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Biomedical subjects

M Higgins

Publications and source records attributed to M Higgins.

At least 37 records · Page 2Linked to original sources
PubMed2000

The patients' perception of recovery after coronary angioplasty.

Coronary angioplasty and stent placement is associated with short hospital stays. Patients are expected to recover at home, alone, following limited care time with nurses. The purpose of the study was to describe participants' perceptions of recovery after angioplasty. Eight men and three women were interviewed 1 month after discharge from hospital. Verbatim transcripts were analysed for major themes using the qualitative techniques of grounded theory. Data analysis revealed three major categories: awareness of the problem, coping response and appraisal of the situation. These were linked via a problem solving process. In step one, the problem was identified. In step two, coping responses were taken to try and solve the problem. In step three, the results of the coping responses were appraised or evaluated. These categories were further defined by four phases identified as: pre-admission, admission, during the angioplasty and recovery. This paper describes the recovery phase. Awareness of the problem in the recovery phase was associated with 'relief from chest pain' for most participants. In contrast, anxiety continued and was associated with 'uncertainty over future health'. Participants described coping responses of "taking control of their life again" by undertaking both physical and psychological strategies. Finally, the situation was appraised to be either a 'good' or a 'bad' recovery. This appraisal was based on such considerations as the absence of chest pain, improvement in well-being and energy levels. The results of this study highlight patients' concerns and support the need for greater emphasis on their psychosocial needs. This care must be provided within the time constraints of short hospital stays. Nurses must also consider providing support to patients in the pre-admission and recovery phases.

Adaptation, Psychological↗
PubMed2000

The Family Risk Score for coronary heart disease: associations with lipids, lipoproteins, and body habitus in a middle-aged bi-racial cohort: The ARIC study.

PURPOSE: To examine the association between the Family Risk Score (FRS) for coronary heart disease (CHD) and body mass index (BMI), waist-to-hip ratio (WHR), high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, triglycerides, and lipoprotein(a) protein [Lp(a)]. METHODS: FRS was computed from observed and expected CHD events using family data collected from 11467 black and white adults of the Atherosclerosis Risk in Communities Study (ARIC). BMI, WHR, and lipids adjusted for study center, race, education, BMI (except BMI), WHR (except for BMI and WHR), cigarette smoking, alcohol, and Keys' score were compared among low (FRS < -0.5), average (-0.5 to 0.5), and high (> 0.5) FRS using analysis of covariance. The association between FRS and these risk factors was compared to that for simpler estimates of family risk. RESULTS: Adjusted means of BMI, WHR, LDL, LP(a), and triglycerides were positively associated with FRS, whereas HDL cholesterol was inversely associated with FRS. Of demographic and behavioral factors, cigarette smoking was most strongly associated with FRS. Based on additional comparisons of adjusted means, high vs. low levels of FRS appear to correlate better with CHD risk factors than do the simpler family history assessments. CONCLUSIONS: In situations were genetic or clinical information is not available, FRS may be a favorable measure of familial burden for CHD.

Adult↗
PubMed2000

A proposed method for the measurement of anesthetist care variability.

OBJECTIVE: Some critical events in anesthesiology occur as seemingly preventable misadventures, their exact origins indeterminable. Inexperienced anesthetists, anesthesia machine malfunctions, lack of vigilance and human error inevitably initiate some incidents. Anesthesia training improves recognition and decision-making. Avoiding crisis initiation and amelioration of those that do occur is one role of the consultant anesthesiologist. Safe patient care requires medical and procedural knowledge, technical expertise, and control of resources in a complex milieu. Anesthesia simulators are clinical laboratories where anesthetists can sharpen both cognitive and manual skills. Dynamic scenarios allow opportunities for anesthetists to explore and experience crises as they develop and apply their knowledge while attempting to manage these events. Simulator-based scenarios are reproducible and large amounts of useful data can be collected and saved. The authors hypothesize these data can be utilized to compare performance of anesthetists and to measure improvement of individual anesthetists over time. METHODS: We have designed "Stable Anesthesia," a prototypic scenario to test anesthetists' capabilities under the stress of performance guidelines. Three subjects performed anesthesia using the simulator and this protocol. Data from the simulator were archived by the system and analyzed by the authors. RESULTS: A simple mathematical analysis gave good separation of data from three subjects of different training level. CONCLUSIONS: It is suggested that the use of the techniques mentioned here may be of value in the development of a standardized testing protocol for anesthetists.

