Endothelin-induced inositol phosphate formation in rat kidney. Studies on receptor subtypes, G-proteins and regulation during ontogenesis

The aim of this study was to characterize the properties of endothelin (ET)-receptor subtypes mediating inositol phosphate (IP)-formation in rat kidney and their regulation during ontogenesis. In renal cortical slices of adult rats (12–16 weeks old) ET's concentration-dependently increased IP-formation with an order of potency ET -1 ET 3. While the non-selective ET receptor antagonist bosentan (10 M) completely suppressed ET-induced IP-formation, the ETA-receptor antagonist BQ-123 (10 M) inhibited it only by 70%, the ET_B-receptor antagonist IRL 1038 (1 M) by 25%; combined application of BQ-123 + IRL 1038 caused complete inhibition of ET-1-induced IP-formation. Pretreatment of isolated renal cells with pertussis toxin (PTX, 500 ng/ml) overnight did not attenuate but significantly increased ET-1-induced IP-formation. Ontogenetic studies in renal slices from neonatal, 1, 2, 3, 6, 12 and 24 weeks old rats revealed that ET-1-induced IP-formation maturation-dependently declined being highest in neonatal rats (increase: 169% over basal) and lowest in 24 weeks old rats (increase: 47% over basal). This decline in ET-induced IP-formation was accompanied by a decrease in renal ET receptor number and the amount of immunodetectable G_q/11 (assessed by Western-blotting using the QL-antiserum). Moreover, ET receptor subtypes changed during the maturation process: from neonates to 12 weeks old rats number and functional responsiveness of ET_A-receptors declined, while that of ET_B-receptors increased. We conclude that in adult rat renal cortex ET-induced IP-formation is mediated by activation of both ET_A- and ET_B-receptors and does not involve a PTX-sensitive G-protein. ET-induced IP-formation declines during the maturation process; this is associated with a decrease in ET-receptor number and the immunodetectable amount of G_q/11.     

The self-employed and the self-driven: two coronary-prone subpopulations from the Zeist study

In four Dutch communities, Zeist, De Bilt, Driebergen, and Doorn (total population, 111,000 inhabitants), all patients who suffered acute coronary events between July 1970 and March 1974 were recorded. By combining data from this study with data from the 1971 national census of the Netherlands, it was possible to demonstrate that the incidence of acute coronary events is twice as high for self-employed men as for employed men and as much as seven times as high for self-employed women as for housewives. The incidence of acute coronary events is practically the same for self-employed women aged 45-69 years as for men of the same age in the general population. Men aged 35-64 years whose nature is such that they feel driven to do all their work with great intensity and against the clock ("self-driven men") suffer myocardial infarction seven times as frequently as others and are 2.4 times as likely to die of fatal coronary attack. Only 10% of the self-employed male referents, but 50% of the self-employed male cases, consider themselves self-driven. On the other hand, experiences of excessive working hours and time pressures are not related to the incidence of acute coronary events. These results were not influenced by and were independent of other known risk indicators.     

Erfassung muskuloskeletaler Beschwerden mittels Fragebogen

Zusammenfassung Der standardisierte Fragebogen zur Erfassung muskuloskeletaler Beschwerden des japanischen Komitees zum Studium arbeitsbedingter Gesundheitsstörungen im Hals-Arm-Gebiet wurde auf Deutsch übertragen und seine Reliabilität und Validität überprüft. Im Fragebogen wird anhand eines Körperschemas nach der Häufigkeit (nie/selten, gelegentlich, fast täglich) von Beschwerden (Schmerzen, Steifigkeit, Müdigkeit) in 12 Körperregionen gefragt. Der Fragebogen wurde gleichzeitig mit ärztlichen Palpationsuntersuchungen bei 644 Personen aus zwölf Berufsgruppen im Dienstleistungssektor eingesetzt. Auf Grund einer Faktoranalyse der Fragebogenresultate kann festgestellt werden, dass Beschwerden regional getrennt (nämlich im Nacken-Schultergebiet, dem Rücken und je der rechten und linken oberen Extremität) auftreten und für diese Regionen die Symptome zu Indizes zusammengefasst werden können. Diese Indizes sind reliabel (Cronbach 0.8). Mit zunehmenden Indexwerten nehmen schmerzhafte Palpationsbefunde stetig zu. Beschwerden korrelieren mit vermehrtem Medikamentenkonsum und Arztkonsultationen. Der Fragebogen stellt folglich ein valides Untersuchungsinstrument für muskuloskeletale Beschwerden am Arbeitsplatz dar.

