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Biomedical subjects

S King

Publications and source records attributed to S King.

At least 73 records · Page 4Linked to original sources

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Clinical Competence↗

Influence of age on outcome after percutaneous transluminal coronary angioplasty.

This study estimates the influence of age on outcomes (mainly survival) of 21,516 patients who underwent percutaneous transluminal coronary angioplasty (PTCA) between 1980 and 1996. We prospectively analyzed the patients in 5 age groups: <50, 50 to 59, 60 to 69, 70 to 79, and > or =80 years old. During the in-hospital period after PTCA, mortality increased from 0.28% in patients aged <50 to 3.45% in patients aged > or =80; Q-wave myocardial infarction was not significantly associated with age, and the 2 older groups were referred less often to coronary artery bypass graft surgery. During follow-up, lasting up to 10 years, the hazard of death was significantly influenced by age; Q-wave myocardial infarction was influenced by age, although the magnitude of the effect was relatively small and of questionable clinical significance; and coronary artery bypass graft surgery was performed less often in the 2 older age groups. Additional PTCA was similarly performed among the age groups. Age, diabetes mellitus, systemic hypertension, heart failure class, angioplasty in graft vessel, number of coronary vessels narrowed, and previous myocardial infarction were predictors of death over the 10-year follow-up. Age was the most important correlate of death after PTCA, with a 65% increase in the hazard of death for each 10-year increase in age. Age has an independent effect on early and late survival after PTCA.

Age Distribution↗

The Hdj-2/Hsc70 chaperone pair facilitates early steps in CFTR biogenesis.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride ion channel constructed from two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBD) and a regulatory (R) domain. The NBDs and R-domain are cytosolic and how they are assembled with the MSDs to achieve the native CFTR structure is not clear. Human DnaJ 2 (Hdj-2) is a co-chaperone of heat shock cognate 70 (Hsc70) which is localized to the cytosolic face of the ER. Whether Hdj-2 directs Hsc70 to facilitate the assembly of cytosolic regions on CFTR was investigated. We report that immature ER forms of CFTR and DeltaF508 CFTR can be isolated in complexes with Hdj-2 and Hsc70. The DeltaF508 mutation is localized in NBD1 and causes the CFTR to misfold. Levels of complex formation between DeltaF508 CFTR and Hdj-2/Hsp70 were approximately 2-fold higher than those with CFTR. The earliest stage at which Hdj-2/Hsc70 could bind CFTR translation intermediates coincided with the expression of NBD1 in the cytosol. Interestingly, complex formation between Hdj-2 and nascent CFTR was greatly reduced after expression of the R-domain. In experiments with purified components, Hdj-2 and Hsc70 acted synergistically to suppress NBD1 aggregation. Collectively, these data suggest that Hdj-2 and Hsc70 facilitate early steps in CFTR assembly. A putative step in the CFTR folding pathway catalyzed by Hdj-2/Hsc70 is the formation of an intramolecular NBD1-R-domain complex. Whether this step is defective in the biogenesis of DeltaF508 CFTR will be discussed.

Carrier Proteins↗

Screening Mammography Program of British Columbia: pattern of use and health care system costs.

BACKGROUND: The use of mammography for screening asymptomatic women has increased dramatically in the past decade. This report describes the changes that have occurred in the use of bilateral mammography in British Columbia since the provincial breast cancer screening program began in 1988. METHODS: Using province-wide databases from both the breast cancer screening program and the provincial health insurance plan in BC, the authors determined the number and costs of bilateral mammography services for women aged 40 years or older between Apr. 1, 1986, and Mar. 31, 1997. Unilateral mammography was excluded because it is used for investigating symptomatic disease and screening abnormalities, and for follow-up of women who have undergone mastectomy for cancer. RESULTS: As the provincial breast cancer screening program expanded from 1 site in 1988 to 23 in 1997, it provided an increasing proportion of the bilateral mammographic examinations carried out each year in BC. In fiscal year 1996/97, 65% of bilateral mammographic examinations were performed through the screening program. The cost per examination within the screening program dropped as volume increased. Thirty percent more bilateral mammography examinations were done in 1996/97 than in 1991/92, but health care system expenditures for these services increased by only 4% during the same period. In calendar year 1996, 21% of new breast cancers were diagnosed as a result of a screening program visit. INTERPRETATION: Substantial increases in health care expenditures have been avoided by shifting bilateral mammography services to the provincial screening program, which has a lower cost per screening visit.

Adult↗

Dietary advice to reduce fat intake is more successful when it does not restrict habitual eating patterns.