Anesthesiology↗
PubMed2000

Body mass index and the prevalence of hypertension and dyslipidemia.

OBJECTIVE: To describe and evaluate relationships between body mass index (BMI) and blood pressure, cholesterol, high-density lipoprotein-cholesterol (HDL-C), and hypertension and dyslipidemia. RESEARCH METHODS AND PROCEDURES: A national survey of adults in the United States that included measurement of height, weight, blood pressure, and lipids (National Health and Nutrition Examination Survey III 1988-1994). Crude age-adjusted, age-specific means and proportions, and multivariate odds ratios that quantify the association between hypertension or dyslipidemia and BMI, controlling for race/ethnicity, education, and smoking habits are presented. RESULTS: More than one-half of the adult population is overweight (BMI of 25 to 29.9) or obese (BMI of > or =30). The prevalence of high blood pressure and mean levels of systolic and diastolic blood pressure increased as BMI increased at ages younger than 60 years. The prevalence of high blood cholesterol and mean levels of cholesterol were higher at BMI levels over 25 rather than below 25 but did not increase consistently with increasing BMI above 25. Rates of low HDL-C increased and mean levels of HDL-C decreased as levels of BMI increased. The associations of BMI with high blood pressure and abnormal lipids were statistically significant after controlling for age, race or ethnicity, education, and smoking; odds ratios were highest at ages 20 to 39 but most trends were apparent at older ages. Within BMI categories, hypertension was more prevalent and HDL-C levels were higher in black than white or Mexican American men and women. DISCUSSION: These data quantify the strong associations of BMI with hypertension and abnormal lipids. They are consistent with the national emphasis on prevention and control of overweight and obesity and indicate that blood pressure and cholesterol measurement and control are especially important for overweight and obese people.

Adult↗
PubMed2000

Nongenomic effects of aldosterone on Ca2+ in M-1 cortical collecting duct cells.

BACKGROUND: Aldosterone at physiological levels induces rapid (<5 min) increases in intracellular protein kinase C (PKC) activity and a rise in calcium and pH in mineralocorticoid hormone target epithelia, such as distal colon and sweat gland. The end targets of these rapid responses in epithelia are Na+/H+ exchange and K+ channels. METHODS: The mouse cortical collecting duct (CCD) M-1 cell line was grown to confluency and loaded with Fura-2 for spectrofluorescence measurements of intracellular free calcium at 37 degrees C bathed in Krebs solution. RESULTS: Aldosterone (1 nmol/L) produced a rapid, transient peak increase in [Ca2+]i in M-1 cells. This effect was abolished upon removal of extracellular Ca2+, but was unaffected by pretreatment with spironolactone (10 micromol/L) or actinomycin D (10 micromol/L). However, pretreatment with the specific PKC inhibitor chelerythrine chloride (1 micromol/L) prevented the aldosterone-induced rise in [Ca2+]i. Dexamethasone, at a concentration 10,000-fold higher than aldosterone (10 micromol/L), also produced a transient increase in [Ca2+]i, but this response was significantly smaller than that of aldosterone. In contrast, hydrocortisone had no effect on [Ca2+]i at either nmol/L or micromol/L concentrations. Both of the sex steroids, 17beta-estradiol (10 nmol/L) and progesterone (10 nmol/L), induced protein kinase C-dependent increases in [Ca2+]i. CONCLUSIONS: Aldosterone and sex steroid hormones activate intracellular calcium signaling in CCD cells via a nongenomic PKC-dependent pathway, which may have important implications for renal transport.

Aldosterone↗
PubMed2000

Pyrazinamide is not active against Mycobacterium tuberculosis residing in cultured human monocyte-derived macrophages.

