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PubMed1999

Predictive medicine: computational techniques in therapeutic decision-making.

The current paradigm for surgery planning for the treatment of cardiovascular disease relies exclusively on diagnostic imaging data to define the present state of the patient, empirical data to evaluate the efficacy of prior treatments for similar patients, and the judgement of the surgeon to decide on a preferred treatment. The individual variability and inherent complexity of human biological systems is such that diagnostic imaging and empirical data alone are insufficient to predict the outcome of a given treatment for an individual patient. We propose a new paradigm of predictive medicine in which the physician utilizes computational tools to construct and evaluate a combined anatomic/physiologic model to predict the outcome of alternative treatment plans for an individual patient. The predictive medicine paradigm is implemented in a software system developed for Simulation-Based Medical Planning. This system provides an integrated set of tools to test hypotheses regarding the effect of alternate treatment plans on blood flow in the cardiovascular system of an individual patient. It combines an Internet-based user interface developed using Java and VRML, image segmentation, geometric solid modeling, automatic finite element mesh generation, computational fluid dynamics, and scientific visualization techniques. This system is applied to the evaluation of alternate, patient-specific treatments for a case of lower extremity occlusive cardiovascular disease.

Arterial Occlusive Diseases↗
PubMed1996

Measuring contraceptive effectiveness: a conceptual framework.

We present a conceptual model that outlines the four measures of how well a contraceptive method works: 1) efficacy, 2) effectiveness, 3) perfect-use pregnancy rate, and 4) typical-use pregnancy rate. Moreover, we illustrate how four variables influence these measures: 1) capacity to conceive, 2) frequency and timing of intercourse, 3) degree of compliance, and 4) inherent protection of the method. Because of inter-individual as well as intra-individual variability of the first three variables, generalizing results from a contraceptive clinical trial to other populations is problematic. There is a hierarchy of generalizability of the four outcome measures, with the typical-use pregnancy rate the least generalizable but the easiest to measure, and efficacy the most generalizable but the most difficult to measure. These four variables should be considered in the design and analysis of future contraceptive clinical trials. Finally, this article illustrates why the terms "pregnancy rate" and "failure rate" are not synonymous and why we recommend that the latter term not be used.

Clinical Trials as Topic↗
PubMed2003

Technology use and psychosocial factors in the self-reporting of musculoskeletal disorder symptoms in call center workers.

PROBLEM: Evidence exists to suggest that working with computer terminals and keyboards is associated with the development and exacerbation of a range of musculoskeletal disorders (MSDs). Research has suggested that psychosocial factors may be of more importance than computer use factors in the development of MSDs in the computing workplace. METHOD: A questionnaire-based study was undertaken to test this hypothesis in a sample of 67 call center workers. A Spearman's rho was performed on the data, as well as chi(2) tests on the individual variables. RESULTS: It was found that overall, computer use factors were significantly associated with self-reporting of MSD symptoms, whereas psychosocial factors had no such association. However, certain individual psychosocial factors emerged as having a significant association with MSD symptoms. DISCUSSION: The findings suggest that specific areas of call center work have associations with poor worker health and possible long-term MSD problems. These areas appear to be workload and particular management-worker relations, rather than computer use. SUMMARY: This suggests that the relationship among computer use, psychosocial factors, and MSD is a complex area that would benefit from more research. IMPACT ON INDUSTRY: This study raises issues about the importance of psychosocial and organizational factors and employee welfare in the call center working environment.

Adult↗
PubMed2000

Menstrual cycle, contraception, and performance.

