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Biomedical subjects

P Nilsson

Publications and source records attributed to P Nilsson.

At least 19 recordsLinked to original sources
PubMed2003

Mapping of quantitative trait loci controlling trypanotolerance in a cross of tolerant West African N'Dama and susceptible East African Boran cattle.

Trypanosomosis, or sleeping sickness, is a major disease constraint on livestock productivity in sub-Saharan Africa. To identify quantitative trait loci (QTL) controlling resistance to trypanosomosis in cattle, an experimental cross was made between trypanotolerant African N'Dama (Bos taurus) and trypanosusceptible improved Kenya Boran (Bos indicus) cattle. Sixteen phenotypic traits were defined describing anemia, body weight, and parasitemia. One hundred seventy-seven F2 animals and their parents and grandparents were genotyped at 477 molecular marker loci covering all 29 cattle autosomes. Total genome coverage was 82%. Putative QTL were mapped to 18 autosomes at a genomewise false discovery rate of <0.20. The results are consistent with a single QTL on 17 chromosomes and two QTL on BTA16. Individual QTL effects ranged from approximately 6% to 20% of the phenotypic variance of the trait. Excluding chromosomes with ambiguous or nontrypanotolerance effects, the allele for resistance to trypanosomosis originated from the N'Dama parent at nine QTL and from the Kenya Boran at five QTL, and at four QTL there is evidence of an overdominant mode of inheritance. These results suggest that selection for trypanotolerance within an F2 cross between N'Dama and Boran cattle could produce a synthetic breed with higher trypanotolerance levels than currently exist in the parental breeds.

Anemia↗
PubMed2003

Hyperinsulinaemia as long-term predictor of death and ischaemic heart disease in nondiabetic men: The Malmö Preventive Project.

OBJECTIVES: Prospective studies have indicated that hyperinsulinaemia/insulin resistance is a risk factor for ischaemic heart disease (IHD), the risk decreasing with time of follow-up. Few studies have so far investigated the role of hyperinsulinaemia in the prediction of long-term total mortality. SETTING: Section of Preventive Medicine, Department of Medicine, University Hospital, Malmö, Sweden. SUBJECTS: A total of 6074 nondiabetic, middle-aged, healthy Swedish males. SCREENING EXAMINATION: We determined IHD risk factors including blood glucose and plasma insulin before and 2 h after an oral glucose tolerance test (OGTT). Total follow-up time was 19 years. Hyperinsulinaemia was defined as values above the 10th decentile of fasting or 2 h insulin concentration. MAIN OUTCOME MEASURES: Total mortality and cardiac event (CE) rate for IHD. RESULTS: Unadjusted relative risks (RRs) for both death and CE were J-shaped with the highest relative risk (RR: 1.4-1.6) in the hyperinsulinaemic group compared with all other men. The RRs for death and CE were significant for fasting insulin but became nonsignificant after adjustment for other risk factors and also with a longer follow-up. The risk of death in hyperinsulinaemic men, defined on the basis of 2-h insulin level, increased with time of follow-up and was still significantly increased after 19 years [RR: 1.32 (95% CI: 1.05-1.65], even after adjustment for other risk factors. CONCLUSIONS: Fasting hyperinsulinaemia was a predictor of total mortality and IHD in nondiabetic men, although not more significantly after adjustment for other risk factors and with lengthening of follow-up time. The 2-h postglucose hyperinsulinaemia appeared to be a stronger and independent predictor of mortality over long-term follow-up. These findings support the view that insulin resistance with associated cluster of risk factors predicts increased long-term risk of mortality and IHD.

Adult↗
PubMed2003

Lung function, insulin resistance and incidence of cardiovascular disease: a longitudinal cohort study.

