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Biomedical subjects

K MacDonald

Publications and source records attributed to K MacDonald.

At least 37 records · Page 2Linked to original sources

A preliminary survey of oncologists' perceptions of quality of life information.

Quality of life (QOL) of cancer patients has become the focus of increasing research in oncology, and a frequently measured endpoint in clinical trials. Very little attention has been paid to the perspective of physicians on quality of life information, and its role in clinical decision-making. This report describes the findings of research focused on exploring the perspectives of physicians about quality of life information that is available for cancer patients. On the basis of qualitative data gathered through in-depth interviews with 60 oncologists in the first phase of this project, we have developed a self-administered questionnaire (MD-QOL survey) designed to assess oncologists' views on QOL. This survey was administered to an international group of gynecologic oncologists. The objectives of this study were to assess the face validity of the initial items in the MD-QOL, to expand the pool of items, and to assess the feasibility of utilizing a self-administered questionnaire to assess physicians' perspectives on QOL information. Twenty-eight oncologists responded to the questionnaire. The majority of respondents felt that QOL can be measured and that it should be measured from the patient's own perspective. Half of the physicians felt that currently available QOL information is useful in clinical practice. Ninety-three percent of respondents felt that the greatest benefit of QOL information is 'being able to treat the whole patient'. Forty one percent of respondents felt that length of survival is more important to patients than quality of life. However, only 7% of the respondents felt that the primary job of physicians is to save lives, and that QOL should not be a predominant concern for physicians. The inclusion of QOL in randomized trials was perceived as encouraging both patient and physician participation. The results of this survey are being used to further explore these critical issues.

Adult↗

Effects of hemisphere speech dominance and seizure focus on patterns of behavioral response errors for three types of stimuli.

We used a protocol consisting of a continuous presentation of stimuli with associated response requests during an intracarotid sodium amobarbital procedure (IAP) to study the effects of hemisphere injected (speech dominant vs. nondominant) and seizure focus (left temporal lobe vs. right temporal lobe) on the pattern of behavioral response errors for three types of visual stimuli (pictures of common objects, words, and abstract forms). Injection of the left speech dominant hemisphere compared to the right nondominant hemisphere increased overall errors and affected the pattern of behavioral errors. The presence of a seizure focus in the contralateral hemisphere increased overall errors, particularly for the right temporal lobe seizure patients, but did not affect the pattern of behavioral errors. Left hemisphere injections disrupted both naming and reading responses at a rate similar to that of matching-to-sample performance. Also, a short-term memory deficit was observed with all three stimuli. Long-term memory testing following the left hemisphere injection indicated that only for pictures of common objects were there fewer errors during the early postinjection period than for the later long-term memory testing. Therefore, despite the inability to respond to picture stimuli, picture items, but not words or forms, could be sufficiently encoded for later recall. In contrast, right hemisphere injections resulted in few errors, with a pattern suggesting a mild general cognitive decrease. A selective weakness in learning unfamiliar forms was found. Our findings indicate that different patterns of behavioral deficits occur following the left vs. right hemisphere injections, with selective patterns specific to stimulus type.

Adult↗

Contamination of houses by workers occupationally exposed in a lead-zinc-copper mine and impact on blood lead concentrations in the families.

