Expression of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 (KDR/Flk-1) in ischemic skeletal muscle and its regeneration

Vascular endothelial growth factor (VEGF) is a hypoxia-inducible endothelial cell mitogen and survival factor. Its receptor VEGFR-2 (KDR/Flk-1) mediates these effects. We studied the expression of VEGF and VEGFR-2 in ischemic human and rabbit skeletal muscle by immunohistochemistry and in situ hybridization. Human samples were obtained from eight lower limb amputations because of acute or chronic critical ischemia. In chronically ischemic human skeletal muscle VEGF and VEGFR-2 expression was restricted to atrophic and regenerating skeletal myocytes, whereas in acutely ischemic limbs VEGF and VEGFR-2 were expressed diffusely in the affected muscle. Hypoxia-inducible factor-1alpha was associated with VEGF and VEGFR-2 expression both in acute and chronic ischemia but not in regeneration. Hindlimb ischemia was induced in 20 New Zealand White rabbits by excising the femoral artery. Magnetic resonance imaging and histological sections revealed extensive ischemic damage in the thigh and leg muscles of ischemic rabbit hindlimbs with VEGF expression similar to acute human lower limb ischemia. After 1 and 3 weeks of ischemia VEGF expression was restricted to regenerating myotubes and by 6 weeks regeneration and expression of VEGF was diminished. VEGFR-2 expression was co-localized with VEGF expression in regenerating myotubes. Macrophages and an increased number of capillaries were associated with areas of ischemic muscle expressing VEGF and VEGFR-2. In conclusion, two patterns of VEGF and VEGFR-2 expression in human and rabbit ischemic skeletal muscle are demonstrated. In acute skeletal muscle ischemia VEGF and VEGFR-2 are expressed diffusely in the affected muscle. In chronic skeletal muscle ischemia and in skeletal muscle recovering from ischemia VEGF and VEGFR-2 expression are restricted to atrophic and regenerating muscle cells suggesting the operation of an autocrine pathway that may promote survival and regeneration of myocytes.     

Confrontations with reality: Crisis intervention services for traumatized families after a school bus accident in Norway

In August 1988 a Swedish schoolbus with 23 children and 11 adult passengers crashed into a tunnel wall in Norway. Twelve children and four parents died, 18 of the passengers survived. The victims' relatives (parents, spouses, siblings, and others) were transported to Norway and given a confronting support program at the University hospital in Bergen. The crisis intervention program is described: how the relatives were helped to confront and actively cope with some of the stressful situations from which traumatized families very often are protected. One year later 42 of the relatives answered a questionnaire evaluating the confronting support program that was offered during their stay in Norway. A majority of the respondents did not regret their participation in the program. The answers indicate that passivity and helplessness can be counteracted through a combination of confrontation with reality and emotional support.The study has received financial support from Skandia Insurance Co. (Sweden), Haukeland University Hospital and Norwegian Research Council for Science and the Humanities (377.92/021).     

Ferrous fumarate deteriorated plasma antioxidant status in patients with Crohn disease

BACKGROUND: Iron deficiency anaemia is a frequent complication of Crohn disease. Treatment with ferrous iron (Fe2-) compounds is often unsatisfactory and is associated with gastrointestinal side effects. Theoretically, oral iron supplementation may even be harmful, because iron may reinforce intestinal inflammation by catalysing production of reactive oxygen species. We investigated the effect of ferrous iron on disease activity and plasma antioxidant status in patients with active Crohn disease. METHODS: Ten patients with Crohn disease and iron deficiency and 10 healthy controls were given ferrous fumarate 120 mg for 7 days. The Crohn Disease Activity Index, gastrointestinal complaints and blood samples for antioxidant status, anaemia, inflammation and iron absorption were investigated on day 1 and day 8. RESULTS: During 1 week of ferrous fumarate supplementation, the Crohn Disease Activity Index tended to increase (P = 0.071). Patients experienced aggravation of diarrhoea, abdominal pain and nausea. Plasma-reduced cysteine was lower (P = 0.038) in patients than it was in controls. One week of ferrous iron supplementation further decreased reduced cysteine (P < 0.001) and significantly decreased plasma-reduced glutathione (P = 0.004) in the patients. Serum iron increased significantly in patients after an oral iron load test (from 5.8 +/- 3.2 micromol/L to 30.9 +/- 13.1 micromol/L). CONCLUSIONS: Treatment of iron deficiency with ferrous fumarate deteriorated plasma antioxidant status and increased specific clinical symptoms in patients with active Crohn disease. Plasma reduced cysteine may be a sensitive indicator for oxidative stress in the intestine.     