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Summary The standardized illustrated questionnaire on musculoskeletal disorders of the Japanese Committee on Occupational Cervico-brachial Disorders was translated into German. This questionnaire, composed of 37 items about the occurrence (never/seldom, occasionally, almost daily) of symptoms (pain, stiffness, fatique) in twelve body regions, was used together with medical examinations (pressure points), and further information was gathered on the consumption of analgetics and medical visits prompted by musculoskeletal symptoms. The questionnaire's reliability and validity were tested in 644 persons from twelve occupational groups within the service sector. Factoranalyses showed that symptoms can be grouped into four distinct regions of occurrence: neck/shoulder/area, back/low back, and both left and right upper extremities. Indices based on these regions are consistent (Cronbach 0.8). Palpation findings steadily increase with increasing index values. The consumption of medicaments and medical visits positively correlate with the indices. Consequently the questionnaire is judged to be a valid instrument for studying musculoskeletal disorders at the workplace.

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Résumé Le questionnaire illustré et standardisé sur les symptômes musculaires et osseux du comité japonais sur la cervico-brachialgie professionelle a été traduit en allemand et sa reliabilité et validité ont été testées. Le questionnaire est composé de 37 variables sur la fréquence (jamais/rarement, par occasion, presque toujours) des symptômes (douleur, raideur, fatigue) dans douze régions du corps. Il était distribué simultanément aux examens médicaux parmi 644 personnes de douze groupes d'employés dans le secteur de service. D'autres informations concernent la fréquence de la consommation des analgésiques et des visites médicales pour des douleurs musculaires. Une analyse factorielle a montré que les symptômes peuvent être groupés en quatre régions du corps: nuque/épaules, dos et les extrémités supérieurs. Les indices sur ces régions sont consistant (Cronbach 0.8). Les douleurs provoquées par la palpation augmentent avec la valeur de l'index. La consommation des analgésiques et les consultations sont correlées avec les indices. Par conséquent, le questionnaire illustré est un instrument valable pour étudier les problèmes musculaires sur les lieux de travail.

     

Single-dose toxicokinetics of aluminum in the rat

The toxicokinetics of aluminum (Al) in male Wistar rats was studied after single intragastric (IG) doses of 1000 and 12000 g Al/kg and intravenous (IV) doses of 10, 100, 1000, and 12000 g Al/kg. Serial blood samples, daily samples of urine and feces as well as brain, liver, kidney, spleen, quadriceps muscle, and femur samples were collected. Al was measured by atomic absorption spectrometry. Al blood profiles after IV doses were adequately described by a two-compartment open model. Al toxicokinetics was dose dependent and appeared to plateau at 12000 g/kg. At IV doses between 10 and 1000 g/kg the terminal half-life of elimination from whole blood (t_1/2) increased from 29.9±7.8 to 209.3±32.6 min, and the total body clearance (CL) decreased from 2.45±0.64 to 0.28±0.03 ml min^–1 kg^–1. Following an IV bolus of 10 and 100 g/kg the administered Al was recovered completely from urine (94.4%±9.9% and 98.5%±3.2%). Twenty-nine days after the IV dose of 1000 g/kg daily renal excretion decreased to baseline values while only 55.1%±8.0% of the dose was excreted. Nineteen days after the single IV dose of 1000 g/kg Al accumulated in liver (28.1±7.7 versus 1.7±0.5 g/g of control rats) and spleen (72.5±21.1 versus <0.4 g/g). After the single 1000 g/kg IG dose no absorption of Al was detectable. The IG dose of 12000 g/kg resulted in a maximum blood Al level of 47.9±12.4 g/l after 50 min. The blood concentration time curve fitted a one-compartment open model with a half-life of absorption of 28.2±3.6 min and a t_1/2 of 81.2±20.2 min. Cumulative renal Al excretion was 0.18%±0.10% of the dose and oral bioavailability was 0.02%. Seventeen days after the 12000 g/kg IG dose the Al content in femur samples was increased (2.7±1.3 versus 0.6±0.4 g/g). In no case was fecal elimination of incorporated Al observed.     

