Altered acylcarnitine metabolism and inflexible mitochondrial fuel utilization characterize the loss of neonatal myocardial regeneration capacity.

Myocardial regeneration capacity declines during the first week after birth, and this decline is linked to adaptation to oxidative metabolism. Utilizing this regenerative window, we characterized the metabolic changes in myocardial injury in 1-day-old regeneration-competent and 7-day-old regeneration-compromised mice. The mice were either sham-operated or received left anterior descending coronary artery ligation to induce myocardial infarction (MI) and acute ischemic heart failure. Myocardial samples were collected 21 days after operations for metabolomic, transcriptomic and proteomic analyses. Phenotypic characterizations were carried out using echocardiography, histology and mitochondrial structural and functional assessments. In both groups, MI induced an early decline in cardiac function that persisted in the regeneration-compromised mice over time. By integrating the findings from metabolomic, transcriptomic and proteomic examinations, we linked regeneration failure to the accumulation of long-chain acylcarnitines and insufficient metabolic capacity for fatty acid beta-oxidation. Decreased expression of the redox-sensitive mitochondrial Slc25a20 carnitine-acylcarnitine translocase together with a decreased reduced:oxidized glutathione ratio in the myocardium in the regeneration-compromised mice pointed to a defect in the redox-sensitive acylcarnitine transport to the mitochondrial matrix. Rather than a forced shift from the preferred adult myocardial oxidative fuel source, our results suggest the facilitation of mitochondrial fatty acid transport and improvement of the beta-oxidation pathway as a means to overcome the metabolic barrier for repair and regeneration in adult mammals after MI and heart failure.

Predictors associated with treatment initiation and switch in a real-world chronic hepatitis B population from five European countries.

In Europe, healthcare systems differ between countries and different factors may influence Chronic hepatitis B (CHB) treatment choices in different counties. This analysis from a prospective, longitudinal, non-interventional study in five EU countries aimed to explore determinants associated with treatment initiation or switch in patients with CHB. A total of 1267 adult patients with compensated CHB in Germany, France, Poland, Romania and Turkey were prospectively followed for up to 2 years (March 2008-December 2010). Determinants of treatment initiation or switch were analysed using multivariate Cox proportional hazards regression. Median time since CHB diagnosis was 2.6 (0-37.7) years. Among 646 treatment-naïve patients, the probability of treatment initiation during follow-up was higher: in Germany (P = 0.0006), Poland (P < 0.0001) and Romania (P = 0.0004) compared with Turkey; in patients with alanine transaminase (ALT) 1-2 × upper limit of normal (ULN) (P = 0.0580) or >2 × ULN (P = 0.0523) compared with ALT ≤ 1 × ULN; and in patients with hepatitis B virus (HBV) DNA ≥ 2000 IU/mL (P < 0.0001) compared with HBV DNA <2000 IU/mL or undetectable. Among 567 treated patients, 87 switched treatment during follow-up. The probability of treatment switch was higher: in France (P = 0.0029), Germany (P = 0.0078) and Poland (P = 0.0329) compared with Turkey; and in patients with HBV DNA <2000 (P < 0.0001) or ≥ 2000 IU/mL (P < 0.0001), compared with undetectable. Viral load and ALT level were identified as the major drivers of treatment initiation. HBV DNA level was also a significant determinant of treatment switch. Results were statistically different across EU countries.

The effects of water velocity on the Ceratomyxa shasta infectious cycle.

Ceratomyxa shasta is a myxozoan parasite identified as a contributor to salmon mortality in the Klamath River, USA. The parasite has a complex life cycle involving a freshwater polychaete, Manayunkia speciosa and a salmonid. As part of ongoing research on how environmental parameters influence parasite establishment and replication, we designed a laboratory experiment to examine the effect of water flow (velocity) on completion of the C. shasta infectious cycle. The experiment tested the effect of two water velocities, 0.05 and 0.01 m s(-1), on survival and infection of M. speciosa as well as transmission to susceptible rainbow trout and comparatively resistant Klamath River Chinook salmon. The faster water velocity facilitated the greatest polychaete densities, but the lowest polychaete infection prevalence. Rainbow trout became infected in all treatments, but at the slower velocity had a shorter mean day to death, indicating a higher infectious dose. Infection was not detected in Chinook salmon even at a dose estimated to be as high as 80,000 actinospores per fish. The higher water velocity resulted in lower C. shasta infection prevalence in M. speciosa and decreased infection severity in fish. Another outcome of our experiment is the description of a system for maintaining and infecting M. speciosa in the laboratory.

The cost of diabetes and diabetes care.