OBJECTIVES: To explore whether a reduced lung function is a risk factor for developing diabetes and insulin resistance (IR), and whether such relationship contributes to the largely unexplained association between lung function and incidence of cardiovascular disease (CVD). DESIGN: Forced vital capacity (FVC) was assessed at baseline. Incidence of diabetes and IR [according to the homeostasis model assessment (HOMA) model] was assessed in a follow-up examination after 13.9 +/- 2.6 and 9.4 +/- 3.6 years for men and women, respectively. After the follow-up examination, incidence of CVD (stroke, myocardial infarction or cardiovascular death) was monitored over 7 years. SETTING: Populations-based cohort study. SUBJECTS: Initially nondiabetic men (n = 1436, mean age 44.6 years) and women (n = 896, mean age 49.8 years). RESULTS: Prevalence of IR at the follow-up examination was 34, 26, 21 and 21%, respectively, for men in the first (lowest), second, third and fourth quartile of baseline FVC (P for trend <0.0001). The corresponding values for women were 30, 29, 25 and 17%, respectively (P for trend <0.001). Adjusted for potential confounders, the odds ratio (OR) for IR (per 10% increase in FVC) was 0.91 (CI: 0.84-0.99) for men and 0.89 (CI: 0.80-0.98) for women. FVC was similarly significantly associated with the incidence of diabetes (OR = 0.90, CI: 0.81-1.00), adjusted for sex and other confounders. The incidence of CVD after the follow-up examination was significantly increased only amongst subjects with low FVC who had developed IR (RR = 1.7, CI: 1.02-2.7). CONCLUSION: Subjects with a moderately reduced FVC have an increased risk of developing IR and diabetes. This relationship seems to contribute to the largely unexplained association between reduced lung function and incidence of CVD.

Adult↗
PubMed2002

Multi-centre assessment of the Spiegelberg compliance monitor: interim results.

Analyses of a multi-centre database of 71 patients at risk of raised ICP showed that in head injured patients (n = 19) and tumour patients (n = 13) clear inverse relationships of ICP vs compliance exist. SAH patients (n = 5) appear to exhibit a biphasic relationship between ICP and compliance, however greater numbers of patients need to be recruited to this group. Patients with hydrocephalus (n = 34) show an initial decrease in compliance while ICP is less than 20 mmHg, thereafter compliance does not show a dependence upon ICP. A power analysis confirmed that sufficient numbers of patients have been recruited in the hydrocephalus group and a ROC analysis determined that a mean compliance value of 0.809 (lower and upper 95% CL = 0.725 & 0.894 resp.) was a critical threshold for raised ICP greater than 10 mmHg. Preliminary time-series analyses of the ICP and compliance data is revealing evidence that the cumulative time compliance is in a low compliance state (< 0.5 ml/mmHg), as a proportion of total monitoring time, increases more rapidly than the cumulative time ICP is greater than 25 mmHg. Before trials testing compliance thresholds can be designed, we need to consider not just the absolute threshold, but the duration of time spent below threshold. A survey may be required to identify a consensus of what is the minimum duration of raised ICP above 25 mmHg needed to instigate treatment.

Automation↗
PubMed2002

Early cerebral hyperglycolysis after subarachnoid haemorrhage correlates with favourable outcome.

BACKGROUND: Intracerebral microdialysis (MD) was applied in patients with severe subarachnoid haemorrhage treated in a neurosurgical intensive care unit in order to explore their cerebral energy metabolism. METHOD: Brain MD fluid levels of glucose, lactate and pyruvate were measured for 3 to 12 days in 20 patients and 2,635 hourly samples were analysed. The MD data were related to computerized tomography and clinical outcome, assessed by the Glasgow Outcome Scale. FINDINGS: The study showed that most patients who made a good recovery had a specific curve pattern when plotting the studied metabolites over time, characterised by a distinct decrease in MD-glucose and a parallel increase in both MD-lactate and pyruvate. Patients who had an unfavourable outcome lacked this distinct curve pattern and exhibited more irregular changes, including increased levels of both MD-glucose and lactate and low MD-pyruvate levels. INTERPRETATION: This exploratory study suggests that accumulation of interstitial lactate and pyruvate, together with decreasing levels of glucose is a favourable prognostic pattern presumably reflecting increased glucose metabolism. Such hyperglycolysis may be elicited in patients with recovery potential to cope with an extreme metabolic demand set in motion by a brain insult to restore brain cell homeostasis and integrity.

Adolescent↗
PubMed2002

The use of placebo-controlled and non-inferiority trials for the evaluation of new drugs in the treatment of postmenopausal osteoporosis.

Registration of new agents for the treatment of postmenopausal osteoporosis has been based over the past few years on placebo-controlled phase III trials with the incidence of patients with new vertebral/nonvertebral fractures as the most usual primary endpoint. The use of a placebo in diseases where an active treatment is available has been a matter of debate following the update of the Declaration of Helsinki by the World Medical Association which questioned this trial design. Current regulatory recommendations within the European Union suggest that placebo-controlled trials are still the best option when assessing the efficacy and safety of new drugs intended for the treatment of postmenopausal osteoporosis. This suggestion seems to be in apparent contradiction with the current content of the Declaration of Helsinki. This paper addresses the ethics and feasibility of placebo-controlled trials in the treatment of postmenopausal osteoporosis, in the light of available therapeutic options, and discusses possible alternative approaches in those patients where placebo treatment could be deemed to be unethical. It is concluded that placebo-controlled trials remain the most efficient design to establish the efficacy and safety of a new agent for the treatment of postmenopausal osteoporosis. Such trials are feasible and ethically acceptable in patients with osteoporosis but without prevalent vertebral fractures. Conversely, in patients with prevalent vertebral fractures, placebo-controlled trials are ethically questionable and non-inferiority trials are more appropriate. A relative margin of non-inferiority of 20-30% is suggested, to be discussed on a case by case basis.

