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Biomedical subjects

S MacDonald

Publications and source records attributed to S MacDonald.

At least 37 records · Page 2Linked to original sources

Seroprevalence of Helicobacter pylori, incidence of gastric cancer, and peptic ulcer-associated hospitalizations in a Canadian Indian population.

The living conditions of many aboriginal communities in Canada may place their residents at risk for H. pylori infection. Our aims were to determine: (1) the seroprevalence of H. pylori in a traditional Indian community, (2) the clinical relevance of H. pylori infection in this population, and (3) if H. pylori could be identified by polymerase chain reaction from the local water. A demographic questionnaire was administered, and blood was collected from subjects in an Indian community in northwestern Manitoba. The serum was analyzed by ELISA for IgG to H. pylori and to CagA. ABO and Lewis antigens were tested. Age-adjusted incidence of gastric cancer and of hospitalizations associated with diagnoses of peptic ulcer were determined for the Indian and non-Indian Manitoba population in the years 1989-1993. Nested PCR was performed on lake water using H. pylori-specific primers and the amplicons probed with an internal Dig-labeled probe. Three hundred six (59%) of approximately 518 individuals who were resident in the community at the time of the study were enrolled. The ELISA for H. pylori was positive in 291 (95%). There was no association between H. pylori seropositivity and age, sex, gastrointestinal complaints, medications, housing characteristics, and ABO or Lewis antigen status. CagA was positive in 84.5% of infected subjects. The average annual age-adjusted incidence of hospitalizations associated with diagnoses of peptic ulcer disease in Manitoba was higher for treaty-status Indians (394.3/100,000) than for non-Indians (203.8/100,000), but gastric cancer rates were similar (11.2/100,000 vs 11.6/100,000). No H. pylori DNA was detected in the lake water. In conclusion, the seroprevalence of CagA-positive H. pylori is high in this representative Manitoban Indian community. This may be associated with an increased risk for peptic ulcer disease but is not associated with an increased risk for gastric cancer.

Adolescent↗

How useful is contrast enhancement after a normal unenhanced computed tomography brain scan?

An audit was performed of contrast use in 400 CT brain scans performed with and without contrast enhancement; all 400 scans were re-read by a second reader who did not know the result of the original reading. From this initial series 184 scans were identified in which the unenhanced series had been read as normal by both observers. Of these 184 studies, only one enhanced scan showed an abnormality, and this lesion is thought to be benign. In conjunction with published literature it is concluded that it is reasonable not to give contrast if there is a low expectation of a lesion being present, and if the unenhanced scan is normal. Protocols are presented for the use of intravenous contrast in CT brain scans.

Brain↗

Ochratoxin A in dried vine fruit: method development and survey.

A method is described for the determination of concentrations of the mycotoxin ochratoxin A in dried vine fruits (currants, raisins and sultanas) using acidic methanolic extraction, immunoaffinity chromatography clean-up and HPLC determination. The limit of detection was estimated as 0.2 microgram/kg, and recoveries of 63-77% were achieved at 5 micrograms/kg. HPLC-mass spectrometric confirmation of the identity of ochratoxin was obtained. Ochratoxin A and aflatoxins were determined in 60 samples of retail dried vine fruits purchased in the United Kingdom. Ochratoxin A was found in excess of 0.2 microgram/kg in 19 of 20 currant, 17 of 20 sultana and 17 of 20 raisin samples examined, an overall incidence of 88%. The maximum level found was 53.6 micrograms/kg. No aflatoxin was found in any sample analysed, using a method with a detection limit of 0.2 microgram/kg for each of aflatoxin B1, B2, G1 and G2.

Aflatoxins↗

Stemming the tide: reducing cardiovascular disease and renal failure in Australian Aborigines.