SETTING: Mycobacteriology Laboratory, National Jewish Medical and Research Center, Denver, Colorado. OBJECTIVE: To evaluate the antimicrobial activity of pyrazinamide against Mycobacterium tuberculosis in cultured human monocyte-derived normal and activated macrophages. DESIGN: Monocytes separated from human blood were incubated in plastic plates for seven days to mature into macrophage monolayers. After activation with TNF-alpha or IFN-gamma or without prior treatment, the macrophages were infected with M. tuberculosis. Various concentrations of pyrazinamide (PZA), morphazinamide (MZA) or isoniazid (INH) were added the next day, and the viable counts of the intracellular bacteria were determined at days 0, 4, and 8. RESULTS: No inhibitory activity of PZA at any concentration was detected, while clear dose-dependent bacteriostatic and bactericidal activities were demonstrated by MZA and INH in the same experimental model. CONCLUSIONS: PZA has neither bacteriostatic nor bactericidal activity against M. tuberculosis persisting or multiplying in cultured monocyte-derived human macrophages, and it might be that the well-known effectiveness of this drug in tuberculosis patients is not related to its supposed activity against intracellular bacterial subpopulations.

Antitubercular Agents↗
PubMed1999

Lewis blood group phenotype as an independent risk factor for coronary heart disease (the NHLBI Family Heart Study).

In the Copenhagen Male Study, men with Lewis blood group phenotype Le(a-b-) were found to have increased risk for coronary heart disease (CHD); such a relation has not been confirmed in men, and has not been evaluated in women. In the NHLBI Family Heart Study, we determined the Lewis blood type of 1,620 white subjects (790 male and 830 female subjects). The Lewis(a-b-) phenotype was found in 142 subjects (8.8%), 6.3% of subjects from randomly chosen families and 9.7% of subjects from families found to be at high risk for CHD. A history of CHD was present in 39.1% of men with Le(a-b-) versus 27.2% of men with other Lewis types; for women, the corresponding numbers were 12.3% versus 9.4%, respectively. In multivariate analysis, adjusting for age, sex, and risk group, the odds ratio for CHD was 2.0 (95% confidence interval = 1.2 to 3.1) for Le(a-b-) versus other Lewis groups. Mean values for body mass index, blood pressure, total cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol, glucose, insulin, homocysteine, and fibrinogen were not significantly different between Le(a-b-) subjects and others, but triglycerides (p = 0.002) were higher in the Le(a-b-) subjects. However, inclusion of all risk factors in multivariate analysis did not diminish the increased risk for CHD associated with the Le(a-b-) phenotype. We conclude that the Le(a-b-) phenotype is associated with an increased risk for CHD; its effect does not appear to act predominantly through conventional cardiovascular risk factors. At present, mechanisms of effect are unknown.

Adult↗
PubMed1999

Accuracy of proband reported family history: the NHLBI Family Heart Study (FHS).

Proband-reported family histories are widely used in research and counseling, yet little is known about the validity of family history reporting. The Family Heart Study (FHS), a population-based study of familial cardiovascular disease, gathered family history information from 3,020 middle-aged probands in four U.S. communities. Probands reported on the history of coronary heart disease (CHD), diabetes, hypertension, and asthma among a total of 10,316 living relatives (9,186 siblings, 1,130 parents) and 2,685 spouses. Questionnaires were returned by 6,672 siblings, 901 parents, and 2,347 spouses, yielding response rates of 73, 79, and 87%, respectively. Utilizing the relatives' self-report as the standard, sensitivity of the proband report on their spouse, parent, and sibling was 87, 85, and 81% for CHD, 83, 87, and 72% for diabetes, 77, 76, and 56% for hypertension, and 66, 53, and 39% for asthma, respectively. Most specificity values were above 90%. Analyses using generalized estimating equations (GEE) were performed to evaluate differences in proband accuracy based on the proband's age, gender, disease state, center, and ethnicity. In multivariate models, age, gender, and disease status were significantly associated with the accuracy of proband's report of sibling disease history, but had little effect on the accuracy of their report on spouses or parents. In general, older probands were significantly less accurate reporters of disease than younger probands. These results demonstrate that CHD family history can be captured effectively based on proband reports, but suggest that additional family contacts may be helpful when working with older probands or with chronic diseases that have few recognized medical events or procedures.

