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[Work and worker reactions in homes for the aged].

This article describes an investigation of relationships between work characteristics and worker reactions in three elderly homes of a Dutch foundation. Moreover, main effects as well as moderating effects of some relevant individual variables were studied. Variables were measured by means of questionnaires; 144 subjects from the caring and household departments took part in the study. From the results it appeared that social support, growth opportunities and work pressure are related to work satisfaction, work motivation and health complaints. The individual variables need for autonomy and coping strategies showed main effects as well as moderating- (buffer-) effects. On the basis of the findings practical consequences for the management of personnel and work have been formulated.

Adaptation, Psychological↗

[The development of the anti-phospholipase A2 antibody response in horses inoculated with venom for the production of polyvalent antisnake serum in Costa Rica].

The development of antibody response against phospholipase A2 activity of Bothrops asper venom was studied in a group of adult and healthy horses used in the production of the polyvalent antivenom at the Instituto Clodomiro Picado. Simultaneously, the general condition of the animals during the immunization schedule was also studied. There was a great individual variability in the immune response, although most of the horses studied reached the highest neutralizing titer after injection of doses of venom of 30 mg and 50 mg. On the other hand, in horses that had been previously immunized and were infected for a second immunization, the highest antibody titer was observed 16-22 days after inoculation. There were only mild alterations in the general condition of the horses as a consequence of venom inoculation. However, local abscesses, fistulae and fibrosis were observed at the site of venom injection. On the basis of the conspicuous individual variability observed, it is proposed that the immune response in horses used in the production of antivenom must be evaluated on individual basis, instead of working with pools of serum samples.

Animals↗

[Prevention of aspergillosis with itraconazole in neutropenic patients: importance of drug monitoring].

Itraconazole is being used increasingly as prophylaxis of systemic aspergillosis in patients with immunodepression. Therapeutic itraconazole monitoring by plasma concentrations measurement is justified by its dose-dependent pharmacokinetics, drug interactions, and frequent bioavailability modifications observed in immunocompromised patients. A first study was carried out in 16 patients with haematological malignancies, given chemotherapy plus itraconazole 400-800 mg/day in a single dose as prophylactic treatment. Therapeutic through drug plasma concentration (Cmin > or = 250 ng/ml of itraconazole, or > or = 750 ng/ml of itraconazole plus hydroxyitraconazole) was not reached in 5/16 patients. Moreover results emphasised the wide inter and intra-individual variability of the steady-state plasma concentrations. In another study we used a multiple dose regimen (100-200 mg x 3/day), instead of a single dose regimen. An adequate Cmin value was found in 34/36 patients. In conclusion, the wide inter and intra-individual variability of itraconazole pharmacokinetics necessitate regularly to measure the drug plasma concentrations in patients with life-threatening fungal infections.

Antifungal Agents↗

NF1 mutation rather than individual genetic variability is the main determinant of the NF1-transcriptional profile of mutations affecting splicing.

A significant number of neurofibromatosis type 1 (NF1) mutations result in exon skipping. The majority of these mutations do not occur in the canonical splice sites and can produce different aberrant transcripts whose proportions have not been well studied. It has been hypothesized that differences in the mutation-determined NF1-transcriptional profile could partially explain disease variability among patients bearing the same NF1 splice defect. In order to gain insight into these aspects, we analyzed the proportion of the different transcripts generated by nine NF1-splicing mutations in 30 patients. We assessed the influence of the mutation in the NF1-related transcriptional profiles and investigated the existence of individual differences in a global manner. We analyzed potential differences in tissue-specific transcriptional profiles and evaluated the influence of sample processing and mRNA nonsense-mediated decay (NMD). Small transcriptional differences were found in neurofibromas and neurofibroma-derived Schwann cells (SC) compared to blood. We also detected a higher cell culture-dependent NMD. We observed that mutation per se explains 93.5% of the profile variability among mutations studied. However, despite the importance of mutation in determining the proportion of NF1 transcripts generated, we found certain variability among patients with the same mutation. From our results, it seems that genetic factors influencing RNA processing play a minor role in determining the NF1-transcriptional profile. Nevertheless neurofibromin studies would clarify whether these small differences translate into significant functional changes that could explain the great clinical expressivity observed in the disease or any of the disease-related traits.

Alleles↗

Effect of exercise on serum enzyme activities in humans.

