Zinc Administration Improves Gastric Alcohol Dehydrogenase Activity and First-Pass Metabolism of Ethanol in Alcohol-Fed Rats

The effects of zinc on first-pass metabolism (FPM) of ethanol and gastric and hepatic alcohol dehydrogenase (ADH) activities have been investigated in two groups of male Wistar rats fed a liquid ethanol diet with normal zinc content (7.6 mg/liter), or zinc supplemented (76 mg/liter), for 21 days, and in two pair-fed groups receiving the same diets without ethanol. Alcoholic rats with normal dietary zinc had lower FPM (1.64 ± 0.25 vs. 2.43 ± 0.20 mM ± hr, p < 0.05) and gastric ADH activity (184 ± 7 vs. 335 ± 41 μmol/min/mg protein, p < 0.01) than control rats. Zinc supplementation did not produce any change in FPM or in gastric ADH activity in control rats. By contrast, in alcoholic rats, the zinc supplement increased gastric ADH activity (247 ± 31 vs. 184 ± 7 μmol/min/mg protein, p < 0.05) and decreased the areas under the curve of blood ethanol concentrations after the intragastric administration of 0.25 g/kg of body weight of ethanol (0.78 ± 0.07 vs. 1.71 ± 0.24 mM ± hr, p < 0.05), thereby increasing the FPM. In conclusion, in alcohol-fed rats, the administration of zinc supplements restores gastric ADH activity and improves the FPM of ethanol. These effects may be one of the mechanisms in which zinc has a beneficial role in preventing the development of alcoholic hepatic lesions.     

Quadruple-2 protease inhibitors (PI)-therapy does not accelerate viral decay and suppression in PI-naive HIV-1 infected patients with severe immunosuppression and high viral load as compared with standard triple therapy

To analyse if a four-drug combination including two protease inhibitors (PIs) accelerates viral decay and suppression as compared with standard triple therapy in heavily immunosuppressed HIV-1 infected patients, an open label clinical trial was designed. PIs naive patients receiving their first highly active antiretroviral therapy were included if their CD4 cell count was lower than 200/mm3 and their HIV viral load (VL) >100,000 RNA copies/mL. Every patient received two analogues and was randomized in two groups receiving either one PI (saquinavir soft gel capsule) or two PIs (saquinavir + nelfinavir). Viral efficacy (VL <50), time to reach VL <50, viral clearance rate constant and plasmatic elimination half-life were determined. In all, 30 patients were enrolled. No viral variable was significatively improved by the four-drug combination in the short term. No clinical benefit should be expected with a four-drug (two PIs) regimen in patients with low CD4+ cell count and high VL.     

Comparison of effectiveness of sirolimus-eluting stents versus bare metal stents for percutaneous coronary intervention in patients at high risk for coronary restenosis or clinical adverse events

We evaluated the clinical effect of selective use of sirolimus-eluting stents (SESs) in real-world, high-risk patients. A total of 4,237 consecutive patients who underwent percutaneous coronary intervention (SES, n = 872, bare metal stents [BMSs], n = 3,365) was enrolled in a prospective regional survey. A prespecified high-risk subset of patients was selected on the basis of clinical and angiographic characteristics. A propensity score analysis was performed to compare patients who received SESs with those who received BMSs. Patients in the SES group more often had diabetes and more frequently had previous myocardial infarction or coronary revascularization, type C lesions, and multivessel procedures. Patients who presented with acute myocardial infarction were treated more often with BMSs. At 9 months, the use of SESs was associated with fewer major adverse cardiac events (death, myocardial infarction, or target lesion revascularization; hazard ratio 0.56, 95% confidence interval 0.37 to 0.85) and target lesion revascularizations (hazard ratio 0.43, 95% confidence interval 0.20 to 0.91). This decrease was more evident in a prespecified high-risk subgroup of patients (major adverse cardiac events, 8.0% SES vs 15.6% BMS, hazard ratio 0.45, 95% confidence interval 0.29 to 0.72). We conclude that selective SES use in real-world patients who have high-risk clinical and angiographic characteristics is associated with significant decreases in major adverse cardiac events and repeat revascularizations compared with BMS use.     