Although understanding of the unique physiology of the female athlete has increased, there are still many questions to be answered. Endogenous and exogenous female sex steroids have been shown to influence various cardiovascular, respiratory, and metabolic parameters, but these changes probably have minimal impact on the ability of most recreational athletes to participate in and enjoy their sport. Statistically significant data may or may not have clinical or performance relevance. By the same token, a statistically nonsignificant change may mean the difference between first and second place to an elite athlete. For an athlete concerned about maximizing performance, individual variability in menstrual cycle changes to various performance parameters must be considered. It is difficult to predict how accurately controlled laboratory findings from a study population apply to an individual competitor on the playing field. Athletes taking OCs for contraception or for menstrual cycle control may be able to minimize any potential side effects and performance influences by taking the lower dose triphasic pills and the newer progestins. For women with menstrual dysfunction, OCs may provide a predictable hormonal milieu for training and competition. Further scientific study is needed using large-scale, prospective, randomized clinical trials on trained athletes and accurate hormonal measurements to determine the phase of the menstrual cycle to determine short- and long-term effects of cycle phase and OCs in exercising women. As more questions continue to be answered, physicians and sport scientists will be better able to guide women not only to maximize their performance but to ensure lifelong good health.

Body Temperature Regulation↗
PubMed2000

Genetic determinants of plasma lipid response to dietary intervention: the role of the APOA1/C3/A4 gene cluster and the APOE gene.

Polymorphisms at the APOA1/C3/A4 gene cluster and the APOE gene have been extensively studied in order to examine their potential association with plasma lipid levels, coronary heart disease risk and more recently with inter-individual variability in response to dietary therapies. Although the results have not been uniform across studies, the current research supports the concept that variation at these genes explains a significant, but still rather small, proportion of the variability in fasting and postprandial plasma lipid responses to dietary interventions. This information constitutes the initial frame to develop panels of genetic markers that could be used to predict individual responsiveness to dietary therapy for the prevention of coronary heart disease. Future progress in this complex area will come from experiments carried out using animal models, and from carefully controlled dietary protocols in humans that should include the assessment of several other candidate gene loci coding for products that play a relevant role in lipoprotein metabolism (i.e. APOB, CETP, LPL, FABP2, SRBI, ABC1 and CYP7).

Apolipoproteins A↗
PubMed1989

Motor fibers in the canine distal caudal cutaneous sural nerve--dual innervation of the hind limb plantar muscles.

The function of the communicating branch of the distal caudal cutaneous sural (DCCS) nerve to the tibial nerve was investigated in 7 adult dogs and was found to contain the motor component of this nerve. This function was studied by direct visualization of the contraction of the hind limb plantar muscles and by direct electrophysiologic recording of motor unit action potentials in these muscles, following stimulation of the DCCS nerve. Contraction of all of the mm. interossei, the mm. lumbricales, the m. adductor digiti quinti and the m. adductor digiti secundi was observed with the stimulation of either the tibial or the DCCS nerves, although there was a qualitative variability in the plantar muscles exhibiting the strongest contraction with stimulation of the latter nerve. This communicating branch was not found in one of the experimental dogs, suggesting some individual variability in the DCCS nerve anatomy and subsequent function. This study conclusively demonstrated that the canine DCCS nerve contains both motor and sensory nerve fibers, which is similar to this nerve in the rat, but anatomically and functionally different to that in the human and the cat.

Anatomy, Comparative↗
PubMed1984

Histochemical evaluation of secretory glycoproteins in human salivary glands with lectin-horseradish peroxidase conjugates.