An epidemic of cardiovascular disease (CVD) and end stage renal disease (ESRD) has developed among Aborigines in the Northern Territory; CVD deaths increased over the 1980s (tripling among women!), and are now more than five times those of non-Aboriginal people, while ESRD rates are increasing more than 20-fold and are doubling every three to four years. Dialysis costs (>$75,000 per person/year) pose a crisis for health care budgets, but premature mortality is the greater human catastrophe. Health services are not meeting the challenge of timely diagnosis, prevention and containment. We screened 90% of adults (20+ years) in one community, with CVD mortality among the highest in Australia, and ESRD rates increased 60-fold. Seventy-five per cent of persons were smokers. Central obesity was common, but BMIs only modestly increased by Caucasian standards, 23% had hypertension (>140/90), 29% had diabetes or impaired glucose tolerance (IGT) (peaking at 65% of persons aged 40-49 years), high triglyceride and insulin levels were common, and 55% had albuminuria (albumin/creatinine ratio (ACR), >3.4 gm/moL). Progressive albuminuria predicted renal failure. ACR was correlated with age, BMI, blood pressure, lipid, glucose and insulin levels, heavy drinking and past and current skin infections, and, inversely with birth weight. ACR correlated strongly with a composite CV risk score, and in a two to five year follow-up, microalbuminuria (ACR 3.4-33) and overt albuminuria (ACR 34+) have both predicted increased rate of premature death from natural causes of lower ACRs. Thus albuminuria marks CV risk/disease. This implies that renal and CV disease share common risk factors, and should respond to the same interventions, and that this response might be monitored through ACR levels. Robust public health programmes could reduce all these reversible risk factors, lowering disease rates over the intermediate term, however, few such programmes are in place. Modification of disease in persons already afflicted is a parallel responsibility. To this end, in November 1995, we introduced a treatment programme with Coversyl (perindopril, Servier) for all persons in the study community with hypertension (>140/90), for all diabetics with ACR 3.4+ and for all nondiabetic, non-hypertensive persons with progressive overt albuminuria (ACR 34+). One-quarter of all adults, or 224 persons have enrolled; 162 have reached one year of treatment and 100 have passed two years. Compliance is reasonable and enthusiasm high. Average SBP has fallen 12 mmHg (24 mmHg in hypertensive persons), while average ACR and estimated glomerular filtration rate (GFR) have stabilised. This contrasts favourably with the pretreatment course (average 2.7 years) in the same persons, when SBP had increased by 3 mmHg, ACR had increased by 15% and GFR had decreased by 3.5 mL/min each year. Cautious estimates suggest a >50% fall in ESRD, and a reduction in all-cause and CV deaths, even at this early stage, although more extended observation is needed. These data predict a dramatic and rapid fall in morbidity, premature deaths and health care costs if these basic principles of medical care are extended to all Aboriginal people. A national, concerted, multi-disciplinary effort to implement a coherent, effective strategy to this end is of great urgency.

Adult↗

Validation of a novel luminal flow velocimeter with video fluoroscopy and manometry in the human esophagus.

There is currently no ideal method for concurrently assessing intraluminal pressures and flows in humans with high temporal resolution. We have developed and assessed the performance of a novel fiber-optic laser-Doppler velocimeter, mounted in a multichannel manometric assembly. Velocimeter recordings were compared with concurrent fluoroscopy and manometry following 50 barium swallows in healthy subjects. During these swallows, the velocimeter sensor was situated in either the proximal (24 swallows) or the distal (26 swallows) esophagus. It signaled intraluminal flow following 46 of 50 swallows. A greater mean number of deflections were recorded in the distal compared with the proximal esophagus (4. 3 vs. 2.4, P = 0.001). The maximal flow velocity recorded did not differ between the proximal and distal esophagus (76.7 vs. 73.8 mm/s). No velocimeter signals commenced after fluoroscopic lumen occlusion. The velocimeter signals were closely temporally related to fluoroscopic barium flow. Upward catheter movement on swallowing sometimes appeared to cause a velocimeter signal. Manometrically "normal" swallows were no different from "abnormal" swallows in the number and velocity of deflections recorded by the velocimeter. This novel instrument measures intraluminal flow velocity and pressures concurrently, thus enabling direct study of pressure-flow relationships. Flow patterns differed between the proximal and distal esophagus.

