baseline. Study subjects were enrolled between 1979 and 1988. Stereo color fundus photographs were obtained annually. Two eye endpoints were recorded: duration when retinopathy was first detected, and when proliferative retinopathy was detected. Glycemic control was assessed by quarterly determinations of glycohemoglobin (GHb). Life-table analyses were performed relating duration of diabetes, sex, GHb, and age of diabetes onset to development of retinopathy. RESULTS: Retinopathy did not develop before 2 years' duration or before puberty. The prevalence of retinopathy was 50% by 9 years' duration and 100% by 20 years' duration. Retinopathy developed in females approximately 2 years sooner than in males, but plotting duration as postpubertal years resulted in nearly identical rates. Retinopathy developed significantly earlier in subjects with prepubertal onset of diabetes than in subjects with postpubertal onset if duration was plotted as postpubertal years. When separated into three groups based on GHb levels (< 7.5%, 7.5%-9%, > 9%), retinopathy developed approximately 2 years later in subjects in the less than 7.5% GHb group than those in the higher GHb groups. Proliferative retinopathy developed in 11 subjects. Their mean GHb level was higher than the mean GHb for those without proliferative retinopathy (10.9 versus 8.6%; P < 0.01). The higher the level of GHb, the sooner proliferative changes were detected. CONCLUSION: Long-term glycemic control is significantly related to both development and progression of retinopathy. Prepubertal duration of diabetes is a significant risk factor for the development of retinopathy.

Adolescent↗

Association of anaesthetist's checklist for anaesthetic machines. Problem with detection of significant leaks.

Eight experienced anaesthetists performed a 'cockpit drill', following instructions in the Association of Anaesthetist's checklist, on an anaesthetic machine that had a significant leak (3 l.min-1 at a pressure of 16 kPa). Only one anaesthetist detected the leak and this was by audible means rather than by any of the protocol's set manoeuvres. We demonstrated that a leak of 3 l.min-1 from the flowmeter block resulted in an inspired oxygen concentration of 6% when the anaesthetic machine was used with a minute volume divider ventilator.

Anesthesiology↗

Efficacy of BCG vaccine against leprosy and tuberculosis in northern Malawi.

Protection afforded by BCG (bacillus Calmette-Guérin) vaccines against tuberculosis and leprosy varies widely between different populations. In the only controlled trial which assessed protective efficacy of BCG (Danish and Pasteur strains) against both diseases, there was slightly more protection against leprosy than against tuberculosis. We have studied the protective efficacy of BCG (Glaxo, freeze dried) vaccine against these two diseases in Karonga District, northern Malawi. BCG vaccination was introduced into this population in 1974. Prior information about BCG scar status was available for 83,455 individuals followed up between 1979 and 1989. 414 new cases of leprosy and 180 new cases of tuberculosis were found in this population over that period. Protection was estimated at 50% or greater against leprosy, and there was no evidence for lower protection against multibacillary (84%; 95% confidence interval 26% to 97%) than against paucibacillary (51%; 30% to 66%) disease. There was no statistically significant protection by BCG against tuberculosis in this population. These findings add to the evidence that BCG vaccines afford greater protection against leprosy than against tuberculosis.

Adolescent↗

Homologies between the contiguous and fragmented rRNAs of the two Plasmodium falciparum extrachromosomal DNAs are limited to core sequences.

Plasmodium falciparum contains two extrachromosomal DNAs, a 6 kb linear element and a 35 kb circular DNA; both encode rDNA sequences. The 6 kb element rDNAs comprise fragments of both large and small subunit rRNAs. Comparison of these with corresponding rDNA sequences from the 35 kb DNA and E. coli show that sequences conserved between the three are largely confined to highly conserved core regions; in fact, most of the 6 kb rDNA sequences correspond to core regions. Both the 6 kb element and 35 kb rDNAs show less conservation to each other than to E. coli sequences, suggesting that the two extrachromosomal DNAs of P. falciparum are not closely related. The characteristics of the fragmented rRNAs from the 6 kb element suggest they are functional, possibly in mitochondrial ribosomes.

Animals↗

Basis of unique red cell membrane properties in hereditary ovalocytosis.

Hereditary ovalocytes from a Mauritian subject are extremely rigid, with a shear elastic modulus about three times that of normal cells, and have increased resistance to invasion by the malaria parasite Plasmodium falciparum in vitro. The genetic anomaly resides in band 3; the protein gives rise to chymotryptic fragments with reduced mobility in SDS/polyacrylamide gel electrophoresis, but this is a result of anomalous binding of SDS and not a higher molecular weight. Analysis of the band 3 gene reveals (1) a point mutation (Lys56----Glu), which also occurs in a common asymptomatic band 3 (Memphis) variant and governs the electrophoretic properties, and (2) a deletion of nine amino acid residues, including a proline residue, encompassing the interface between the membrane-associated and the N-terminal cytoplasmic domains. The interaction of the mutant band 3 with ankyrin appears unperturbed. The fraction of band 3 capable of undergoing translation diffusion in the membrane is greatly reduced in the ovalocytes. Cells containing the asymptomatic band 3 variant were normal with respect to all the properties that we have studied. Possible mechanisms by which a structural change in band 3 at the membrane interface could regulate rigidity are examined.

Adult↗

Subcellular fractionation of the two organelle DNAs of malaria parasites.