Paraffin sections of submandibular, sublingual, minor salivary, and parotid glands from ten human autopsy cases were stained with a battery of ten lectins conjugated to horseradish peroxidase. Variable affinity for one or another lectin between mucous cells in a gland evidenced cellular heterogeneity in mucin production. Mucous cells of a given type of gland varied among individuals, but for a single individual appeared markedly but not completely similar from one type of salivary gland to another. The individual variation related, in part, to the ABO blood group and secretor status of the individual. For mucous cells in secretors of blood group A and B all antigens stained strongly for the presence of terminal alpha-N-acetylgalactosamine or alpha-galactose, respectively. Mucous cells in AB secretors contained both antigens, whereas those of O (H) secretors lacked both. Mucous cells of three presumed nonsecretors, two of whom were immature infants and possibly too young to produce ABO antigen, failed to stain. Mucous cells in glands from the presumed nonsecretors, however, revealed a staining pattern consistent with the presence of Lea antigen. Mucous cells of nonsecretors stained with Lotus tetragonolobus agglutinin but not with Ulex europeus I agglutinin, whereas mucous cells of ABO secretors stained with both lectins. This difference in lectin binding indicated that sites reactive only with Lotus tetragonolobus agglutinin contain 1----4 linked fucosyl residues and sites stained by both lectins contain fucose linked 1----2 to the oligosaccharide. Staining of mucous cells of nonsecretors with Pisum sativum agglutinin indicate that either the lectin binds to internal N-acetylglucosamine of Lea substance or the mucous cells contain an N-glycosidic glycoprotein of the type thought to bind this lectin. Serous cells stained less strongly than mucous cells and differed in lectin affinities from one type of gland to another in an individual. Staining of serous cells of a given gland varied markedly among different subjects. This individual variability did not relate to blood group as terminal sugars demonstrative of A or B blood group antigens were not detected in any serous cells. Serous cells in the submandibular glands from the two immature infants were unreactive with all lectin conjugates. Secretions in parotid and submandibular serous cells generally contained a higher content of fucose than those in sublingual serous cells, which contained higher levels of a terminal galactose-sialic acid dimer. Some but not other cells of striated and interlobular ducts of submandibular glands of one subject stained for alpha-N-acetylgalactosamine.

ABO Blood-Group System↗
PubMed2004

Tolerability of antiseizure medications: implications for health outcomes.

Epilepsy is a disorder of abnormal excitability and synchronicity of aggregates of neurons that lead to paroxysmal behavioral or perceptual change. Most antiepileptic drugs (AEDs) decrease membrane excitability or increase postsynaptic inhibition, and may alter synchronization of neuronal networks. The attributes of an AED that reduce the tendency toward seizures may cause disruption of normal cerebral processes. Previous clinical studies suggest wide inter-individual variability of the effects of such AEDs. The options for antiepileptic treatment have dramatically expanded in the past decade and now allow tailoring of intervention for optimal management of individual patients. Current strategies to improve epilepsy care should include systematic monitoring to identify adverse effects of AEDs, and future approaches may involve creative applications of neuroimaging and genetic technologies to match patient characteristics to AED attributes.

Anticonvulsants↗
PubMed1998

Individual sensitivity to cytogenetic effects of 1,2:3,4-diepoxybutane in cultured human lymphocytes: influence of glutathione S-transferase M1, P1 and T1 genotypes.

Although some blood parameters have been suggested to modulate in-vitro induction of sister chromatid exchanges by 1,2:3,4-diepoxybutane (DEB), a metabolite of 1,3-butadiene, the increased sensitivity has largely been assigned to a homozygous deletion of glutathione S-transferase T1 gene (GSTT1 null genotype). However, some DEB-sensitive individuals have been shown to be GSTT1 positive (having at least one undeleted GSTT1 allele). To examine potential causes for this overlap, we evaluated the effect of GSTM1, GSTP1, and GSTT1 genotypes, together with various life-style and blood parameters, on the DEB induction of sister chromatid exchanges and cells with chromosomal aberrations (aberrant cells) in lymphocyte cultures of 115 and 62 human donors, respectively. Our results supported the important role of the GSTT1 genotype in DEB sensitivity; 76% of cultures from GSTT1 null donors but only 4% of those from GSTT1 positive donors were DEB-sensitive, as defined by sister chromatid exchange measurements. The GSTT1 genotype also clearly affected DEB-induced aberrant cells, 92% of GSTT1 null and 8% of GSTT1 positive donors being sensitive to DEB. All individuals showing a high response to DEB in both sister chromatid exchange and aberrant cell analyses were GSTT1 null. Baseline aberrant cell measurements but not sister chromatid exchange measurements were marginally higher among GSTT1 null donors compared with GSTT1 positive donors. GSTM1 and GSTP1 genotypes had no influence on these cytogenetic end-points. Blood transaminases, gamma-glutamyl transferase, urea, creatinine and white blood cell count showed a clear negative association with DEB-induced aberrant cells, whereas wine drinkers had more aberrant cells than non-drinkers. A higher sister chromatid exchange-response to DEB was observed in lymphocytes from women and smokers than from men and non-smokers, respectively. Erythrocyte count correlated negatively with DEB-induced sister chromatid exchanges. Thus, a variety of parameters seemed to modulate the individual DEB-sensitivity together with the GSTT1 genotype. Although the known contributing factors accounted for a considerable part of individual variability in sister chromatid exchanges (59.4%) and aberrant cells (46.7%) in DEB treatment, they did not, however, fully explain the overlap in cytogenetic response between GSTT1 positive and null individuals.

