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Biomedical subjects

C McDonald

Publications and source records attributed to C McDonald.

At least 73 records · Page 4Linked to original sources

Case report: gastrointestinal tuberculosis simulating Crohn's disease.

A male Caucasian presented with abdominal pain and a right iliac fossa mass. There were no risk factors for Mycobacterium tuberculosis infection. He was investigated by upper and lower gastrointestinal endoscopy, chest and small bowel radiology. The latter showed stricturing of the third and fourth parts of the duodenum, mid-jejunum and terminal ileum. Biopsies were non-specific and he was thought to have Crohn's disease. Subsequent treatment with corticosteroids resulted in improved well being and weight gain; however, the patient demonstrated disease progression with the development of complex fistulae and Escherichia coli septicaemia. At surgery the patient was found to have an ileal inflammatory mass with fistulae to the sigmoid colon. The terminal ileum, fistulae and a segment of colon were resected. Treatment with anti-tuberculous drugs ensued and the patient is now asymptomatic after 15 months of follow-up. This case serves to highlight the difficulty in making the diagnosis of gastrointestinal tuberculosis, a disease that may mimic Crohn's disease, and the need for caution in the use of corticosteroids in any disease in which tuberculosis enters into the differential diagnosis. The role of surgery in making the diagnosis and managing the complications, in conjunction with anti-tuberculous drugs, and the prospect of cure are exemplified by this case.

Adult↗

Role of the Kv4.3 K+ channel in ventricular muscle. A molecular correlate for the transient outward current.

The expression of 15 different K+ channels in canine heart was examined, and a new K+ channel gene (Kv4.3), which encodes a rapidly inactivating K+ current, is described. The Kv4.3 channel was found to have biophysical and pharmacological properties similar to the native canine transient outward current (I(to)). The Kv4.3 gene is also expressed in human and rat heart. It is concluded that the Kv4.3 channel underlies the bulk of the I(to) in canine ventricular myocytes, and probably in human myocytes. Both the Kv4.3 and Kv4.2 channels are likely to contribute to the I(to) in rat heart, and differential expression of these two channels can account for observed differences in the kinetic properties of the I(to) in different regions of rat ventricle. There are significant differences in the pattern of K+ channel expression in canine heart, compared with rat heart, and these differences may be an adaptation to the different requirements for cardiac function in mammals of markedly different sizes. It is possible that the much longer ventricular action potential duration observed in canine heart compared with rat heart is due, in part, to the lower levels of Kv1.2, Kv2.1, and Kv4.2 gene expression in canine heart.

Amino Acid Sequence↗

Fluctuations in syringe-pump infusions: association with blood pressure variations in infants.

Flow continuity of two brands of syringe pumps and four brands of syringes was studied as a possible cause of hemodynamic fluctuations observed in neonates. Cyclical fluctuations were observed in the blood pressure of 14 neonates receiving dopamine infusions by syringe pump at flow rates from 0.2 to 1 mL/hr. Atom 235 and IVAC 770 pumps and various sizes of Terumo, Becton Dickinson, Omnifix, and IVAC syringes were evaluated. Flow continuity was assessed by using a gravimetric technique. The force needed to initiate and maintain syringe plunger motion was also measured. Noncontinuous flow was encountered most commonly with Terumo syringes, which delivered boluses at regular intervals at flow rates up to 5 mL/hr. The interval was dependent on flow rate and was similar to the time between the blood pressure fluctuations observed clinically. The syringe plunger force exhibited regular fluctuations indicative of the plunger sticking, and simultaneous measurement of flow established a direct temporal relationship with boluses. The other syringes tested did not exhibit such fluctuations. No differences were found between the two syringe pumps. Syringe plunger sticking, resulting in intermittent boluses and potential blood pressure fluctuations, may occur at low flow rates and with certain syringe brands. This appeared to be the cause of hemodynamic fluctuations in neonates receiving dopamine infusions.

Blood Pressure↗

Is lung cancer associated with asbestos exposure when there are no small opacities on the chest radiograph?

This study was designed to test the hypothesis that the risk of lung cancer from asbestos exposure is confined to persons with radiographic evidence of pulmonary fibrosis. Occupational and smoking histories were obtained from 271 patients with a confirmed diagnosis of primary lung cancer and 678 referents (279 with other respiratory disease and 399 with cardiac disease). Histories were reviewed blind to assess the timing, duration, and probability of exposure to asbestos. To allow for a lag between asbestos exposure and the development of lung cancer, subjects were classified by the time they had spent in an occupation entailing definite or probable exposure more than 15 years before diagnosis. The presence and extent of fibrosis was assessed blindly from chest radiographs by three readers and scored for small opacities with the ILO 1989 International Classification of Radiographs of the Pneumoconioses. 93 (34.3%) cases had worked in an occupation with definite or probable asbestos exposure compared with 176 (25.8%) referents (crude odds ratio for lung cancer 1.49, 95% CI 1.09-2.04). After adjustment for age, sex, smoking history, and area of referral, the odds ratio (95% CI) was 2.03 (1.00-4.13) in the subgroup of 211 with a median ILO score for small parenchymal opacities of 1/0 or more, and 1.56 (1.02-2.39) in the 738 with a score of 0/1 or less (ie, those without radiological evidence of pulmonary fibrosis). These results suggest that asbestos is associated with lung cancer even in the absence of radiologically apparent pulmonary fibrosis.