Malaria parasites contain two extrachromosomal DNAs, a 6 kb repetitive linear molecule which is assigned on the basis of its genetic content to the mitochondria, and a 35 kb transcriptionally active circular molecule whose intracellular location is not known. We used the polymerase chain reaction to detect and estimate the numbers of both molecules in sub-cellular fractions derived from the rodent parasite Plasmodium yoelii. The two DNA molecules were not coordinately partitioned by the fractionation process, the 6 kb molecule being more abundant, relative to the 35 kb circle, in a fraction enriched for mitochondria, the converse being true for a less dense fraction of unknown identity. This implies that the two molecules are located in different cellular compartments, and is consistent with other evidence suggesting they have different evolutionary origins.

Animals↗

Invasion of hereditary ovalocytes by Plasmodium falciparum in vitro and its relation to intracellular ATP concentration.

Hereditary ovalocytes (stomatocytic ovalocytes), when examined within 1-2 days from the time that the blood sample is drawn, are invaded by Plasmodium falciparum in culture to the extent of at least 55% of normal control cells. The ovalocytes have extremely rigid membranes, characterised by a shear elastic modulus some 3-4 times greater than that of normal cells. The extent of invasion falls off very much more rapidly than that into normal cells on storage, and we surmise that this is the reason for earlier reports of resistance of ovalocytes to malarial invasion in vitro. The initial loss of susceptibility to invasion with time is not accompanied by any change in membrane rigidity, but is primarily a consequence of a rapid decline in intracellular ATP concentration: this falls to below the threshold level required for invasion (approx. 0.1 mM) over a period in which the ATP in normal cells remains almost constant. Incubation in a metabolic regenerating medium leads to a rise in the intracellular ATP concentration and invasion by P. falciparum is recovered, though to a much lower extent than in normal cells. The resistance of ovalocytes to invasion becomes irreversible, due possibly to degradative processes in the membrane, on further storage. The developing parasites in ovalocytes have a reduced number of merozoites and show distinct morphological abnormalities.

Adenosine Triphosphate↗

Effect of intra-erythrocytic magnesium ions on invasion by Plasmodium falciparum.

Exclusion of magnesium ions from resealed ghosts or their extraction from intact human red cells by means of an ionophore results in a reversible drop in susceptibility to invasion by Plasmodium falciparum merozoites in vitro. Resealed ghosts, containing magnesium-ATP and diluted cytosol, are invaded with high efficiency only when the original hypotonic lysis is carried out in the presence of magnesium ions. This effect is not related to the loss of membrane-associated constituents when magnesium ions are absent. Ghosts containing calcium ions, together with the protective agent, flunarizine, were essentially resistant to invasion; this effect is again at least partially reversible. A possible explanation of these phenomena is that entry of the merozoite may be inhibited by breakdown of the host cell phospholipid asymmetry, with the appearance of aminophospholipids at the outer cell surface.

Adenosine Triphosphate↗

The use of propofol and alfentanil by infusion in military anaesthesia.

A total intravenous technique using propofol and alfentanil was used successfully in four battlefield casualties treated at a British Military Field Hospital during the recent Gulf conflict. All patients made a rapid recovery of adequate quality for prompt evacuation. We believe that the use of propofol and alfentanil as an induction and maintenance regimen for military anaesthesia merits further evaluation and comparison with established techniques.

Alfentanil↗

Origins of the parasitophorous vacuole membrane of the malaria parasite, Plasmodium falciparum, in human red blood cells.

We have attempted to determine whether the parasitophorous vacuole membrane, in which the malaria parasite (merozoite) encapsulates itself when it enters a red blood cell, is derived from the host cell plasma membrane, as the appearance of the invasion process in the electron microscope has been taken to suggest, or from lipid material stored in the merozoite. We have incorporated into the red cell membrane a haptenic phospholipid, phosphatidylethanolamine, containing an NBD (N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)) group, substituted in the acyl chain, and allowed it to translocate into the inner bilayer leaflet. After invasion of these labelled cells by the parasite, Plasmodium falciparum, immuno-gold electron microscopy was used to follow the distribution of the labelled lipid; this was found to be overwhelmingly in favour of the host cell membrane relative to the parasitophorous vacuole. Merozoites of P. knowlesi were allowed to attach irreversibly to red cells without invasion, using the method of pretreatment with cytochalasin. The region of contact between the merozoite and the host cell membrane was in all cases devoid of the labelled phosphatidylethanolamine. These results lead us to infer that the parasitophorous vacuole membrane is derived wholly or partly from lipid preexisting in the merozoite.

Animals↗

Convicted impaired drivers and high-risk drivers: how similar are they?

The present study was a partial replication of one by D.M. Donovan (1980). Donovan's results indicated that convicted impaired drivers (DWIs) and high-risk drivers were overlapping populations with shared deviant characteristics. The present study, like Donovan's, compared three types of drivers: DWI, high-risk (either high-accident or high-violation) and general population control. Unlike Donovan, the present study attempted to match the age and sex distributions of the groups. Data were obtained from personal interviews and driver records. The DWI group was the most deviant on behavioral and personality measures and had more accidents and traffic convictions than did controls. High-risk drivers were more deviant than controls on several measures but the two groups were quite similar in other respects. The results suggest that some of the deviance attributed to high-risk drivers by Donovan may have been exaggerated by confounding with age. Secondly, the heterogeneity within the DWI and high-risk driving populations appears to outweigh their differences.

Accidents, Traffic↗

Cytomegalovirus retinitis in AIDS.

Cytomegalovirus (CMV) retinitis is the most common retinal opportunistic infection in people with the acquired immune deficiency syndrome (AIDS). Ordinarily, CMV causes little morbidity in an immunocompetent person. However, in the immunosuppressed patient this virus is responsible for progressive retinal destruction with necrosis leading to a devastating loss of vision. This paper will provide the practitioner with a clinical approach to the presentation, diagnosis and management of patients with CMV retinitis secondary to AIDS.

Acquired Immunodeficiency Syndrome↗