Adult↗
PubMed2001

Differential expression of human nucleoside transporters in normal and tumor tissue.

Responses to nucleoside analog drugs used in the treatment of cancers and viral infections can vary considerably between individuals. Genetic variability between individuals in their ability to transport drugs may be a contributory factor. Nucleoside transporters (NTs) move nucleosides and analog drugs across cell membranes. Four human NTs have been cloned: hENT1, hENT2, hCNT1, and hCNT2. Human NT expression profiles are not well defined; therefore, we undertook a comprehensive quantitative analysis of the differential expression of NTs within normal and tumor tissue. Results show tissue specific expression of the different NTs in normal tissue while matched normal/tumor tissue cDNA array data show considerable variability in all NT expression profiles from different individuals, in particular decreased expression in tumor tissue. Decreased NT expression in tumor tissue may contribute to reduced drug uptake and the development of resistance. These data suggest that nucleoside analog drug therapies may be optimized by determining individual NT expression profiles.

Antineoplastic Agents↗
PubMed2003

[Variability of the structure of area 39 of inferior parietal cortex in the left and right hemispheres of adult human brain].

The cytoarchitecture of area 39 of inferior parietal cortex region in the left and right cerebral hemispheres was studied in usual individuals and in professionally gifted world-famed people. The series of frontal sections, stained using Nissl cresyl violet method, were examined. The profile areas of neurons in cortical layers III and V were measured and their distributions were analyzed. In the group of gifted people, individual variability of the characteristics studied was found to be significantly increased, especially in the right cerebral hemisphere, while the relative content of both very small and very large neurons was elevated.

Adult↗
PubMed1986

Variable mounting levels in the female rat: the influence of experience and acute effects of testosterone.

Ovariectomized female rats were tested for mounting behaviour along 4 different procedures in order to investigate which factors may contribute to the variability of this behaviour observed in different experiments. Mounting behaviour was facilitated by repeated testing (group A). Estradiol-benzoate, when given for a short period of time (group B), induced a dramatic and long-lasting increase in mounting in females which were repeatedly tested according to the procedure of group A. Prolonged adaptation to the test environment (group C) did not facilitate mounting in repeatedly tested females. The 3 procedures used did not reduce inter-individual variability. Highly significant, positive, inter-test correlation coefficients indicated that relative individual differences in mounting remained highly stable throughout testing. Facilitatory effects of testosterone propionate (TP, 500 micrograms, injected once 48 h prior to testing) on mounting behaviour appeared to stimulate existing behavioural tendencies, rather than activating new patterns of behaviour: TP facilitated mounting in groups A and B, but not in group C. Neither did TP facilitate mounting in a group which had been left sexually naive (group D) until the time of TP-injection. It is concluded that highly stable inter-individual differences in mounting behaviour are present in the adult female rat. Differences in sensitivity for gonadal hormones are not likely to underly these individual differences.

Adaptation, Psychological↗
PubMed2006

Verbatim and gist recall of sentences by dyslexic and non-dyslexic adults.

