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PubMed1991

Subcutaneous insulin absorption explained by insulin's physicochemical properties. Evidence from absorption studies of soluble human insulin and insulin analogues in humans.

OBJECTIVE: To study the influence of molecular aggregation on rates of subcutaneous insulin absorption and to attempt to elucidate the mechanism of absorption of conventional soluble human insulin in humans. RESEARCH DESIGN AND METHODS: Seven healthy male volunteers aged 22-43 yr and not receiving any drugs comprised the study. This study consisted of a single-blind randomized comparison of equimolar dosages of 125I-labeled forms of soluble hexameric 2 Zn2+ human insulin and human insulin analogues with differing association states at pharmaceutical concentrations (AspB10, dimeric; AspB28, mixture of monomers and dimers; AspB9, GluB27, monomeric). After an overnight fast and a basal period of 1 h, 0.6 nmol/kg of either 125I-labeled human soluble insulin (Actrapid HM U-100) or 125I-labeled analogue was injected subcutaneously on 4 separate days 1 wk apart. Absorption was assessed by measurement of residual radioactivity at the injection site by external gamma-counting. RESULTS: The mean +/- SE initial fractional disappearance rates for the four preparations were 20.7 +/- 1.9 (hexameric soluble human insulin), 44.4 +/- 2.5 (dimeric analogue AspB10), 50.6 +/- 3.9 (analogue AspB28), and 67.4 +/- 7.4%/h (monomeric analogue AspB9, GluB27). Absorption of the dimeric analogue was significantly faster than that of hexameric human insulin (P less than 0.001); absorption of monomeric insulin analogue AspB9, GluB27 was significantly faster than that of dimeric analogue AspB10 (P less than 0.01). There was an inverse linear correlation between association state and the initial fractional disappearance rates (r = -0.98, P less than 0.02). Analysis of the disappearance data on a log linear scale showed that only the monomeric analogue had a monoexponential course throughout. Two phases in the rates of absorption were identified for the dimer and three for hexameric human insulin. The fractional disappearance rates (%/h) calculated by log linear regression analysis were monomer 73.3 +/- 6.8; dimer 44.4 +/- 2.5 from 0 to 2 h and 68.9 +/- 3.5 from 2.5 h onward; and hexameric insulin 20.7 +/- 1.9 from 0 to 2 h, 45.6 +/- 5.0 from 2.5 to 5 h, and 70.6 +/- 6.3 from 5 h onward. CONCLUSIONS: Association state is a major determinant of rates of absorption of insulin and insulin analogues. The lag phase and the subsequent increasing rate of subcutaneous soluble insulin absorption can be explained by the associated state of native insulin in pharmaceutical formulation and its progressive dissociation into smaller units during the absorption process.

Absorption↗

PubMed2005

Women living alone have an increased risk to develop diabetes, which is explained mainly by lifestyle factors.

OBJECTIVE: The purpose of this study was to assess the role of household conditions for the progression to diabetes in women with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A total of 461 women, aged 50-64 years, with IGT defined by an oral glucose tolerance test, had baseline advice on physical exercise, diet, smoking, and alcohol habits. Physical examination, blood tests, and questionnaires were completed at baseline and after 2.5 years. Household status was categorized into living alone or with a partner, other adults, or children. RESULTS: Women living alone had a 2.68-fold increased risk (95% CI 1.02-7.05) of developing diabetes after adjustments for biological risk factors. Further stepwise adjustments for education, occupation, subjective mental health, exercise, diet, and alcohol showed remaining significant odds ratios (ORs), decreasing from 3.26 (1.19-8.96) to 3.03 (1.02-8.99). However, when smoking status was added, the OR became nonsignificant, 2.07 (0.62-6.88). More women who lived alone smoked and did not reduce their daily cigarette consumption compared with women in other household conditions. At follow-up, women living alone had reduced their alcohol consumption and were more often abstainers and fewer had healthy dietary habits or had improved their diet. Physical exercise did not differ among the groups. Separate analyses of any other household status did not show any excess risk for development of diabetes. CONCLUSIONS: Women living alone had a higher risk to progress from IGT to diabetes, mostly explained by smoking, alcohol, and dietary habits. Household conditions should be accounted for when assessing future risk for diabetes.