Adult↗

The effect of bracing on varus gonarthrosis.

BACKGROUND: The purpose of this study was to compare a custom-made valgus-producing functional knee (unloader) brace, a neoprene sleeve, and medical treatment only (control group) with regard to their ability to improve the disease-specific quality of life and the functional status of patients who had osteoarthritis in association with a varus deformity of the knee (varus gonarthrosis). METHODS: The study design was a prospective, parallel-group, randomized clinical trial. Patients who had varus gonarthrosis were screened for eligibility. The criteria for exclusion included arthritides other than osteoarthritis; an operation on the knee within the previous six months; symptomatic disease of the hip, ankle, or foot; a previous fracture of the tibia or femur; morbid obesity (a body-mass index of more than thirty-five kilograms per square meter); skin disease; peripheral vascular disease or varicose veins that would preclude use of a brace; a severe cardiovascular deficit; blindness; poor English-language skills; and an inability to apply a brace because of physical limitations such as arthritis in the hand or an inability to bend over. Treatment was assigned on the basis of a computer-generated block method of randomization with use of sealed envelopes. The patients were stratified according to age (less than fifty years or at least fifty years), deformity (the mechanical axis in less than 5 degrees of varus or in at least 5 degrees of varus), and the status of the anterior cruciate ligament (torn or intact). The patients were randomly assigned to one of three treatment groups: medical treatment only (control group), medical treatment and use of a neoprene sleeve, or medical treatment and use of an unloader brace. The disease-specific quality of life was measured with use of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the McMaster-Toronto Arthritis Patient Preference Disability Questionnaire (MACTAR), and function was assessed with use of the six-minute walking and thirty-second stair-climbing tests. The primary outcome measure consisted of an analysis of covariance of the change in scores between the baseline and six-month evaluations. RESULTS: One hundred and nineteen patients were randomized. The control group consisted of forty patients (thirty-one men and nine women; mean age, 60.9 years); the neoprene-sleeve group, of thirty-eight patients (twenty-seven men and eleven women; mean age, 58.2 years); and the unloader-brace group, of forty-one patients (twenty-eight men and thirteen women; mean age, 59.5 years). Nine patients withdrew from the study. At the six-month follow-up evaluation, there was a significant improvement in the disease-specific quality of life (p = 0.001) and in function (p< or =0.001) in both the neoprene-sleeve group and the unloader-brace group compared with the control group. There was a significant difference between the unloader-brace group and the neoprene-sleeve group with regard to pain after both the six-minute walking test (p = 0.021) and the thirty-second stair-climbing test (p = 0.016). There was a strong trend toward a significant difference between the unloader-brace group and the neoprene-sleeve group with regard to the change in the WOMAC aggregate (p = 0.062) and WOMAC physical function scores (p = 0.081). CONCLUSIONS: The results indicate that patients who have varus gonarthrosis may benefit significantly from use of a knee brace in addition to standard medical treatment. The unloader brace was, on the average, more effective than the neoprene sleeve. The ideal candidates for each of these bracing options remain to be identified.

Bone Diseases, Developmental↗

Investigating fatigue of less than 6 months' duration. Guidelines for family physicians.