Aged↗

A comparative study of the interaction of Myocrisin with albumin and gamma-globulin.

The reactions of Myocrisin with albumin and gamma-globulin have been investigated using atomic absorption spectrometry and gel filtration. Albumin rapidly binds gold up to the levels predicted from the concentration of free sulphydryl groups present in the protein. However, in the presence of glutathione, gold incorporation is increased, suggesting that in vivo, free thiols (glutathione, thiomalate) may facilitate gold uptake by the protein. In comparison, gamma-globulin is found to be capable of binding up to one atom of gold per molecule of protein in a slow reaction which requires high Myocrisin concentrations.

Binding Sites↗

The Edinburgh randomised trial of breast cancer screening: results after 10 years of follow-up.

The Edinburgh Randomised Trial of Breast Cancer Screening recruited 44,288 women aged 45-64 years into the initial cohort of the trial during 1978-81, and 10 years of follow-up is now complete. A total of 22,944 women were randomised into the study group and were offered screening for 7 years; the remaining women formed the control group. After 10 years, breast cancer mortality is 14-21% lower in the study group than in the controls depending on the precise definition of the end point. These differences are not statistically significant; for breast cancer as the underlying cause of death the relative risk is 0.82 (95% confidence interval 0.61-1.11). Rates of locally advanced and metastatic cancer were substantially lower in the study group, but screening has failed to achieve marked reductions in rates of small node-positive cancers. Those women who accepted the final invitation to screening have been monitored over the 3 year period prior to their first screen under the UK service screening programme. Interval cases, expressed as a proportion of the control incidence, increased from 12% in the first year to 67% in the third year. The reduction in breast cancer mortality for older women (aged at least 50 years) is the same as that for the total study group for this duration of follow-up. For analyses of breast cancer mortality in younger women updates recruited to the trial from 1982 to 1985 (10,383 women with 6-8 years' follow-up) have been included. The reduction in breast cancer mortality for women aged 45-49 years at entry was 22% (relative risk = 0.78, 95% confidence interval = 0.46-1.31).

Breast Neoplasms↗

A bridge too near? Injecting drug users' sexual behaviour.

One-hundred-and-fifty injecting drug users were interviewed about their sexual behaviour, and types of sexual relationships and partners in the past year. The aims of the study were to assess the extent of changes in sexual HIV-risk behaviour patterns and to understand aspects of respondents' sexual relationships, as well as HIV/AIDS knowledge. We found few changes in sexual behaviour. The ability to assess personal HIV-risk varied widely across the sample and intoxication during sexual activity was widely reported. Whilst the use of condoms was infrequent, young respondents were more likely to use condoms, but have more sexual partners, hence a likely erosion of any net gain may have occurred. Over half of the respondents were in sexually monogamous relationships and there were no significant gender-related differences in respect of regular partners' IDU-status. Estimated rates of seroprevalence in Perth are low and with the effectiveness of deterrence dependent on visible negative outcomes, it may be difficult to ensure safer-sex messages are heeded. These concerns are raised and facilitation of safer-sex among IDUs are discussed. Further areas of research are recommended.

Adolescent↗

Two tests for assessing remote public knowledge: a tool for assessing retrograde amnesia.

Guidelines for the construction and development of tests of remote memory are provided. These guidelines follow from methodological considerations and from certain theoretical issues we believe that remote memory tests should address if they are to further our understanding of amnesia. These include: the pattern of temporal gradient; memory for different broad classes of information such as famous names and famous events; and recall and recognition of different types of detail such as contextual and non-contextual information associated with remote memory. With respect to the first of these, we argue that it is impossible to fully evaluate competing hypotheses about temporally graded retrograde amnesia unless items are selected from at least two difficulty levels, and from at least two time periods. The construction of two equivalent tests of remote memory, one for famous people, the other for famous events, is described, and the theoretical issues listed earlier were addressed using these tests in a study comparing the remote memory of 13 organic amnesics and 13 age- and IQ-matched controls. The principal findings were as follows. There was only weak evidence that amnesics' remote memory for famous people and events was temporally graded over a 20 year period, and recognition memory and memory for non-contextual detail were equally impaired. Mayes, Meudell, and Pickering's (1985) context memory deficit hypothesis was supported, however, because amnesics were more impaired in their ability to date recognised items. In addition, although there was little support for a temporally graded retrograde impairment on the recognition question, there was much clearer evidence for the temporal dating question. Also, one patient, SR, showed a selective deficit in dating recognised names and events from the 1980s. Finally, the correlations between measures of anterograde and retrograde amnesia were all non-significant. Suitable items for the construction of remote memory tests probing the four decades 1950s to 1980s are presented. A subset of these, from the 1970s and 1980s, were shown to have satisfactory psychometric qualities, and can therefore be recommended for more widespread clinical use, although more extensive normative data than that provided here will be necessary.

