Histamine N-methyl transferase: inhibition by drugs.

1. Histamine N-methyl transferase activity was measured in samples of human liver, brain, kidney, lung and intestinal mucosa. The mean (+/- s.d.) rate (nmol min-1 mg-1 protein) of histamine N-methylation was 1.78 +/- 0.59 (liver, n = 60), 1.15 +/- 0.38 (renal cortex, n = 8), 0.79 +/- 0.14 (renal medulla, n = 8), 0.35 +/- 0.08 (lung, n = 20), 0.47 +/- 0.18 (human intestine, n = 30) and 0.29 +/- 0.14 (brain, n = 13). 2. Inhibition of histamine N-methyl transferase by 15 drugs was investigated in human liver. The IC50 for the various drugs ranged over three orders of magnitude; chloroquine was the most potent inhibitor. 3. The average IC50 values for chloroquine were 12.6, 22.0, 19.0, 21.6 microM in liver, renal cortex, brain and colon, respectively. These values are lower than the Michaelis-Menten constant for histamine N-methyltransferase in liver (43.8 microM) and kidney (45.5 microM). Chloroquine carried a mixed non-competitive inhibition of hepatic histamine N-methyl transferase. Some side-effects of chloroquine may be explained by inhibition of histamine N-methyl transferase.     

Advantages of Delayed Sternal Closure in Cardiac-Compromised Adult Patients

Severe hemodynamic dysfunction may follow closure of the median sternotomy in patients with myocardial edema, cardiac dilatation, postcardiotomy shock, or raised endexpiratory alveolar pressure. Open sternotomy and delayed sternal closure (DSC) is a well described adjunct in complicated cardiac operations, which is more widely applied in neonates. In this article we report our results in using open sternotomy in eight adult patients from January 1994 to February 1995 (excluding patients who needed ventricular assistance devices [VADs]). Three patients died in hospital: 1 case of multiorgan failure; 1 case of refractory low cardiac output syndrome; and 1 case of respiratory distress syndrome. Our experience confirms that DSC is an effective means of dealing with postoperative hemodynamic impairment. Furthermore, this technique may represent an intermediate step between intra-aortic balloon counterpulsation and VADs and should be given a role in the prophylaxis of low postoperative cardiac output and multiorgan failure, particularly when contraindications to VAD exist.     

Effects of strength training on throwing velocity and shoulder muscle performance in teenage baseball players

Exercise protocols designed to improve muscle function and athletic performance are continually developed and revised, often without published research supporting their efficacy. This study compared the effects of isokinetic (IKN) and accommodative isotonic training in the individualized, dynamic, variable resistance (IDVR) mode. Twenty-seven teenage baseball players were tested isokinetically for dominant shoulder rotational peak torque and power and for throwing velocity. They were then randomly assigned to 5 weeks of IKN training, IDVR training, or a control group of no training. Following the training period, pretest protocols were repeated. Analysis of variance of differences in means and Newman-Keuls post hoc tests showed statistically significant increases in throwing velocity and external rotator torque in the IDVR group but not the IKN group. External rotator power improved in both groups. Internal rotator torque and power were not improved in either group. Results suggest that IDVR may be more effective than IKN training in improving throwing velocity and external rotator torque production. Clinicians should consider using IDVR protocols in improving shoulder muscle function and throwing performance. J Orthop Sports Phys Ther 1992;15(5):223-228.     

Pressure changes in the carpal tunnel with movement of the pisiform bone

Seven fresh cadaveric forearms were studied to investigate the effects of medial and lateral positioning of the pisiform bone on pressure within the carpal tunnel. The wick catheter, a device used to transmit interstitial fluid pressure, was inserted into the carpal tunnels of the cadavers. Pressures in the tunnel with the pisiform in a resting position, medial position, and lateral position were measured via a water manometer. A significant increase in pressure was noted between the resting position and both the medial and lateral positions ( p = 0.001). No significant difference was found between the medial and lateral positions ( p > 0.05). Findings suggest that the use of movement of the pisiform as a conservative treatment in carpal tunnel syndrome is questionable. J Orthop Sports Phys Ther 1982;4(1):47-50.     

Does the perceived accuracy of urine drug testing impact clinical decision-making?