Increased serum enzyme activity after exercise was first reported in 1958; subsequent studies have established that many factors determine the degree to which the serum activities of a variety of enzymes increase during and after exercise. The serum activities of those enzymes found especially in muscle, particularly creatine kinase, increase in proportion to the intensity and duration of the preceding exercise, peaking 24 hours after exercise; the effect of duration is dominant, so that the highest postexercise serum enzyme activities are found after very prolonged competitive exercise such as ultradistance marathon running or triathlon events. Weight-bearing exercises which include eccentric muscular contractions such as bench stepping and downhill running induce the greatest increases in serum enzyme activities; serum enzyme activities increase very little even after prolonged participation in those non-weight-bearing activities such as swimming and cycling which do not include eccentric muscular contractions. Prolonged (greater than 2 hours) daily training or competition in weight-bearing activities produces chronically elevated serum enzyme activities. Serum enzyme activities increase more with exercise in males, Blacks and the untrained than they do in females, Whites and the trained, respectively; age does not appear to influence the degree to which serum enzyme activities increase with exercise. There is a remarkable individual variability in the degree to which serum enzyme activities increase with exercise; a 50-fold difference in post-race serum creatine kinase activities has been found in healthy and equally trained athletes completing the same 90km ultramarathon footrace. The biochemical explanation for this degree of individual variability is not currently understood; possibly persons who show abnormally large increases in serum enzyme activities with exercise may have as yet unrecognised subclinical myopathies. No circadian rhythms have been identified for serum enzyme activities; activities rise during the day because of increased physical activity. The rise in serum enzyme activities is greater after exercise at altitude or in the heat than after equivalent exercise at sea level or in the cold. The most likely explanation for the increased serum enzyme activities that follow prolonged weight-bearing activities that also cause marked muscle soreness, is myofibrillar damage in particular sarcomeric Z-disk disruption.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical Enzyme Tests↗

Cortical language localization in left, dominant hemisphere. An electrical stimulation mapping investigation in 117 patients.

The localization of cortical sites essential for language was assessed by stimulation mapping in the left, dominant hemispheres of 117 patients. Sites were related to language when stimulation at a current below the threshold for afterdischarge evoked repeated statistically significant errors in object naming. The language center was highly localized in many patients to form several mosaics of 1 to 2 sq cm, usually one in the frontal and one or more in the temporoparietal lobe. The area of individual mosaics, and the total area related to language was usually much smaller than the traditional Broca-Wernicke areas. There was substantial individual variability in the exact location of language function, some of which correlated with the patient's sex and verbal intelligence. These features were present for patients as young as 4 years and as old as 80 years, and for those with lesions acquired in early life or adulthood. These findings indicate a need for revision of the classical model of language localization. The combination of discrete localization in individual patients but substantial individual variability between patients also has major clinical implications for cortical resections of the dominant hemisphere, for it means that language cannot be reliably localized on anatomic criteria alone. A maximal resection with minimal risk of postoperative aphasia requires individual localization of language with a technique like stimulation mapping.

Adolescent↗

Forearm blood flow measurements using computerized R-wave triggered strain-gauge venous occlusion plethysmography: unilateral vs. bilateral measurements.

The human forearm is a well established model to study local vascular reactivity in humans in vivo, using strain-gauge venous occlusion plethysmography to measure blood flow and changes in blood flow in the forearm. To reduce the intra-individual variability of the forearm blood flow (FBF), it has been advocated that simultaneous measurements of contralateral forearm blood flow is obligatory. Therefore, the use of the calculated forearm ratio (FR) is recommended instead of using the actual FBF. In the present study we compared the intra-individual variability of forearm blood flow measurements and the forearm ratio, by using computerized R-wave triggered strain-gauge venous occlusion plethysmography, to test if bilateral expression of measurements is better than unilateral. Results were obtained in eight volunteers. Intra-arterial infused sodium nitroprusside induced a dose dependent increase in forearm blood flow and a dose dependent increase in the calculated forearm ratio. Intra-arterial infused norepinephrine induced a dose dependent decrease in forearm blood flow and a dose dependent decrease in the calculated forearm ratio. The differences between the variation coefficients of the forearm blood flow measurements and the calculated forearm ratio were different. These results support our hypothesis that by using a computerized, R-wave triggered system for unilateral forearm blood flow measurement is a more reliable outcome than the calculated forearm ratio derived from bilateral measurements.

Adult↗

The effects of a gonadotrophin-releasing hormone agonist on treatment with low dose follicle stimulating hormone in polycystic ovary syndrome.