Forty-eight college students, 24 of them dyslexic, were presented with four sentences of increasing complexity. Participants were asked to repeat each sentence and a record was kept of the number of repetitions required before 100% correct accuracy was achieved. None of the 24 control participants required a total of more than eight repetitions over the four sentences, whereas among the dyslexics the total number of repetitions needed ranged from one to 25. Dyslexic participants were unpredictable in their performance from one level of difficulty to the next and inter-individual variability was far greater in the dyslexic group than in the control group. Overall, despite their relatively poor performance in achieving verbatim accuracy relative to non-dyslexic participants, dyslexic individuals regularly managed to preserve the gist of the sentences. Some theoretical issues arising from these results are discussed.

Adolescent↗
PubMed1998

Serum leptin concentration and insulin sensitivity in men with abdominal obesity.

OBJECTIVE: We have examined the association between generalized adiposity, abdominal adiposity, insulin sensitivity, and serum levels of leptin in a cross-sectional study of abdominally obese men. RESEARCH METHODS AND PROCEDURES: Thirty men, 48 to 66 years of age with a body mass index (BMI) of between 25 kg/m2 and 35 kg/m2 and a waist hip ratio of >0.95, were included in the study. Serum leptin concentration was measured using radioimmunoassay. Total body fat percentage was determined from total body potassium, abdominal adiposity was measured by computed tomography, and the glucose disposal rate (GDR) was measured during an euglycemic, hyperinsulinemic glucose clamp. RESULTS: Significant correlations were found between serum leptin concentration and BMI, percentage body fat, abdominal subcutaneous adipose tissue, serum insulin, GDR, and 24-hour urinary-free cortisol. In a multiple regression analysis, it was shown that abdominal subcutaneous adipose tissue, GDR, and BMI explained 72% of the variability of serum leptin concentration. GDR demonstrated an independent inverse correlation with serum leptin concentration. DISCUSSION: In abdominally obese men with insulin resistance, it was demonstrated that most of the individual variability in serum leptin concentration was explained by the amount of subcutaneous abdominal adipose tissue, insulin sensitivity, and BMI.

Abdomen↗
PubMed1991

Outcome of acute supratentorial cerebral infarction in patients under 60. Development of a prognostic grading system.

Thirty-five patients under the age of 60 were admitted to the Neurosurgical Department of the Inselspital with acute supratentorial ischaemic strokes between February 1985 and June 1990. The mean delay from the onset of the symptoms until emergency room admission was 10 hours. CT scan, Doppler sonography, and angiography were done routinely at the time of admission and CT was repeated 24 hours later. Initial treatment consisted of mannitol, low-molecular dextran and prednisolone. Intravenous nimodipine was added to the protocol in 1987. Intensive care including hyperventilation and intracranial pressure monitoring was instituted in cases of deteriorating level of consciousness and considerable oedema as visualized on the primary or repeat CT scan. Eight patients developing severe intracranial hypertension and/or unilateral mydriasis despite hyperventilation and osmotherapy underwent decompressive craniectomy. A total of 9 patients died in the acute stage, all but one due to a cerebral cause. At 6 months, only 6 patients were without significant neurological or neuropsychological deficits. Fourteen patients were moderately disabled and 6 were severely disabled. There were no vegetative survivors. A number of demographic, clinical and radiological variables were investigated for a possible prognostic significance. A grading scale was developed for each variable. Of the initial neurological deficits, degree of motor paralysis, gaze deviation, and decreased level of consciousness correlated with an unfavourable result. While the prognostic significance of each of these individual variables was only moderate, the combined score of these 3 variables correlated better with outcome (r = 0.62). More advanced age was found to correlate with a less favourable prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Pregnancy and childbirth among the Amish.

This study examined Amish patterns of perinatal health care utilization from the perspective of Amish women and local health care providers in Geauga County, Ohio. Participant observation and interviews with health care providers and 15 Amish women yielded data on perinatal beliefs and utilization patterns for 76 pregnancies. While local health care providers regard the Amish as suboptimally utilizing prenatal care, this study found a consistent pattern of health seeking behavior. In the absence of symptoms perceived to be serious, Amish women initiated prenatal care earlier for first pregnancies and progressively later with increasing parity. Amish women's perinatal health care utilization must be seen within the context of barriers of transportation, cost, and child care needs. The Amish do not automatically reject medical technology, but select those aspects that are congruent with and that will support and maintain their way of life. Further, despite outward appearances of homogeneity, Amish women display individual variability in responding to pregnancy and childbirth.