Flow cytometric analysis of intestinal intraepithelial lymphocytes in the diagnosis of refractory celiac sprue

The etiology of refractory celiac sprue (RCS) is unclear. In a high proportion of cases, the clonal nature of intestinal intraepithelial lymphocytes (IEL) can be demonstrated and a pathogenetic implication of intestinal IEL has been postulated. The prognosis of this subgroup of RCS is poor, with a high risk to develop an overt lymphoma and uncontrolled malabsorption despite steroid/immunosuppressive therapy. Cases with a relatively indolent clinical course, however, exist and their early diagnosis may be difficult. To gain insight into the pathogenic implication of intestinal IEL in refractory celiac sprue, we have performed an extensive phenotypic and functional characterization of clonal intestinal IEL in a patient with an indolent form of refractory celiac sprue, using multiparametric flow cytometry. The abnormal lymphocyte infiltrate lacked surface membrane expression of CD3/T-cell receptor (TCR) complexes (TCR(-), CD4(-), CD8(-), sCD3(-)), but contained intracellular CD3(epsilon) (CyCD3(+)) and surface CD103(+) and CD7(+). In particular, these cells showed a unique spontaneous ex-vivo cytokine secretion profile with an increased percentage of CD3(-) IEL containing TNF-alpha and IL-10, in the absence of IL-2, IL-4 and IFN-gamma. Altogether our results suggest that flow cytometry immunophenotyping of intestinal IEL, in cases suspected of celiac disease and their complicated forms, could be of great help in the correct diagnosis of RCS and the understanding of the immunopathogenic mechanisms of the disease and their clinical and/or therapeutical implications.     

Effective cryoablation of a lateral accessory pathway within the distal coronary sinus

Limited information is available on the efficacy of cryoablation in the coronary venous system in humans. A patient with a lateral accessory pathway was referred to our center after several unsuccessful endocardial and epicardial (within the coronary sinus) attempts using standard radiofrequency energy. Ablation was subsequently performed successfully by applying cryoenergy distally into the coronary sinus, using a temperature of -50 degrees C and a freezing application time of 45 s. There were no complications. Angiography of the left coronary circumflex artery and coronary venous system was performed at 12 months follow-up using cardiac multislice computed tomography, and no coronary stenosis or anatomic anomaly was found. Neither pre-excitation or any arrhythmia recurred during follow-up. This experience suggests that ablating in the distal coronary sinus can be safely performed using cryoenergy.     

Predictors and Clinical Impact of Prosthesis-Patient Mismatch After Self-Expandable TAVR in Small Annuli

ObjectivesThe aim of this study was to define predictors of prosthesis-patient mismatch (PPM) and its impact on mortality after transcatheter aortic valve replacement (TAVR) with self-expandable valves (SEVs) in patients with small annuli.BackgroundTAVR seems to reduce the risk for PPM compared with surgical aortic valve replacement, especially in patients with small aortic annuli. Nevertheless, predictors and impact of PPM in this population have not been clarified yet.MethodsPredictors of PPM and all-cause mortality were investigated using multivariable logistic regression analysis from the cohort of the TAVI-SMALL (International Multicenter Registry to Evaluate the Performance of Self-Expandable Valves in Small Aortic Annuli) registry, which included patients with severe aortic stenosis and small annuli (annular perimeter <72 mm or area <400 mm² on computed tomography) treated with transcatheter SEVs: 445 patients with (n = 129) and without (n = 316) PPM were enrolled.ResultsIntra-annular valves conferred increased risk for PPM (odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.16 to 4.81), while post-dilation (OR: 0.46; 95% CI: 0.25–0.84) and valve oversizing (OR: 0.53; 95% CI: 0.28–1.00) seemed to protect against PPM occurrence. At a median follow-up of 354 days, patients with severe PPM, but not those with moderate PPM, had a higher all-cause mortality rate compared with those without PPM (log-rank p = 0.008). Multivariable Cox regression confirmed severe PPM as an independent predictor of all-cause mortality (hazard ratio: 4.27; 95% CI: 1.34 to 13.6).ConclusionsAmong patients with aortic stenosis and small aortic annuli undergoing transcatheter SEV implantation, use of intra-annular valves yielded higher risk for PPM; conversely, post-dilation and valve oversizing protected against PPM occurrence. Severe PPM was independently associated with all-cause mortality.     

