Effects of (R)-8-OH-DPAT and the enantiomers of UH-301 on motor activities in the rat: antagonism of (R)-8-OH-DPAT-induced effects.

The effects of the enantiomers of 5-fluoro-8-hydroxy-2-(dipropylamino)tetralin, UH-301 and the potent 5-HT1A-receptor agonist (R)-8-hydroxy-2-(dipropylamino)tetralin, (R)-8-OH-DPAT, on locomotion, rearing and total activity were studied in rats. The experiments were performed as tests either of exploratory activity in non-habituated rats or of motor activity of rats habituated to the environment for 2 h before drug injection. (R)-8-OH-DPAT increased locomotion and total activity and decreased rearing in both conditions. (R)-UH-301 increased locomotion and slightly also total activity in habituated rats and decreased rearing in both conditions. (S)-UH-301 decreased locomotion and rearing in both conditions but only in doses of 10 mumol/kg and above. Lower doses of (S)-UH-301 (10 mumol/kg) antagonized (R)-8-OH-DPAT-induced increases of locomotion and total activity. As (S)-UH-301 decreased rearing, per se, it was not able to antagonize the (R)-8-OH-DPAT induced decrease. These results further support previous data that (S)-UH-301 is a 5-HT1A antagonist while (R)-UH-301 is a 5-HT1A agonist.     

Cardiac output determination during intravenous cardioangiography using x-ray fluorescence analysis

Cardiac output was determined with an indicator dilution technique during digital venous angiography of the left ventricle in 11 patients. The contrast medium injected into the right atrium was used as indicator. During and after the injection of contrast medium one blood sample per second was obtained through a catheter placed in the descending aorta. The samples were analyzed for iodine content with x-ray fluorescence analysis and cardiac output determined ad modum Stewart-Hamilton. Thermodilution was used as a reference method. The results indicate that the indicator dilution method with the use of contrast medium might be used for calibration of videodensitometric methods for blood flow measurements.     

The economics of general thromboembolic prophylaxis

The clinical and economic effects of each of 3 alternatives—no prophylaxis, general prophylaxis, and selective treatment—have been assessed in conjunction with 3 types of surgery—general surgery, the subset surgery for cholelithiasis, and elective hip surgery. The costs of thromboembolic and hemorrhagic complications have been calculated from the figures for 28 patients hospitalized at the Department of Surgery, Malmö General Hospital, Malmö, Sweden. The anticipated number of thromboembolic complications—and thus even the number of fatal pulmonary embolisms—can be minimized in all 3 types of surgery by means of general prophylaxis. General prophylaxis with low-dose heparin is, however, accompanied by the greatest incidence of hemorrhagic complications. Health care costs are minimized with general prophylaxis in elective hip and general surgery, while no prophylaxis is the best alternative in surgery for cholelithiasis. From the patient's point of view, general prophylaxis minimizes the duration of thromboembolic disease in general surgery as well as in elective hip surgery. In surgery for cholelithiasis, however, no differences in health loss for the individual are shown between the 2 main alternatives, no prophylaxis and general prophylaxis. Selective treatment means treatment after diagnosis of thrombosis with some screening method. The alternative selective treatment was the least satisfactory of those 3 studied.

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Resumen Los efectos clínicos y económicos de cada una de 3 alternatives en la profilaxis tromboembólica (no profilaxis, profilaxis general con heparina de baja dosis, y tratamiento selectivo) fueron valorados en 3 tipos de cirugía: cirugía general (abdominal), el subgrupo de cirugía general para colelitiasis, y cirugía electiva de cadera. Los costos de las complicaciones tromboembólicas y hemorrágicas fueron calculados a partir de las cifras observadas en 28 pacientes hospitalizados en el Departmento de Cirugía. El número de predicción de complicaciones tromboembólicas, y el número de embolismos pulmonares fatales pueden ser minimizados en los 3 tipos de cirugía mediante la profilaxis general. Sin embargo, la profilaxis general con heparina de baja dosis se acompaña de la más alta incidencia de complicaciones hemorrágicas.Los costos de la atención pueden ser minimizados mediante la profilaxis general en cirugía electiva de cadera y en cirugía general abdominal, en tanto que la no profilaxis es la mejor alternativa para la cirugía de colelitiasis.Desde el punto de vista del paciente, la profilaxis general minimiza la duración de la enfermedad tromboembólica en la cirugía general abdominal así como en la cirugía electiva de cadera. En la cirugía para colelitiasis, sin embargo, no se demuestran diferencias entre las dos alternatives principales, no profilaxis y profilaxis general.El tratamiento selectivo significa tratamiento una vez establecido el diagnóstico de trombosis mediante algún método de tamizaje. La alternativa de tratamiento selectivo fue la menos satisfactoria de las 3 alternatives estudiadas.