Alcohol Drinking↗

PubMed2006

Generalized lysosome-associated membrane protein-2 defect explains multisystem clinical involvement and allows leukocyte diagnostic screening in Danon disease.

Danon disease, an X-linked dominant disorder, results from mutations in the lysosome-associated membrane protein-2 (LAMP2) gene and presents with hypertrophic cardiomyopathy, skeletal myopathy, and mental retardation. To investigate the effects of LAMP2 gene mutations on protein expression in different tissues, we screened LAMP2 gene mutations and LAMP-2 protein deficiency in the skeletal muscle of nine unrelated patients with hypertrophic cardiomyopathy and vacuolar myopathy. We identified three novel families (including one affected mother) with unreported LAMP2 gene null mutations and LAMP-2 protein deficiency in skeletal and myocardial muscle, leukocytes, and fibroblasts. LAMP-2 protein deficiency was detectable in various tissues, including leukocytes, explaining the multisystem clinical involvement. Skeletal muscle immunopathology showed that mutant protein was not localized in the Golgi complex, vacuolar membranes expressed sarcolemmal-specific proteins, and the degree of muscle fiber vacuolization correlated with clinical muscle involvement. In our female patient, muscle histopathology and LAMP-2 protein analysis was inconclusive, indicating that diagnosis in females requires mutation identification. The random X-chromosome inactivation found in muscle and leukocytes excluded the possibility that selective involvement of some tissues in females is due to skewed X-chromosome inactivation. Therefore, biochemical analysis of leukocytes might be used for screening in male patients, but genetic screening is required in females.

Adult↗

PubMed2006

Do mirror neurons explain misattribution of emotions in music?

It is speculated that certain listeners' misattribution of anger in the music of avant garde jazz saxophonists could be explained by the activity of mirror neurons. There is a neurological basis for the human tendency to imitate what is perceived in another person. This may lead to an inference that whatever comparable activity would be required to achieve a similar condition in the imitator is the condition being experienced by the person being imitated.

Anger↗

PubMed1995

Explaining exercise behavior and satisfaction with social exchange theory.

This study tested the hypothesis that the variables specified by social exchange theory (perceived rewards of exercising, perceived costs of exercising, social and tangible investments, and available alternative activities) are associated with exercise behavior and satisfaction. 190 health club members completed a questionnaire assessing attitudes toward exercise, exercise behavior, and demographic information. Exercise frequency and satisfaction were regressed on the social exchange theory variables and demographic covariates. Exercise satisfaction, the number of investments in exercise, and the number of available alternative activities were significantly related to exercise frequency, and the number of perceived rewards of exercise and the number of investments were significantly related to exercise satisfaction. These results suggest that social exchange theory is useful for explaining exercise behavior.

Adult↗

PubMed2003

Are sex differences in sexual vs emotional jealousy explained better by differences in sexual strategies or uncertainty of paternity?

In a classic 1992 study, Buss, Larson, Westen, and Semmelroth reported that men were more distressed by the sexual infidelity of a partner and women were more distressed by a partner's emotional infidelity. Buss, et al. suggested that men are concerned about uncertainty of paternity, that is, the possibility of raising another man's child while believing that the child is his own. However, data can be explained in terms of men's greater preference for short-term sexual strategies. This research yielded support for the latter explanation for the samples in this present research.