Cardiac damage in hypertensive patients with inverse white coat hypertension. Hospitalet study

BACKGROUND: Few studies have assessed the relationship between ambulatory blood pressure (BP) and cardiac damage in essential hypertensive patients with inverse white coat hypertension (IWCH). OBJECTIVES: To determine the frequency of IWCH in untreated grade 1-2 hypertension and to assess possible differences in cardiac damage among patients with IWCH, white coat hypertension (WCH) and the rest of patients with grade 1-2 hypertension. PATIENTS AND METHODS: Two hundred and eleven patients with grade 1-2 hypertension were sequentially included. A good quality 24-h ambulatory BP monitoring was obtained in 204 patients (age: 41 +/- 12 years, 56% males). IWCH was defined as a daytime systolic and/or diastolic BP higher than diagnostic office systolic and/or diastolic BP, respectively. WCH was defined as a daytime BP < 135/85 mmHg. A good quality echocardiogram was obtained in 174 patients. We considered left ventricular hypertrophy a left ventricular mass index (LVMI) > or = 125 g/m2. RESULTS: We found IWCH in 29 subjects (14%), and WCH in 68 (33%). Office BP in patients with IWCH was in an intermediate position between WCH and the rest of grade 1-2 hypertension patients. The IWCH patients showed 24-h, daytime and night-time BP higher than the other groups. Left ventricular mass was significantly greater in patients with IWCH than in the other grade 1-2 hypertension patients after adjusting for age, gender, body mass index, smoking and office BP (regression coefficient 28.14, 95%CI: 7.36-48.91). CONCLUSION: IWCH is independently associated with higher values of left ventricular mass in patients with grade 1-2 hypertension.     

Value of automated segmental motion analysis in the assessment of aortic stenosis severity

BACKGROUND AND AIMS OF THE STUDY: Left ventricular (LV) contraction is slowed in patients with aortic stenosis (AS). Although the possible role of LV systolic function abnormalities in the assessment of AS severity has been evaluated, current echocardiographic techniques cannot offer precise quantification of LV motion velocity. The study aim was to evaluate an automated segmental motion analysis (ASMA) system to assess AS severity. METHODS: Twenty-two patients with AS, sinus rhythm and preserved LV ejection fraction were studied prospectively. Patients underwent both conventional Doppler echocardiography to measure transaortic gradient and aortic valve area by the continuity equation, and ASMA of the interventricular septum. The ASMA line graph mode displays changes in area through the cardiac cycle. The RR interval and time from the R-wave to peak maximum area shortening were measured, and an ASMA index was calculated. RESULTS: A significant and strong inverse correlation was found between aortic valve area and ASMA index (r = -0.78; 95% CI -0.90 to -0.55; p <0.001). The area under the ROC curve in the diagnosis of severe AS (aortic valve area < or =0.8 cm2) was 0.97 (95% CI 0.90-1.0). Sensitivity, specificity, positive and negative predictive values and overall accuracy for an ASMA index >0.40 were 100, 91.7, 92.3, 100 and 95.8%, respectively. CONCLUSION: The ASMA system may be valuable in evaluating AS, as it offers a strong correlation with aortic valve area calculated by the continuity equation, and very high sensitivity and specificity in the diagnosis of severe AS.     

Selective immediate hypersensitivity to cefepime.

Cefepime is a fourth-generation cephalosporin with a broad antimicrobial spectrum and good activity against both gram-positive and gram-negative organisms. We present the case of a 61-year-old man who developed an immediate urticarial reaction after receiving a single dose of cefepime. Skin tests were positive to cefepime and negative to the other beta-lactam antibiotics. Controlled administration of amoxicillin-clavulanic acid and ceftazidime was well tolerated by the patient. To the best of our knowledge, this is the first report of selective hypersensitivity to cefepime demonstrated by skin and challenge tests. Complete allergological studies, including challenge tests with other beta-lactam antibiotics that produce a negative result in skin tests, should be considered in these patients.