Abstract

Background: Urine drug testing techniques have different rates of false-positive and false-negative test results. However, clinicians may have highly varying perceptions of test accuracy and may compensate for perceived inaccuracy by incorporating other factors into their interpretation of observed test results. Thus, there is the potential for adverse consequences from decisions based on inaccurate test results or interpretation. Methods: We surveyed 466 members of the American Society of Addiction Medicine to examine clinicians’ perceptions of the accuracy of 2 types of urine drug tests, immunoassay (IA) and liquid chromatography–tandem mass spectrometry (LC-MS/MS), and the extent to which behavioral and demographic factors influence the interpretation of test results. Participants read 4 brief vignettes describing positive and negative test results in hypothetical patients who differed along several dimensions (gender, age, race/ethnicity, comorbid mental disorder, court-ordered versus voluntary status, treatment compliance). Outcome variables include likelihood of renewed drug use, likelihood of test error, whether to request additional testing, and whether to report the violation to a probation officer. Results: The strongest predictor of study outcomes was treatment compliance (consistent versus inconsistent attendance), as this was the only independent variable to generate effect sizes of medium strength. Significant effect sizes were also found for type of test used (IA versus LC-MS/MS), legal status (court-mandated versus voluntary), presence of a comorbid mental disorder, treatment history, and race, although effect sizes for these variables were small and less consistently observed. Conclusions: These results highlight the potential for error in clinician judgments about urine drug testing. Not only were participants likely to underestimate the accuracy of “confirmatory” LC-MS/MS testing, but vignettes suggested that a number of historical and demographic factors may influence interpretation of test results.     

Preoperative Glucose and Protein Metabolism: The Influence of Diabetes Mellitus Type 2 in Patients With Colorectal Tumors

Hypermetabolism, abnormal plasma amino acid profiles, increased gluconeogenesis, and changes in liver and muscle protein turnover are well-described undesirable effects in patients with cancer and diabetes mellitus type 2 (DM2) The aim of the present study was to analyze the specific impact and interaction of these 2 disease patterns on patients’ preoperative glucose and protein metabolism. Eight nondiabetic and 8 diabetic patients devoid of cachexia underwent a stable isotope infusion study on the day before surgery for colorectal cancer or adenoma with high-grade dysplasia. Protein and glucose kinetics were assessed in a fasted state by L-[1-¹³C]leucine and [6,6²H₂]glucose. In diabetic patients, glucose metabolism was found to be elevated as the plasma glucose level increased (P = 0.013) and endogenous rate of appearance of glucose tended to be higher compared to nondiabetic patients (P = 0.083). Protein metabolism was not affected by the metabolic state of the 2 groups. Resting energy expenditure was higher in diabetic patients (P = 0.028). Under postabsorptive conditions, noncachectic patients with DM2 suffering from colorectal tumors showed an elevated turnover in glucose metabolism whereas the nondiabetic counterparts failed to demonstrate any metabolic changes due solely to malignancy.     

Differential roles of migratory and resident DCs in T cell priming after mucosal or skin HSV-1 infection

Although mucosal surfaces represent the main portal of entry for pathogens, the mechanism of antigen presentation by dendritic cells (DCs) that patrol various mucosal tissues remains unclear. Instead, much effort has focused on the understanding of initiation of immune responses generated against antigens delivered by injection. We examined the contributions of migratory versus lymph node–resident DC populations in antigen presentation to CD4 and CD8 T cells after needle injection, epicutaneous infection, or vaginal mucosal herpes simplex virus (HSV) 1 infection. We show that upon needle injection, HSV-1 became lymph-borne and was rapidly presented by lymph node–resident DCs to CD4 and CD8 T cells. In contrast, after vaginal HSV-1 infection, antigens were largely presented by tissue-derived migrant DCs with delayed kinetics. In addition, migrant DCs made more frequent contact with HSV-specific T cells after vaginal infection compared with epicutaneous infection. Thus, both migrant and resident DCs play an important role in priming CD8 and CD4 T cell responses, and their relative importance depends on the mode of infection in vivo.     

Mitral valve replacement with the SORIN valve. Long-term follow-up of 1,161 patients

From 1 March 1977 through 31 December 1987, 1,252 patients underwent mitral valve replacement with a SORIN-Biomedica 60 degrees tilting-disc prosthesis at our institution. Hospital mortality was 7.3% (91 patients); prosthesis-related deaths, expressed as a percentage of hospital mortality, accounted for 12.1% of these early deaths. The 1,161 patients who survived hospitalization have been followed up for a total of 4,835 patient-years (range, 1 to 128 months; mean, 50.4 +/- 27.3 months). Forty-three (3.7%) of these patients were lost to follow-up. The late mortality was 6.3% (1.5% +/- 0.2% per patient-year), and the 10-year actuarial survival rate, excluding hospital mortality, was 89.1% +/- 1.6%. The 10-year actuarial (and linearized) rates of freedom from valve-related complications were as follows: embolism, 94.4% +/- 1.0% (0.93% +/- 0.1% per patient-year); thrombosis of the prosthesis, 99.8% +/- 0.1% (0.06% +/- 0.03% per patient-year; hemorrhage, 93.7% +/- 1.5% (0.95% +/- 0.1% per patient-year); prosthetic valve endocarditis, 99.3% +/- 0.3% (0.14% +/- 0.05% per patient-year); reoperation, 90.6% +/- 2.1% (1.1% +/- 0.2% per patient-year); and overall complications, 76.6% +/- 2.5% (2.9% +/- 0.2% per patient-year). No structural deterioration was noted. These data not only confirm our previous reports concerning the reliability and durability of the SORIN prosthesis but also reveal a significant reduction, over the long term, in the overall incidence of valve-related complications.