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Biomedical subjects

L Lindström

Publications and source records attributed to L Lindström.

At least 19 recordsLinked to original sources

Estimation of genetic and environmental factors for melanoma onset using population-based family data.

Estimation of genetic and environmental contributions to cancers falls in the framework of generalized linear mixed modelling with several random effect components. Computational challenges remain, however, in dealing with binary or survival phenotypes. In this paper, we consider the analysis of melanoma onset in a population of 2.6 million nuclear families in Sweden, for which none of the current survival-based methodologies is feasible. We treat the disease outcome as a binary phenotype, so that the standard proportional hazard model leads to a generalized linear model with the complementary-log link function. For rare diseases this link is very close to the probit link, and thus allows the use of marginal likelihood for the estimation of the variance components. We correct for the survival length bias by censoring the parent generation within each family at the time they attain the same cumulative hazard as the child generation, thus improving the validity of the estimates. Our finding that childhood shared environment in addition to genetic factors had a considerable effect on the development of melanoma is consistent with epidemiological studies.

Adolescent↗

Negatively condition dependent predation cost of a positively condition dependent sexual signalling.

Predation is considered as an important factor constraining the expression of sexual signals. Nevertheless, direct quantitative evidence for predation provoking significant viability costs on individuals signalling at high rates is scarce. Moreover, it is unclear whether high rate signallers are able to balance presumably increased predation costs. We examined whether a condition dependent audible sexual signal, drumming, makes Hygrolycosa rubrofasciata male spiders more prone to predation by pied flycatchers (Ficedula hypoleuca), and whether sexual signalling rate is related to escaping ability once attacked. When birds were given a choice between two spider males manipulated to drum either one or three bouts per minute using playbacks, naïve birds attacked the males randomly regardless of the drumming rate. However, experienced birds chose significantly more often the males with high signalling rate. When spiders were allowed to escape, males with high sexual signalling rate tended to be better at escaping attacks than males with low sexual signalling rate. This study provides evidence that high signalling rate increases the risk of predation, but simultaneously males with high mobility, which correlates positively with signalling rate seemed to be better at compensating this cost.

Animals↗

HIV/AIDS information and services: the situation experienced by adolescents with disabilities in Rwanda and Uganda.

PURPOSE: The study had two aims: (2) To explore whether knowledge about HIV and AIDS was similar among adolescents with disabilities compared with their non-disabled peers; and (2) To determine factors which may increase vulnerability of disabled adolescents to HIV infection and/or inappropriate access to HIV-related services. METHOD: A qualitative study using focus group discussions and sem-structured interviews was conducted with purposefully selected participants in Rwanda and Uganda. The participants included disabled adolescents, non-disabled adolescents, parents, teachers, members of disabled people's organisations and representatives of HIV/AIDS organisations. Interviews explored issues of HIV/AIDS knowledge, access to HIV/AIDS services and perceptions of personal risk. RESULTS: Barriers preventing adequate access to information about HIV and AIDS experienced by adolescents with disabilities depended on the nature and severity of the impairment. For example, parents and health workers were unable to communicate with deaf adolescents using sign language, adolescents with physical impairments were often unable to access community meetings about HIV and print material was not adapted for those with visual impairments. Further, assumptions by health workers and community members that people with disabilities were not sexually active led to the marginalisation of disabled people from HIV services. Adolescents with disability described low self-esteem and issues of self-efficacy affecting control of safer sexual relationships. A high level of targeted abuse, rape and exploitation was reported leading to vulnerability among this population. CONCLUSION: The impact of the HIV epidemic among people with disabilities is a neglected area. This study supports the need to develop strategies in HIV prevention programmes that include people with disabilities.

Acquired Immunodeficiency Syndrome↗

Multiple benefits of gregariousness cover detectability costs in aposematic aggregations.

