Effect of Furosemide,Hydrochlorothiazide and Sodium Restriction on Rat Adrenoceptors

Abstract: The interaction of thiazide diuretics and furosemide with adrenoceptors was investigated in normal rat in vivo by determining the effect of sodium-deficient diet alone or combined with hydrochlorothiazide or furosemide on adrenoceptors in heart, kidney and skeletal muscle. In addition, interaction of diuretics with renal adrenoceptors in vitro was investigated. Sodium-deficient diet alone retarded growth significantly, and this effect was increased by simultaneous treatment with furosemide 10–4. mg/kg body weight and day subcutaneously. No consistent alteration was demonstrated in density or affinity of α₁-, α₂- and β-adrenoceptors due to the in vivo treatment. In vitro, furosemide inhibited the equilibrium specific binding of radioligands to α₁-, _α2- and β-adrenoceptors to rat kidney paniculate fraction concentration-dependently. Furosemide increased K_d (equilibrium dissociation constant) and reduced B_max (number of specific binding sites) of the radioligands as determined by Scatchard analysis of binding saturation data. The Pseudo-Hill coefficient of the inhibition by furosemide of ¹²⁵I-iodocyanopindolol binding was 1.47, indicating a complex interaction consistent with a non-competitive inhibition. In conclusion, the results do not support the hypothesis that sodium deficiency alone or with diuretic treatment for one week alters tissue adrenoceptors in the normal rat. The pattern of inhibition by furosemide of ligand binding to adrenoceptors suggests that furosemide binds to an allosteric site on the receptors or to an adjacent macromolecule.     

Development of working alliance over the course of psychotherapy

Objectives. The goal was to investigate patients' rating of working alliance in longer‐term individual psychotherapy (N=201), in order to determine different patterns of development and predictors of positive versus negative development. Design. The study explored patient factors that might be associated with positive versus negative development of the alliance, from early in treatment until the end. Subgroups of patients with different alliance development were compared, in order to identify predictors of these groups. Methods. The data analyses identified patients who demonstrated significant change in the perceived quality of alliance using the reliable change index. Most patients were expected to have a stable alliance, and fewer were expected to have improving or deteriorating alliance. Results. We found three patterns: stable alliance, improving alliance, and deteriorating alliance. Seventy per cent of the therapies had a stable alliance, which was maintained throughout the treatment, supporting the assumption that the quality of the early alliance is important for the therapy process. We observed different pre‐treatment scores of Target Complaint and Expectation of Change in Target Complaint between the subgroups with different development of the working alliance. Higher Expectation of Change was associated with improving alliance, whereas the combination of higher Target Complaint scores and lower Expectation of Change was associated with deteriorating alliance. Also, lower score on Global Assessment Scale (<50) was associated with deteriorating alliance. Clinical case vignettes illustrate the developments of improving and deteriorating alliance. Conclusion. Several pre‐treatment patient characteristics were associated with development of alliance in positive versus negative directions. Clinical implications are discussed.     

Strain during gastric contractions can be measured using Doppler ultrasonography

This study was undertaken to explore if strain of the muscle layers within the gastric wall could be measured by transabdominal strain rate imaging (SRI), a novel Doppler ultrasound (US) method. A total of 9 healthy fasting subjects (8 women, 1 man; ages 22 to 55 years) were studied and both grey-scale and Doppler US data were acquired with a 5- to 8-MHz linear transducer in cineloops of 97 to 256 frames. Rapid stepwise inflation (5 to 60 mL) of an intragastric bag was carried out and bag pressure and SRI were measured simultaneously. SRI enabled detailed studies of layers within the gastric wall in all subjects. Great variations in strain distribution of the muscle layers were found. Radial strain was much higher in the circular than in the longitudinal muscle layer. Strains derived from SRI correlated well with strains obtained with B-mode measurements (r = 0.98, p < 0.05). During balloon distension, we found an inverse correlation between pressure and radial strain (r = -0.87, p < 0.05). Intraobserver correlation of strain estimation was r = 0.98 (p < 0.05) and intraobserver agreement was 0.2% +/- 18.6% (mean difference +/- 2SD, % strain). Interobserver correlation was r = 0.84 (p < 0.05) and interobserver agreement was 6.9% +/- 56.8%. SRI enables detailed mapping of radial strain distribution of the gastric wall and correlates well with B-mode measurements and pressure increments.     

The Effects of a Standardized Herbal Remedy Made from a Subtype of Rosa canina in Patients with Osteoarthritis: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial

Background: A standardized rose-hip powder produced from the seeds and husks of fruit from a subtype of Rosa canina has been reported to inhibit leukocyte functions that cause cell injury in osteoarthritis.Objective: The aim of this study was to assess the impact of standardized rose-hip powder on mobility of the hip and knee joints, activities of daily living, quality of life, and pain in patients with osteoarthritis.Methods: Patients with a diagnosis of osteoarthritis of either the hip or knee, verified on radiography, participated in this randomized, placebo-controlled, double-blind study. Half of the patients were given five 0.5-g capsules of standardized rose-hip powder twice daily for 4 months, and the other half received identical placebo capsules twice daily for the same period. Mobility of the hip or knee was measured in both groups after the initial screening and again after 4 months of therapy.Results: One hundred patients (65 women, 35 men; mean [SD] age, 65.2 [11.1] years) were divided into 2 treatment groups of 50 patients each. Hip joint mobility improved significantly in the treatment group compared with the placebo group (P = 0.033). Similarly, pain decreased significantly in the treatment group compared with the placebo group (P = 0.035). Two patients (4%) from each group withdrew during the early stages of the trial for reasons not related to treatment.Conclusions: In this study population, standardized rose-hip powder reduced symptoms of osteoarthritis, as 64.6% of patients reported at least some reduction of pain while receiving treatment. Standardized rose-hip powder may improve hip flexion and reduce pain in patients with osteoarthritis.     