OBJECTIVE: To develop an evidence-based systematic approach to assessment of adult patients who present to family physicians complaining of fatigue of less than 6 months' duration. The guidelines present investigative options, making explicit what should be considered in all cases and what should be considered only in specific situations. They aim to provide physicians with an approach that, to the extent possible, is based on evidence so that time and cost are minimized and detection and management of the cause of the fatigue are optimized. QUALITY OF EVIDENCE: MEDLINE was searched from 1966 to 1997 using the key words "family practice" and "fatigue." Articles about chronic fatigue syndrome were excluded. Articles with level 3 evidence were found, but no randomized trials, cohort studies, or case-control studies were found. Articles looking specifically at the epidemiology, demographics, investigations, and diagnoses of patients with fatigue were chosen. Articles based on studies at referral and specialty centres were given less weight than those based on studies in family physicians' offices. MAIN MESSAGE: Adherence to these guidelines will decrease the cost of investigating the symptom of fatigue and optimize diagnosis and management. This needs to be proved in practice, however, and with research that produces level 1 and 2 evidence. CONCLUSIONS: Adults presenting with fatigue of less than 6 months' duration should be assessed for psychosocial causes and should have a focused history and physical examination to determine whether further investigations should be done. The guidelines outline investigations to be considered. The elderly require special consideration. These guidelines have group validation, but they need to be tested by more physicians in various locations and types of practices.

Adult↗

Looking over the horizon: an Internet-based international course in healthcare management.

The International Course in Healthcare Management is predicated on the belief that comparative benefits can most effectively be 'taught' by enabling students to work directly with colleagues in other countries, sharing views, discussing differences, and checking understandings on how healthcare is structured and managed in different countries. The course focuses on four countries--Canada, Germany, Finland and Ireland--which offer an interesting range and mix of approaches to healthcare, and yet are sufficiently similar to ensure relative ease of understanding. The course, which is delivered and taught jointly by faculty from five participating institutions in the four countries using the Internet as the distance delivery medium, is an integral component of each institution's participating department's graduate program. The aims of the course are: to enable the participants to develop an in-depth understanding of the healthcare systems of each country; to foster a deeper understanding, through comparative analysis, of each participant's own healthcare system; and to facilitate the development of new insights into ways of addressing common concerns in healthcare management. The course is structured around a series of case studies organized under four main themes: financing and funding; delivery issues; impact of health service reforms; and evidence-based management.

Canada↗

Total parenteral nutrition in the critically ill patient: a meta-analysis.

CONTEXT: Nutritional support has become a standard of care for hospitalized patients, but whether total parenteral nutrition (TPN) affects morbidity and mortality is unclear. OBJECTIVE: To examine the relationship between TPN and complication and mortality rates in critically ill patients. DATA SOURCES: Computerized search of published research on MEDLINE from 1980 to 1998, personal files, and review of relevant reference lists. STUDY SELECTION: We reviewed 210 titles, abstracts, and papers. Primary studies were included if they were randomized clinical trials of critically ill or surgical patients that evaluated the effect of TPN (compared with standard care) on complication and mortality rates. We excluded studies comparing TPN with enteral nutrition. DATA EXTRACTION: Relevant data were abstracted on the methodology and outcomes of primary studies. Data were abstracted in duplicate, independently. DATA SYNTHESIS: There were 26 randomized trials of 2211 patients comparing the use of TPN with standard care (usual oral diet plus intravenous dextrose) in surgical and critically ill patients. When the results of these trials were aggregated, TPN had no effect on mortality (risk ratio [RR], 1.03; 95% confidence interval [CI], 0.81-1.31). Patients who received TPN tended to have a lower complication rate, but this result was not statistically significant (RR, 0.84; 95% CI, 0.64-1.09). We examined several a priori hypotheses and found that studies including only malnourished patients were associated with lower complication rates but no difference in mortality when compared with studies of nonmalnourished patients. Studies published since 1989 and studies with a higher methods score showed no treatment effect, while studies published in 1988 or before and studies with a lower methods score demonstrated a significant treatment effect. Complication rates were lower in studies that did not use lipids; however, there was no difference in mortality rates between studies that did not use lipids and those studies that did. Studies limited to critically ill patients demonstrated a significant increase in complication and mortality rates compared with studies of surgical patients. CONCLUSIONS: Total parenteral nutrition does not influence the overall mortality rate of surgical or critically ill patients. It may reduce the complication rate, especially in malnourished patients, but study results are influenced by patient population, use of lipids, methodological quality, and year of publication.