Understanding the early evolution of aposematic (warning) coloration has been a challenge for scientists, as a new conspicuous morph in a population of cryptic insects would have a high predation risk and would probably die out before local predators learnt to avoid it. Fisher presented the idea of aggregation benefit through the survival of related individuals; however, his theory has been strongly debated as the mechanisms that favour grouping have never been explored experimentally with the incorporation of detectability costs. Here we create a comprehensive 'novel world' experiment with the great tit (Parus major) as a predator to explore simultaneously the predation-related benefits and costs for aposematic aggregated prey, manipulating both group size and signal strength. Our results show that grouping would have been highly beneficial for the first aposematic prey individuals surrounded by naive predators, because (1) detectability risk increased only asymptotically with group size; (2) additional detectability costs due to conspicuous signals were marginal in groups; (3) even naive predators deserted the group after detecting unpalatability (dilution effect); and (4) avoidance learning of signal was faster in groups. None of these mechanisms require kin selection.

Animals↗

Strong antiapostatic selection against novel rare aposematic prey.

The evolution of aposematism, a phenomenon where prey species conspicuously advertise their unprofitability to predators, is puzzling. How did conspicuousness evolve, if it simultaneously increased the likelihood of an inexperienced predator to detect the prey and presumably kill it? Antiapostatic selection, where rare prey is predated relatively more often, is considered as another major difficulty for aposematism to evolve. However, the risk of being conspicuous in low frequencies has not been experimentally tested. We designed an experiment to test how frequency (4%, 12%, 32%) of conspicuous aposematic prey and its dispersion type (solitary vs. aggregated) affect an initial predation risk of the prey and in avoidance learning of predators. Wild great tits (Parus major) were predators on artificial prey in a "novel world." The relative mortality of aposematic prey was antiapostatic, thus the frequency-dependent predation was most severe at low frequencies. In all frequencies, aggregated aposematic prey survived better than solitary prey. Surprisingly, learning was not determined by a fixed number of unpalatable prey eaten, but at low frequencies fewer aposematic individuals eaten generated predators' avoidance learning. However, per-capita risk for the prey remained highest at low frequencies. Our results underscore the problems of initial evolution of rare conspicuous morphs. Aggregated prey suffered less from predation, indicating selective advantage of aggregation over solitary living for a conspicuous individual.

Animals↗

Predator experience on cryptic prey affects the survival of conspicuous aposematic prey.

Initially, aposematism, which is an unprofitable trait, e.g. noxiousness conspicuously advertised to predators, appears to be a paradox since conspicuousness should increase predation by naive predators. However, reluctance of predators for eating novel prey (e.g. neophobia) might balance the initial predation caused by inexperienced predators. We tested the novelty effects on initial predation and avoidance learning in two separate conspicuousness levels of aposematic prey by using a 'novel world' method. Half of the wild great tits (Parus major) were trained to eat cryptic prey prior to the introduction of an aposematic prey, which potentially creates a bias against the aposematic morph. Both prey types were equally novel for control birds and they should not have shown any biased reluctance for eating an aposematic prey. Knowledge of cryptic prey reduced the expected initial mortality of the conspicuous morph to a random level whereas control birds initially ate the conspicuous morph according to the visibility risk. Birds learned to avoid conspicuous prey in both treatments but knowledge of cryptic prey did not increase the rate of avoidance learning. Predators' knowledge of cryptic prey did not reduce the predation of the less conspicuous aposematic prey and additionally predators did not learn to avoid the less conspicuous prey. These results indicate that predator psychology, which was shown as reluctance for attacking novel conspicuous prey, might have been important in the evolution of aposematism.

Animals↗

Pyrazine odour makes visually conspicuous prey aversive.

Unpalatable insects frequently adopt multimodal signals to ward off predators, incorporating sounds and odours into their colourful displays. Pyrazine is an odour commonly used in insect warning displays, and has previously been shown to elicit unlearned biases against common warning colours, e.g. yellow and red in naive predators. We designed two experiments to test for similar effects of pyrazine on the conspicuousness of prey, perhaps the most ubiquitous aspect of aposematic coloration. In the first experiment, we offered predators (Gallus gallus domesticus) a choice between conspicuous crumbs and cryptic crumbs in the presence or absence of pyrazine. In the second experiment, we manipulated the birds' experience of conspicuous prey during an initial training phase. Only in the presence of pyrazine did birds show a bias against conspicuously coloured food, and this occurred whether or not they had previously experienced food that contrasted with the background. This emergent behaviour relied upon the visual and odorous signal components being presented together. These unlearned, yet hidden, responses against conspicuousness demonstrate that there are initial benefits to prey being conspicuous when the multimodal nature of warning signals is accounted for.

