Correction to: α-Phellandrene attenuates tissular damage, oxidative stress, and TNF-α levels on acute model ifosfamide-induced hemorrhagic cystitis in mice.

The published online version contains figure in poor quality.

α-Phellandrene attenuates tissular damage, oxidative stress, and TNF-α levels on acute model ifosfamide-induced hemorrhagic cystitis in mice.

Hemorrhagic cystitis (HC) is the major dose-limiting adverse effect of the clinical use ifosfamide (IFOS). The incidence of this side effect can be as high as 75%. Mesna has been used to reduce the risk of HC, although 5% of patients who get IFOS treatment may still suffer from HC. In previous studies, our group demonstrated that α-phellandrene (α-PHE) possesses anti-inflammatory activity, which opens the door for its study in the attenuation of HC. The objective of this study was to investigate the potential uroprotective effect of the α-PHE in the mouse model of IFOS-induced HC. In order to analyze the reduction of the urothelial damage, the bladder wet weight, hemoglobin content, and the Evans blue dye extravasation from the bladder matrix were evaluated. To investigate the involvement of neutrophil migration and lipid peroxidation and involvement of enzymatic and endogenous non-enzymatic antioxidants, the tissue markers myeloperoxidase (MPO), malondialdehyde, nitrite/nitrate (NOx), superoxide dismutase (SOD), and reduced glutathione (GSH) were evaluated. TNF-α and IL-1ß were measured by ELISA immunoassay technique. The results show that pretreatment with α-PHE significantly reduced urothelial damage that was accompanied by a decrease in the activity of MPO, MDA, and NOx levels and prevention of the depletion of SOD and GSH in bladder tissues. In the assessment of cytokines, α-PHE was able to significantly reduce TNF-α level. However, it does not affect the activities of IL-1ß. These data confirm that α-PHE exerts potent anti-inflammatory properties and demonstrates that α-PHE represents a promising therapeutic option for this pathological condition.

Indigenous microbiota and Leishmaniasis.

Animals are colonized by their indigenous microbiota from the early days of life. The estimated number of associated bacterial cells in humans is around of 10(14) per individual, most of them in the gut. Several studies have investigated the microbiota-host relationship, and the use of germfree animals has been an important tool in these studies. These animals, when infected with a pathogen, have shown to be sometimes more resistant and other times more susceptible than conventional animals. Leishmaniasis is a worldwide public health problem and presents a spectrum of clinical manifestations. However, very few studies have addressed the role of the indigenous microbiota on the outcome of this disease. In this review, we will highlight and discuss the data available on the ways by which the microbiota can influence the outcome of the disease in murine experimental models of cutaneous infection with Leishmania.

Successful weaning from mechanical ventilation after coronary angioplasty.

Weaning failure can be caused by myocardial ischaemia during the switch from mechanical to spontaneous ventilation. We report ischaemic left ventricular failure and ischaemic mitral insufficiency during weaning. Angiography showed that the coronary vessels were stenosed. Transluminal angioplasty made weaning possible. We conclude that acute ischaemic mitral insufficiency may contribute to cardiac failure during weaning and that angioplasty, by reversing it, can allow successful weaning.

[Pathology and dental care in the context of cardiovascular conditions: myths, beliefs and realities]. / Pathologies et soins dentaires dans le cadre des affections cardiovasculaires: mythes, croyances et réalités.

The knowledge regarding the links between dental and cardiac affections are generally based on empirical concepts and lead to unjustified clinical practices. Infectious endocarditis (IE) is the principal cardiac diseases concerned with dental procedures. Although in France, the incidence of IE is stable, the incidence of oral bacteria at the origin of IE is diminishing. The risk of IE and thus the indication of antibioprophylaxis depend upon the subjacent cardiopathy and dental treatment. Antibioprophylaxis has to be very strict in patients with high or moderate risks of IE but is not necessary in low risk patients. In all cases, a good oral and dental hygiene and a regular dentist follow up are the most effective methods of preventing IE. Coronary artery disease and dental affections are associated because they present similar risk factors (i.e. smoking, excessive sugar consumption) and also because inflammation increases the risk of acute coronary syndrome. Today, dental cares are not contraindicated in patients with recent coronary syndrome if precise protocols are followed. Concerning the hemorrhagic risk during dental care in patients treated by anticoagulants and/or antithrombotics, dental cares and extractions are possible if INR or heparinemy are within the therapeutic limits and local haemostasis is meticulous. In addition, aspirin does not require to be stopped before minor dental treatments. Finally a better collaboration between dentists and cardiologists would allow an optimum management of patients with cardiac disease requiring dental cares.

[Aldosterone and its antagonists in heart failure]. / L'aldostérone et ses antagonistes dans l'insuffisance cardiaque.

THE ROLE OF ALDOSTERONE: Aldosterone is the key hormone in salt-water homeostasis. In heart failure, it participates in the appearance and maintenance of signs of congestion. Predominantly synthesised in the glomerular area of the cortico-adrenal glands, extra adrenal production areas have recently been identified notably in the brain, the heart and the large artery trunks. Aldosterone is activated in the cells by the intracellular mineral corticoid receptor. IN CARDIOVASCULAR-PATHOLOGIES: In chronic heart failure, patients treated with conversion enzyme inhibitor may escape from the renin-angiotensin blockade and this may lead to increased aldosterone plasma levels. This increase can induce not only vascular lesions and myocardial fibrosis but also renal and cerebral lesions. THE EFFECTS OF SPIRONOLACTONE: In patients with NYHA stage III or IV heart failure, addition of spironolactone to the treatment with conversion enzyme inhibitor, diuretic and/or digitalis leads to a reduction in morbidity and mortality, as demonstrated in the RALES study. The mechanisms by which spironolactone has a beneficial effect remain discussed. IN CLINICAL PRACTICE: The prescription of spironolactone is limited by hormonal side effects it provokes. IN THE FUTURE: Eplerenone, a new competitive aldosterone receptor antagonist that appears to be devoid of such side effects and which, at least experimentally may well have the same beneficial effects, is presently under clinical assessment.

