Drug use and validity of substance use self-reports in veterans seeking help for posttraumatic stress disorder.

The present study assessed drug use and the validity of self–reports of substance use among help–seeking veterans referred to a specialty clinic for the assessment of posttraumatic stress disorder (PTSD). Patients (n?=?341) were asked to provide a urine sample for use in drug screening as part of an evaluation of PTSD. Self–reports of substance use were compared with same–day supervised urine samples for 317 patients who volunteered to participate in a drug screening. Results suggested that self–reports were generally quite valid. Only 8% of the cases involved patients not reporting substance use detected by urine screens. A total of 42% of the participants were identified as using drugs of abuse (excluding alcohol) through self–report and urine drug screens. Among participants using drugs, PTSD diagnosis was significantly associated with greater marijuana and depressant use as compared with stimulant (cocaine and amphetamines) use. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Synthesis, biochemical evaluation, and classical and three-dimensional quantitative structure-activity relationship studies of 7-substituted-1,2,3,4-tetrahydroisoquinolines and their relative affinities toward phenylethanolamine N-methyltransferase and the alpha2-adrenoceptor

7-Substituted-1,2,3,4-tetrahydroisoquinolines (7-substituted-THIQs) are potent inhibitors of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28), the enzyme involved in the biosynthesis of epinephrine. Unfortunately, most of these compounds also exhibit strong affinity for the alpha2-adrenoceptor. To design a selective (PNMT vs alpha2-adrenoceptor affinity) inhibitor of PNMT, the steric and electrostatic factors responsible for PNMT inhibitory activity and alpha2-adrenoceptor affinity were investigated by evaluating a number of 7-substituted-THIQs. A classical quantitative structure-activity relationship (QSAR) study resulted in a three-parameter equation for PNMT (PNMT pKi = 0.599pi - 0.0725MR + 1. 55sigmam + 5.80; n = 27, r = 0.885, s = 0.573) and a three-parameter equation for the alpha2-adrenoceptor (alpha2 pKi = 0.599pi - 0. 0542MR - 0.951sigmam + 6.45; n = 27, r = 0.917, s = 0.397). These equations indicated that steric effects and lipophilicity play a similar role at either active site but that electronic effects play opposite roles at either active site. Two binding orientations for the THIQs were postulated such that lipophilic and hydrophilic 7-substituents would not occupy the same region of space at either binding site. Using these two binding orientations, based on the lipophilicity of the 7-substituent, comparative molecular field analysis (CoMFA) models were developed that showed that the steric and electrostatic interactions at both sites were similar to those previously elaborated in the QSAR analyses. Both the QSAR and the CoMFA analyses showed that the steric interactions are similar at the PNMT active site and at the alpha2-adrenoceptor and that the electrostatic interactions were different at the two sites. This difference in electrostatic interactions might be responsible for the selectivity of THIQs bearing a nonlipophilic electron-withdrawing group at the 7-position. These QSAR and CoMFA results will be useful in the design of potent and selective (PNMT vs alpha2-adrenoceptor affinity) inhibitors of PNMT.     

The role of CD8 and CD4 T cells in intestinal allograft rejection: a comparison of monoclonal antibody-treated and knockout mice

Studies were performed to determine the effects of PTH and related compounds on phosphatidylcholine (PC) hydrolysis in UMR-106 cells and the pathway by which the PTH effects occurred. The responses were compared with those of phorbol 12,13-dibutyrate (PDBu). Both bovine PTH-(1-34) [bPTH-(1-34)] and PDBu stimulated PC hydrolysis within 10 min. Significant effects were elicited by concentrations of 0.3-1 nM bPTH-(1-34) and 5 nM PDBu. Dose-dependent increases were seen at higher concentrations of both compounds, however, the response to bPTH-(1-34) was reduced at 30 nM. Bovine or human PTH-(1-34) and human PTH-related peptide-(1-34) [hPTHrP-(1-34)] were equipotent in their effects, whereas bovine [Nle(8,18)Tyr34]PTH-(3-34) amide [bPTH-(3-34)] and hPTH-(1-31) amide [hPTH-(1-31)] were less potent than bPTH-(1-34). bPTH-(3-34) did not antagonize the effects of bPTH-(1-34). Down-regulation of protein kinase C isozymes by 24-h treatment with PDBu completely prevented the stimulatory effect of PDBu on PC hydrolysis, but did not significantly affect the stimulatory effect of bPTH-(1-34). Both bPTH-(1-34) and PDBu stimulated transphosphatidylation of PC, indicating a phospholipase D-stimulated mechanism. The results suggest that in the UMR-106 cell line PTH can stimulate activation of PLD by a mechanism other than through protein kinase C.     