Asthma↗
PubMed1999

The attributable mortality and costs of primary nosocomial bloodstream infections in the intensive care unit.

Primary nosocomial bloodstream infection (BSI) is a common occurrence in the intensive care unit (ICU) and is associated with a crude mortality of 31.5 to 82.4%. However, an accurate estimate of the attributable mortality has been limited because of confounding by severity of illness. We undertook this study to assess the attributable mortality and costs associated with an episode of BSI. Infected patients were defined as those who had an episode of BSI during the study period. Uninfected control subjects were matched to the infected patients based upon a number of factors, including predicted mortality on the day prior to infection. The main outcome measures were crude ICU mortality, length of stay, and costs. We found no difference in the crude mortality for the infected and the uninfected patients (35.3 and 30.9%, respectively, p = 0.51). However, among survivors, the patients with nosocomial bloodstream infections did have excess length of stay (mean, 10 d; median, 5 d; p = 0.007) and increased direct costs (mean difference, $34,508; p = 0.008). After matching for severity of illness, we could not detect an association between primary nosocomial bloodstream infections and increased ICU mortality. We did find that primary nosocomial bloodstream infections increased ICU length of stay and costs.

Case-Control Studies↗
PubMed1999

Lower pulmonary function and cerebral subclinical abnormalities detected by MRI: the Atherosclerosis Risk in Communities study.

STUDY OBJECTIVES: To investigate the association between pulmonary function and (1) cerebral infarction and (2) white matter lesions (WMLs), identified by MRI and believed to represent subclinical lesions of arteriosclerosis, generalized hypoperfusion, or ischemia of the brain. DESIGN: Population-based, cross-sectional study. SETTING: Two communities in the United States. PARTICIPANTS: A sample of 1,917 African-American and white men and women 55 to 72 years old who were selected from the second follow-up examination of the Atherosclerosis Risk in Communities Study cohort. INTERVENTIONS: Observational study. MEASUREMENTS AND RESULTS: The lung function indexes, FEV1 and FVC, were assessed according to American Thoracic Society criteria. Subclinical cerebral infarction and WMLs were assessed by MRI. After adjusting for age, ethnicity, gender, height, and height squared, a 1-SD decrease of FEV1 in nonsmokers was associated with odds ratios (95% confidence interval [CI], 1.31 to 2.03) of 1.63 for infarction and 1.35 (95% CI, 1.08 to 1.69) for WMLs. Of those in the lowest quartile of FEV1, 15% had infarction and WMLs, in contrast to 6% of the individuals in the uppermost quartile of FEV1. Consistent associations were also observed by using FVC as an index of pulmonary function. Similar patterns of association were found among current smokers. The associations were not altered by additional adjustment of conventional risk factors of cardiovascular disease, comorbidity, or cognitive function. CONCLUSION: The results from this population-based study suggest that lower pulmonary function is associated with subclinical cerebral abnormalities.

Brain↗
PubMed1998

Genetic and biochemical studies establish that the fungicidal effect of a fully depeptidized inhibitor of Cryptococcus neoformans myristoyl-CoA:protein N-myristoyltransferase (Nmt) is Nmt-dependent.

Cryptococcus neoformans is a fungal pathogen that causes chronic meningitis in 10% of patients with AIDS. Genetic and biochemical studies were conducted to determine whether myristoyl-CoA:protein N-myristoyltransferase (Nmt) is a target for development of a new class of fungicidal drugs. A single copy of a conditional lethal C. neoformans NMT allele was introduced into the fungal genome by homologous recombination. The allele (nmt487D) produces temperature-sensitive myristic acid auxotrophy. This phenotype is due, in part, to under-myristoylation of a cellular ADP ribosylation factor (Arf) and can be rescued by forced expression of human Nmt. Two isogenic strains with identical growth kinetics at 35 degreesC were used to test the biological effects of an Nmt inhibitor. CPA8 contained a single copy of wild type C. neoformans NMT. HMC1 contained nmt487D plus 10 copies of human NMT. Since a single copy of nmt487D will not support growth at 35 degreesC, survival of HMC1 depends upon its human Nmt. ALYASKLS-NH2, an inhibitor derived from an Arf, was fully depeptidized: p-[(2-methyl-1-imidazol-1-yl)butyl]phenyl-acetyl was used to represent the GLYA tetrapeptide, whereas SKLS was replaced with a chiral tyrosinol scaffold. Kinetic studies revealed Ki (app) values of 1.8 +/- 1 and 9 +/- 2.4 microM for purified fungal and human Nmts, respectively. The minimal inhibitory concentration of the compound was 2-fold lower for CPA8 compared with HMC1. A single dose of 100 microM produced a 5-fold greater inhibition of protein synthesis in CPA8 versus HMC1. The strain specificity of these responses indicates that the fungicidal effect was Nmt-dependent. These two strains may be useful for screening chemical libraries for Nmt-based fungicidal compounds with relatively little activity against the human enzyme.