Costing depression and its management: an Australian study

OBJECTIVE: To examine the cost impact of referral to a Mood Disorders Unit (MDU), by comparing pre-service and post-service costs, and MDU and control samples. METHOD: We studied tertiary referral MDU patients and a control group of consultants' depressed patients, with the principal comparison intervals being: (i) 12 months prior to and (ii) 6 months following baseline assessment, with costs annualised to allow the impact of assessment and treatment recommendation to be determined. In addition, we assessed any 'personal cost' of depression. RESULTS: Following baseline assessment, MDU referrals showed a reduction in costs, while controls' costs increased, largely driven by contrasting directions in hospitalisation and social welfare costs. We identify variables associated with high and increased costs, including features of the earlier stages of the disorder, whether social welfare was received, diagnostic subtype and personality dysfunction, with multivariate analyses refining the variable sets. Self-report data indicated that patients judged the 'personal cost' of depression to exceed more formal cost parameters, so that to experience depression is itself depressogenic. CONCLUSIONS: This first Australian attempt to cost depression and its management in the clinical setting more provides a methodology for wider application in service evaluation studies rather than delivers an unequivocal answer to whether a specialist Mood Disorders Unit is cost efficient or not.     

Microembolic signals and clinical outcome in patients with acute stroke – a prospective study

The occurrence of microembolic signals (MES) in patients with transient ischemic attack (TIA) or stroke has already been described; the influence of the time interval between onset of symptoms and transcranial Doppler monitoring (TCD) on the MES rate or MES prevalence and the possible prognostic value of the early detected MES rate on the outcome of TIA or stroke symptoms in a 3 month interval are discussed. In a prospective study we evaluated 61 patients consecutively admitted to our stroke unit after their first ischemic neurological deficit involving the vascular territory of MCA and/or ACA. All of the patients underwent a 30-minute bilateral transcranial Doppler monitoring of their MCAs for the identification of MES. Monitoring was performed within 12.3 + -9.3 (average mean + -SD) hours of stroke onset for the first time, the second time 48 hours after first TCD monitoring. Prognosis for the recovery of neurological deficits was evaluated by using the Barthel index (BI) and Scandinavian Stroke Scale (SSS) at the time of admission of the patient to the stroke unit, and with Barthel indices after one month and after 3 months. As a result, 56% of all patients showed MES in at least one of the two registrations. MES were recorded not only on the symptomatic side. The MES prevalence between both TCD monitorings was significantly different (total MES prevalence: 1st TCD: 26 patients: 2nd TCD: 13 patients; p < 0.04; ipsilateral MES prevalence: 1st TCD: 19 patients; 2nd TCD: 9 patients; p < 0.01). The regression analysis showed a significant influence of the total MES rate on both neurological scores at admission (SSS: 0.03; Barthel index: 0.04), but not for the Barthel scores after one and three months. In conclusion, we found an influence of the time interval between onset of neurological symptoms of TIA or stroke on the MES rate and the prevalence of MES. The prevalence of MES or the MES rate, found after a short time interval to the onset of symptoms, did not have a prognostic value on the outcome of neurological deficits up to a three month follow-up.     

Lesion pattern in patients with multiple sclerosis and depression

To assess if a specific lesion pattern or changes of the basal limbic system as seen in primary depression and depression associated with neurodegenerative disorders might be identified in depressive multiple sclerosis (MS) patients, we submitted 78 MS patients to a MRI examination consisting of a quantitative measurement of lesions and of hyperintense signals from the pontomesencephalic midline (raphe). Furthermore relaxometry of the pontomesencephalic midline, a transcranial ultrasound examination rating its echogenicity semiquantitatively and a standardized neurological, neuropsychiatric and neuropsychological assessment were obtained. Thirty-one patients fulfilled the DSM-IV criteria for depression. Depressed MS patients had a significantly larger temporal lesion load than non-depressed MS patients, especially on the right side. A trend of difference was detected for lesions of the right parietal lobe, the right frontal lobe, the cerebellum and the total lesion load. Neither hyperintense signals or relaxometry nor echogenicity of the region at the level of the pontomesencephalic midline were significantly different between the groups. We conclude that depression in MS patients is not associated with an alteration of the basal limbic system at the brainstem as seen in Parkinson's disease or unipolar depression but with an increased lesion load of the projection areas of the basal limbic system.     

