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Biomedical subjects

P Miller

Publications and source records attributed to P Miller.

At least 163 records · Page 9Linked to original sources
PubMed1994

Binding of benzoquinoid ansamycins to p100 correlates with their ability to deplete the erbB2 gene product p185.

Several benzoquinoid ansamycins, e.g., herbimycin A and geldanamycin, have been widely used as inhibitors of tyrosine kinases. We recently reported that exposure to herbimycin A and several analogs depletes the erbB2 gene product p185 in human breast cancer cells. In order to explore the mechanism of this specific degradation of p185, a biologically active ansamycin incorporating a photoaffinity label was synthesized. This compound, CP202509, specifically bound to a 100 kD protein (p100) in intact SKBr3 cells and in fibroblasts transfected with the c-erbB2 or v-src oncogenes. Binding of other ansamycin analogs to p100, as measured indirectly by their ability to inhibit CP202509 binding, correlated with their ability to lower p185 protein and phosphotyrosine in SKBr3 cells. These results suggest that the ansamycins may deplete tyrosine kinases through binding to this protein.

Affinity Labels↗
PubMed1994

Depletion of the erbB-2 gene product p185 by benzoquinoid ansamycins.

Herbimycin A, a benzoquinoid ansamycin, is widely used as an inhibitor of tyrosine kinases. We have examined the effects of herbimycin A and several analogues on p185, the tyrosine kinase encoded by the erbB2 gene in human breast cancer cells. Exposure to 0.35 microM herbimycin A reduced tyrosine phosphorylation of p185 in SKBr3 cells by 80% after 2 h, and the p185 protein level was reduced by 90% after 6 h. The reduction of p185 resulted primarily from increased degradation of p185; cellular protein synthesis was reduced only 16% in SKBr3 cells treated with herbimycin A, RNA synthesis was inhibited only 10%, and erbB2 mRNA levels were unchanged. Examination of the major cellular glycoproteins indicated that most glycoproteins were unaffected under conditions that substantially depleted p185. Studies with cell lines transfected with erbB2 containing defined deletions indicated that susceptibility to the depletion of p185 by herbimycin and its analogues required the domain encoded by amino acids 751-971. The benzoquinoid ansamycins therefore initiate a process of specific degradation of tyrosine kinases by a mechanism that remains unknown.

Anti-Bacterial Agents↗
PubMed1994

Radiological scoring of osteoarthritis progression in STR/ORT mice.

The progressive changes observed in the knee and ankle joints of male STR/ORT mice, which spontaneously develop osteoarthritis (OA), were quantified by a radiological scoring system. The knee scores for males increased with age whereas those for females plateaued from 5 months. Comparison of scores for the knee and ankle joints showed that the male knee scores increased directly with age but were not significantly different from female scores until 7 months whereas the male ankle scores increased dramatically at 5-6 months and plateaued thereafter. In addition, correlations between patellar and calcaneal displacement showed that they rarely occurred together in the same limb, suggesting that knee and ankle OA are almost independent events. Although an association between high knee scores and patellar displacement was noted, even at 11 months of age not all mice with OA had displaced patellae, demonstrating that patellar displacement cannot be a primary event. Remarkably, summing the scores of all calcified structures in the ankle and knee joints revealed that the scores became significantly greater for males than for females by 3 months of age. It is considered that calcification is an earlier event than cartilage erosion and that OA in male STR mice may result from calcification placing abnormal stresses on joints.

Age Factors↗
PubMed1994

Chondro-osseous metaplasia, bone density and patellar cartilage proteoglycan content in the osteoarthritis of STR/ORT mice.

The evolution of osteoarthritis (OA) was compared in male and female STR/ORT mice and in male CBA mice with particular emphasis on the changes in para-articular structures which occur before the classical degenerative phenomena in the articular cartilage of the knee. In male STR but not female STR mice or male CBA mice, chondro-osseous metaplasia was found in the tendinous structures which surround the joint and in the major ligamentous entheses such as the patellar ligament. This change was detectable from the age of three months. By contrast, changes in the articular surfaces of the knee were never detected before four months while the total patellar proteoglycan content in male STR animals increased from three months. Line density profile measurements on radiographs of the knees revealed that changes in the bone density of the sub-chondral zone of the articular surfaces only increased in affected animals after the development of severe OA changes in the joint. It is suggested that the model of OA which develops in male STR/ORT mice is secondary to soft tissue changes, particularly chondro-osseous metaplasia in para-articular structures.