Animals↗

D(2) and 5HT(2A) receptor occupancy of different doses of quetiapine in schizophrenia: a PET study.

OBJECTIVE: Quetiapine is a novel antipsychotic agent with many atypical features, including low D(2) and higher 5HT(2A) affinity in vitro, low propensity to induce extra-pyramidal side effects and minimal effects on prolactin levels. The purpose of this study was to investigate, using positron emission tomography (PET), the relationship between plasma concentrations of different doses of quetiapine and occupancy of D(2) and 5HT(2A) receptors in schizophrenic patients. METHODS: Five patients were treated with quetiapine (titrated to 750 or 450 mg/day) for 28 days, subsequently reduced weekly in a descending-dose schedule. Dopamine D(2) and 5HT(2A) occupancies were determined using [(11)C] raclopride and [(11)C] N-methylspiperone as ligands, respectively, and PET imaging. RESULTS: Mean D(2) receptor occupancies of 41 and 30% were observed at quetiapine doses of 750 and 450 mg/day. At lower dose levels no occupancy could be determined. Quetiapine induced a consistently higher degree of 5HT(2A) receptor occupancy, with mean occupancies of 74 and 57% at doses of 750 and 450 mg/day, respectively. No EPS emerged during the trial and most of the pre-trial EPS resolved during the study. CONCLUSIONS: In clinically effective doses, quetiapine induced low occupancy at D(2) receptors, which is consistent with atypical antipsychotics such as clozapine, and probably explains the lack of EPS observed in this trial. Correlations between receptor occupancy and plasma concentrations of quetiapine could not be calculated, although receptor occupancy increased with higher plasma concentrations for the 450 and 750 mg doses.

Adult↗

Atrioventricular plane displacement correlates closely to circulatory dimensions but not to ejection fraction in normal young subjects.

AIMS: Mitral atrioventricular plane displacement (AVPD) provides information about left ventricular systolic function. M-mode of systolic annulus amplitude or tissue Doppler imaging of systolic annulus velocity are the current methods of evaluating AVPD. A correlation to ejection fraction (EF) has been demonstrated in patients with coronary artery disease and left ventricular dysfunction. Our aim was (i) to investigate the mitral AVPD of normal subjects with different physical work capacities and (ii) to further evaluate AVPD as an index of left ventricular systolic function. METHODS AND RESULTS: Twenty-eight healthy men mean age 28 years (20-39) were included: endurance trained (ET) (n=10), strength trained (ST) (n=9) and untrained (UT) (n=9). The systolic AVPD was recorded at four sites, septal, lateral, anterior and posterior, using M-mode. Left ventricular volumes were calculated according to Simpson's rule. Systolic AVPD was higher in endurance trained, 16.9 +/- 1.5 mm, as compared with both strength trained, 13 +/- 1.6 (P<0.001) and untrained, 14 +/- 1.6 (P<0.001). Left ventricular systolic AVPD correlated strongly with end-diastolic volume (r=0.82), stroke volume (r=0.80) and maximal oxygen consumption per body weight (r=0.72). The correlation between AVPD and EF was poor (r=0.22). CONCLUSION: In the subjects studied, with a range of normal cardiac dimensions, AVPD correlated to stroke volume, end-diastolic volume and maximal oxygen consumption per body weight, but not to EF. On theoretical grounds, it also seems reasonable that a dimension like AVPD is related to other cardiac dimensions and volumes, rather than to a fraction, like EF. AVPD is one parameter that is useful for evaluation of left ventricular systolic function but is not interchangeable with other measurements such as EF.

Adult↗

Echocardiographic assessment of arrhythmogenic right ventricular cardiomyopathy.