The number of people with diabetes mellitus worldwide is estimated to be 221 million in 2010 compared to about 124 million in 1997. The dominant part of diabetic persons was in 1997 represented by Type 2 (97%). WHO expect the number of adults (20 years and older) with diabetes (i.e. a mix of Type 1 and 2) to rise to 300 millions in 2025 from 135 millions in year 1995. On average people with diabetes are three times more likely to be hospitalized than non-diabetic individuals. The risk for hospitalization is slightly diversified, venous complications being the least risky (1.7 times) and heart-related complications the most risky (3.1 times). The risk of premature death is higher for persons with diabetes compared to those without diabetes, and the life time expectancy is 10-15 times shorter. US data shows that diabetes is the leading cause of blindness and accounts for 40% of the new cases of end-stage renal disease. The risk for leg amputation is 15-40 times higher and the risk for heart disease and stroke is two to four times higher for people with diabetes compared with people without diabetes. Recent studies show that the health care expenditures are as much as five times higher for individuals with diabetes compared to individuals without diabetes. In Sweden in 1994, three times more resources were spent on treating complications compared to what was spent on control of the disease. Studies show that intensive treatments cost more than traditional treatment, but also cut costs substantially for the treatment of late complications. The main message was that early intervention and intensified treatment had a better effect on the late complications. The basic message is quite simple: diagnose more persons with diabetes earlier, introduce and improve treatment.

[Of what significance is abnormal result of smear test? Anxiety because of insufficient information in connection with abnormal result of cervical smear test]. / Vad betyder cellförändringarna? Dålig information om avvikande cytologprov skapar onödig oro.

The purpose of the study was to investigate possible differences in psychological response between two groups of women after pathological cervical smear tests (CIN I or recurrent CIN I and/or CIN II-III respectively). 43 women participated. A standardised questionnaire was used. In 75 percent of the cases the result was given over the telephone. The number of women who reacted with medium to strong anxiety in the CIN I group (15/22) did not differ from those in the group with CIN II-III (15/21). 45 percent of the women in the CIN I group thought their lesions to be malignant. 64 percent of the women in the CIN I group, as compared to 38 percent of the women in the CIN II-III group, benefitted from the additional information they asked for and received. A majority of the women would have liked more information as well as the opportunity to discuss the findings in a more personal way.

Bone marrow-derived macrophages express functional CGRP receptors and respond to CGRP by increasing transcription of c-fos and IL-6 mRNA.

Calcitonin gene-related peptide (CGRP) is a sensory neuropeptide with inflammatory and immunoregulatory properties. CGRP inhibits IL-7 responses by B cell precursors by direct and indirect mechanisms. We recently found that CGRP induces IL-6 and TNF-alpha in long-term bone marrow cultures and that IL-6 and TNF-alpha also inhibit IL-7 responses. Because these are heterogeneous cultures, it was not clear which cells produced IL-6 and TNF-alpha. To determine whether bone marrow-derived macrophages (BMDM) were the source, we did studies to determine whether BMDMs express mRNAs for CGRP receptors and whether CGRP induces c-fos, IL-6, and TNF-alpha mRNA. We found that BMDMs express mRNAs for CRLR and RAMP1, the minimal components for CGRP receptors. CGRP also stimulated dose- and time-dependent increases in c-fos and IL-6. In contrast, CGRP did not induce TNF-alpha in BMDMs. These results suggest that BMDMs are a source of CGRP-induced IL-6 in bone marrow.

Plasma thrombopoietin levels in liver cirrhosis and kidney failure.

BACKGROUND: Recently, c-Mpl ligand (thrombopoietin, TPO) has been cloned by several groups and found to be a primary regulator of thrombopoiesis. Its mRNA expression has been detected in several organs including kidneys, bone marrow stroma cells, muscles, and is very strongly expressed in the liver. OBJECTIVE: To clarify thrombopoiesis and the regulation of TPO in severe liver and renal failure. DESIGN: We analysed plasma TPO levels in patients with biopsy verified liver cirrhosis (n = 18; mean platelet count 115 +/- 54 x 109 L-1), in patients on chronic haemodialysis as a result of end-stage renal failure (n = 20; mean platelet count 295 +/- 94 x 109 L-1), and in healthy individuals (n = 20; mean platelet count 250 +/- 40 x 109 L-1). Plasma was prepared from EDTA-anticoagulated whole blood and a commercially available ELISA kit was used for the analysis. RESULTS: The mean plasma TPO concentration amongst the normal individuals was 50 +/- 14 pg mL-1. In the patients with liver cirrhosis and in patients on haemodialysis the mean TPO levels were 62 +/- 19 pg mL-1 and 46 +/- 17 pg mL-1, respectively. The mean plasma TPO concentration for the cirrhotic patients was significantly higher than the mean recorded for the healthy volunteers (P = 0.031), whereas no statistically significant differences in plasma TPO were seen between the group of end-stage renal failure and normals. CONCLUSION: Our results suggest that TPO production is maintained in liver cirrhosis and in renal failure, and that the thrombocytopenia in liver cirrhosis is not due to an impaired TPO production.