Cardiovascular risk factors and hearing loss: The HUNT study

Objective: The purpose of the present paper was to examine the association between prospectively and cross-sectionally assessed cardiovascular risk factors and hearing loss. Design: Hearing was assessed by pure-tone average thresholds at low (0.25–0.5 kHz), middle (1–2 kHz), and high (3–8 kHz) frequencies. Self-reported or measured cardiovascular risk factors were assessed both 11 years before and simultaneously with the audiometric assessment. Cardiovascular risk factors were smoking, alcohol use, physical inactivity, waist circumference, body mass index, resting heart rate, blood pressure, triglycerides, total serum cholesterol, LDL cholesterol, HDL cholesterol, and diabetes. Study sample: A population-based cohort of 31 547 subjects. Results: After adjustment for age, sex, level of education, income, recurrent ear infections, and noise exposure, risk factors associated with poorer hearing sensitivity were smoking, diabetes, physical inactivity, resting heart rate, and waist circumference. Smoking was only associated with hearing loss at high frequencies. The effects were very small, in combination explaining only 0.2–0.4% of the variance in addition to the component explained by age and the other cofactors. Conclusion: This cohort study indicates that, although many cardiovascular risk factors are associated with hearing loss, the effects are small and of doubtful clinical relevance.     

Dichotic listening performance predicts language comprehension

Dichotic listening performance is considered a reliable and valid procedure for the assessment of language lateralisation in the brain. However, the documentation of a relationship between language functions and dichotic listening performance is sparse, although it is accepted that dichotic listening measures language perception. In particular, language comprehension should show close correspondence to perception of language stimuli. In the present study, we tested samples of reading-impaired and normally achieving children between 10 and 13 years of age with tests of reading skills, language comprehension, and dichotic listening to consonant-vowel (CV) syllables. A high correlation between the language scores and the dichotic listening performance was expected. However, since the left ear score is believed to be an error when assessing language laterality, covariation was expected for the right ear scores only. In addition, directing attention to one ear input was believed to reduce the influence of random factors, and thus show a more concise estimate of left hemisphere language capacity. Thus, a stronger correlation between language comprehension skills and the dichotic listening performance when attending to the right ear was expected. The analyses yielded a positive correlation between the right ear score in DL and language comprehension, an effect that was stronger when attending to the right ear. The present results confirm the assumption that dichotic listening with CV syllables measures an aspect of language perception and language skills that is related to general language comprehension.     

Perceptions and acceptability of piloted Taenia solium control and elimination interventions in two endemic communities in eastern Zambia

Infections with Taenia solium cause significant public health and economic losses worldwide. Despite effective control tools, long‐term sustained control/elimination of the parasite has not been demonstrated to date. Success of intervention programs is dependent on their acceptability to local communities. Focus group discussions (FGDs) and questionnaires (QS) were conducted in two study communities in eastern Zambia to assess local perceptions and acceptance of two piloted intervention strategies: one targeting pigs only (‘control’ study arm), and one integrated human‐ and pig‐based (‘elimination’) strategy. QS (n = 227) captured data regarding participation in project activities, knowledge and perceptions of T. solium and of the interventional drugs used in the study. FGDs (n = 18) discussed perceived advantages and disadvantages of the interventions and of the project's delivery and value. QS data revealed 67% of respondents participated in at least one educational activity, and 80% correctly identified at least one disease targeted by the education. All elimination study arm respondents (n = 113) had taken the human treatment, and 98% intended to do so next time. Most (70%) indicated willingness to pay for future treatments (median 0.20 USD per dose). Of pig‐owning respondents, 11/12 (92%) had allowed their pigs to be treated/vaccinated and all intended to do so again next time. Four pig owners indicated willingness to pay 0.10–0.50 USD per dose of treatment or vaccine. FGD feedback revealed positive perceptions of interventions; people reported improved health in themselves and their pigs, and fewer cysticerci in pork. Latrine use, hand washing, meat inspection and proper cooking of pork had reportedly increased since the program's inception. Preliminary assessment indicates that the piloted intervention methods are generally acceptable to the communities. The reported willingness of many respondents to pay for the medications would contribute to the feasibility of long‐term, government‐led T. solium intervention programs in future.     