The objective of this study was to investigate whether the incidence of monofollicular growth during stimulation with low dose follicle stimulating hormone (FSH) changes when adjuvant gonadotrophin-releasing hormone agonist (GnRHa) pre-treatment is administered in polycystic ovary syndrome (PCOS). One group of patients (group 1) suffering from clomiphene resistant PCOS was stimulated with low dose FSH. The results were compared with those from another group of similar patients (group 2) subsequently stimulated with low dose FSH combined with GnRHa. In group 1 15 patients had 39 stimulation cycles performed; in group 2 13 patients had 33 stimulation cycles performed. In group 1 44% of cycles were monofollicular, whilst the corresponding figure in group 2 was 14% (P = 0.04). Evidence was found for postponed atresia in group 2. In both groups 1 and 2 inter-individual and intra-individual variability of the FSH dose inducing follicular growth were observed. We concluded that during the use of GnRHa, stimulation with low dose FSH less frequently resulted in monofollicular growth, possibly due to postponed atresia. Furthermore, the use of GnRHa does not abolish the inter- and intra-individual variability of the FSH dose inducing ongoing follicular growth.

Adult↗

Exhaled nitric oxide in healthy children: variability and a lack of correlation with atopy.

Nitric oxide (NO) is a free radical produced by several lung cells via the enzyme nitric oxide synthetase (NOS) and can be easily measured in exhaled air by chemiluminescence analysis. As the iso-enzyme iNOS may be induced by cytokines and endotoxin, NO is elevated in several chronic inflammatory airway diseases. Prior to using exhaled nitric oxide (eNO) as a non-invasive marker of airway inflammation in daily routine, the role of possibly influencing factors such as age, time of the day, smoking exposure and intra-individual variability have to be clarified. NO concentrations were measured in 107 healthy children aged 4-18 years at an expiratory flow of 184 ml/s. Spirometry and a skin-prick test were performed and a questionnaire on family history of atopy, personal symptoms of atopic disease and smoke exposure was completed. For intra-individual variability nitric oxide was measured in six children three times daily on 6 consecutive days. Median eNO concentration was 5.7 p.p.b., and increased significantly with age but did not vary with gender. No correlation was found between eNO and smoke exposure, positive skin-prick test, FEV1, MEF25 and time of the day. There was no circadian rhythm found in the six children measured on 6 consecutive days, but the eNO showed an intra-individual coefficient of variation of 25.9%. With the help of a two-compartment model of the lung the alveolar NO concentration was estimated to be 4.1 p.p.b and was shown to be constant with age, whereas the airway part of NO steadily increased with age. When comparing eNO values with standardized measurement techniques, the age of the children and the large intra-subject coefficient of variation have to be taken into account, whereas in healthy children subject-specific factors such as atopic history, gender and skin test reactivity did not affect eNO measurement.

Breath Tests↗

Exercise time: a possible source of misleading results during long-term pharmacological studies by multiple stress testings in coronary artery disease.

The assessment of chronic pharmacological treatment of stable angina requires serial exercise stress testings. It is well known that exercise tolerance can be improved by the training effect of performing repeated testings. Our study investigated the values of heart rate, systolic blood pressure, rate-pressure product, and duration of exercise at 0.1 mV ST depression during exercise and the same parameters plus the maximal ST-segment depression at peak exercise, collected from three different tests. The first and second were performed at one-week intervals before, and the third (75 days after the first), was performed after a double-blind study with a drug versus placebo. We found a significant increase of exercise duration at 0.1 mV ST depression and at peak exercise, while 6 of 12 patients increased exercise duration from the second to the third test. Individual variability of exercise duration showed increasing values, ranging from 0 to 71% (first vs. third test). In contrast, the ratio of heart rate and systolic blood pressure did not differ between the tests. Our data criticized the use of mean values of exercise time for pharmacological studies; moreover, individual variability could affect results independently of drug or placebo administration. These findings should be taken into account in order to exclude misleading results.

Adrenergic beta-Antagonists↗

[Individual anatomic variability of particular thalamic nuclei in children and adolescents with respect to stereotaxic coordinates].

As demonstrate macro-microscopic and stereologic investigations performed in 120 preparations of children and adolescent brain, the anterior, medial and lateral nuclei in the thalamus have a complex geometric form which does not change with age. Their linear dimentions and stereotaxic coordinates increase somewhat. These changes are described by means of mathematical models as regression equations. Individual changeability of the nuclear groups, situating within the studied ones are evidently subjugated to the same regularities. The individual variants revealed are not connected with side of the brain, form of the skull and sex. The combination of the methods used gives reliable results.

Adolescent↗

Estimation of the conduction velocity of sympathetic sudomotor C fibres in healthy subjects: study of sympathetic skin reflex.