The weighting exercise for the Swedish version of the EuroQol.

The EuroQol weighting exercise consists of three parts. In the first, the respondents state their own health using five dimensions with three levels in each, and then they rate their own health state on a visual analogue scale. In the second part, respondents attach weights to some of the possible health states. The last part contains questions about background information. The present article presents such weights derived from a sample of the Swedish population. The sample of 1000 Swedish citizens was drawn randomly from a national address register. The overall response rate was 54.2%, though 315 (31.5%) of the responses were ultimately deemed usable. Most of the health states included in the weighting exercise were well-chosen. Most of them were represented by at least one of the respondents. The respondent characteristics that had any influence on the valuation of health states in the weighting exercise was rating of own health, age and level of education, where a higher rating of own health, higher age and lower level of education resulted in higher valuations.

Specific-antibody-secreting cells in the rectums and genital tracts of nonhuman primates following vaccination.

To determine optimal strategies to induce specific-antibody-secreting cells (specific ASC) in the rectal and vaginal mucosae, we immunized monkeys with a prototype mucosal immunogen, cholera toxin (CT), given locally or via gastric or parenteral administration. Repeated rectal or vaginal CT immunizations induced strong mucosal and systemic ASC responses. The mucosal responses were, however, confined to the immunization sites and comprised high levels of both specific antitoxin immunoglobulin A (IgA) and IgG. Large numbers of specific IgA and IgG ASC were detected in cell suspensions from dissociated genital and rectal tissues, demonstrating local accumulation of effector B cells at these sites. Intragastric immunization with CT did not per se give rise to cervicovaginal or rectal ASC responses but did prime for a rectal IgA ASC response to local booster immunization. Both rectal and vaginal immunizations also induced circulating blood IgG ASC and IgA ASC. In conclusion, these results show that local administration of antigen to the rectal or vaginal mucosa results in higher ASC responses than systemic or distant mucosal delivery. Furthermore, both the vaginal and the rectal mucosae can serve as inductive sites for systemic ASC responses. These observations should be relevant to the development of vaccines against sexually transmitted diseases such as that caused by human immunodeficiency virus.

Urinary albumin excretion and heart rate variability in obese women.

OBJECTIVE: The aim of this work was to examine the relationship between cardiac autonomic function and urinary albumin excretion in obesity. SUBJECTS: These were 27 obese non-diabetic postmenopausal women and 18 non-obese healthy postmenopausal women. MEASUREMENTS: Urinary albumin excretion as well as plasma nitrate, both indices of capillary function, were measured. Power spectral analysis of heart rate variability was performed, as a measurement of vagal function. An oral glucose tolerance test (OGTT) was performed and blood lipids were analysed. RESULTS: The obese women were characterized by higher fasting insulin, sum of glucose, triglycerides and lower high density lipoprotein cholesterol (HDL), the latter of borderline significance, than controls. Urinary albumin excretion (UAE), plasma nitrate and heart rate variability were not different between obese and control women. However, in obese women log UAE correlated positively with systolic and diastolic blood pressure, and inversely with heart rate variability, the latter independent of body mass index (BMI) and the waist/hip circumference ratio. CONCLUSION: It was concluded that this inverse association between UAE and parasympathetic activity in obese women may be an early sign of derangements of endothelial function and autonomic nervous system control, which may contribute to the increased risk of cardiovascular mortality in abdominal obesity.

Beam characteristics of a new generation 50 MeV racetrack microtron.

The first of a new generation of microtron accelerators has been installed and tested. It is currently in use for multisegment conformal radiotherapy at our institution. The unit produces x rays and electrons from 10 to 50 MeV in 5 MeV increments. It incorporates a 64 leaf, doubly focused multileaf collimator (MLC), which can be used to shape x-ray and electron beams. Both x-ray and electron beams are produced by magnetically scanning the electron beams from the accelerator. The new generation unit incorporates a purging magnet to sweep away any primary or secondary electrons that pass through the target(s). In this paper, the beam characteristics of the accelerator that were studied during acceptance testing are described. Representative examples of depth doses, beam profiles, output factors, and elementary beam distributions are presented and discussed, in comparison with the earlier generation of microtron accelerators and with other radiotherapy machines.