OBJECTIVE: To determine the relative and combined effects of dietary advice to lower fat intake and alter eating frequency on nutrient intake and plasma lipid levels in men with recently diagnosed hyperlipidemia. DESIGN: In this 4-week dietary intervention trial, a 7-day food diary was used in the week preceding the intervention and on the third week of the intervention to determine eating frequency. A 7-day dietary history and lipid profile (after subjects had fasted) were taken at baseline and at the end of the 4 weeks of dietary intervention. SUBJECTS: Eighty nonobese, free-living men with newly diagnosed primary hypercholesterolemia. INTERVENTION: Group 1: fat intake was reduced and eating frequency decreased. Group 2: Fat intake was reduced and eating frequency maintained. Group 3: Fat intake was maintained and eating frequency decreased. Group 4: Fat intake was maintained and eating frequency increased. MAIN OUTCOME MEASURES: Changes in lipid profiles of the subjects and evaluation of subjects' perception of the dietary advice they received. STATISTICAL ANALYSES PERFORMED: Baseline and intervention values were compared using a paired t test; 2-way analysis of variance was used across treatment groups. RESULTS: Dietary advice to lower fat intake significantly lowered total and low-density lipoprotein cholesterol levels; this advice also decreased intake of total fat and saturated fatty acids significantly, but less so in the group asked to restrict eating occasions to 3 per day. Advice to alter eating frequency was found to be difficult to follow. APPLICATIONS: Lipid-lowering dietary advice should be incorporated into the existing eating frequency pattern of each person.

Adult↗

Viral infections in interferon-gamma receptor deficiency.

Interferon-gamma receptor deficiency is a recently described immunodeficiency that is associated with onset of severe mycobacterial infections in childhood. We describe the occurrence of symptomatic and often severe viral infections in 4 patients with interferon-gamma receptor deficiency and mycobacterial disease. The viral pathogens included herpes viruses, parainfluenza virus type 3, and respiratory syncytial virus. We conclude that patients with interferon-gamma receptor deficiency and mycobacterial disease have increased susceptibility to some viral pathogens.

Antigens, CD↗

Acute renal failure following cardiac surgery.

BACKGROUND: Acute renal failure requiring dialysis (ARF-D) occurs in 1.5% of patients following cardiac surgery, and remains a cause of major morbidity and mortality. While some preoperative risk factors have been characterized, the influence of preoperative and intraoperative factors on the occurrence of ARF following cardiac surgery is less well understood. METHODS: Preoperative and intraoperative data on 2843 consecutive adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) from February 1, 1995 to February 1, 1997 were recorded and entered into a computerized database. Two definitions of renal failure were employed: (i) ARF defined as a rise in serum creatinine (Cr) of 1 mg/dl above baseline; and (ii) ARF-D defined as the development of ARF for which some form of dialytic therapy was required. The association between preoperative and intraoperative variables and the development of ARF was assessed by multivariate logistic regression. RESULTS: A total of 2672 of the 2844 patients underwent isolated coronary artery bypass grafting (CABG) surgery, the remaining 172 underwent valve surgery with or without bypass grafting. Of the CABG patients 7.9% developed ARF and 0.7% developed ARF-D. The mortality for patients who developed ARF was 14% (OR 15, P = 0.0001) compared with 1% among those who did not develop ARF. The mortality for CABG patients who developed ARF-D was 28% (OR 20, P = 0.0001) compared with 1.8% among those who did not require dialysis. Variables that were significantly associated with the development of ARF by multivariate analysis included: increased age, elevated preoperative serum Cr, duration of CPB, presence of a carotid artery bruit, presence of diabetes, reduced cardiac ejection fraction and increased body weight. Variables independently associated with ARF-D included serum Cr, duration of CPB, carotid artery bruit and presence of diabetes. The utility of these models for predicting the development of ARF and ARF-D was confirmed by bootstrapping techniques. Because of the small number of patients who underwent valve surgery, none of these variables were significantly associated with the development of ARF or ARF-D in this group of patients. CONCLUSION: The development of ARF or ARF-D is associated with a high mortality following CABG surgery. We have identified perioperative variables, which may be useful in stratifying risk for the development of ARF.

Acute Kidney Injury↗

Expressed emotion and relapse in young schizophrenia outpatients.

High familial expressed emotion (EE) reliably predicts 9-month relapse rates in schizophrenia patients. Difficulties interpreting the EE-relapse finding arise, however, because EE is usually assessed during a hospital admission, yet relapse following discharge is predicted. Researchers in Scotland assessed EE in relatives while the patients were out of hospital; using conservative relapse criteria, they failed to find higher subsequent 6- and 12-month relapse rates among patients living in high-EE homes (McCreadie and Phillips 1988). Our goal was to determine the ability of EE to predict relapse in a sample of 69 schizophrenia outpatients using both conservative criteria (for 6-and 12-month rates) and standard relapse criteria (for 9- and 18-month rates). According to the conservative criteria, EE failed to predict 6- and 12-month relapse. According to the standard criteria, 9-month relapse rates were significantly greater among patients in high-EE households. In parental homes, relapse at both 9 months and 18 months was best predicted by fathers' critical comments and mothers' emotional overinvolvement. Relapse was not associated with medication compliance and the amount of contact with high-EE relatives.