The aim of this study was to establish a simple method for estimating the conduction velocity (CV) of post-ganglionic sympathetic sudomotor C fibres (SSFCV) in the upper and lower limbs by simultaneously measuring the sympathetic skin reflex (SSR) in two distant sites. Fifty healthy volunteers were studied. SSRs were recorded with standard surface electrodes applied to both proximal (axilla and crural line) and distal sites for each limb (hand and foot). The CV of the efferent branch of the SSR was calculated by dividing the difference in the latencies of the response from two recording sites by the distance between the sites (axilla-hand for upper limb; crural line-foot for lower limb). Day-to-day reproducibility and intra-individual variability of the SSFCV were calculated. For the upper limbs, the SSFCV in the axilla-hand tract was 2.0+/-0.3 m/sec (range 1.6-2.4 m/sec). For the lower limb, the SSFCV in the crural line-foot tract was 1.4+/-0.4 m/sec (range 1.2-1.6 m/sec). Mean intra-individual variability of the SSFCV for the upper and lower limbs was 0.11 and 0.09, respectively. The coefficient of variation of the SSFCV for the upper and lower limbs was 5.1% and 5.4%, respectively. Our data show that this simple and non-invasive method can reliably be used to measure the CV of the sympathetic sudomotor fibres, in suitable temperature conditions, and may be useful when investigating the physiological functions of peripheral nerves in patients with peripheral neuropathies.

Action Potentials↗

The relationship between alcohol and individual differences variables on attitudes and behavioral skills relevant to sexual health among heterosexual young adult men.

The purpose of this experiment was to investigate the effects of alcohol, alcohol sex expectancies, and sexual sensation seeking on determinants of sexual health behavior according to the Information-Motivation-Behavioral Skills (IMB) model. The participants were 48 heterosexual young adult males who attended 2 laboratory sessions. During Session 1, participants completed a set of screening and individual differences measures, and during Session 2 they were randomly assigned to 1 of 3 beverage conditions: control, alcohol (0.65 g alcohol/kg body weight), or placebo. Following the experimental manipulation, all participants completed measures regarding attitudes toward condom use, intention to engage in risky sex, and condom use negotiation skills. The results showed that participants who consumed alcohol had poorer negotiation skills and greater intention to engage in risky sex compared to participants who did not drink alcohol. Although alcohol did not affect any dimension of attitude regarding condom use, attitude about condoms' effects on sex, as well as sexual sensation seeking, were correlated with both intention ratings and skills. Multiple regression models, including both attitudes and sensation seeking, showed that attitudes accounted for 20-25% of variance independent of beverage condition in predicting intention ratings and skills. The findings were consistent with past research showing that alcohol consumption can have detrimental effects on determinants of sexual health behavior and that individual differences factors can enhance the power of models like the IMB to predict such behavior.

Adult↗

Neighbourhood non-employment and daily smoking: a population-based study of women and men in Sweden.

BACKGROUND: To examine whether neighbourhood non-employment is associated with daily smoking after adjustment for individual characteristics, such as employment status. METHODS: Cross-sectional study of a simple, random sample of 31,164 women and men aged 25-64, representative of the entire population in Sweden. Data were collected from the years 1993-2000. The individual variables included age, sex, employment status, occupation and housing tenure. Logistic regression was used in the analysis with neighbourhood non-employment rates measured at small area market statistics level. RESULTS: There was a significant association between neighbourhood non-employment rates and daily smoking for both women and men. After adjustment for employment status and housing tenure the odds ratios of daily smoking were 1.39 (95% CI = 1.22-1.58) for women and 1.41 (95% CI = 1.23-1.61) for men living in neighbourhoods with the highest non-employment rates. The individual variables of unemployment, low occupational level and renting were associated with daily smoking. CONCLUSION: Neighbourhood non-employment is associated with daily smoking. Smoking prevention in primary health care should address both individuals and neighbourhoods.

Adult↗

Development of anticipatory postural adjustments in a bimanual load-lifting task in children.

Anticipatory postural adjustments (APA) are needed to perform a movement without perturbing posture. We investigated the development of APA in 3- to 4-year-old children during a bimanual load-lifting task. The task required maintaining a stable elbow position despite imposed or voluntary unloading of the forearm. Although children can compensate the consequences of unloading by using APA, their performance did not reach an adults' level. In addition, children showed high intra-individual variability in the voluntary situation, revealed by the coexistence of both adult-like and immature patterns in kinematic and electromyographic data. In conclusion, the present study reports that APA, associated with a bimanual load-lifting task, are still being set up in 3- to 4-year-old-children. The intra-individual variability should decrease with age and be associated with a progressive mastering of the timing parameters characterizing APA.