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Résumé Les effets cliniques et financiers de 3 comportements variables: absence de prophylaxie, prophylaxie, traitement sélectif ont été évalué en fonction de trois types de chirurgie: chirurgie générale, chirurgie spéciale de la lithiase biliaire, chirurgie élective de la hanche. Les coûts des complications thrombo-emboliques et hémorragiques ont été calculés à partir des données numériques concernant 28 malades hospitalisés dans le service de chirurgie. Le nombre envisagé des complications thromboemboliques et par conséquent le nombre d'embolie pulmonaire fatale a été réduit dans les 3 types de chirurgie choisis grâce au traitement prophylactique. Cependant il convient de noter que le traitement prophylactique à l'aide de faible dose d'héparine s'accompagne de complications hémorragiques plus nombreuses.Les coûts des soins de la chirurgie élective de la hanche et de la chirurgie générale sont réduits grâce au traitement prophylactique alors que l'absence de traitement prophylactique représente la meilleure modalité à observer dans le traitement de la chirurgie biliaire.En ce qui concerne le point de vue du malade le traitement prophylactique réduit la durée de la maladie thromboembolique compliquant la chirurgie générale ou la chirurgie de la hanche. En revanche dans la chirurgie de la lithiase biliaire aucun inconvénient pour la santé du malade ne s'observe que le traitement prophylactique soit ou ne soit pas appliqué.Le traitement sélectif qui répond au traitement institué après que le diagnostic ait été posé par des méthodes de dépistage est la moins satisfaisante des trois attitudes envisagées.

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Supported by grant no. 00759 from the Swedish Medical Research Council.     

Changes in CSF pressures during experimental acute arterial subdural bleeding in pig

Summary The effects of acute arterial subdural bleeding on cerebrospinal fluid (CSF) pressure and 12 other vital parameters were studied in spontaneously breathing pigs (group 1, n=9) and in mechanically ventilated pigs (group 2, n=18) to analyze quantitatively the bleeding course and the lethal mechanism.Spontaneously breathing animals all succumbed after a mean bleeding volume of 45.6±8.9ml, corresponding to about 50 per cent of the intracranial volume, and a mean bleeding duration of 11.0±2.6 min. Rapid rise in CSF pressures, marked transtentorial pressure gradients, and progressive reductions of cerebral perfusion pressure leading to a permanently iso-electric EEG, apnoea and to a terminal rise in arterial pressure (Cushing response), was the rule in these animals.The mechanically ventilated animals had smaller bleeding volumes (34.3±8.1 ml), but longer bleeding durations (13.8±5.8 min). In this group 7 animals survived. They had no pressure gradients, and only moderate changes in arterial pressure and EEG. The 11 animals that succumbed had marked transtentorial pressure gradients, but smaller increments in arterial pressure than the spontaneously breathing animals.At autopsy, subdurally located blood was found throughout the intracranial and spinal subdural compartments and along the spinal nerve roots in both groups.The results of this study suggest that survival after acute subdural haematoma is influenced by the presence of transtentorial pressure gradients and by the spinal sac acting as a space for expansion. The beneficial effect of artificial ventilation is discussed.This study has been supported by the University of Oslo, The Anders Jahre Foundation for The Advance of Research, and by the Norwegian Society for fighting Cancer.     

Spatial learning impairments in rats with selective immunolesion of the forebrain cholinergic system.

A monoclonal antibody to the low-affinity NGF receptor, 192 IgG, coupled to a cytotoxin, saporin, was recently introduced as an efficient selective neurotoxin for the NGFr-bearing cholinergic neurones in the rat basal forebrain. In the present study we report that an intracerebroventricular injection of this 192 IgG-saporin conjugate induces a severe, long-lasting spatial learning impairment, as assessed in the Morris water-maze task. This behavioural impairment was associated with 65-90% depletion of choline acetyltransferase activity (ChAT) in the hippocampus and cortex. ChAT activity associated with other cholinergic neurone systems in the brain (striatum, mesencephalon, spinal cord), was left virtually unaffected. This new immunotoxin holds great promise as a tool for selective and efficient lesions of the forebrain cholinergic system in functional and behavioural studies.     