OBJECTIVE: To evaluate the pathway of leaded dust from a lead-zinc-copper mine to houses of employees, and the impact on blood lead concentrations (PbB) of children. METHODS: High precision lead isotope and lead concentration data were obtained on venous blood and environmental samples (vacuum cleaner dust, interior dustfall accumulation, water, paint) for eight children of six employees (and the employees) from a lead-zinc-copper mine. These data were compared with results for 11 children from occupationally unexposed control families living in the same city. RESULTS: The median (range) concentrations of lead in vacuum cleaner dust was 470 (21-1300) ppm. In the houses of the mine employees, vacuum cleaner dust contained varying higher proportions of mine lead than did airborne particulate matter measured as dustfall accumulated over a three month period. The median (range) concentrations of lead in soil were 30 (5-407) ppm and these showed no evidence of any mine lead. Lead in blood of the mine employees varied from 7 to 25 micrograms/dl and was generally dominated by mine lead (> 60%). The mean (SD) PbB in the children of the mine employees was 5.7 (1.7) micrograms/dl compared with 4.1 (1.4) micrograms/dl for the control children (P = 0.02). The PbB of all children was always < 10 micrograms/dl, the Australian National Health and Medical Research Council goal for all Australians. Some of the control children had higher PbB than the children of mine employees, probably from exposure to leaded paint as six of the eight houses of the control children were > 50 years old. In five of the eight children of mine employees > 20% of PbB was from the lead mine. However, in the other three cases of children of mine employees, their PbB was from sources other than mine lead (paint, petrol, background sources). CONCLUSIONS: Houses of employees from a lead mine can be contaminated by mine lead even if they are not situated in the same place as the mine. Delineation of the mine to house pathway indicates that lead is probably transported into the houses on the clothes, shoes, hair, skin, and in some cases, motor vehicles of the workers. In one case, dust shaken from clothes of a mine employee contained 3000 ppm lead which was 100% mine lead. The variable contamination of the houses was not expected given the precautions taken by mine employees to minimise transportation of lead into their houses. Although five out of the eight children of mine employees had > 20% mine lead in their blood, in no case did the PbB of a child exceed the Australian National Health and Medical Research Council goal of 10 micrograms/dl. In fact, some children in the control families had higher PbB than children of mine employees. In two cases, this was attributed to a pica habit for paint. The PbB in the children of mine employees and controls was independent of the source of lead. The low PbB in the children of mine employees may reflect the relatively low solubility (bioavailability) of the mine dust in 0.1 M hydrochloric acid (< 40 %), behaviour--for example, limited mouthing activity--or diet.

Adult↗

Progressive entorhinal cortex lesions accelerate hippocampal sprouting and spare spatial memory in rats.

Accelerating hippocampal sprouting by making unilateral progressive lesions of the entorhinal cortex spared the spatial memory of rats tested for retention of a learned alternation task. Subsequent transection of the sprouted crossed temporodentate pathway (CTD), as well as a simultaneous CTD transection and progressive entorhinal lesion, produced a persistent deficit on the memory task. These results suggest that CTD sprouting, which is homologous to the original perforant path input to the dentate gyrus of the hippocampus, is behaviorally significant and can ameliorate at least some of the memory deficits associated with hippocampal deafferentation.

Animals↗

Guidance and activation of murine macrophages by nanometric scale topography.

We studied the guidance and activation of macrophages from the P388D1 cell line and rat peritoneum by topographic features on a nanometric scale. Cells were plated on plain fused silica substrata or substrata with microfabricated grooves and steps, 30-282 nm deep. The contact of cells with the patterned surface activated cell spreading and adhesion and increased the number of protrusions of the cell membrane. These changes were accompanied by an increase in the amount of F-actin in cells. The accumulation of F-actin and vinculin in cells was observed along the edges of single steps or grooves. Formation of focal contacts along discontinuities in the substratum was accompanied by the phosphorylation of tyrosine colocalized with F-actin and vinculin. A similar pattern of staining was seen in cells stained for vitronectin receptor, alphaV integrin, but not for integrins alpha5beta1 or alpha3beta1. Cells cultured on nanogrooves showed a higher phagocytotic activity than cells cultured on plain substrata. We show that macrophages can react to ultrafine features of topography of a size comparable to that of a single collagen fiber and become activated by the contact with topographic features.

Animals↗

Risk factors for Chlamydia trachomatis pelvic inflammatory disease among sex workers in Nairobi, Kenya.