Acyltransferases↗
PubMed1998

Evidence for multiple determinants of the body mass index: the National Heart, Lung, and Blood Institute Family Heart Study.

The body mass index (BMI) is a complex phenotype representing the amount of fat mass, lean mass, body build and proportions, and it is likely to be affected by various metabolic processes, hormonal effects, energy intake and expenditure, and interactions within and among these broad categories of etiologic factors. Nonetheless, several previous studies have reported evidence for major gene segregation for the BMI in various populations. Data on a random sample of Caucasian families participating in the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study were analyzed to document the extent of familial resemblance and to investigate whether a similar monogenic inheritance pattern could be detected. Genetic analysis was carried out on age- and sex-adjusted BMI values. Familial correlations were significant implying a maximal heritability, including all genetic and environmentally inherited additive factors, of 41% to 59%. Segregation analysis revealed the presence of two maximum likelihood solutions, one characterized as a recessive Mendelian gene and the other as a major effect with an ambiguous transmission pattern. The presence of two such solutions is consistent with detection of two separate factors, each influencing the BMI distribution in a substantive manner. The evidence also supports a multifactorial background for BMI and suggests that the frequencies of these two factors, one of which appears to be a gene, may vary among diverse populations in the United States.

Body Mass Index↗
PubMed1998

Angiotensinogen and angiotensin converting enzyme genotypes and carotid atherosclerosis: the atherosclerosis risk in communities and the NHLBI family heart studies.

BACKGROUND: Polymorphisms of the renin-angiotensin system are associated with cardiovascular pathology. Therefore, the association of the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene and the T235 (methionine to threonine substitution) polymorphism of the angiotensinogen (AGT) gene with intima-media thickness of the carotid artery was investigated. METHODS AND RESULTS: Subjects were randomly selected from two centers participating in both the Atherosclerosis Risk in Communities (ARIC) and NHLBI Family Heart Studies. Probands were 45-64 years of age who were free of cardiovascular disease and had B-mode ultrasound measured carotid intima-media thickness. Multiplex polymerase chain reaction amplification was used to evaluate the ACE I/D and AGT T235 polymorphisms: genotype information was available on 495 and 475 participants, respectively. The frequencies of the ACE D and AGT T alleles were 0.56 and 0.52, respectively; 30% were homozygous for the ACE D allele, and 29% were homozygous for the AGT T allele. After adjustment for systolic blood pressure, antihypertensive medication use, diabetes, age, sex and LDL cholesterol, the mean intima-media thickness was 0.729, 0.732 and 0.721 mm in the ACE DD, ID, and II genotypes, respectively (partial F test 1.53, P = 0.22), and 0.727, 0.732 and 0.724 mm in the AGT MM, MT, and TT genotypes, respectively (partial F test 0.91, P = 0.40). Combining the genotypes for ACE and AGT, there were also no differences in intima-media thickness across the eight joint genotypes. CONCLUSION: We found no evidence that the ACE I/D and AGT T235 polymorphisms of the renin-angiotensin system were associated with carotid intima-media thickness in this population-based sample of middle-aged adults with no history of cardiovascular disease. The lack of an association between these variants and intima-media thickness may indicate that early atherosclerosis is mediated by factors other than these RAS polymorphisms.

Angiotensinogen↗