Adult↗

PubMed2006

Paretic upper-limb strength best explains arm activity in people with stroke.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the relationship among variables of upper-limb impairment, upper-limb performance in activities of daily living (activity), and engagement in life events and roles (participation) in people with chronic stroke. SUBJECTS: The subjects were 93 community-dwelling individuals with stroke (> or =1 year). METHODS: This study, which was conducted in a tertiary rehabilitation center, used a cross-sectional design. The main measures of impairment were the Modified Ashworth Scale, handheld dynamometry, sensory testing (monofilaments), and the Brief Pain Inventory. The main measures of activity were the Chedoke Arm and Hand Activity Inventory (CAHAI) and the Motor Activity Log (MAL). The main measure of participation was the Reintegration to Normal Living (RNL) Index. RESULTS: Paretic upper-limb strength (force-generating capacity) (r=.89, P<.01), grip strength (r=.69, P<.01), and tone (resistance to passive movement) (r=-.80, P<.01) were the impairment variables that were most strongly related to activity. Tone (r=-.23, P<.05) and CAHAI scores (r=.22, P<.05) had a significant, but weak, relationship to participation. Upper-limb strength accounted for 87% of the variance of the CAHAI scores and 78% of the variance of the MAL scores. In the participation models, tone and CAHAI scores accounted for 5% of the variance of the RNL Index scores. DISCUSSION AND CONCLUSION: Paretic upper-limb strength had the strongest relationship with variables of activity and best explained upper-limb performance in activities of daily living. Grip strength, tone, and sensation also were factors of upper-limb performance in activities of daily living. Increased tone and upper-limb performance in activities of daily living had a weak relationship with participation.

Activities of Daily Living↗

PubMed1989

How to explain a constant subjective vertical at constant high speed rotation about an earth-horizontal axis.

When rotated in darkness about an earth-horizontal axis at speeds above 0.2-0.5 Hz, subjects, instead of feeling rotated, experience a constant (though extrapersonally diverse) position in space and a constant visual vertical (SV). Computer simulation shows that this phenomenon cannot be explained by the extant models of Mayne (1) and Ormsby (2) about the interaction of otoliths and semicircular canals. It follows, however, from a static theory of the SV (3) if, as in the presently proposed dynamic model, the otolith afference is processed by a low-pass filter. At high speed rotation this filter can only be passed by the force-independent, temporally invariant components of the otolith information. Such force-independent components are bound to result from biassed resting discharges, and have previously been shown to affect the SV and the self-adopted horizontal position. The interaction of otoliths and canals proposed by the model does provide a veridical vertical in a working range of angular frequencies and hence a basis for inertial navigation.

Acceleration↗

PubMed1989

Can regional differences in consumption of tranquillizers and hypnotics be explained by variations in general practitioners' threshold of prescribing? A methodological study.

Large differences exist in the consumption of tranquillizers and hypnotics within and between countries. The present study investigates the hypothesis that regional differences in the utilization of tranquillizers and hypnotics are associated with corresponding differences in thresholds of prescribing. A questionnaire that described in a standardized manner 12 patients with a symptomatology of anxiety and insomnia was sent to all general practitioners in two regions (south/north) in Norway. In the south, tranquillizers and hypnotics are used much more frequently than in the north. Based on written simulations of patients, no differences in thresholds of prescribing was found between the general practitioners in the two regions. Neither could the doctors' choice of drugs, nor their recommendations for dosage and duration of treatment, explain the different consumption of tranquillizers and hypnotics in the two regions. The method could, however, be criticized for insufficient validity, since our case stories were less controversial with respect to psychotropic drug prescribing than intended.

Drug Prescriptions↗

PubMed1990

Theoretical models to explain the association of HLA-B27 with ankylosing spondylitis.

A critical examination of the five different models proposed to explain the "AS-B27" problem, has demonstrated, that two of these, the two-gene theory and the plasmid theory are no longer considered to provide satisfactory explanations of the phenomena. The remaining three theories are molecular mimicry, chemotaxis hypothesis and the receptor theory. It is difficult at this stage to decide which of these three models provides the best solution to the "AS-B27" problem, but a majority of research workers favour the receptor theory.

Animals↗

PubMed1997

Simultaneous manifestation of free-running and entrained rhythms in the rat motor activity explained by a multioscillatory system.