Achilles Tendon↗
PubMed1994

High risk or low: how location on a "risk ladder" affects perceived risk.

Efforts to explain risk magnitude often rely on a "risk ladder" in which exposure levels and associated risk estimates are arrayed with low levels at the bottom and high ones at the top. Two experiments were conducted to test the hypothesis that perceived threat and intended mitigation vary with the location of the subject's assigned level on the risk ladder. Subjects were New Jersey homeowners, asked to assume a particular level of radon or asbestos contamination in their homes, to read a brochure explaining the risk, and then to complete a questionnaire. Both studies found that the difference between an assigned level one-quarter of the way up the ladder and the same level three-quarters of the way up the ladder significantly affected threat perception; the effect on mitigation intentions was significant in only one of the studies. Variations in assigned risk also affected threat perception and mitigation intentions. Variations in test magnitude (e.g., 15 fibers per liter vs. 450 fibers per cubic foot, roughly equivalent risks) had no effect, nor did the distinction between radon and asbestos affect the dependent variables. These findings suggest that communicators can design risk ladders to emphasize particular risk characteristics.

Analysis of Variance↗
PubMed1994

Biodegradable, effective substitute for xylene in the Ehrlich indole procedure.

Three extracting reagents were compared for effectiveness in the Ehrlich indole procedure: xylene (the recommended reagent), Hemo-De (a terpene-based product containing d-limonene), and Micro-Clear (an isoparaffinic hydrocarbon). Thirty-three strains representing 12 species of indole-positive aerobes or facultative anaerobes and 50 strains representing 11 species of indole-positive strict anaerobes were tested using the three reagents. Xylene extraction allowed indole detection in all of the isolates tested. Micro-Clear allowed detection in all of the aerobic isolates and in 49 of 50 anaerobes. Hemo-De allowed indole detection in 32 of 33 aerobes and in 49 of 50 anaerobes. There was no significant difference in the results among the reagents. Because Micro-Clear is biodegradable, nonflammable, noncarcinogenic, and odorless, we feel that this product should be considered a safe and effective substitute for xylene in the Ehrlich indole procedure.

Bacterial Typing Techniques↗
PubMed1994

Psychological status, syndromatic measures, and compliance with nasal CPAP therapy for sleep apnea.

38 male patients with obstructive sleep apnea were asked to complete 2 weeks of rating symptoms, physical examination, diagnostic polysomnography, and MMPI testing prior to being placed on nasal continuous positive airway pressure (CPAP) therapy. Six months later, 26 (72.2%) of the 36 subjects available for follow-up showed continued compliance. A regression analysis conducted with those 28 subjects who completed all pretreatment measures showed that continued therapy was predicted by such pretreatment measures as patients' body mass index, ratings of daytime sleepiness and nocturnal sleep quality, and MMPI Depression and Hypochondriasis scale scores (R2 = 0.63). Eventual compliers had a higher Body Mass Index, reported less daytime sleepiness and better nocturnal sleep quality, and scored lower on the MMPI D and Hs scales prior to treatment than did the noncompliers. A linear discriminant function analysis with analog cross-validation showed these five predictors would identify approximately 80% of eventual noncompliers and 97% of those who display compliance. It was concluded that subjective report and personality measures may be useful in predicting long-term use. Additional studies are needed to assess the clinical significance of the noted MMPI scale elevations among sleep apnea patients in general and among those patients who display eventual noncompliance.

Adult↗
PubMed1994

Application of physiotherapy outcome measures to the managed care model.

Managed Care (MC) is a multidisciplinary model for health care delivery that organizes and sequences the caregiving process. Its objectives include: 1) to reduce length of stay and resource consumption, and 2) to measure, maintain or improve patient outcomes related to care received. Our tertiary care facility is the first Canadian hospital to implement MC. Patient care is directed through the use of a Care Map. Each map is specific to a pathological state and its treatment, i.e. Total Knee Replacement (TKR), and consists of a Patient Problem List, with related patient-centred outcomes, and a Critical Path. The Critical Path outlines the temporal sequence of the provision of care. Most key events on a Care Map are determined anecdotally. The purpose of this project was to collect outcome information in patients assigned to the Total Knee Replacement Care Map in an attempt to validate the existing Care Map or make recommendations for revisions. Inter-rater and intra-rater reliability of knee range of motion-was calculated using the Intra Class Correlation Coefficient (ICC). ICC values ranged from .64-.97. Seventeen patients were assessed. All patients were measured on Day 6 and 8 of the Care Map. This process has resulted in validation of certain range estimates and recommendations for revision of others.