Different osteosyntheses for Colles' fracture: A mechanical study in 42 cadaver bones

Background and purpose In recent years several different plate designs for internal fixation of fractures of the distal radius have been developed. However, few biomechanical studies have been performed to compare these new implants. The purpose of this study was to compare the mechanical properties of 5 different commercially available plates (3 volar and 2 dorsal) with standard K-wire fixation using a distal radial cadaver model.Material and methods 42 human radial bones from 26 cadavers were included. The bone mineral density (BMD) was measured by DEXA in all bones, and the radial bones were assigned to 6 equiv alent groups based on bone density and total amount of mineral. A distal radial osteotomy was done and a dorsal 30-degree wedge of bone was removed. 1 K-wire fixation group and 5 plate groups were tested for rigidity, yield load, and maximum load.Results When data from dorsally and volarly applied plates were pooled, we did not find any statistically significant differences between them regarding stiffness, yield load, and maximum load. The K-wire group showed significantly lower yield load than 3 of the plate groups. There were no statistically significant differences in yield load between the 5 plate groups. The K-wire group showed lower rigidity than the plate groups. The K-wire group and 1 plate group failed at a statistically significant lower maximum load than the 4 other plate groups.Interpretation The volar plates had the same mechanical stability as the dorsally applied plates, and they are therefore a good alternative to dorsally applied plates. K-wire osteosynthesis was inferior to plate osteosyntheses regarding all mechanical properties.     

Psychological distress among immigrants from high- and low-income countries: findings from the Oslo Health Study

This study compared psychological distress between immigrants from high- and low-income countries living in Oslo, and investigated whether pre- or post-migration factors could explain any such differences in distress levels. A cross-sectional survey with self-administered questionnaires was conducted between 2000 and 2001 among 812 immigrants from high-income countries and 1434 immigrants from low-income countries living in Oslo. The Hopkins Symptom Checklist (HSCL)-10 was used to measure psychological distress. The prevalence rates of psychological distress among immigrants from high- and low-income countries were 10.3% and 24.3%, respectively (P=0.001). Unadjusted odds ratio (OR) of distress among the latter group was 2.38 with 95% confidence interval (CI) 1.73-3.29. The first adjustment (socio-demographic variables) hardly attenuated the difference reported (adjusted OR =2.25, 95% CI 1.58-3.21), the second adjustment (socio-demographic and pre-migration variables) reduced the difference (adjusted OR =1.86, 95% CI 1.28-2.69) while the last adjustment (socio-demographic and pre- and post-migration variables) attenuated the difference below the level of significance (adjusted OR =1.33, 95% CI 0.88-2.01). This means that both pre-migration and post-migration factors were associated with the higher level of distress among immigrants from low-income countries, the post-migration factors in the host country probably being the most important.     

Multiplexed proximity ligation assays to profile putative plasma biomarkers relevant to pancreatic and ovarian cancer

BACKGROUND: Sensitive methods are needed for biomarker discovery and validation. We tested one promising technology, multiplex proximity ligation assay (PLA), in a pilot study profiling plasma biomarkers in pancreatic and ovarian cancer. METHODS: We used 4 panels of 6- and 7-plex PLAs to detect biomarkers, with each assay consuming 1 microL plasma and using either matched monoclonal antibody pairs or single batches of polyclonal antibody. Protein analytes were converted to unique DNA amplicons by proximity ligation and subsequently detected by quantitative PCR. We profiled 18 pancreatic cancer cases and 19 controls and 19 ovarian cancer cases and 20 controls for the following proteins: a disintegrin and metalloprotease 8, CA-125, CA 19-9, carboxypeptidase A1, carcinoembryonic antigen, connective tissue growth factor, epidermal growth factor receptor, epithelial cell adhesion molecule, Her2, galectin-1, insulin-like growth factor 2, interleukin-1alpha, interleukin-7, mesothelin, macrophage migration inhibitory factor, osteopontin, secretory leukocyte peptidase inhibitor, tumor necrosis factor alpha, vascular endothelial growth factor, and chitinase 3-like 1. Probes for CA-125 were present in 3 of the multiplex panels. We measured plasma concentrations of the CA-125-mesothelin complex by use of a triple-specific PLA with 2 ligation events among 3 probes. RESULTS: The assays displayed consistent measurements of CA-125 independent of which other markers were simultaneously detected and showed good correlation with Luminex data. In comparison to literature reports, we achieved expected results for other putative markers. CONCLUSION: Multiplex PLA using either matched monoclonal antibodies or single batches of polyclonal antibody should prove useful for identifying and validating sets of putative disease biomarkers and finding multimarker panels.