OBJECTIVE: To evaluate new echocardiographic modes in the diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). DESIGN: Prospective observational study. SETTING: University Hospital. SUBJECTS: 15 patients with ARVC and a control group of 25 healthy subjects. METHODS: Transthoracic echocardiography included cross sectional measurements of the right ventricular outflow tract, right ventricular inflow tract, and right ventricular body. Wall motion was analysed subjectively. M mode and pulsed tissue Doppler techniques were used for quantitative measurement of tricuspid annular motion at the lateral, septal, posterior, and anterior positions. Doppler assessment of tricuspid flow and systemic venous flow was also performed. RESULTS: Assessed by M mode, the total amplitude of the tricuspid annular motion was significantly decreased in the lateral, septal, and posterior positions in the patients compared with the controls. The tissue Doppler velocity pattern showed decreased early diastolic peak annular (E(A)) velocity and an accompanying decrease in early (E(A)) to late diastolic (A(A)) velocity ratio in all positions; the systolic annular velocity was significantly decreased only in the lateral position. Four patients had normal right ventricular dimensions and three were judged to have normal right ventricular wall motion. The patient group had also a significantly decreased tricuspid flow E:A ratio. CONCLUSIONS: Tricuspid annular measurements are valuable, easy to obtain, and allow quantitative assessment of right ventricular function. ARVC patients showed an abnormal velocity pattern that may be an early but non-specific sign of the disease. Normal right ventricular dimensions do not exclude ARVC, and subjective detection of early changes in wall motion may be difficult.

Adult↗

Lack of effect of synthetic pericardial substitute on right ventricular function after coronary artery bypass surgery. An echocardiographic and magnetic resonance imaging study.

Abnormal right heart function after cardiac surgery is a well-known finding. Inadequate preservation during the operation and restricted cardiac motion due to pericardial adhesions have been proposed as underlying mechanisms. This study focuses on the impact of a pericardial substitute implantation on right ventricular function, using echocardiography and magnetic resonance imaging. A test group of six patients (mean age 54 years) was examined before surgery, and 4-15 days and 5-9 months after coronary artery bypass surgery, where the pericardium was closed with a biodegradable pericardial patch. A group of 11 patients (mean age 63 years) in whom the pericardium was left open served as controls. Tricuspid annulus motion was markedly decreased, abnormal septal motion was present and decreased systolic to diastolic ratio in the vena cava superior flow was present in all patients in both groups one week after surgery. At the late follow-up, all patients still had decreased tricuspid annulus motion, while 17% of the patients in the test group and 22% of the patients in the control group (ns) demonstrated normal septal motion. We conclude that closing the pericardium with a biodegradable patch does not affect the postoperative changes in right heart function normally seen after open-heart surgery.

Aged↗

Pulsed tissue Doppler evaluation of mitral annulus motion: a new window to assessment of diastolic function.

Diastolic dysfunction is an important cause of cardiac heart failure. To date detailed assessment of diastolic left ventricular (LV) function has required invasive methods which are impractical in the clinical routine. The prevailing non-invasive method has been Doppler echocardiography with use of mitral inflow and pulmonary vein inflow parameters, measurements providing no direct assessment of either ventricular relaxation or compliance, and influenced by multiple haemodynamic factors. We sought to determine the tissue Doppler pattern from the mitral annulus motion in normals and in patients with expected LV-diastolic dysfunction. Using pulsed tissue Doppler we recorded peak velocities from the mitral annulus motion in 16 young normals, 10 older normals and in two groups of patients expected to have an LV-diastolic relaxation abnormality, i.e. 15 patients with systemic hypertension and 10 patients with significant aortic stenosis. The peak early diastolic (E) annulus velocity was significantly (P < 0.001) lower in older normals compared with young, and the late diastolic velocity (A) was higher (P < 0.01). Compared with the older normals, patients showed significantly lower E-velocities (P < 0.05 hypertensive patients), more pronounced in the patients with aortic stenosis (P < 0.001), but the A-velocities were not higher. In systole a decrease in peak velocity was noted with increasing age and in patients with aortic stenosis. In conclusion, pulsed tissue Doppler measurement of annulus motion seems to provide valuable and easily obtainable information about LV-diastolic function, and furthermore there is striking change in velocity pattern with increasing age which necessitates age-matched reference values.