Social support, negative life events and mental health.

BACKGROUND: In a 10-year follow-up of a survey from Oslo, 503 persons were reinterviewed using the same questionnaire. METHOD: The questionnaire includes information about social support, 'locus of control' and mental health as well as negative life events and long-lasting mental strain during the year prior to the follow-up. RESULTS: The study confirms the "buffer hypothesis", that social support protects against the development of mental disorder only when the individual is exposed to stressors, like negative life events. This buffering effect was especially strong for depression. CONCLUSIONS: The buffering effect only applies to the 'externals'--those who have personality-related feelings of powerlessness and lack of control over their own lives. The 'internals' do not have the same need for social support to cope with life stressors, and have low symptom scores even when negative life events are combined with relative weak social support.

Setting health care priorities in Sweden: the politician's point of view.

In this report, the results of interviews with sixty local health care politicians in southern Sweden will be presented. It is evident from the material that despite their formal responsibility, the politicians are of the opinion that other actors exert greater influence upon the allocation of resources. They do not think that health care expenditure need be extended, whereas fields such as care of the elderly and preventive medicine ought to receive extended contributions at the expense of other publicly financed activities such as general mammography and in vitro fertilization. Somewhat more than a third of the politicians hold that the goal stipulated in the Swedish Health Care Act, i.e. to provide good health and care on equal terms, has not been fulfilled. Their attitudes towards priority criteria such as personal responsibility, age, life expectancy, parenthood and productivity differ from case to case, and there is no clear-cut consensus. However, approximately half of the respondents agree wholly or partly that a person who promises to alter his or her unhealthy habits should be treated before someone who does not make such a promise. The same applies to the principle that those employed ought to be given priority in operating queues, and in consequence of this utility perspective there are also increased demands upon the physicians to take economy into consideration in treating an individual patient.

EuroQol: health-related quality of life measurement. Results of the Swedish questionnaire exercise.

The EuroQol Group, which currently comprises 7 centres in 5 countries, has been testing the feasibility of jointly developing a standardised non-disease-specific instrument for describing and valuing health-related quality of life. The instrument employs a visual analogue scale of the 'thermometer' type to allow respondents to rank a number of health states. As part of the Swedish IHE's contribution to the EuroQol Group's work, questionnaires were sent to 1000 people randomly selected to provide a representative sample of the Swedish population aged 16-84 years. 349 persons responded and 208 provided sufficient information for detailed analysis. From these 208 it proved possible to derive health status information in a quantitative form. The most interesting result was that the health state valuations from this survey indicated a striking similarity with those of EuroQol studies in Frome (England) and Bergen op Zoom (The Netherlands). The lessons learned from undertaking the survey are briefly discussed. The Swedish IHE is encouraged by the exercise to continue to play its part in the continuing developments of the EuroQol methodology.

Quality of life of adults with growth hormone deficiency: a controlled study.

The quality of life of 23 adults with growth hormone deficiency (GHD) who had received growth hormone (GH) therapy was compared with that of 47 normal individuals in a control group. The GHD group had a poorer quality of life than the control group. Statistically significant differences were found between the groups for social isolation, physical mobility, sleep, and emotional status. More individuals in the control group had a driving licence and were married than in the GHD group.

Screening and rescreening for colorectal cancer. A controlled trial of fecal occult blood testing in 27,700 subjects.

All inhabitants of the city of Göteborg who in 1982 were between 60 and 64 years of age (27,700) were randomly divided into a test and a control group. The 13,759 subjects in the test group were invited to perform Hemoccult II (Smith Kline Diagnostic, Sunnyvale, CA) fecal occult blood testing over 3 days and to repeat the testing after 16 to 22 months. At the first screening 9,040 (66%) completed the test, and 7,770 (58%) completed the test at the second screening. In the first screening the test group was divided into two subgroups in which the tests were rehydrated and unhydrated before development. All tests were rehydrated in the second screening; 1.9% and 5.8% of the tests were positive in the unhydrated and rehydrated subgroups, respectively. The number of diagnosed neoplasms in the first screening was significantly larger (P less than 0.01) in the rehydrated group compared to the unhydrated group, 50 and 24 neoplasms, respectively. Sixteen of 61 carcinomas in the test group were found in the interval between the two screenings, 19 of the carcinomas at the second screening, and ten among the nonresponders. Rehydration of the Hemoccult II test is a necessity. Significantly more carcinomas (61) were found in the test group compared to the control group (20). There was a trend toward favorable tumor staging in the test group compared to the control group.