Adult↗

Enzymatic assay for measurement of zidovudine triphosphate in peripheral blood mononuclear cells.

In this report, we describe a new method to measure intracellular zidovudine triphosphate (ZDV-TP) levels in peripheral blood mononuclear cells (PBMCs) from patients treated with ZDV by utilizing inhibition of human immunodeficiency virus type 1 reverse transcriptase activity by ZDV-TP. Intracellular levels of ZDV-TP were determined with our enzymatic assay in PBMCs isolated from the blood of healthy individuals incubated with different concentrations of labeled ZDV and were validated by high-performance liquid chromatography separation and liquid scintillation counting of the radioactive ZDV-TP. These methods gave virtually identical results over a range of ZDV-TP concentrations from 150 to 900 fmol. ZDV-TP recoveries were over 90%, and the limit of quantitation of ZDV-TP by this method was 20 to 50 fmol. To demonstrate the utility of the method, plasma ZDV and intracellular ZDV-TP concentrations were measured at serial time points over 6 h in 12 human immunodeficiency virus-infected volunteers following a single 100- or 500-mg oral dose of ZDV. Systemic oral clearance rates were similar to those in previous studies with adults but were highly variable (range, 0.86 to 2.75 liters/h/kg of body weight). The area under the plasma concentration versus time curve increased significantly (P < 0.0005) with the dose from a median value of 1.2 mg.h/liter at the lower dose to 4.2 mg.h/liter at the higher dose. Median intracellular ZDV-TP levels ranged from 5 to 57 and 42 to 92 fmol/10(6) cells in volunteers administered 100 and 500 mg of ZDV, respectively. Intracellular ZDV-TP levels rose to a plateau value by 2 h and remained consistent to 6 h. Although the higher dose and higher areas under the curve yielded consistently higher intracellular ZDV-TP levels, systemic pharmacokinetics explains only a modest proportion of the variability in cellular pharmacokinetic. The ZDV-TP bioassay should prove useful in further studies of ZDV metabolism in patient-derived PBMCs at the doses of ZDV currently administered.

Antiviral Agents↗

Antisense BCR-ABL oligomers cause non-specific inhibition of chronic myeloid leukemia cell lines.

We have examined the effects of antisense oligomers (AOs) of various lengths, sequences and chemistry on the proliferation of eight different cell lines, five derived from patients with chronic myelogenous leukemia (CML) and three from other sources. In general, phosphodiester AOs were inactive, presumably due to degradation by nucleases present in fetal calf serum. Both BA2 and B3A2 phosphorothiolate AOs (but not corresponding sense oligomers) significantly inhibited the proliferation of three CML cell lines (BV173, LAMA84, and KYO1), but the effect was independent of the type of breakpoint expressed by each cell line, suggesting that the inhibition was sequence dependent but not sequence specific. The CML cell lines tested showed different sensitivities to inhibition of proliferation by AOs--lines with defective expression of the normal ABL protooncogene (e.g. BV173) were more readily inhibited than lines with a normal ABL message (e.g. K562). We conclude that further studies are necessary to delineate the precise mechanism(s) by which CML cell proliferation is inhibited by AOs.

Base Sequence↗

Food.

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Animals↗

Residential care for elderly people: a decade of change.

OBJECTIVE: To determine the changes between 1979 and 1990 in demography and dependency levels in elderly people in residential care. DESIGN: Censuses of those aged 65 years and over in any type of residential care at midnight on 11 December 1979 and 27 November 1990. SETTING: Leicestershire District Health Authority (population 865,133, 1991 census), coterminous with county and social services boundaries. MAIN OUTCOME MEASURES: Age, sex, length of stay, and dependency levels (measured by activities of daily living). RESULTS: In 1990 (1979), 6079 (4678) elderly people were enumerated in 241 (133) establishments, a 30% increase in the numbers of elderly people in residential care and an 82% increase in the number of establishments between 1979 and 1990. Dependency levels rose between 1979 and 1990 in all but the geriatric sector, the greatest increases being found in private residential homes where the largest percentage increase in the number of residents had occurred. CONCLUSIONS: Dependency levels in residential care have risen substantially, particularly in the private sector, even beyond levels expected from the greater numbers of elderly people. With the impending move to community care, dependency levels are likely to rise further, and more appropriate staff training and medical input to homes will become necessary.

Activities of Daily Living↗