Adrenoceptors on blood cells from patients with primary Raynaud's phenomenon.

1. alpha 2-Adrenoceptors on platelet membranes and beta 2-adrenoceptors on lymphocytes were studied in 24 patients with primary Raynaud's phenomenon and in 24 age- and sex-matched control subjects. In two subgroups, a standardized mental arithmetic test and a finger-cooling test were performed. 2. Baseline blood pressure, heart rate and forearm blood flow did not differ between the two groups. 3. Baseline skin microcirculation (laser Doppler flux) was decreased in primary Raynaud's phenomenon (19 +/- 15 arbitrary units) compared with control subjects (33 +/- 14 arbitrary units) (P less than 0.01). 4. Baseline plasma noradrenaline concentration (2.00 +/- 1.44 versus 1.16 +/- 0.36 nmol/l) and alpha 2-adrenoceptor density (301 +/- 119 versus 210 +/- 82 fmol/mg) were increased in patients with primary Raynaud's phenomenon in comparison with the control subjects. The alpha 2-adrenoceptor density/beta 2-adrenoceptor density ratio in patients with primary Raynaud's phenomenon was, with a value of 0.37 +/- 0.04, higher than in the control subjects, where a value of 0.25 +/- 0.02 was measured (P less than 0.001). Plasma adrenaline concentration, beta 2-adrenoceptor density and the antagonist affinity to both receptor subtypes did not differ between both groups under baseline conditions. 5. Whereas during the finger-cooling test no differences were seen in the responses of the parameters measured, the mental arithmetic test induced an increase in laser Doppler flux in patients with primary Raynaud's phenomenon and a decrease in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of pain and urinary symptoms on quality of life in young men with chronic prostatitis-like symptoms

BACKGROUND: Our aims in the present study were to estimate the influences of pain and urinary symptoms on quality of life, and to determine which of these two variables has the most predictive power with respect to quality of life in young men with chronic prostatitis-like symptoms. METHODS: Chronic prostatitis-like symptoms were measured by the National Institutes of Health-Chronic Prostatitis Symptom Index. Of the 28,841 men aged 20 years who lived in the study community, 18,495 men (a response rate 64.1%) agreed to participate in the study. A total of 1057 men who complained of symptoms indicative of chronic prostatitis were included in the study. The influences of pain and urinary symptoms on quality of life were determined using logistic regression analysis. The receiver operating characteristic (ROC) curve was used to estimate the predictive ability of each of these variables with respect to quality of life. RESULTS: Results from multivariate analysis showed that both pain and urinary symptoms were associated with an increased likelihood of impaired quality of life, although pain contributed more to a reduced quality of life than urinary symptoms. Relative to men who experienced mild pain, men who experienced moderate pain had a 3.9-fold risk of poor quality of life (odds ratio [OR], 3.87; 95% confidence interval [CI], 2.86-5.23; P < 0.001) and those who experienced severe pain had a 15.7-fold risk of reduced quality of life (OR, 15.68; 95% CI, 6.59-37.35; P < 0.001). Moderate urinary symptoms were associated with a 1.4-fold risk of bother (OR, 1.41; 95% CI, 1.01-1.99; P < 0.001) and severe urinary symptoms were associated with 2.4-fold risk (OR, 2.39; 95% CI, 1.37-4.12; P < 0.001), relative to mild urinary symptoms. Comparison of the effects of pain and urinary symptoms showed that pain severity had the most predictive power for bother, quality of life, and quality-of-life impact. The areas under the ROC curves for bother, quality of life, and quality-of-life impact were 71.3%, 69.3% and 72.5%, respectively. CONCLUSION: Urinary symptoms and pain might be associated with an increased likelihood of impaired quality of life in young men with chronic prostatitis-like symptoms. In addition, our findings suggest that pain severity is the most influential variable for determining quality of life in this population.     

Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells.