Biomechanical Phenomena↗

The influence of (R)- and (S)-warfarin, vitamin K and vitamin K epoxide upon warfarin anticoagulation.

The contribution of (R)- and (S)-warfarin enantiomers, vitamin K and vitamin K epoxide and patient factors to inter-individual variability in daily warfarin requirements were examined in a group of 73 patients. Simple correlation analysis showed a significant positive relationship between INR values and plasma (S)-warfarin concentrations (r = 0.25; p = 0.038). Multivariate analysis for relationships with INR demonstrated a highly significant positive relationship between INR and (S)-warfarin (p = 0.004) and plasma vitamin K epoxide concentrations (p = 0.028), and a significant negative relationship between INR and plasma vitamin K concentrations (p = 0.034). Twenty five percent of variation in INR could be explained by these variables (adjusted R2 = 0.25). Correlation analysis of data showed that warfarin dosage was significantly and negatively correlated with patient age (r = -0.42; p <0.0001). Patient age accounted for 25% of variation in warfarin dosage requirements (R2 = 0.25). The combined effects of age and vitamin K appear to account for much of the inter-individual variability in warfarin dosage requirements.

Adult↗

Common genetic polymorphisms in the 5'-flanking region of the SULT1A1 gene: haplotypes and their association with platelet enzymatic activity.

SULT1A1 is a phase II detoxification enzyme involved in the biotransformation of a wide variety of endogenous and exogenous phenolic compounds. Human platelet SULT1A1 enzymatic activity shows marked inter-individual variability and a common coding polymorphism, SULT1A1*1/*2, has been described that accounts for a proportion of this variability. We examined the 5'-flanking region of the SULT1A1 gene to determine if genetic variability in this portion of the gene influenced enzymatic activity. Direct sequencing revealed five common genetic polymorphisms (-624G>C, -396G>A, -358A>C, -341C>G and -294T>C) that were present at different allele frequencies in Caucasian, African-American and Chinese groups. Platelet SULT1A1 enzymatic activity was significantly correlated with individual promoter region polymorphisms and the associations were different between African-Americans and Caucasians. Haplotypes were constructed and platelet enzymatic activity according to haplotype was examined. The haplotypes were also significantly correlated with activity; haplotypes GAACT and GGACT (accounting for 13% and 5% of inter-individual variability in platelet activity, respectively) were important in Caucasians while haplotypes GAACC, GAACT and GGACC (accounting for 8%, 5% and 4% of variability) were significantly associated with activity in African-Americans. The coding region polymorphism, SULT1A1*1/*2 was in linkage disequilibrium with the promoter region polymorphisms and showed no effect on activity when examined in the context of the 5'-flanking region polymorphisms. These studies indicate that variation in the promoter region of the SULT1A1 gene exerts a significant influence on enzymatic activity.

5' Flanking Region↗

Kinetics of the humoral immune response to multiple treatments with exogenous gonadotropins and relation to ovarian responsiveness in domestic cats.

OBJECTIVE: To investigate ovarian responses and kinetics of gonadotropin-binding immunoglobulin production in domestic cats repeatedly treated with equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG) at short or long treatment intervals. DESIGN: Queens were treated 3 or 4 times with a standard eCG/hCG regimen at short (49 to 57 days) or long (130 to 135 days) intervals and subjected to laparoscopy after each treatment to evaluate ovarian follicular development. Serial serum samples were assessed by ELISA for the presence of eCG-binding immunoglobulins. ANIMALS: 11 clinically normal sexually mature female cats. RESULTS: Queens repeatedly stimulated with eCG/hCG at long intervals typically had no decrease (P > 0.05) in ovarian follicle production or in maturity of recovered oocytes, whereas queens treated at short intervals had reduced (P < 0.05) follicular development and compromised oocyte maturity by the third stimulation. For both interval groups, ELISA data indicated individual variability in seroconversion after eCG/hCG challenge exposure. In general, queens treated at short intervals had higher peak anti-eCG immunoglobulin titer than did queens treated at long intervals; high titer at the time of eCG/hCG injection, or rapid increases in titer immediately after injection were predictive (P < 0.05) of poor ovarian responses. CONCLUSIONS: Results suggest that individual variability in immune responses and intervals between repeated gonadotropin treatments determine whether queens develop immunologically mediated ovarian refractoriness to exogenous gonadotropins. Intervals of at least 4 months between successive eCG/hCG treatments are recommended for assisted reproductive procedures in domestic and nondomestic cats.

Analysis of Variance↗