Among 302 female sex workers in Nairobi, Kenya, who were followed for 17.6 +/- 11.1 months, 146 had one or more infections with Chlamydia trachomatis; 102 had uncomplicated cervical infection only, 23 had C. trachomatis pelvic inflammatory disease (PID), and 21 had combined C. trachomatis and Neisseria gonorrhoeae PID. As determined by multivariate logistic regression analysis, risk factors for C. trachomatis PID included repeated C. trachomatis infection (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.3-2.4; P = .0004), antibody to C. trachomatis heat-shock protein 60 (OR, 3.9; CI, 1.04-14.5; P = .04), oral contraceptive use (OR, 0.28; 95% CI, 0.08-0.99; P = .048), and number of episodes of nongonococcal nonchlamydial PID (OR, 1.7; 95% CI, 1.1-2.7; P = .02). Among human immunodeficiency virus (HIV)-seropositive women, a CD4 lymphocyte count of <400/mm3 was an additional independent risk factor for C. trachomatis PID (OR, 21.7; 95% CI, 1.2-383; P = .036); among HLA-typed women, HLA-A31 was independently associated with C. trachomatis PID (OR, 5.6; 95% CI, 1.1-29.4; P = .043). The results suggest an immune-mediated pathogenesis for C. trachomatis PID.

Adult↗

Behavioral interventions for reduction of sexually transmitted disease/HIV transmission among female commercial sex workers and clients in Bali, Indonesia.

OBJECTIVE: To describe and evaluate a behavioral intervention targeted to low-price female commercial sex workers (CSW) in large brothel complexes, their pimps, and their male clients. DESIGN AND METHODS: Fieldwork was conducted during 1994 in Bali, Indonesia. Intervention activities included an education program for CSW, pimp training, condom sales and distribution, and client media. Theoretical perspectives guiding the intervention were the Health Belief Model and social cognitive theory. Baseline and evaluation surveys were conducted to evaluate the intervention. RESULTS: Both AIDS and sexually transmitted disease (STD) knowledge increased significantly over the intervention period. Condom use for vaginal sex with paid partners the day before the interview increased substantially in the two intervention areas: 18-75% and 29-62%. Condom use also increased in the control area, although the difference between baseline and evaluation measures was smaller. Multivariate analyses indicated that programmatic factors such as attendance at education sessions and reading the project brochure were related to condom use. CONCLUSIONS: Increasing community knowledge and awareness among low-price CSW, pimps, and clients regarding AIDS and STD using trained outreach workers is feasible and effective. In summary, this study has documented the effectiveness of a behavioral intervention for CSW and their clients.

Acquired Immunodeficiency Syndrome↗

The reliability of pressure sore risk-assessment tools.

Regular use of a risk-assessment tool may help increase and maintain staff awareness of pressure sore risk. All staff need to be educated in the use of the selected tool, to ensure reliability between users. A tool's threshold score should not be presumed appropriate in all patient areas. Care should be taken when using these scores to allocate preventive resources.

Humans↗

Life without amniocentesis: elevated maternal serum alpha-fetoprotein in the Manitoba program 1986-91.

Pregnant women demonstrating an elevated maternal serum alpha-fetoprotein level are at increased risk for fetal neural tube defect or other anomaly. Diagnostic procedures to evaluate these pregnancies include high-resolution ultrasound and amniocentesis to measure amniotic fluid levels of alpha-fetoprotein and N-acetylcholinesterase. We wished to examine the efficacy of detailed ultrasound examination alone, in evaluation of women with 'unexplained' elevation of maternal serum alpha-fetoprotein. The results showed that no neural tube defects were missed in the assessment of 1325 pregnancies with a raised level of maternal serum alpha-fetoprotein over 6 years, despite complete reliance on ultrasound in 98%. Detailed fetal ultrasound evaluation by experienced personnel is adequate to identify all cases of neural tube defects in a selected high-risk population.

Journal Article↗

Circulating insulin-like growth factor I concentrations in clinically severe obese patients with and without NIDDM in response to weight loss.