Critical Care↗

Expression of beta-endorphin and its receptors in the spinal cord of obese-diabetic ob/ob mice.

Immunocytochemistry was used to demonstrate the presence of beta-endorphin, and quantitative autoradiography with [125I]beta-endorphin was used to study beta-endorphin binding sites, in spinal cord of lean and obese diabetic ob/ob mice. The proportion of beta-endorphin-positive neurones was approximately 6-fold higher in the ventral horn, and 2-fold higher in the dorsal horn of ob/ob mice than in lean controls. The maximum density of beta-endorphin binding sites was significantly higher in the dorsal horn and intermediate zone of ob/ob mice. The Kd value for the binding was similar in the ventral horn and intermediate zone in lean and ob/ob mice, but slightly lower in the dorsal horn of ob/ob mice. The findings indicate upregulation of both beta-endorphin and its receptors in spinal neurones of ob/ob mice.

Animals↗

Influence of outer pore residue K533 on the inhibition of Kv1.4 potassium channels by n-alkyl sulphate anions.

We have previously shown that although n-octyl sulphate (OS-) and n-dodecyl sulphate (DDS-) anions had similar effects on the kinetics and activation voltage dependence of RCK1 (Kv1.1), RCK4 (Kv1.4) and Shaker B channels expressed in Xenopus oocytes, both compounds produced a large decrease in the maximum conductance of RCK4 channels while significantly increasing the conductance of RCK1 and Shaker B. We suggested that this channel-specific inhibition might depend on the nature of the amino-acid residue corresponding to position 533 in RCK4. We now present data on the effects of n-alkyl sulphates on an RCK4 mutant in which the wild-type lysine at position 533 was changed to the corresponding tyrosine residue in RCK1. At a concentration of 15 microM, DDS- caused a 48% reduction in the wild-type current at 50 mV but a 32% increase in the mutant current. n-Hexyl sulphate and OS- had similar differential effects. The activation and inactivation kinetics of the mutant current were still accelerated by n-alkyl sulphates and 15 microM DDS- moved the conductance/voltage curves of both wild-type and mutant channels some 24 mV in the hyperpolarizing direction. The K533Y mutation thus had a selective effect on current inhibition by n-alkyl sulphates.

Animals↗

Seroprevalence of Borrelia burgdorferi sensu lato infection in blood donors and park rangers in relation to local habitat.

Serum samples were obtained from blood donors in eleven selected locations in Ireland and tested for antibodies to Borrelia burgdorferi s.l. by enzyme immunoassay (EIA) and immunoblot (IB). The highest seroprevalence (8.7%) was found in Portumna, an area rated as high risk because of the presence of public access woodland harbouring both ticks and spirochaete reservoir hosts. The lowest seroprevalence (0.0%) was found in Ballina, an area where there is no suitable woodland though ticks are common on pastures grazed by cattle and sheep. These results support the findings of an earlier less extensive study and suggest that infection with B. burgdorferi s.l. in Ireland is mainly associated with mixed woodland containing deer and a variety of spirochaete reservoir hosts. The lack of association of tick-infested farmland with seropositive samples suggests that exposure to ticks alone is not a reliable indicator of risk of Lyme borreliosis. This is supported by the fact that none of 38 park rangers, all of whom are regularly bitten by ticks, were seropositive for B. burgdorferi s.l. The low overall seroprevalence of 3.4% in Ireland correlates with the rarity of clinical cases compared with continental European countries, and is due in part to the scarcity of high risk Lyme borreliosis habitat.

Animals↗

Phosphorylation of Raf-1 serine 338-serine 339 is an essential regulatory event for Ras-dependent activation and biological signaling.