Viability after myocardial infarction: can it be assessed within five minutes by low-dose dynamic iodine-123-iodophenylpentadecanoic acid imaging with a multicrystal gamma camera?

Although positron emission tomography (PET) assesses myocardial viability (V) accurately, a rapid, inexpensive substitute is needed. Therefore, the authors developed a low-dose (1 mCi) Iodine-123-Iodophenylpentadecanoic Acid (IPPA) myocardial viability scan requiring analysis of only the first three minutes of data acquired at rest with a standard multicrystal gamma camera. Twenty-one patients > 2 weeks after myocardial infarction (MI) (24 MIs, 10 anterior, 14 inferoposterior, 21 akinetic or dyskinetic) had cardiac catheterization and resting IPPA imaging. V was determined by either transmural myocardial biopsy during coronary bypass surgery (12 patients, 14 MIs) or reinjection tomographic thallium scan (9 patients, 10 MIs), and 50% of MIs were viable. The IPPA variables analyzed were: time to initial left ventricular (LV) uptake in the region of interest (ROI), the ratio of three-minute uptake in the ROI to three-minute LV uptake, three-minute clearing (counts/pixel) in the ROI (decrease in IPPA after initial uptake), and three-minute accumulation (increase in IPPA after initial uptake) in the ROI. Rules for detecting V were generated and applied to 10 healthy volunteers to determine normalcy. While three-minute uptake in nonviable MIs was only 67% of volunteers (P < 0.0001) and 75% of viable MIs, uptake alone identified only 50% of viable MIs and 75% of nonviable MIs. IPPA clearing, however, was > or = 13.5 counts/pixel in 10/12 (83%) of viable MIs, and IPPA accumulation > or = 6.75 counts/pixel identified one more viable MI, for a sensitivity for V of 11/12 (92%), with a specificity of 11/12 (92%), and a 100% normalcy rate. The authors conclude low-dose IPPA (five-minute acquisition with analysis of the first three minutes of data) has potential for providing rapid, inexpensive V data after MI. Since newer multicrystal cameras are mobile, IPPA scans can be done in emergency rooms or coronary care units generating information that might be useful in decisions regarding thrombolysis, angioplasty, or bypass surgery.     

Induction of proinflammatory cytokine and antioxidant enzyme gene expression following brief myocardial ischaemia

PURPOSE: In a recent study we found an increased resistive index immediately after extracorporeal shock wave lithotripsy (ESWL) in patients older than 60 years, which suggests renovascular disturbance. The present 26-month followup study was undertaken to investigate the relevance of elevated resistive index levels and the incidence of new onset hypertension. MATERIALS AND METHODS: Of the initial 76 patients 57, including 20 of the 23 at risk patients 60 or greater years, group 3), were followed for more than 26 +/- 6 months after ESWL. Followup included 2 resistive index measurements by Doppler ultrasound of the treated and the contralateral kidney, at least 2 blood pressure measurements 1 week apart and excretory urography as well as determination of plasma renin activity in 9 patients. RESULTS: With 1 exception, elevated resistive index levels and hypertension were observed exclusively in patients older than 60 years. In these patients the resistive index ranged between 0.65 and 0.86 (mean plus or minus standard deviation 0.74 +/- 0.05, normal less than 0.7). This increase in resistive index was statistically significant (p < 0.0001). Compared to the levels obtained immediately after ESWL, the resistive index continued to increase in all 9 patients older than 60 years who had hypertension (45%), whereas in the normotensive patients the resistive index was either stable or decreased. There was a strong positive correlation (0.903) between pathological resistive index levels and blood pressure. CONCLUSIONS: Patients older than 60 years are at risk for disturbances of renal perfusion as assessed by the resistive index, and 45% of these patients have new onset hypertension within 26 months of treatment.     

Carcinoid of the gallbladder. A report of a clinical case treated by video laparoscopic cholecystectomy

The authors report a clinical case of the gallbladder carcinoid tumour treated with laparoscopic cholecystectomy. After a short analysis of the classification, the malignant potentiality and the symptoms of gallbladder carcinoids, they conclude that it is possible to treat carcinoids with laparoscopic cholecystectomy, but only in some selected cases, that is to say in the absence of factors indicative of local invasion and that in the other cases it is preferable the classic surgical treatment of laparotomic resection.