Phospholipidosis (PLD) is characterized by an intracellular accumulation of phospholipids in lysosomes and the concurrent development of concentric lamellar bodies. Recently, H. Sawada et al. (2005, Toxicol. Sci. 83, 282-292) identified 17 genes as potential biomarkers of PLD in HepG2 cells. The present study was undertaken to determine if this set of genes measured by quantitative PCR could be validated in the same cell line. The objective was also to investigate the dose-response relationship to further validate the assay and to select the concentrations to use for screening activities. In a first experiment (one concentration tested), out of the 17 genes, the best gene biomarkers of PLD (i.e., 11 genes) were selected for practical screening reasons. Based on these genes, 91.6% (i.e., 11 of 12) of the compounds known to induce PLD were identified as positive and all the negative compounds (i.e., five of five) were also confirmed. When the data obtained in the first experiment were compared to the data by Sawada et al., (2005) the coefficient of correlation calculated was slightly higher than 75%. In the second experiment (26 compounds [all 17 compounds from the first experiment plus 9 other compounds] tested at a minimum of three concentrations), 93.3% (14/15) of the compounds known to induce PLD were identified as such and all the negative controls (six compounds) were also confirmed. Three compounds likely to induce PLD were identified as positive in our assay. Finally, two compounds for which no data are available were also tested. When both experiments 1 and 2 were compared, the coefficient of correlation for 16 compounds tested at the same concentrations reached 87.7%. In conclusion, the present study further confirms the utility of gene expression in HepG2 cells to identify a potential to induce PLD. Finally, based on the data presented, researchers are encouraged to use a range of minimum three concentrations (e.g., 12.5, 25, and 50 microM) to screen for PLD in the human HepG2 cell line.     

“Helper:” A critical events prompter for unexpected emergencies

Objective. The medical practitioner is faced with an increasing list of protocols and algorithms related to patient care. These recommendations are often difficult to recall, particularly in stressful emergency situations. Using advanced cardiac life support (ACLS) protocols, we built a computer-based system to exhibit precompiled response plans for medical emergencies. To validate the usefulness of this prompting device, we tested application of two of the nine ACLS algorithms, pulseless ventricular fibrillation/ventricular tachycardia (Vfib/Vtach) and bradycardia, in a simulated operating room (OR) environment.Methods. The system utilized the software authoring system IconAuthor (Aimtec Inc., Nashua, NH) and a touch-screen monitor (DiamondScan, Microtouch, Methuen, MA). Prior to testing our system, all 39 subjects were given time to familiarize themselves with its operation. Subsequently, all subjects were videotaped while managing a standard simulated anesthetic. During the anesthetic, the subjects were presented with two emergency scenarios, not viewed during the familiarization period. The electrocardiographic (EKG) signals for normal sinus rhythm, ventricular fibrillation, and second-degree heart block were presented. By random selection, the prompter was available to half of the subjects for help with arrhythmia management (experimental group), while to half it was not (control group).Results. A total of 39 subjects completed the exercise. Use of the prompter enabled significantly more subjects to administer correct drugs and dosages during ventricular fibrillation. The correct lidocaine dose was chosen more often by the experimental group than by the control (p=0.015); similarly MgSO₄ was appropriately ordered more often in the experimental group (p=0.003). During second-degree heart block, atropine was correctly followed with a dopamine infusion (p=0.004), and epinephrine infusion was ordered for refractory bradycardia (p=0.002) more often in the experimental than the control group.Conclusions. These data demonstrate the value of a prompting device at the anesthesia workstation. We foresee the use of such prompters in many areas of medicine.This study was made possible by a grant from the Anesthesia Patient Safety Foundation. Results were presented, in part, at the meeting of the STA/SEA Orlando, Florida, January 1994.     