Aged↗
PubMed1994

Diarrhoea and mortality in Menoufia, Egypt.

From 1982 the Ministry of Health of Egypt implemented the National Control of Diarrhoeal Diseases Project (NCDDP) which attempted to improve case management of childhood diarrhoea by making oral rehydration salts (ORS) widely available and used, to improve feeding patterns during diarrhoea, and other measures. National data indicate a high level of success in achieving the targets. However, impact evaluation is hampered by weak national baseline information available prior to NCDDP on case management of diarrhoea and causes of infant and childhood mortality. A study in Menoufia Governorate in 1979-80 obtained such information. Consequently, in 1988 the area was revisited to examine subsequent changes. Findings showed marked improvement in case management of diarrhoea and rapid mortality decline, with diarrhoeal mortality apparently declining somewhat faster than mortality from other causes.

Child↗
PubMed1993

Ways of coping with chronic fatigue syndrome: development of an illness management questionnaire.

Chronic fatigue syndrome (CFS) is a disorder of uncertain aetiology, and there is uncertainty also about the appropriate way in which patients should manage the illness. An illness management questionnaire (IMQ) was designed to assess coping in CFS. This was completed by 207 patients, in parallel with the COPE scales (a general measure of coping that can be applied situationally), and measures of functional impairment, anxiety and depression. The IMQ yielded four factors: maintaining activity, accommodating to the illness, focusing on symptoms and information-seeking. Scales based upon these factors together predicted 26, 27 and 22% of the variance in functional impairment, anxiety and depression, respectively, and each scale had significant relationships with relevant scales of the COPE, supporting the interpretation of the factors. It is suggested that the IMQ may be employed to relate ways of coping to outcomes in CFS, and to assess coping as a mediator of change in cognitive-behavioural interventions.

Adaptation, Psychological↗
PubMed1993

Chlorthalidone attenuates the reduction in total cholesterol and small, dense LDL cholesterol subclass associated with weight loss.

Thiazide diuretics are known to raise total and LDL cholesterol. To assess whether chlorthalidone affected levels of putatively atherogenic small, dense LDL (LDL 3), we conducted a 12 week double blind randomized, placebo controlled clinical trial in 34 nonsmoking men aged 35 to 57 years with mild hypertension (DBP 90 to 104 mm Hg). Our a priori hypothesis that chlorthalidone raised LDL 3 levels was not confirmed. However, the fall in LDL 3 (P = .03) and total cholesterol (P = .08) associated with weight loss was attenuated by chlorthalidone. Since weight loss is commonly prescribed during the clinical management of hypertensives with concomitant hypercholesterolemia, consideration should be given to the attenuating effect of chlorthalidone on cholesterol reduction in the management of these patients.

Adult↗
PubMed1993

Age differences in patient recovery patterns following coronary artery bypass surgery.

OBJECTIVE: The purpose of this study was to determine whether physical, psychological and social recovery within the first 6 weeks following coronary artery bypass surgery varied by age. METHODS: A repeated measures design was used for this study. Data were collected from a convenience sample of three age groups of patients at the following times: prior to hospital discharge and at 1, 3 and 6 weeks after discharge. The three age groups studied were less than 60 years, 60 to 70 years and more than 70 years. Data were collected by interview and mail questionnaires. The initial sample consisted of 258 patients, of whom 184 completed the study. Eleven instruments were used to measure recovery including the Sickness Impact Profile, Beck Depression Inventory, Rosenberg Self-Esteem scale and the Symptom Inventory. RESULTS: No significant differences were found among the age groups for any of the physical, psychological or social recovery measures. Within each age group physical, psychological and social recovery improved significantly over time. Although patients more than 70 years of age remained in the hospital significantly longer, once discharged, they did not have more difficulty with recovery than the other age groups. DISCUSSION: As expected, all age groups experienced significant improvement in recovery over time. CONCLUSIONS: Contrary to what past research about cardiac surgery and the elderly might lead one to expect, in this study, the oldest patients did not have the poorest recovery patterns. Persons more than 70 years had recovery patterns similar to those of younger age groups.

Adult↗