Haemodynamic effects of glyceryl trinitrate during continuous 24 hour infusion in patients with heart failure.

OBJECTIVE--To investigate whether the susceptibility to tolerance to glyceryl trinitrate is similar in different vascular beds in patients with chronic heart failure. PATIENTS--Twenty patients with heart failure underwent a continuous infusion of glyceryl trinitrate over 24 hours followed by administration of N-acetylcysteine (5 g intravenously) in a bolus. MAIN OUTCOME MEASURES--Haemodynamic measurements under control conditions, at peak titration of glyceryl trinitrate at 24 hours, and after N-acetylcysteine; plasma renin activity and packed cell volume. RESULTS--After 24 hours of infusion the acute reduction in right atrial pressure had largely waned, while pulmonary vascular resistance remained improved and systemic resistance, which was not reduced at peak titration, significantly decreased with respect to control conditions. The effects of N-acetylcysteine and hormonal responses were different in patients who did and did not develop tolerance to glyceryl trinitrate. CONCLUSIONS--The haemodynamic profile of glyceryl trinitrate changed substantially during the study from a predominantly venodilator action at peak titration to a predominantly arteriolar dilatation after 24 hours of infusion. The different effects of N-acetylcysteine and the different hormonal responses confirm the multifactorial pathogenesis of tolerance to glyceryl trinitrate.     

Clinical and angiographic findings in angina at rest

The purpose of this study was to delineate the clinical, ECG, and angiographic features of a large series of consecutive patients with angina at rest. Transient ST segment elevation during pain was observed in 219 patients (group I), while 220 patients showed ST segment depression during pain (group II). Group II patients were found to have higher incidence of hypertension (p less than 0.001), prior myocardial infarction (p less than 0.0005), history of exertional angina (p less than 0.0005), and a progressive aggravation of symptoms before hospitalization (p less than 0.0005), while group I patients had a prevalence of recent onset angina (p less than 0.05) and more frequently developed severe ventricular arrhythmias during pain (p less than 0.0005). Furthermore, a larger number of patients showing ST segment depression during chest pain had multivessel disease (p less than 0.0005), left main involvement (p less than 0.005), and lower values of left ventricular ejection fraction (p less than 0.001) than patients with ST segment elevation during pain. Survival curves of medically treated patients showed a significantly better long-term prognosis in patients of group I (p less than 0.01). The direction of the ST segment shift during anginal attacks at rest may therefore allow a classification of patients included into the broad spectrum of unstable angina. This distinction should be taken into consideration in studies aimed at evaluating long-term prognosis or the results of medical and surgical therapy.     

Comparison of results of echo-dobutamine and ECG-dobutamine tests in the diagnosis of coronary disease]

The aim of the study was to compare the results of 2D-Echocardiographic (ECHO) vs 12-lead Electrocardiographic (ECG) monitoring during Dobutamine (DOB) infusion performed as a stress test in patients referred for the evaluation of chest pain of suspected ischemic origin. Fourty-seven consecutive patients, 40 m and 7 f, mean age 52 +/- 9 years, were studied after interruption of any antianginal therapy. DOB was infused in 5-minute stages with incremental doses of 5 mcg/kg/min up to a maximal dose of 40 mcg/kg/min. 2D-ECHO monitoring could not be performed in 3 out of 47 patients because of a poor acoustic window. Thus, the overall feasibility was 94% for 2D-ECHO DOB test vs 100% for ECG DOB test (p = ns). The ECG and 2D-ECHO findings were compared in the remaining 44 patients. Criteria for positivity were: transient regional dyssynergy absent or of lesser degree in the baseline examination for 2D-ECHO; ST-segment shift > 0.1 mV from baseline for ECG. The test was stopped when a regional wall motion abnormality developed even in the absence of significant ECG changes. Angiographically assessed coronary artery disease (CAD) was considered significant when a > 50% reduction of the luminal diameter in at least 1 major coronary vessel occurred. There were 10/44 patients with no significant CAD and 34/44 patients with CAD; 16 had single, 18 double or triple and/or left main vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Muscle magnetic resonance imaging abnormalities in X‐linked myopathy with excessive autophagy

Introduction: X‐linked myopathy with excessive autophagy (XMEA) is an X‐linked recessive myopathy due to recently reported mutations in the VMA21 gene. Methods: Four men from 2 separate families were studied. The clinical presentation, genetic data, muscle biopsy, and muscle MRI were analyzed. Results: A known VMA21 mutation, c.163+4A>G, and a new mutation, c.163+3A>G, respectively, were found in the 2 families. The clinical course was characterized by onset in childhood and progressive muscle weakness with a limb‐girdle pattern. Muscle biopsy revealed a mild myopathy with an increased number of giant autophagic vacuoles. Whole‐body muscle MRI showed that pelvic girdle and proximal thighs were the most and earliest affected territories, with sparing of rectus femoris muscles. Muscle changes essentially consisted of degenerative fatty replacement. Conclusions: This study highlights a distinctive MRI pattern of muscle involvement, which can be helpful for diagnosis of XMEA, even before muscle biopsy or genetic analysis. Muscle Nerve 52: 673–680, 2015     

A new MPZ mutation associated with a mild CMT1 phenotype presenting with recurrent nerve compression

