Effect of canrenone on left ventricular mechanics in patients with mild systolic heart failure and metabolic syndrome: the AREA-in-CHF study.

BACKGROUND AND AIM: We analyzed the effect of the mineralocorticoid receptor antagonist canrenone on LV mechanics in patients with or without metabolic syndrome (MetS) and compensated (Class II NYHA) heart failure (HF) with reduced ejection fraction (EF≤45%) on optimal therapy (including ACE-i or ARB, and ß-blockers). METHODS AND RESULTS: From a randomized, double-blind placebo-controlled trial (AREA-in-CHF), patients with (73 on canrenone [Can] and 77 on placebo [Pla]), based on modified ATPIII definition (BMI≥30kg/m(2) instead of waist girth) or without MetS (146 by arm). In addition to traditional echocardiographic parameters, we also evaluated myocardial mechano-energetic efficiency (MME) based on a previously reported method. At baseline, Can and Pla did not differ in age, BMI, blood pressure (BP), metabolic profile, BNP, and PIIINP. Compared with MetS-Pla, and controlling for age, sex and diabetes, at the final control MetS-Can exhibited increased MME, preserved E/A ratio, and decreased atrial dimensions (0.04

Plasma biomarker profiling in the detection of growth promoter use in calves.

The detection of illicit growth promoter use during meat production within the European Union is reliant on residue testing which is a limiting factor on the number of animals which can be tested and consequently compromises the efficacy of testing procedures. The present study examined a novel detection strategy based on the profiling of plasma component concentrations in response to growth promoter administrations. Calves subjected to nortestosterone decanoate, 17beta-oestradiol benzoate and dexamethasone were found to have altered urea, aminoterminal propeptide of type III procollagen and sex hormone binding globulin profiles in response to treatments. These findings demonstrate the potential of using the identification of perturbed profiles within a panel of biomarkers which cover a spectrum of biological activity to reveal growth promoter abuse.

Influence of 17beta-oestradiol, nortestosterone and dexamethasone on the adaptive immune response in veal calves.

In veal calf production androgens, estrogens and glucocorticoids are used to stimulate growth. However, sexhormones and glucocorticoids also influence the function of the immune system. From studies in humans and mice, androgens are known as immunosuppressive, while estrogens stimulate the production of antibodies and glucocorticoids also enhance the T-helper 2 response. To investigate whether the adaptive immune system is influenced by hormone administration, calves were treated with a hormone cocktail containing androgens, estrogens and glucocorticoids and vaccinated against Mycobacterium avium spp. paratuberculosis. The activity of the adaptive immune system was measured by using an antigen specific elispot assay (ES), lymphocyte stimulation test (LST) and an enzyme-linked immuno sorbent assay (ELISA). The results showed that the hormone treatment did not lead to significant differences in the function of the adaptive immune system between the hormone treated and the not hormone treated group while growth was stimulated in the hormone treated group.

[Gastrointestinal stromal tumors: five case reports and review of the literature]. / Tumori stromali gastrointestinali: cinque casi clinici e revisione della letteratura.

Being a rare entity, GISTs represents the most common subset of mesenchymal tumours that arise from the digestive tract. Their immunohistochemical and histopathologic features distinguish them from other gastrointestinal mesenchymal neoplasms. These tumours have been the matter of considerable debate in the literature regarding their histogenesis, criteria for diagnosis, prognostic features and treatment. GISTs express Kit protein that not only is a marker for diagnosis but has also permitted to identify a specific medical treatment. The exceptional interest aroused in the literature leads us to make a review about this subject reporting five cases treated in the last 2 years.

[Abdominal Wells rectopexy with patch micromesh PTFE (Goretex)]. / Rettopessi per via addominale secondo Wells con patch mycromesh PTFE (Goretex).

The aim of this study is to discuss the surgical treatment of rectal prolapse. The surgical therapy offers many different options. Beginning from 1970 the anterior rectopexy has been considered a technique with good results, also in the elderly patient, when the general conditions allow it. Author's experience concerns the surgical treatment of 4 patients (2 males and 2 females) with complete symptomatic rectal prolapse, treated with anterior access laparotomy with the technique of Wells, leaving 1/3 of anterior rectal wall free from suture. Patients had a regular postoperative course; only in 1 case there was a delay of the canalization. At 1 year after the rectopexy the results are satisfactory, with absence of recurrence and troubles of the evacuation. The high percentage of successes of the anterior rectopexy is founded on: 1) the mobilization of the rectum, complete or only posterior; the rectal vessels must be respected, but there isn't consent on the opportunity of the section of the lateral ligaments. It may cause a denervation of the anorectum with an alteration of the fecal evacuation; and 2) the process of cicatritation by the employment of mesh and PTFE material that fix the rectum to the sacred maintains it as in the desired position.

[Indications and potential benefits of implantable automatic defibrillator endowed with biventricular pacing]. / Indicazioni e potenziali benefici dell'impianto di un defibrillatore automatico dotato di stimolazione biventricolare.