Adult↗

Influence of atracurium on the diaphragm mean action potential conduction velocity in canines.

BACKGROUND: It has been shown that progressive neuromuscular blockade (NMB) affects the electromyogram power spectrum and compound muscle action potential duration in skeletal muscle. These measures are linked to the mean muscle action potential conduction velocity (APCV), but no studies have confirmed a relation between the mean APCV and NMB. The aim of this study was to determine whether diaphragm mean APCV is affected by NMB. METHODS: The effects of NMB on diaphragm mean APCV were evaluated in five mongrel dogs. Progressive NMB was induced by slow intravenous infusion of atracurium. During spontaneous breathing, the diaphragm mean APCV was determined by electromyogram signals, in the time and frequency domains. The magnitude of NMB was quantified by the amplitude of the compound muscle action potential and by changes in muscle shortening during supramaximal stimulation of the phrenic nerve. RESULTS: Progressive NMB was associated with a decrease in diaphragm mean APCV. At approximately 70% reduction in the compound muscle action potential amplitude, diaphragm mean APCV had decreased more than 20%. Recovery after NMB was characterized by a restoration of the mean APCV to control values. CONCLUSION: This study shows that progressive NMB paralyzes motor units within the diaphragm in an orderly manner, and the blockade first affects muscle fibers with high APCV before it affects fibers with lower APCV.

Action Potentials↗

The effects of preexercise stretching on muscular soreness, tenderness and force loss following heavy eccentric exercise.

The present study sought to investigate the effects of preexercise stretching on delayed onset muscle soreness (DOMS), i.e. soreness, tenderness and loss of muscle force, that usually occurs after strenuous or unaccustomed eccentric exercise. Ten female volunteers performed 10 sets of 10 maximal isokinetic eccentric contractions for knee flexion with both legs after a 5-min ergometer cycling warm-up. Prior to the exercise for one leg, randomly chosen, 4 x 20 s of static stretching for the hamstring muscle group was implemented. Rated soreness, tenderness on algometer pressure and loss of maximal eccentric contractile force was evaluated preexercise and 24, 48 and 96 h postexercise. The exercise bout produced severe DOMS, with parameters peaking and troughing at 48 h postexercise. However, no significant differences were found, regarding any of the parameters, when comparing stretched and nonstretched legs. The present study thus suggests that preexercise static stretching has no preventive effect on the muscular soreness, tenderness and force loss that follows heavy eccentric exercise.

Adult↗

N-[11C]methylspiperone PET, in contrast to [11C]raclopride, fails to detect D2 receptor occupancy by an atypical neuroleptic.

The occupancy of the atypical neuroleptic quetiapine (Seroquel) at the D2 dopamine receptor was investigated using the PET tracers [11C]raclopride and N-[11C]methylspiperone in a group of five schizophrenic patients. A steady-state treatment condition was ensured by dosing the patients with 750 mg quetiapine daily during 3 weeks followed by a period of tapering off the dose. For each patient, PET examinations were performed with both tracers at two of the following doses: 750, 450, 300 and/or 150 mg. As control, a group of six healthy untreated volunteers was investigated. The D2 binding potential in the putamen and the caudate nucleus was determined by using an evaluation method based on the method proposed by Patlak and Blasberg. The receptor occupancy was determined by assuming that the group of healthy volunteers is representative of untreated drug-naive schizophrenic patients. While a significant linear trend of increasing occupancy with increasing quetiapine dose (reaching 51% +/- 10% occupancy at the 750 mg dose) was detected with [11C]raclopride (P < 0.01), no such trend was apparent for N-[11C]methylspiperone (P > 0.09, maximal occupancy values were 2% +/- 3%, measured for the group of three patients on 450 mg). The study suggests that N-[11C]methylspiperone cannot be used for the assessment of D2 receptor occupancy induced by quetiapine. The result is discussed in terms of endogenous dopamine, tracer kinetics and equilibrium dissociation constants.

Adult↗