Socioeconomic position and variations in coping strategies in musculoskeletal pain: a cross-sectional study of 1,287 40- and 50-year-old men and women.

OBJECTIVE: To examine the association between socioeconomic position and coping strategies in musculoskeletal pain. DESIGN AND SUBJECTS: Cross-sectional study of a random sample of 40- and 50-year-old Danes, participation rate 69%, n=7,125. The study included 1,287 persons who reported functional limitations due to musculoskeletal pain. METHODS: Data was collected by postal questionnaires and scales were developed on problem-solving coping and avoidant coping, based on a range of preliminary studies. Multivariate logistic regression analyses was used to study the correlation with socioeconomic position, measured by occupational social class. RESULTS: Among women, there was no correlation between social class and avoidant coping, but a significant decrease in the use of problem-solving coping by decreasing social class, adjusted odds ratio (OR) = 2.64 (95% confidence interval (CI) 1.31-5.32) in social class V vs social classes I + II. Among men, there was no correlation between social class and problem-solving coping, but a significant increase in the use of avoidant coping with decreasing social class, adjusted OR = 3.31 (95% CI 1.75-6.25) in V vs I + II. CONCLUSION: It is important for clinicians who advise and support patients in their response to musculoskeletal pain to be aware of socioeconomic differences in coping strategies. Gender differences in the association between socioeconomic factors and coping should be further investigated.     

Efficacy of diphenhydramine against cough in humans: a review

Aim To determine the efficacy of diphenhydramine against cough due to respiratory infection or irritation in patients/subjects without comorbidities. Method Two reviewers independently identified English language studies, searching on: clinical trials, randomized, diphenhydramine (OR dimenhydrinate), antitussive agents, cough (combine using AND). Sources were: Medline (1966–2005), Embase (1980–2005), Cochrane and references from retrieved articles. Two other reviewers, blinded to study origin selected studies, inclusion criteria being: diphenhydramine monotherapy against placebo, double-blinded, randomized, clinical trial, intention-to-treat, dropout information. The blinded reviewers evaluated the selected studies on a quality scale. Results Eleven articles were identified, 7 were rejected (4 not placebo controlled, 2 had no diphenhydramine, 1 not blinded), leaving 4 articles, that were included in the evaluation and scored 20, 21, 25 and 26 out of a maximum of 32. In these selected studies, a total of 162 people were examined, 65 on diphenhydramine, 63 on placebo and 34 in a crossover setting. There was a total of 13 dropouts. The crossover studies demonstrated significant effect; 27–56% reduction in 20 healthy volunteers and 21–26% reduction in 13 patients (originally 14, one outlier left out), whereas the active versus placebo studies did not. Conclusion In spite of the 60 years that the substance has been on the market, only few studies have properly evaluated the effect of diphenhydramine against cough. Presumptions about efficacy of diphenhydramine against cough in humans are not univocally substantiated in literature.     

Percutaneous Transhepatic Cholangiodrainage as Rescue Therapy for Symptomatic Biliary Leakage Without Biliary Tract Dilation After Major Surgery

Symptomatic biliary leakage following major upper abdominal surgery is a severe complication resulting in increased morbidity and mortality. Treatment options usually include either endoscopic intervention or surgical revision. These options may be burdened by a high perioperative risk for the patient (e.g., patients with severe disease) or simply may not be possible (e.g., nonpreserved gastroduodenal passage). In the past, percutaneous transhepatic cholangiodrainage did only seem to be a viable option for patients with dilated bile ducts. Here, we present our experience in a consecutive series of patients with symptomatic biliary leakage following major upper abdominal surgery and without dilation of the biliary system that underwent percutaneous transhepatic cholangiodrainage. Percutaneous transhepatic cholangiodrainage was feasible in 15 of 18 patients (83.3%). The procedure was technically not possible in three patients (16.7%). In 10 of the 15 patients (66.6%) with feasible percutaneous transhepatic cholangiodrainage, biliary leakage was definitely controlled without the need for surgical revision. Depending on the experience with the interventional procedure, percutaneous transhepatic cholangiodrainage should be considered as an alternative for treatment of symptomatic biliary leakage instead of immediate reoperation. Presented at the Digestive Disease Week 2005 (DDW), Chicago, IL, May 14–19, 2005 (poster presentation).