Heart failure (HF) is associated with a poor long-term survival due to progressive refractory heart dysfunction and sudden cardiac death. Cardiac resynchronization through three-chambered atriobiventricular pacing has been introduced to treat patients with drug-refractory HF and unsynchronized ventricular activation due to left bundle branch block (LBBB). The technique is aimed to overcome inter- and intraventricular conduction delays leading to a ventricular dyssynchrony, characterized by paradoxical septal wall motion, presystolic mitral regurgitation, and reduction in diastolic filling times. Acute studies demonstrated that biventricular pacing (and maybe left ventricular pacing alone) may improve both systolic and diastolic function. First studies on chronically paced patients consistently showed that the QRS shortening was associated with a significant improvement in symptoms, NYHA functional class, left ventricular ejection fraction (LVEF), exercise tolerance, and quality of life. As far as sudden cardiac death prevention in HF is concerned, the implantable cardioverter-defibrillator (ICD) has been demonstrated to be the most effective therapy in patients with prior cardiac arrest due to ventricular fibrillation or poorly tolerated ventricular tachycardia. Low LVEF, unsustained ventricular tachycardia and inducibility at electrophysiological study also may identify high risk patients requiring ICD implantation. Further studies are needed in evaluating the impact of cardiac resynchronization on hard endpoints, such as survival and long-term clinical outcome, as well as in upgrading risk stratification criteria to be used in candidate selection to ICD implantation. However, HF patients with prior cardiac arrest and LBBB should be considered as the optimal candidates to the "ICD implantation combined with biventricular pacing". Conversely, HF patients with LBBB, but without cardiac arrest, could be considered for "biventricular pacing combined with an ICD". The selection criteria for this novel non-pharmacological therapy still have to be defined. The authors emphasize the main indication to ICD implantation combined with biventricular pacing, i.e. HF patients with prior cardiac arrest and LBBB; controversially, while they discuss the other indications to biventricular pacing combined with an ICD.

[Revisiting the clinical examination of the patient with heart failure in the light of data obtained with Doppler echocardiography]. / Rivisitazione dell'esame clinico del paziente con scompenso cardiaco alla luce delle informazioni ottenute con l'ecocardiografia Doppler.

Echocardiography plays a central role in the diagnosis and assessment of heart failure as it allows us to discover missed valvular or congenital heart disease and distinguishes the different pathophysiological forms of cardiomyopathies. Echocardiographic examination shows the presence, the severity and the mechanism of mitral regurgitation. It identifies the pathophysiology of heart failure differentiating systolic from diastolic dysfunction. The different patterns of Doppler transmitral flow curves are correlated with left ventricular filling pressures and with functional capacity of the patient. The assessment of functional impairment of the patient is based not only on the measurement of left ventricular volumes and ejection fraction, but rather on an integrated analysis of several clinical and echocardiographic features including right ventricular volumes and ejection fraction. Prognostic information can be obtained from the echocardiographic examination: a short (< 125 ms) deceleration time of early filling in transmitral flow curve and its persistence despite optimized medical treatment identify patients at very high risk of subsequent death and/or hospitalization. Similarly, pulmonary hypertension measured by Doppler echocardiography is a predictor of poor outcome. Since Doppler echocardiographic assessment of hemodynamic variables in patients with advanced heart failure is accurate and reproducible, this non-invasive methodology may assist with monitoring and optimizing medical therapy in such patients. The symptoms of heart failure as well as the clinical and radiographic findings are neither sensitive nor highly specific to diagnosis. Furthermore clinical findings are not reliable for estimating hemodynamics of the individual patient. At present, the echocardiogram is the most useful and widespread tool used in heart failure patients, with regard to diagnosis, assessment and hemodynamic characterization. Due to the complex nature of the heart failure syndrome, for an exhaustive assessment of the patient, echocardiographic data should be integrated with clinical and laboratory findings.

Comparison of one-year outcome in women versus men with chronic congestive heart failure.

Using information from the Italian Network on Congestive Heart Failure, we examined whether clinical epidemiologic characteristics, drug prescription patterns, and outcome of patients with congestive heart failure differed according to sex and whether gender was an independent risk factor for mortality and hospital admissions.

[Outpatient management program of patients with chronic heart failure]. / Efficacia di un programma integrato di gestione ambulatoriale del paziente con scompenso cardiaco cronico.