Seven groups of 6 young male rats were exposed for 60 calendar days to symmetrical light/dark cycles with different periods (T = 22, 23, 24, 25, 26, 27, and 28 h), and subsequently to constant darkness for 30 days. During exposure to the light/dark cycles, all the animals in all groups presented a motor activity component that was entrained to the external cycles, although the animals subjected to light/dark cycles with periods shorter than 25 hours also presented a nonentrained circadian component. Moreover, in all cases, the effect of masking was present, manifested as a reactivity to the light-dark transitions and as a reduction of activity induced by light. Our results demonstrate that masking, entrainment, and free-running rhythm can be present at the same time. The simultaneous presence of the light-entrained component and the nonentrained component can be explained in terms of a multioscillatory system, in which some oscillators could be entrained to the light/dark cycles while other oscillators could be nonentrained at the same time. Thus, the present study indicates that the circadian system is not necessarily entirely entrained, and that the degree of entrainment may depend on the number of oscillators involved in generating the entrained rhythm.

Animals↗

PubMed1999

Immunization in the first month of life may explain decline in incidence of IDDM in The Netherlands.

A low cumulative incidence of IDDM was reported in Dutch males born in 1962 (Diabetologia 1992: 35: 139-142) compared to males born in previous or later years. The cause for the decreased risk has not been previously explained. We propose that children born in 1962 during an European smallpox epidemic may have received the smallpox vaccine in the first month of life and this may have attributed to the decreased risk of IDDM in these children. We have shown that immunization with several different vaccines starting in the first month of life prevents diabetes in NOD mice and BB rats (Autoimmunity 1996: 24: 137-145) while immunization at birth with the BCG vaccine is associated with an decreased risk of IDDM in humans (Infectious Diseases in Clinical Practice 1997: 6: 449-454). An even bigger decline in diabetes is seen in rodents and associated in humans when one compares immunization starting in the first month of life to immunization starting after 2 months, since the later has been associated with an increased risk of IDDM. Immunization studies in the past have typically followed patients for only several weeks to determine any unplanned affects on autoimmune disease. Due to the potential benefit of reducing the incidence of diabetes by 50% through age 18 we believe clinical trials are warranted to study the effect of timing of immunization on IDDM.

Adolescent↗

PubMed1997

Drug treatment: explaining the gender paradox.

There is something of a gender paradox in drug user treatment. Research consistently indicates that women possess "risk factors" associated with drug use relapse, yet women are no more likely, and possibly less likely, to relapse to drug use. Efforts to explain this paradox involve a longitudinal study of 330 women and men participating in outpatient drug-user treatment associated with the evaluation of the Los Angeles Target Cities Project funded by the Center for Substance Abuse Treatment. The findings offer no support for the drug severity and social support hypotheses, but some support for the treatment engagement hypothesis. Specifically, women participate more frequently in group counseling which, in turn, lowers their rate of relapse in spite of having more "risk factors." Further analyses indicate that the greater participation of women in group counseling does not stem from child-custody or other gender differences in the reasons for entering treatment, nor does it result from the enhanced services associated with the Target Cities Project. Rather, the differences in treatment engagement for women and men may result from gender norms concerning help-seeking, personal independence, strength, and control. The treatment and policy implications of these findings and recommendations for further research are discussed.

Adolescent↗

PubMed1990

Comparison of the mechanisms proposed to explain the hypocholesterolemic effect of soybean protein versus casein in experimental animals.

Diets containing soybean protein generally induce low levels of serum cholesterol in experimental animals, when compared with diets containing casein. The hypocholesterolemia in animals fed soybean protein is associated with increased rates of fecal excretion of bile acids and neutral steroids, low liver cholesterol concentrations, increased numbers of hepatic apo B/E receptors, increased rates of hepatic cholesterol synthesis, increased rates of bile acid synthesis and decreased rates of lipoprotein cholesterol output by the liver. In this communication the development of the hypocholesterolemia induced by soybean protein is described. The various mechanisms that have been proposed to explain the hypocholesterolemic effect of soybean protein are scrutinized, compared and contrasted.

Animals↗

PubMed1984

The Copley-Scott Blair phenomenon. Will it be explained by the effect of an electric double layer?