Trends and development of occupational health services in Norway

Occupational Health Services (OHS) in Norway cover approximately 1.2 million employees, equivalent to 60% of the total work force. They employ nurses (800), physicians (500), physiotherapists (360), safety engineers (400), psychologists (30) and others (400), a total of 2500 full time employmancy. The average cost of the OHS amounts to 150 euros per employee, a total cost of 180 million euros per year. In 1998, the OHS in Norway were evaluated. The evaluation, initiated by the Ministry, revealed that although 80% of the enterprises are fairly satisfied with their OHS, there is still much to be improved, in particular quality development and customer focus. By 2000 the National Practice Guidelines. ("Good OHS") were developed as a joint effort of the professional OHS associations, representatives from the social partners and the NIOH. These guidelines have been evaluated and well accepted by the OHS. Last year the Ministry of Labour appointed an advisory group of experts on OHS. The group was asked to examine: the "branch provision" on obligatory OHS and the availability of health resources; the legislation on OHS tasks; the quality improvement of OHS; and the OHS in small enterprises The report was ready in May 2001 stating that the OHS may be a useful contributor to the improvement of the health, environment and safety in enterprises and included the following recommendations: to establish the OHS for all within 10 years and to ratify relevant ILO convention; to develop a certification system for the OHS; to ensure financial public support of the OHS for the small enterprises; and to expand the OH hospital departments as important supportive agents for the OHS. The report will be a background document for the revision process of the Work Environment Act to be soon put into force.     

Intraoperative color Doppler ultrasound assessment of LIMA-to-LAD anastomoses in off-pump coronary artery bypass grafting

BACKGROUND: Although techniques for off-pump coronary artery bypass grafting (CABG) are continually being refined, angiographic follow-up studies have indicated a higher rate of anastomoses-related stenoses than expected after traditional on-pump CABG. This study was performed to evaluate the use of intraoperative epicardial color Doppler ultrasound to quality-assess left internal mammary artery (LIMA) to left anterior descending coronary artery (LAD) anastomoses performed on the beating heart. METHODS: Twenty-four LIMA-to-LAD anastomoses were evaluated with real-time epicardial ultrasound imaging using an ultrasound transducer positioned between the paddles of the stabilizer during off-pump procedures. The length of the anastomosis (D(A)), diameters of LIMA (D(M)), LAD at the toe of the anastomosis (D1), and 5 mm distally to the anastomosis (D2) were measured, and the ratios between these variables were calculated. The flow velocity through the anastomoses was visualized by color Doppler coding, and flow was assessed with transit-time flowmetry. RESULTS: The epicardial color Doppler ultrasound allowed accurate assessment of the anastomoses. Twenty-three (96%) of the primary anastomoses were confirmed as patent. Mean ratios of D1/D2, D(A)/D2, and D(M)/D2 were 0.89 +/- 0.13, 3.01 +/- 1.04 and 1.32 +/- 0.32, respectively. One anastomosis had a stenosis more than 50% detected by color Doppler ultrasound. After surgical revision, transit-time flow increased from 22 to 40 ml/min. CONCLUSIONS: Intraoperative color Doppler ultrasound allowed adequate imaging for quality assessment of LIMA-to-LAD anastomoses performed on the beating heart. One anastomosis was revised due to a technical error detected by epicardial color Doppler imaging. Epicardial ultrasound scanning is a valuable tool for intraoperative assessment of LIMA-to-LAD anastomoses during off-pump coronary surgery.     

A new liposomal liver-specific contrast agent for CT: first human phase-I clinical trial assessing efficacy and safety

In this first clinical trial liposome-encapsulated iodixanol, CT particles (CTP) were studied. The aims of the present trial were to assess the efficacy of CTP in CT and to determine the safety of different doses of CTP. A total of 47 healthy volunteers were enrolled in the present study. The CTP was administered at doses 10, 30, 70 and 100 mg encapsulated I/kg bw. Efficacy was assessed using single-slice CT of the abdomen and evaluated by dose-response attenuation curves over time in liver, spleen, and abdominal vessels. Safety was assessed by blood tests, clinical examinations and recording of subjective adverse events (AE). The attenuations in liver tissue increased with the dose and maximal values above baseline were 20, 39 and 45 HU at the doses 30, 70 and 100 mg encapsulated I/kg bw, respectively. Maximal increases were seen 12.5 min after contrast administration. As for liver, the attenuations in spleen increased with the dose, but higher attenuations were obtained. In early images clinically significant enhancement was seen in abdominal vessels. Mild and moderate subjective AE were encountered at the doses 70 and 100 mg encapsulated I/kg bw. The CTP is efficacious in enhancing hepatic and splenic tissues and in early imaging of abdominal vessels. Adverse event precludes a clinical use of CTP in the current formulation. Received: 13 June 2000 Revised: 11 September 2000 Accepted: 14 September 2000