Earlier studies have demonstrated decreased levels of circulating Insulin-Like Growth Factor-I (IGF-I) in patients with NIDDM and IDDM (Yde 1969; Rieu and Binoux 1985), with a return to normal in those diabetics who achieve improved metabolic control (Rieu and Binoux 1985; Ameil, Sherwin, Hintz, Gertner, Press and Tamborlane 1984) following insulin therapy. One method of improving metabolic control in clinically severe obese NIDDM patients is the gastric bypass procedure (GBP). This study revealed a significant decrease in serum IGF-I concentrations in clinically severe obese patients with NIDDM (obese NIDDM) (105 ng/dl +/- 11; n = 29) as compared with clinically severe obese patients with normal glucose tolerances (obese control) (143 +/- 11; n = 21) and lean controls (177 +/- 14; n = 19) (p < 0.001). Following a GBP, IGF-I levels increased in the NIDDM group (142 ng/dl +/- 13.0; n = 20) to the extent that no significant difference was seen between postoperative NIDDM, obese controls, and lean controls. Postoperative IGF-I levels in the obese controls (151 +/- 14; n = 9) revealed no difference from preoperative levels. Postoperative obese NIDDM and obese control had a 28% and 29% decrease, respectively, in weight, with no difference between the groups in respect to Body Mass Indices. The NIDDM postoperative group revealed reductions in levels of HbA1C, insulin, and glucose concurrent with elevations in IGF-I when compared with controls. We conclude that improvement in glucose control led to the increase in IGF-I levels.

Adult↗

Surface transport and internalization of the membrane IgM H chain in the absence of the Mb-1 and B29 proteins.

The micron IgH chain is one component of the membrane IgM complex, the endocytic and signal transducing receptor for Ag on the surface of B lymphocytes. It is transported to the cell surface in association with three other B cell-specific proteins, an L chain and the products of the mb-1 and B29 genes. The roles played by these various proteins in mediating the functions of the complex are unclear. To analyze micron function in the absence of other lymphoid-specific proteins, we first attempted to express micron on the surface of nonlymphoid cells. Deletion of the CH1 domain was sufficient to allow surface expression of this protein in transfected COS cells as well as in mouse L cells. To determine whether this extracellularly truncated micron was capable of endocytosis, we used an assay to detect the internalization of anti-mu antibody bound to the surface of transfected cells expressing the protein. Under both cross-linking and non cross-linking conditions, the CH1-deleted micron protein was internalized in endocytic vesicles. We conclude from these observations that a) the CH1 domain of micron contains a retention signal, the elimination of which allows surface transport of this protein, and b) micron by itself is capable of at least one of the functions of the membrane IgM complex.

Amino Acid Sequence↗

Spontaneous desaturations in intubated very low birth weight infants with acute and chronic lung disease.

Patients with chronic lung disease (CLD) have frequent episodes of spontaneous desaturations. Utilizing computerized pulse oximetry (CPO) we quantified the frequency and severity of spontaneous desaturations in very low birth weight (VLBW) infants with CLD. Thirty-four studies by CPO were performed in intubated infants for 4 hours; 17 patients (birth weight, 550-980 g; postnatal age 28-85 days) had CLD, and 17 (birth weight, 520-980 g; postnatal age, 1-7 days) had acute lung disease. Oxygen saturation (SaO2) was measured with the Nellcor N-200 oximeter, its serial output (updated once a second) captured by a computer. Pulse rate, pulse amplitude, and heart rate were also monitored continuously. We measured respiratory system mechanics in 23 patients. Tidal volume (VT), respiratory system compliance (Crs), and resistance (Rrs) were obtained by the PeDS system. Spontaneous desaturation to SaO2 less than 90% occurred for 4.5% of the time in acute patients vs. 27.1% of the time in chronic patients (P less than 0.0001); to SaO2 less than 85%, 0.7% vs. 7.6% of the time in acute vs. chronic patients (P less than 0.002); and to SaO2 less than 80%, 0.4% vs. 2.6% of the time in acute vs. CLD patients (P less than 0.05). Rrs was significantly higher in the ventilated patients with CLD (174 cmH2O/L/s) than in the ventilated patients with acute lung disease (94 cmH2O/L/s, P less than 0.0001). The mean Crs values of the two groups were comparable. Our preliminary data indicate that VLBW infants with CLD receiving assisted ventilation have a greater number of spontaneous desaturation episodes, as compared to patients with acute lung disease.