Adolescent↗

Cerebrovascular alterations in protein kinase C-mediated constriction in stroke-prone rats.

BACKGROUND AND PURPOSE: Cerebrovascular pressure-dependent constriction may involve the smooth muscle production of diacylglycerol, which could facilitate constriction by activating protein kinase C (PKC). A dysfunctional PKC system could promote the loss of pressure-dependent constriction. We attempted to determine whether the alterations in pressure-dependent constriction in the middle cerebral arteries (MCAs) observed in relation to stroke development in Wistar-Kyoto stroke-prone spontaneously hypertensive rats (SHRsp) were associated with defects in the ability of the arteries to constrict in response to PKC activation. METHODS: MCAs were sampled from SHRsp before and after stroke development and in stroke-resistant Wistar-Kyoto spontaneously hypertensive rats. A pressure myograph was used to test the ability of the arteries to constrict in response to a 100 mm Hg pressure step and subsequently to contract in response to phorbol 12,13-dibutyrate in the presence of nifedipine (3 micromol/L). RESULTS: Pressure-dependent constriction and constriction in response to phorbol dibutyrate in the MCAs were inhibited by PKC inhibitors (staurosporine [40 nmol/L], chelerythrine [12 micromol/L], bisindolylmaleimide [5 micromol/L]), declined with age before stroke development in SHRsp, and were absent after stroke. There was a significant relationship between pressure- and phorbol dibutyrate-induced constriction (r=0.815, P<0. 05). CONCLUSIONS: Phorbol esters interact with the same activation site as diacylglycerol to stimulate PKC. An inability to constrict in response to phorbol dibutyrate may reflect unresponsiveness to diacylglycerol and may contribute to the loss of pressure-dependent constriction associated with stroke in the MCAs of SHRsp. The loss of this autoregulatory function before stroke could increase the risk of cerebral hemorrhage.

Animals↗

Validity and reliability of the 6 minute walk in persons with fibromyalgia.

OBJECTIVE: To assess the reliability and construct validity of the 6 minute walk (6MW) in persons with fibromyalgia (FM) and to determine an equation for predicting peak oxygen consumption (pVO2) from the distance covered in 6 minutes. METHODS: Ninety-six women who met the American College of Rheumatology (ACR) criteria for FM were tested on the 6MW and the Fibromyalgia Impact Questionnaire (FIQ). A subset (n = 23) were tested on a separate day for pVO2 during a symptom-limited, incremental treadmill test. Twelve subjects repeated the 6MW five times over 10 days. Heart rate and rating of perceived exertion (RPE) were recorded for each walk. Intraclass correlations were used to determine the reliability of the 6MW. Validity was examined by correlating the 6MW with pVO2 and the FIQ. Body mass index (BMI) and 6MW were independent variables in a stepwise regression to predict pVO2. RESULTS: A significant increase in distance occurred from Walk 1 to Walk 2 (p = 0.000) with the distance maintained on the remaining walks (p = 0.148) The correlations of the 6MW with the FIQ and pVO2 were -0.325 and 0.657, respectively. The regression equation to predict pVO2 from 6MW distance and BMI was: pVO2 (ml/kg/min) = 21.48 + (-0.4316 x BMI) + [0.0304 x distance(m)] (R = 0.76, R2 = 0.66). CONCLUSION: When using the 6MW it is necessary to conduct a practice walk, with the second walk taken as the baseline measure. It was determined from the correlations that the 6MW cannot replace the FIQ as a measure of function. The 6MW may be used as an indicator of aerobic fitness, although obtaining VO2 by means of a graded exercise test is preferable.

Analysis of Variance↗

An improved bladder for pump control during ECMO procedures.

A new inline reservoir called the Better-Bladder, now FDA-cleared for long term use, overcomes some disadvantages of the silicone bladder and bladder box used in extracorporeal membrane oxygenation circuits. The Better-Bladder provides compliance in the venous line and allows for noninvasive pressure measurements. Both features are useful for controlling pump speed as a function of venous line pressure. Bench tests showed that the Better-Bladder measures pressure noninvasively within +/- 4% of invasive (i.e., liquid contacting) pressure measurements in a range from -200 to +500 mmHg and at temperatures from 10 degrees C to 37 degrees C. After 60 days, the error in noninvasive pressure measurement with the Better-Bladder was less than +/- 3%. The Better-Bladder withstood pressurization to 1700 mmHg for ten days without leaking or failing in other ways. The advantages of the Better Bladder, along with its accuracy and durability, suggest its use for short and long term pumping applications.

Bias↗