Aged↗
PubMed2002

Influence of obesity on cardiovascular risk. Twenty-three-year follow-up of 22,025 men from an urban Swedish population.

OBJECTIVE: To assess to what extent the incidence of coronary events and death related to smoking, hypertension, hyperlipidemia and diabetes is modified by obesity. DESIGN: Prospective cohort study. SUBJECTS: A total of 22 025 men aged 27 to 61-y-old at entry. MEASUREMENTS: Incidence of coronary events (CE, ie acute myocardial infarctions and deaths due to chronic ischaemic heart disease) and death during 23 y of follow-up was studied in relation to body mass index (BMI), heart rate, blood pressure, blood lipids, glucose and insulin, lifestyle factors, history of angina pectoris, history of cancer, self-reported health and socio-economic conditions. RESULTS: At the end of follow-up 20% of the obese men were no longer alive, and 13% had had a coronary event. Incidence of CE was 16% lower (RR (relative risk) 0.84; 95% confidence interval (CI) 0.65-1.10) among underweight (n=1171), 24% higher (RR 1.24; CI 1.12-1.37) among overweight (n=7773), and 76% higher (RR 1.76; 95% CI 1.49-2.08) among obese men (n=1343) than it was among men with normal BMI (n=11 738). The risk associated with overweight and obesity remained statistically significant after adjustment for potential confounders (RR 1.18; CI 1.07-1.31; and 1.39; 1.17-1.65, respectively). The association between BMI and mortality was J-shaped. In all, 1.7% of the obese men were smokers with hypertension, hyperlipidaemia and diabetes, 16.3% were not exposed to any of these risk factors. The cardiovascular risk associated with obesity was small in the absence of other risk factors. Between smoking and obesity there was a statistically significant synergistic effect. CONCLUSIONS: Obesity is associated with an increased incidence of coronary events and death. The risk associated with obesity is substantially increased by exposure to other atherosclerotic risk factors, of which smoking seems to be the most important. The preventive potential of these associations should be evaluated in controlled trials.

Adult↗
PubMed2002

Costs for screening, intervention and hospital treatment generated by the Malmö Preventive Project: a large-scale community screening programme.

OBJECTIVES: The purpose of this study was to estimate retrospectively the costs of health care resources used in the Malmö Preventive Project, Sweden and estimate the costs of in-patient care that were avoided because of early intervention. SETTING AND SUBJECTS: A large-scale community intervention programme was conducted from 1974 to 1992 in Malmö, Sweden with the aim of reducing morbidity and mortality of cardiovascular diseases (CVD), alcohol related illnesses, and breast cancer. Between 1974 and 1992, 33 336 male and female subjects were screened for hypertension, hyperlipidaemia, type-2 diabetes and alcohol abuse. Intervention programmes that included life-style modifications, follow-up visits with physicians and nurses and drug therapy were offered to about 25% of screened subjects. METHODS: Recruitment costs were generated through out the screening period. Intervention costs were estimated for 5 years after screening. Excess in-patient care costs were estimated by subtracting hospital consumption for an unscreened, matched cohort from that of the screened cohort over follow-up periods of 13-19 years. Intervention and excess in-patient care costs were estimated until 1996. RESULTS: The net expenditures for recruitment and intervention was SEK253 million and saved costs for in-patient care of SEK143 millions (1998 prices). Considering the opportunity cost of the resources used in the study, the net cost rises to about SEK200 millions. CONCLUSIONS: The results suggest that only part of the intervention costs were offset by reduction in future morbidity health care costs. This is in line with results from prospective analyses of other primary prevention programmes.

Adult↗
PubMed2002

Obesity and myocardial infarction--vulnerability related to occupational level and marital status. A 23-year follow-up of an urban male Swedish population.