Adult↗
PubMed2004

Sexual possibility situations and sexual behaviors among young adolescents: the moderating role of protective factors.

PURPOSE: To examine sexual possibility situations (SPS) and protective practices associated with involvement in intimate sexual behaviors and the initiation of sexual intercourse among young adolescents and to determine if protective factors moderate the relationship between SPS and sexual behaviors. METHODS: Data for these analyses were obtained from the baseline assessment for adolescents conducted as part of an HIV prevention study called "Keepin' it R.E.A.L.!" The study was conducted with a community-based organization (CBO) in an urban area serving a predominantly African-American population. In addition to items assessing SPS, intimate sexual behaviors, and initiation of sexual intercourse, adolescents provided information on the following protective factors: educational goals, self-concept, future time perspective, orientation to health, self-efficacy, outcome expectations, parenting, communication, values, and prosocial activities. Background personal information, including age and gender, was also collected. The analyses were conducted on data from 491 predominantly African-American adolescents, 61% of whom were boys. Variables were combined to form SPS and protective indices that were used in the first set of regression analyses. In a second set of analyses, the indices were unbundled and individual variables were entered into regression analyses. RESULTS: Both SPS and protective indices explained significant portions of variance in intimate sexual behaviors, and the SPS index explained a significant portion of variance in the initiation of sexual intercourse. The regression analysis using the unbundled SPS and protective factors revealed the following statistically significant predictors for intimate sexual behaviors: age, gender, time alone with groups of peers, time alone with a member of the opposite sex, behavior self-concept, popularity self-concept, self-efficacy for abstinence, outcome expectations for abstinence, parental control, personal values, and parental values. A similar regression analysis revealed that age, time alone with a member of the opposite sex, and personal values were significant predictors of initiation of sexual intercourse. CONCLUSIONS: These results provide evidence for the important role of protective factors in explaining early involvement in sexual behaviors and show that protective factors extend beyond personal characteristics to include both familial and peer factors.

Adolescent↗
PubMed1988

Reproducibility of haemodynamic and plasma catecholamine responses to isometric exercise and mental arithmetic in normo- and hyper-tensive subjects.

1. To determine the reproducibility of a mental arithmetic stress test and a handgrip exercise test, we studied the responses of blood pressure, heart rate, forearm blood flow and plasma catecholamines on two occasions, with an interval of at least 1 week, in 24 normotensive and 22 hypertensive subjects. 2. The SE of a single observation of the percentage changes of blood pressure ranged from 3.9 to 9.3% in normotensive subjects and from 3.9 to 7.4% in hypertensive subjects in both tests. For heart rate, these values were 4.9-12.3% in the normotensive subjects and 4.8-5.7% in the hypertensive subjects. However, there was a wide individual scatter of these haemodynamic responses during both tests. The forearm blood flow, only measured during mental arithmetic, had an SE of a single observation of 33.7%. 3. In 10 normotensive subjects the SE of a single observation of the change in plasma noradrenaline was 0.16 nmol/l during handgrip exercise and 0.09 nmol/l during mental arithmetic. The corresponding values for plasma adrenaline were 0.04 and 0.05 nmol/l. 4. In conclusion, although both tests showed a rather low SE of a single observation for the blood pressure and heart rate responses in normo- and hyper-tensive subjects, there was a considerable individual variability. If related to the mean forearm blood flow responses, the SE of a single observation of the forearm blood flow response was of similar magnitude. The limited intra-individual reproducibility of both tests should be borne in mind when interpreting pharmacological intervention studies or studies evaluating sympathoadrenal reactivity in cardiovascular disorders.

Adolescent↗