Hospitalization of patients with heart failure is often caused by poor adherence to drug therapy, by suboptimal utilization of ACE inhibitors and beta-blockers, and by the lack of systematic monitoring of patients after discharge. The aim of the study is to verify the impact of an outpatient management program on the hospitalization rate and functional status of patients with chronic heart failure. Over a five-year period, 435 patients entered our outpatient management program, which includes adjustment in medical therapy, patient education and visits timed according to the patient's status. Fifty-six percent of the patients were in New York Heart functional class I-II; 74% were male; mean age was 62 +/- 11 years. Heart failure was due to coronary heart disease in 42%, dilated cardiomyopathy in 35%, hypertensive heart disease in 13%, other etiologies in 10%. The following changes in medical therapy were made compared to the period before referral: ACE inhibitors in 88% of the patients vs 70% (p < 0.05), mean dose of enalapril and captopril respectively 18 +/- 6 mg vs 11 +/- 4 mg (p < 0.05) and 89 +/- 28 mg vs 61 +/- 34 mg (p < 0.05); digoxin in 71 vs 70% (NS); furosemide in 90 vs 87%; beta-blockers in 16 vs 6% (p < 0.05); amiodarone in 24 vs 16% (p < 0.05); oral anticoagulants in 22 vs 12% (p < 0.05); calcium channel blockers in 10 vs 16% (p < 0.05). During the follow-up period (35 +/- 11 months), there were 111 hospital admissions compared to 518 during the year before recruitment (p < 0.05). Seventy-two patients died (65 for cardiac causes) and four patients underwent cardiac transplantation. Functional status improved (301 patients in I-II functional class and 56 in III-IV after referral compared to 225 and 132 before referral, respectively). Our results were obtained through adjustment in pharmacological therapy, intensive patient education and therapeutic continuity made possible by our outpatient heart-failure clinic organization. It is likely that the increase in costs due to therapeutic adjustment and to the increase in the number of visits is counterbalanced by the reduced rate of hospital admissions.

Can a physician sue a pharmaceutical manufacturer when a drug harms a patient?

Patients who suffer harm from a prescription drug often sue both the prescribing physician and the drug manufacturer, seeking recovery for failure to warn of the drug's potential harm. In many of these cases, the drug manufacturer is relieved of liability under the "learned intermediary" doctrine. If, however, a drug manufacturer misrepresents information or fails to adequately warn a physician about a drug's potential dangers, it may be possible for a physician to maintain a legal cause of action against the manufacturer. This article discusses the legal basis for such a lawsuit and describes two legal cases involving physicians who sued pharmaceutical manufacturers based on inadequate warnings regarding their products.

The overregulation of pharmacy practice.

Many professions are highly regulated, yet few are regulated to the degree pharmacy is. Not only are there large numbers of regulations, but the regulations are so detailed they dictate precisely how pharmacists are to perform both dispensing and clinical services. As a result, pharmacists end up trying to meet the requirements of the regulations rather than exercising professional judgment and providing true pharmaceutical care. Many of the regulations are unnecessary intrusions into the practice of pharmacy and tend to diminish its professionalism.

Advertising, computers, and pharmacy liability. A Michigan court's decision has ramifications for pharmaceutical care.

Arbor Drugs, Inc., advertised that its computer could detect dangerous drug interactions. A pharmacist failed to warn a patient accordingly and the patient suffered a stroke as a result of an interaction between tranylcypromine and a decongestant. The Michigan Court of Appeals held that this failure to warn was actionable under the theories of negligence and fraud as well as under the Michigan Consumer Protection Act. The court's basic message is that pharmacies may be held legally responsible for preventing harm when they represent themselves as being capable of doing so.

[Use of prostheses in the treatment of large laparoceles]. / L'impiego di protesi nel trattamento dei grossi laparoceli.

The Authors report a series of 18 cases of large laparoceles treated with the use of Dacron prosthesis which was installed according to Rives' technique. They observed 0% of recurrence, 1 case (5%) of mortality for pulmonary embolism, 3 cases (16%) of pulmonary embolism and 1 case (5%) of surgical wound infection.

[Heart failure and arrhythmias: the role of ACE inhibitors]. / Insufficienza cardiaca e aritmie: ruolo degli ACE-inibitori.

Mortality of patients with congestive heart failure (CHF) is high; > 40% of deaths are sudden, most often due to sustained ventricular arrhythmias (VA). In such patients frequent ventricular premature beats (VPB) and non sustained ventricular tachycardia (NSVT) are common. The relationship between VA and an increased risk for sudden death has been reported for patients with recent myocardial infarction. Although such relationship is uncertain for patients affected by dilated cardiomyopathy, many authors have reported an association between the frequency and the complexity of VA and the risk of sudden death. Many factors are responsible for VA in CHF: structural abnormalities, electrolyte imbalance, hemodynamic impairment, pharmacologic therapy and abnormal activation of neurohormonal system. ACE inhibitors have reduced VA in several experimental models, suggesting that these drugs decrease heart vulnerability to arrhythmogenic stimuli such as reperfusion and electrical stimulation. Many clinical trials have demonstrated that ACE inhibitors decreased VPB frequency and the prevalence of NSVT. Although ACE inhibitors decrease VA frequency, the reduction in cardiac mortality observed in CONSENSUS31 and in SOLVD32 trials was due only to a decrease in the progression of CHF. Recently the results of V-HeFT II33 trial have shown that the reduction in VA prevalence observed in patients treated with enalapril paralleled a reduction of sudden death. Factors that may contribute to the reduction in VA by ACE inhibitors include: increase in serum potassium; unloading of the ventricle; decrease in myocardial oxygen consumption. However, the most important factor seems related to their interference on neurohormonal system whose abnormal activation is the main mechanism of CHF progression.