BACKGROUND: People, who are single, have a blue-collar job or low income have an increased cardiovascular risk. This study on myocardial infarction sought to explore whether the socio-economic pattern of disease has any relationship with obesity. METHODS: In the cohort are 20,099 middle-aged men of whom 9,150 were manual and 9,190 nonmanual workers and 1,759 were self-employed. A total of 4,081 were single, 16,018 cohabiting. The body mass index (BMI) cut-off values for overweight and obesity were 25-30 and >/=30 kg m-2, respectively. Local and national registers were used to monitor incidence of events over 18 years. RESULTS: Obesity was associated with an increased incidence of coronary events and deaths in each occupational group. Being single significantly increased the risk associated with obesity. After stratification for civil status the risk associated with obesity was limited to those who were single and who either had a blue-collar job or were self-employed. The multivariate-adjusted relative risk (RR) of coronary events and deaths in obese manual workers who were single was 1.91 (95% confidence interval: 1.21-3.02) and 2.54 (1.74-3.69), respectively, times higher than it was amongst those who were cohabiting. Amongst those who were self-employed, the corresponding age-adjusted RRs were 4.79 (1.69-13.57) and 3.80 (1.62-8.93). CONCLUSIONS: Adjusted for lifestyle and biological risk factors, the increased risk of coronary events and death for obese men with manual jobs was applicable only to those who were single. It is concluded that being single significantly increases the cardiovascular risk associated with obesity.

Adult↗
PubMed2002

Insulin resistance in non-diabetic subjects is associated with increased incidence of myocardial infarction and death.

AIMS: To compare the incidence of myocardial infarction and death in non-diabetic subjects with and without insulin resistance. METHODS: Population-based prospective cohort study, in Malmö, Sweden, of 4748 non-diabetic subjects (60% women), aged 46-68 years, with no history of myocardial infarction or stroke. The prevalence of insulin resistance was established by the homeostasis model assessment (HOMA) and defined as values above the sex-specific 75th percentile (1.80 for women and 2.12 for men). Incidence of myocardial infarction and death is based on record linkage with local and national registers. Cox's proportional hazards model was used to assess the influence of insulin resistance after adjustment for age, sex, hyperglycaemia, raised arterial blood pressure, dyslipidaemia, central obesity, smoking and leisure-time physical activity. RESULTS: Sixty-two subjects suffered a coronary event, and 93 subjects died during the 6-year follow-up period. Insulin resistance was after adjustment for other factors included in the insulin resistance syndrome and other potential confounders, associated with an increased incidence of coronary events (relative risk (RR) 2.18; 95% confidence interval (CI) 1.22-3.87; P = 0.008) and deaths (RR 1.62; 1.03-2.55; P = 0.038). CONCLUSIONS: Insulin resistance, as assessed by the HOMA method, was in this cohort of middle-aged non-diabetic subjects associated with an increased incidence of myocardial infarction and death. This risk remained when smoking, low physical activity and factors included in the insulin resistance syndrome were taken into account in a stepwise regression model.

Aged↗
PubMed2002

Socioeconomic environmental factors and hospitalization for acute bronchiolitis during infancy.

UNLABELLED: Bronchiolitis is a major cause of hospitalization during infancy. The aim of this study was to evaluate the influence of socioeconomic factors on the hospitalization of infants with bronchiolitis. All infants below 1 y of age living in the city of Malmö, Sweden, and hospitalized at the University Hospital. Malmö, owing to bronchiolitis during the years 1998 and 1999 were identified. The bronchiolitis hospitalization rates (BHRs) were determined for the infants living in each of the 10 different administrative residential areas of Malmö and correlated with socioeconomic factors (percentage of immigrants, per capita income, unemployment rate and households receiving social benefit) in the respective residential areas. The severity of the disease on admission and during hospital care was assessed by comparing oxygen saturation, days with supplemental oxygen and length of stay. BHR varied more than fourfold between the 10 residential areas. BHR varied significantly with per capita income and the percentage of immigrants. Infants living in the area with the highest social burden were hospitalized almost twice as often as those from the rest of the city, but the severity of disease was similar. CONCLUSION: The association between socioeconomic factors and hospitalization indicates that these factors may have a significant influence on the hospitalization rate in bronchiolitis during infancy.

Acute Disease↗
PubMed2002

Underdosage of the upper-airway mucosa for small fields as used in intensity-modulated radiation therapy: a comparison between radiochromic film measurements, Monte Carlo simulations, and collapsed cone convolution calculations.