S. Oka has offered an elegant explanation of the Copley-Scott Blair phenomenon based on the inclusion of the effect of an electric double layer, which occurs at the interface of phases between the capillary wall and the dispersion medium. The latter is considered as blood, plasma or serum. This explanation has associated the Copley-Scott Blair phenomenon and changes of the apparent viscosity with such electrokinetic phenomena as an electroosmosis and a streaming potential. As has been shown by a qualitative analysis of the formulae obtained by S.Oka, the inclusion of the electrosurface features makes it possible to explain the changes of the apparent viscosity while blood flows through capillaries. And the smaller is the capillary radius, the more substantial are these changes. At the same time, such conclusions may not be considered as a demonstration of the significance of the double layer effects in hemorheology, since the Oka theoretical model should be supplemented with an inclusion of the Debye screening radius, surface conductivity and a feasible overlap of the double layers within a capillary. Requirements on an experimental test of the Oka theoretical model have been formulated.

Blood Flow Velocity↗

PubMed1985

How nursing students explain their success and failure in clinical experiences.

Student motivation is a faculty concern at all strata of the educational process. A major issue in motivation is the student's perception of the situation and explanation of the cause of success or failure. The education literature indicates little research on how student nurses actually perceive and explain their success and failure. This paper addresses success and failure issues by reviewing attribution theory and describing a study of attribution made by student nurses following completion of clinical nursing courses in one school. Explanations were obtained for success and failure both of nursing care provided and for mastery of theory. The data obtained reveal some interesting patterns and indicate the need for further research in this area.

Achievement↗

PubMedDate not supplied

A model to explain the difference between changes in refraction and central ocular surface power after laser in situ keratomileusis.

PURPOSE: After refractive surgery, changes in central ocular surface power are usually less than actual changes in refraction. The aim of this paper was to examine the theoretical changes in the radius of the epithelial-stromal interface and corneal stromal refractive index which could take place to account for some of the empirical findings. METHODS: The parameters of an aspheric human eye model featuring gradient index optics was modified using data from a clinical study evaluating effects of laser in situ keratomileusis (LASIK) for correction of moderate to high myopia. Computations were performed to determine: 1) theoretical postoperative radius of the epithelial-stromal interface and hence distribution of epithelial thickness, and 2) refractive index of the stroma when the epithelium was of fixed uniform thickness. RESULTS: Within the central 2-mm diameter refractive zone of the cornea after LASIK for myopia, either of two factors could account for the difference between changes in central ocular surface power and the actual change in ocular refraction: 1) a steepening of the epithelial-stromal interface resulting from a 400% centrifugal increase in epithelial thickness, or 2) a reduction in stromal refractive index from an average of 1.376 to 1.364. CONCLUSION: The difference between the observed changes in refraction and central ocular surface power could be explained by reduction in stromal refractive index and this could be secondary to a 6.5% increase in water content of the stroma during the postoperative period. The epithelial-stromal interface after LASIK is unlikely to steepen by the extent predicted by our model. This surface is not the source of the difference between the change in refraction and change in central ocular surface power.

Corneal Stroma↗

PubMedDate not supplied

Can the social model explain all of disability experience? Perspectives of persons with chronic fatigue syndrome.

OBJECTIVE: The social model of disability has had a major influence on the academic field of disability studies and on contemporary understandings of the causes and experience of disability. The purpose of this study was to examine the adequacy of the social model for explaining the disability experience of persons with chronic fatigue syndrome (CFS). METHODS: This qualitative study examined the experiences of 47 adults with CFS participating in a research project that aimed to evaluate a participant-designed rehabilitation program. Data were aggregated from focus group interviews, open-ended questionnaires, progress notes, and from a program evaluation questionnaire. Data analysis was based on a grounded theory approach and used triangulation of multiple data sources and member checks to assure dependability of findings. RESULTS: Four themes emerged from the analysis: (1) minimization and mistrust of the disability; (2) negative experiences of impairment; (3) lack of identification with the disability community; and (4) the focus on advocacy as a quest for legitimacy. These themes varied in the extent to which they conformed to the principles set forth by the social model. CONCLUSIONS: Although the social model has important contributions to lend to occupational therapy practice, it is important to recognize that it may not capture the full reality of disability. In particular, the social model has serious limitations in describing the disability experience of individuals with disabilities who do not have visibly obvious disabilities and whose impairments do not conform to the traditional viewpoint of disability.

Adult↗