Role of cytochrome P450IIIA4 in the metabolism of the pyrrolizidine alkaloid senecionine in human liver

Studies were carried out to investigate the metabolism of senecionine by human liver microsomes and the role of human cytochrome P450IIIA4 in this process. Human liver microsomes metabolized senecionine to two major products, (+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP) and senecionine N-oxide. The rates of product formation (DHP and senecionine N-oxide) varied widely with the microsomal samples tested. There was a 30-fold difference in DHP formation and a 25-fold difference in N-oxidation between the poorest metabolizer and the highest metabolizer of senecionine. The conversion of senecionine to DHP and senecionine N-oxide in human liver microsomes was markedly inhibited by the mechanism-based inactivators of P450IIIA4, gestodene and triacetyloleandomycin. Anti-P450IIIA4 IgG, at a concentration of 1 mg/nmol of P450, was found to inhibit completely the formation of DHP and senecionine N-oxide in human liver microsomes (HL101) having low activity toward senecionine. At 5 mg IgG/nmol P450, anti-P450IIIA4 inhibited 90 and 84% respectively of the formation of DHP and senecionine N-oxide in liver microsomes (HL110) with the highest activity toward senecionine. The formation of DHP or senecionine N-oxide was highly correlated with the amount of P450IIIA4 measured in the microsomes using polyclonal anti-P450IIIA4 IgG. The rate of DHP production also had a strong correlation with the rate of senecionine N-oxide formation (r = 0.999) and with the rate of nifedipine oxidation (r = 0.998). Our present studies provide evidence that P450IIIA4 is the major enzyme catalyzing the bioactivation (DHP formation) and detoxication (senecionine N-oxide formation) of senecionine in human liver.     

Comparing reconstruction with ileocecal graft to jejunal interposition pouch after total gastrectomy in rats.

After total gastrectomy, the ileocecal graft may act as a reservoir and protect against reflux but give rise to transposition of the ileum and cause possible changes in bile acid metabolism and nutrition. This study compared the ileocecal graft and jejunal pouch. Male Wistar rats weighing 265 +/- 22 g were submitted to sham operation (S), ileocecal interposition graft (IIG), and jejunal pouch interposition graft (JP) after total gastrectomy. Eight weeks later, the esophagus was examined for evidence of esophagitis. Nutritional biochemistry and weight profile were documented preoperatively and 8 weeks after surgery. The oral glucose tolerance test was performed. Thirty-three rats were operated on and 30 survived for 8 weeks. Esophagitis occurred in seven JP rats. Body weight was significantly higher in IIG than in JP rats (p < .05). Normal glucose tolerance to intragastric glucose load was observed in sham and operated rats. JP rats had a significant decrease in serum albumin, glucose, transferrin, hemoglobin, iron, folate, and calcium, compared to sham (p < .05). Cobalamine was significantly lower in IIG rats than in JP rats (p < .05). In the IIG and JP groups, serum/hepatic total bile acid did not differ significantly from preoperative and sham values. In conclusion, the IIG interposition graft in rats prevented esophagitis, preserved nutrition, and did not interfere with enterohepatic total bile acid circulation.     

Proximal gastric vagotomy. A comparative study between the standard technique and the extended technique associated with denervation of the greater curvature

Forty-six patients in the postoperative period of proximal gastric vagotomy (PGV) for duodenal ulcer (DU) were studied comparatively to verify whether the dividing of the gastroepiploic nerves (Rosati's maneuver) can reduce or not the occurrence of recurrent ulcer as it was proposed. Twenty-one patients who underwent PGV associated with Rosati's maneuver (PGV-R) were compared to 25 after standard PGV (PGV-S), according to several criteria: (1) clinical evaluation; (2) pre and postoperative basal and pentagastrin-stimulated gastric acidity; (3) postoperative basal and pentagastrin-stimulated serum pepsinogen; (4) postoperative basal and sham feeding-stimulated serum gastrin; (5) postoperative endoscopy; (6) endoscopic Congo red test. Both groups were similar (P greater than 0.05) as to age, sex, levels of preoperative gastric acidity and had a 24.4 month average follow-up (12 to 58 months). There has been no significant difference between the techniques studied as to clinical, secretory, morphological or hormonal gastric tests, although PGV-R proved more effective in reducing basal gastric acidity than PGV-S (P less than 0.05). We concluded that Rosati's maneuver does not improve the results obtained with PGV, although it provided greater reduction of basal gastric acidity than PGV-S.