Head-and-neck tumors are often situated at an air-tissue interface what may result in an underdosage of part of the tumor in radiotherapy treatments using megavoltage photons, especially for small fields. In addition to effects of transient electronic disequilibrium, for these small fields, an increased lateral electron range in air will result in an important extra reduction of the central axis dose beyond the cavity. Therefore dose calculation algorithms need to model electron transport accurately. We simulated the trachea by a 2 cm diameter cylindrical air cavity with the rim situated 2 cm beneath the phantom surface. A 6 MV photon beam from an Elekta SLiplus linear accelerator, equipped with the standard multileaf collimator (MLC), was assessed. A 10 x 2 cm2 and a 10 x 1 cm2 field, both widthwise collimated by the MLC, were applied with their long side parallel to the cylinder axis. Central axis dose rebuild-up was studied. Radiochromic film measurements were performed in an in-house manufactured polystyrene phantom with the films oriented either along or perpendicular to the beam axis. Monte Carlo simulations were performed with BEAM and EGSnrc. Calculations were also performed using the pencil beam (PB) algorithm and the collapsed cone convolution (CCC) algorithm of Helax-TMS (MDS Nordion, Kanata, Cahada) version 6.0.2 and using the CCC algorithm of Pinnacle (ADAC Laboratories, Milpitas, CA, USA) version 4.2. A very good agreement between the film measurements and the Monte Carlo simulations was found. The CCC algorithms were not able to predict the interface dose accurately when lateral electronic disequilibrium occurs, but were shown to be a considerable improvement compared to the PB algorithm. The CCC algorithms overestimate the dose in the rebuild-up region. The interface dose was overestimated by a maximum of 31% or 54%, depending on the implementation of the CCC algorithm. At a depth of 1 mm, the maximum dose overestimation was 14% or 24%.

Air↗
PubMed2002

Monitoring of representational difference analysis subtraction procedures by global microarrays.

Various approaches to the study of differential gene expression are applied to compare cell lines and tissue samples in a wide range of biological contexts. The compromise between focusing on only the important genes in certain cellular processes and achieving a complete picture is critical for the selection of strategy. We demonstrate how global microarray technology can be used for the exploration of the differentially expressed genes extracted through representational difference analysis (RDA). The subtraction of ubiquitous gene fragments from the two samples was demonstrated using cDNA microarrays including more than 32 000 spotted, PCR-amplified human clones. Hybridizations indicated the expression of 9100 of the microarray elements in a macrophage/foam cell atherosclerosis model system, of which many were removed during the RDA process. The stepwise subtraction procedure was demonstrated to yield an efficient enrichment of gene fragments overrepresented in either sample (18% in the representations, 86% after the first subtraction, and 88% after the second subtraction), many of which were impossible to detect in the starting material. Interestingly, the method allowed for the observation of the differential expression of several members of the low-abundant nuclear receptor gene family. We also observed a certain background level in the difference products of nondifferentially expressed gene fragments, warranting a verification strategy for selected candidate genes. The differential expression of several genes was verified by real-time PCR.

Cell Line↗
PubMed2001

A transcriptional roadmap to wood formation.

The large vascular meristem of poplar trees with its highly organized secondary xylem enables the boundaries between different developmental zones to be easily distinguished. This property of wood-forming tissues allowed us to determine a unique tissue-specific transcript profile for a well defined developmental gradient. RNA was prepared from different developmental stages of xylogenesis for DNA microarray analysis by using a hybrid aspen unigene set consisting of 2,995 expressed sequence tags. The analysis revealed that the genes encoding lignin and cellulose biosynthetic enzymes, as well as a number of transcription factors and other potential regulators of xylogenesis, are under strict developmental stage-specific transcriptional regulation.

Cell Wall↗
PubMed2001

[Quality assurance of secondary prevention of coronary artery disease. Ongoing project offers possibilities for improved treatment].

Regional programs for secondary prevention of coronary artery disease have been under development for nearly a decade in Sweden. To achieve maximum adherence these programs were created in close collaboration between hospital and primary care physicians. The programs are local applications of national guidelines and aim to support compliance among both patients and physicians. In January 1998 the Swedish Society of Cardiology and the Swedish Association of General Practice launched a program for quality control and quality assurance of these initiatives. So far, 51 of 79 districts have joined the program. Patients' diaries used for risk factor registration contain 7 report cards on the management of risk factors and medication. These cards are sent to a central registry upon release from the hospital, after 3-6 months, and annually for 5 years. Results from the first year point to differences between the various districts with respect to compliance with both local programs and European guidelines. Overall, results are promising and indicate that this program is successful and leads to improved management of patients with coronary artery disease.

Coronary Disease↗