Acute Disease↗

Silent ischaemia in diabetic men with autonomic neuropathy.

Autonomic neuropathy is associated with an increased incidence of silent myocardial infarction and sudden death. The purpose of this study was to investigate the prevalence of silent myocardial ischaemia in diabetic patients with autonomic neuropathy and without. Five standard autonomic function tests were performed on 41 men with diabetes: postural change in blood pressure, postural change in heart rate, heart rate response to deep breathing, heart rate response to Valsalva's manoeuvre, and blood pressure response to sustained handgrip. There were 17 patients with autonomic neuropathy (group A) and 24 with normal autonomic function (group B). All patients underwent 24 hour ambulatory electrocardiographic monitoring to detect silent ischaemia. There was no significant difference in risk factors for coronary artery disease or history of angina pectoris between these groups. The prevalence of silent ischaemia was 64.7% in group A (95% confidence interval (95% CI) 38.33 to 85.79%) and 4.1% in group B (95% CI 0.11 to 21.12%). This represents a relative risk of 42.2 (95% CI 4.5 to 39.4, p less than 0.001). These results are consistent with the concept that autonomic neuropathy may prevent the development of anginal pain and thus obscure the presence of ischaemic heart disease. Twenty four hour ambulatory electrocardiographic monitoring may identify a subgroup of diabetic patients with autonomic neuropathy who have myocardial ischaemia and to whom treatment may be offered.

Autonomic Nervous System Diseases↗

A double-blind, placebo-controlled study of acetylsalicylic acid (ASA) in trained runners.

Acetylsalicylic acid (ASA) is a short-acting oral inhibitor of the cyclooxygenase enzyme. Ingestion of ASA is associated with a decrease in prostaglandins, including those of the E2 series, as well as prostacyclin, and thromboxane. Consumption of therapeutic doses is associated with decreased pain and inflammation and is therefore used in a variety of inflammatory conditions. Platelet aggregation is also inhibited. Because of these observations, and the fact that platelet aggregation has been noted to be altered during exercise, the effects of ASA on exercise tolerance was of interest. We studied 17 healthy male volunteers who regularly ran as a source of exercise. During the study they ingested either 650 mg of ASA or placebo 30 min before running 2 miles (3.2 km). Outcome of the double-blind crossover study was measured by the time required to run a 2-mile distance. No differences between ASA or placebo were noted in the subjects. These data suggest that 650 mg of ASA as a premedication has little effect on exercise performance in normal endurance runners. However, whether ASA may affect pain after exercise or whether other dosage intervals would be more beneficial needs further study.

Adult↗

Maternal serum alpha-fetoprotein in twin pregnancy.

Maternal serum alpha-fetoprotein concentration was measured at 14 to 20 weeks' gestation in 138 twin pregnancies. All patients had at least one ultrasonographic examination (86% before 20 weeks' gestation). Two pregnancies were discordant for open fetal defects (one anencephaly, one gastroschisis). The median serum alpha-fetoprotein value in the remaining 136 twin pregnancies paralleled a curve 2.5 times the median curve for singleton pregnancies over the gestational range studied. Higher serum alpha-fetoprotein values correlated significantly with increasing incidence of fetal and neonatal death, premature delivery (less than 35 weeks' gestation), and twin-to-twin birth discordance (greater than 20%), most pronounced at greater than 4 multiples of the singleton median level. A significant negative correlation between alpha-fetoprotein and birth weight was observed (p less than 0.001), but was related more to prematurity than to poor fetal growth. Theoretically, serum alpha-fetoprotein screening detected 56.5% of the twins in this study when a cutoff level of 2.5 multiples of the median was used, enhancing twin detection in the study population by 40%. These data indicate that maternal serum alpha-fetoprotein screening has a valuable role in the management of twin pregnancy, both in the detection of twins and in the prediction of perinatal outcome in twin pregnancy.

Female↗