Activation of the Raf serine/threonine protein kinases is tightly regulated by multiple phosphorylation events. Phosphorylation of either tyrosine 340 or 341 in the catalytic domain of Raf-1 has been previously shown to induce the ability of the protein kinase to phosphorylate MEK. By using a combination of mitogenic and enzymatic assays, we found that phosphorylation of the adjacent residue, serine 338, and, to a lesser extent, serine 339 is essential for the biological and enzymatic activities of Raf-1. Replacement of S338 with alanine blocked the ability of prenylated Raf-CX to transform Rat-1 fibroblasts. Similarly, the loss of S338-S339 in Raf-1 prevented protein kinase activation in COS-7 cells by either oncogenic Ras[V12] or v-Src. Consistent with phosphorylation of S338-S339, acidic amino acid substitutions of these residues partially restored transforming activity to Raf-CX, as well as kinase activation of Raf-1 by Ras[V12] or v-Src. Two-dimensional phosphopeptide mapping of wild-type Raf-CX and Raf-CX[A338A339] confirmed the presence of a phosphoserine-containing peptide with the predicted mobility in the wild-type protein which was absent from the mutant. This peptide could be quantitatively precipitated by an antipeptide antibody specific for the 18-residue tryptic peptide containing S338-S339 and was demonstrated to contain only phosphoserine. Phosphorylation of this peptide in Raf-1 was significantly increased by coexpression with Ras[V12]. These data demonstrate that Raf-1 residues 338 to 341 constitute a unique phosphoregulatory site in which the phosphorylation of serine and tyrosine residues contributes to the regulation of Raf by Ras, Src, and Ras-independent membrane localization.

Amino Acid Sequence↗

A UK retail survey of aflatoxins in herbs and spices and their fate during cooking.

A survey of aflatoxins in herbs and spices has been carried out and cooking experiments conducted to assess the stability of aflatoxin in spice sauces. Of 157 retail samples which included curry powders, pepper, cayenne pepper, chilli, paprika, ginger, cinnamon and coriander, nearly 95% of samples contained below 10 micrograms/kg total aflatoxins and only nine samples had higher levels. The highest concentration in a retail sample was 48 micrograms/kg in a chilli powder. In addition to retail sampling, 14 consignments of whole chilli and chilli powder were sampled at the port of entry. Only two samples, both chilli powder, were above 10 micrograms/kg; containing 35 and 51 micrograms/kg total aflatoxins. Cooking experiments showed that aflatoxin levels in spiced sauces are not reduced by domestic cooking with either microwave or conventional gas oven heating.

Aflatoxins↗

Utility of a verbal reasoning test in indicating vocational readiness following traumatic brain injury.

Present tests are often inadequate to assess subtle aspects of cognitive-communicative functioning following traumatic brain injury (TBI), making it difficult to predict vocational readiness, particularly for those in professional occupations. This study examined the viability of the Ross Test of Higher Cognitive Processes (RTHCP) as a measure of verbal reasoning deficits following TBI. The verbal reasoning performance of a 43-year-old lawyer with TBI was compared, at two stages in his rehabilitation, to that of a peer group of lawyers (n = 43). The RTHCP detected noticeable differences in speed and accuracy of performance at different stages of recovery. The RTHCP also revealed individual differences among the peer group, who presumably were competent in verbal reasoning. Thus, the RTHCP may be an effective tool to measure subtle deficits in verbal reasoning post-TBI. Some cautions in using this test for the TBI population are presented, as well as suggestions for further test development and validation.

Adult↗

Validity studies of the filial anxiety scale.

Factor analytic and construct validity studies were conducted to explore the validity of Cicirelli's (1988) 13-item Filial Anxiety Scale (FAS). The State-Trait Anxiety Inventory (Spielberger, 1983), and the Marlowe-Crowne Social Desirability Scale (Crowne & Marlowe, 1960), were a part of the investigation. The results offer support for the validity of the FAS subscales and the FAS' usefulness as an instrument for measuring adult children's feelings concerning elder-parent care.

Adult↗