P0 is a transmembrane protein of the immunoglobulin superfamily that plays a role in myelin structure and function. Myelin protein zero gene (MPZ) mutations usually cause a demyelinating variant of Charcot-Marie-Tooth disease type 1B (CMT1B), but there is a wide spectrum of phenotypic manifestation of these mutations. We describe three patients from one family and one separate patient who presented with a demyelinating neuropathy. Some had recurrent lesions at compression sites mimicking hereditary neuropathy with liability to pressure palsies (HNPP). A heterozygous nonsense mutation (Tyr145Stop) corresponding to a T-to-A transition at nucleotide position 435 in exon 3 of the MPZ gene was identified in all patients. This mutation leads to an extracellular truncated protein, which may explain the mild phenotype. Therefore, such MPZ gene mutations should be searched for in cases of demyelinating neuropathy with acute nerve compression as well as in cases of the HNPP phenotype associated with normal the PMP22 gene.     

Impact of lamivudine on the risk of liver-related death in 2,041 HBsAg- and HIV-positive individuals: results from an inter-cohort analysis

BACKGROUND: The impact of lamivudine (3TC) as part of combination antiretroviral therapy (cART) on the risk of liver-related death (LRD) in HIV/hepatitis B virus (HBV)-coinfected patients has not been extensively studied. METHODS: We performed an analysis involving HIV/HBV-coinfected patients in 13 cohorts who initiated cART. The end-point was LRD--that is, death with concomitant decompensated liver disease (DLD) or hepatocellular carcinoma--as the main cause. Incidence rates of LRD after initiation of cART were expressed as number of events per 100 person-years of follow-up (PYFU). A Poisson regression model adjusted for cohort, gender, mode of HIV transmission, CD4+ T-cell count at cART initiation, liver disease pre-cART, duration of 3TC before cART, and hepatitis C virus was used to assess the association between use of 3TC and risk of LRD. Results: We analysed 2,041 patients. Follow-up after starting cART was 7,648 PYFU (5,569 spent on 3TC-containing regimens) with a median per person of 48 months (range: 2-91). Of the total, 217 subjects died; 57 deaths were liver-related resulting in a rate of 7.5 per 1,000 PYFU [95% confidence intervals (CI): 5.6-9.7]. The relative risk of LRD per extra year of 3TC use was 0.73 (95% CI: 0.59-0.90, P = 0.004). CONCLUSION: The use of 3TC was associated with a reduced risk of LRD over 4 years of follow-up. This study supports the current view that the use of 3TC as part of cART should be considered in patients who are tested positive for HBsAg.     

Italian Consensus Statement on Management of HIV-Infected Individuals with Advanced Disease Na?ve to Antiretroviral Therapy

Abstract Background:   Individuals with advanced HIV infection na?ve to antiretroviral therapy represent a special population of patients frequently encountered in clinical practice. They are at high risk of disease progression and death, and their viroimmunologic response following the initiation of highly active antiretroviral therapy may be more incomplete or slower than that of other patients. Infection management in such patients can also be complicated by underlying conditions, comorbidities, and the need for concomitant medications. Aim:   To provide practical guidelines to those clinicians providing care to HIV-infected patients in terms of diagnostic assessment, monitoring, and treatment. Conclusions:   The principals of antiretroviral treatment in asymptomatic na?ve patients with advanced HIV infection are the same as those applicable to the general population with asymptomatic HIV infection. Na?ve patients with advanced HIV infection and a history of AIDS-defining illnesses urgently need antiretroviral treatment, with the choice of antiretroviral regimen and timetable based on such factors as concomitant treatment and prophylaxis, drug interactions, and potential concomitant drug toxicity. Finally, an adequate counseling program – both before and after HIV-testing – that includes aspects other than treatment adherence monitoring is a crucial step in disease management.     

In situ immunophenotype of the inflammatory infiltrate in eosinophilic fasciitis

OBJECTIVE: Eosinophilic fasciitis (EF) is histologically characterized by a fibrous and inflammatory thickening of subcutaneous septal-fascial-perimysial collagenous scaffold. This study aims to define the immunophenotype of inflammatory cells of fascia and muscle underlying the in situ immune response in EF. METHODS: In 11 cases of EF, we determined the phenotype of inflammatory cells, expression of MHC class I and class II antigens, and C5b9 membranolytic attack complex (MAC) deposits by immunohistochemistry analysis of fascia tissue. Muscle biopsies from 9 patients with active dermatomyositis and 5 with active polymyositis were used as controls. Results. In all patients but one, the inflammatory infiltrate was mainly composed of macrophages associated with CD8+ T lymphocytes (CD4/CD8 ratio < 1) and few eosinophils. Cytotoxic properties were found in 14% of CD8+ T lymphocytes, as shown by granzyme B expression. MHC Class I antigens were overexpressed (5/7) by muscle fibers, with a paratrabecular reinforcement in 4 cases. MHC class II antigens were not expressed by muscle fibers except in one case. C5b9 MAC deposits were not detected. CONCLUSION: Our in situ characterization of inflammatory infiltrate demonstrates the predominancy of macrophages and CD8+ T lymphocytes. Some of these CD8+ lymphocytes contain granzyme B, thus suggesting a cytotoxic cellular immune response in EF, which could be triggered by infectious or environmental agents.