Coral Reef Aorta: A Long-Term Study of 21 Patients

n = 11, 52%), renovascular stenosis (n= 9, 43%) with concurrent renovascular hypertension (n= 5, 24%), and angina abdominalis (n= 7, 33%). Most patients had multiorgan vascular disease such as iliofemoral arterial occlusive disease (n= 14, 66%), coronary artery obstruction (n= 8, 38%), or obstruction of the carotid artery (n= 6, 28%). Risk factors did not differ between coral reef patients and those with other occlusive vascular diseases. All patients were treated through vascular operations, including open thromboendarterectomy of the suprarenal (n= 9, 43%), infrarenal (n= 4, 19%), or supra- and infrarenal aorta (n= 8, 38%), and thromboendarterectomy of the following vessels: celiac artery (n= 7, 33%), superior mesenteric artery (n= 12, 57%), inferior mesenteric artery (n= 3, 14%), unilateral renal artery (n= 3, 14%), or bilateral renal artery (n= 9, 43%). Bypass reconstructions were performed in 39% (n= 8). A thoracoabdominal approach was used in 14 patients (67%) and a median laparotomy in 7 (33%). Our results show that coral reef aorta is not confined to either gender. It appears most frequently in the context of general atherosclerotic disease and patients benefit from timely diagnosis and operation before onset of severe, life-threatening visceral and renal complications.     

The prevalence of respiratory symptoms and asthma among school children in three different areas of Norway

The role of exposure to ambient air pollution has been a topic of interest as a potential risk factor for respiratory symptoms and asthma. We expected that the prevalence rates would vary in Norway between the capital, Oslo, the mountainous area Hallingdal and the industrial area Odda. Surveys were conducted in school children, aged 6-16 years, in; Oslo (n=2577), Hallingdal (n=1177) and Odda (n=831). The parent-reported prevalence of wheeze in past year was almost similar in Oslo (13. 1 (95% CI 11. 7-14. 5)) and Upper Hallingdal (14. 2 (13. 1–15. 3)), but lower in Odda (9. 0 (7. 0–11. 0)). The findings for severe respiratory symptoms were almost equal. The age patters within each area differed. The risk of wheeze ever (p < 0.001) and wheeze in past year (p=0.04) decreased with increasing age in Odda, while there was an increase in the risk of exercise induced wheeze in Oslo (p=0.02) and Hallingdal (p < 0.001). The lifetime prevalence of asthma was lowest in Odda (5. 4 (3. 8–7. 0)) compared to Oslo (9. 4 (8. 2–10. 6)) and Hallingdal (8. 5 (6. 8–10. 2)). There was a positive association between physical activity and wheeze in past year. The results do not support the hypothesis that respiratory morbidity is more common in urban than rural areas, age and physical activity can influence the prevalence rates of respiratory symptoms in school children.     

The impact of hormone replacement therapy on quality of life and willingness to pay

Objective To measure the gain in quality of life due to hormone replacement therapy for women with mild and severe menopausal symptoms.
Design Prospective study where data on quality of life and willingness to pay were collected by interview.
Setting Department of Gynaecology at Sodertalje Hospital near Stockholm.
Participants One hundred and four women aged 45 to 65 years treated for menopausal symptoms for at least one month.
Methods Quality oflife was measured by the time tradeoff and rating scale methods. The willingness to pay for hormone replacement therapy was investigated using the contingent valuation method.
Main outcome measures The quality adjusted life year weight measured with the rating scale and time tradeoff methods, and willingness to pay.
Results The increase in the quality adjusted life year weight due to hormone replacement therapy for women with mild symptoms was 0.26 according to the rating scale method and 0.18 according to the time tradeoff method. For women with severe symptoms the quality adjusted life year weight increased by 0.50 according to the rating scale method and by 0.42 according to the time tradeoff method. The mean willingness to pay for hormone replacement therapy per month was 2300 Swedish krone for women with mild symptoms and 4800 Swedish krone for women with severe symptoms (£1 = 10.3 Swedish krone).
Conclusions Hormone replacement therapy leads to a major improvement in quality of life for women with menopausal symptoms. Both for women with mild and severe menopausal symptoms the willingness to pay for the treatment also greatly exceeds the costs, indicating that hormone replacement therapy is economically beneficial for women with menopausal symptoms.