Inflammation, cytokines and anti-inflammatory therapies in heart failure.

Both experimental and clinical studies have shown a role for inflammation in the pathogenesis of heart failure. This seems related to an imbalance between pro-inflammatory and anti-inflammatory cytokines. Certain categories in patients with dilated cardiomyopathy have shown the presence of humoral and cellular immunity activation suggesting a possible relation between myocarditis and dilated cardiomyopathy. Recent studies suggest a link between the circulating levels of cytokines (TNF alpha IL-1 et IL-6), the clinical status and prognostic. However, the mechanisms connecting heart failure and cytokine activation are unclear and the sites of cytokines production remain controversial. In the clinical setting, specific measurements of cytokines are not available. As tests of inflammation, erythrocyte sedimentation rate and C-reactive protein concentration appear to have interesting pronostic values. Current conventional therapy i.e. ACE inhibitors, type I angiotensin II antagonist and beta-blockers have shown some anti-cytokine properties. Recently, immunosuppressive therapies have shown their ability to improve symptoms and LV ejection in selected patients with dilated cardiomyopathy and clear sign of myocardium inflammation. Specific anti-cytokine therapy have been developed and showed interesting results in preliminary clinical studies. However large clinical trials testing this new therapy have been stoppel prematurely because of deterious effects.

[Future molecules in heart failure]. / Molécules du futur dans l'insuffisance cardiaque.

TODAY: The management of heart failure (HF) has considerably progressed over the last two decades. Treatment today relies on prevention and treatment of congestion (limited salt intake, diuretics, converting enzyme inhibitors) and limiting neurohormone stimulation (converting enzyme inhibitors +/- aldactone, beta-blockers). IN THE YEARS TO COME: Based on new concepts, several therapeutic strategies are interesting: blocking over vasoconstrictor systems which have not been taking into account; stimulation of vasodilator and natriuretic systems; modulation of cardiac remodelling; modulation of the immune and inflammatory systems; modification in intrinsic contractility; prevention of rhythm disorders. Among these differing strategies and molecules, it is not easy to predict those that will change the HF prognosis. In any event, their efficacy and safety remain to be demonstrated with large cohort randomised studies. THE PRINCIPLES: To reduce the number of drugs administered, two options appear particularly interesting: measurement of hormone levels (BNP) in order to adjust treatment and administration of molecules with greatest efficacy and safety profiles; limit cardiac remodelling by using new imaging techniques to detect it more precisely and select the molecule(s) exerting the required effect. To target the new molecules better, patients should be classified according to their etiology, stage and progressive profile of their disease, cardiac remodelling, expression of principle endocrine systems and pro-inflammatory cytokines, expression of inflammatory and immune systems and inherent genetic characteristics and response to treatment. This would permit the adaptation of treatment to each individual patient with heart failure.

[Hospital mortality in cardiology. Analysis of deaths occurring in the Federation of Cardiology of a university hospital center]. / Mortalité hospitalière en cardiologie. Analyse des décès survenus au sein de la fédération de cardiologie d'un centre hospitalo-universitaire.

The aim of this study was to examine the nature of cardiovascular deaths occurring in a University Hospital. All the hospital files of 1999 of the Federation of Cardiology of Henri Mondor Hospital, Creteil, of patients who died in the department or after transfer to the intensive care unit or cardiac surgery department, were analysed. Myocardial ischaemia was the leading cause of death, occurring either in the acute phase of transmural infarction or in patients with chronic cardiac failure. Deaths occurring during acute myocardial infarction were associated with late treatment and/or non-reperfusion of the culprit artery. The delay of diagnosis seemed to be secondary to late consultation or difficulty in diagnosis. This resulted in severe left ventricular dysfunction and, in a quarter of cases, mechanical complications. They led to the early death of the patients (2.9 +/- 3.5 days after admission). Campaigns of patient information and education of doctors who see these patients would seem to be the most appropriate approach to reduce the delay before hospital admission in order to reduce mortality related to myocardial infarction. Cardiac failure is a common cause of death in cardiology departments. The deaths of patients occurred after a long follow-up and several days after hospital admission (11 +/- 10 days). Optimisation of the treatment of cardiac failure, the investigation of ischaemic heart disease, the search for new therapeutic strategies of acute cardiac failure and information of patients about their disease, seem to be the principal measures to take to improve the poor prognosis of this disease.

[Role of nitric oxide in heart failure]. / Rôle du monoxyde d'azote dans l'insuffisance cardiaque.

The benefit effects of nitric oxide (NO) donors in acute heart failure have led to the development of vasodilators as treatment of chronic heart failure. However, the mechanisms involved in the effects of NO are complex and still discussed. In chronic heart failure, the eNOS downregulation in vascular endothelium explains the alteration of endothelial function. In addition, in the myocardium, cytokines induce the expression of inducible nitric oxide synthase (iNOS) which increase NO production by myocytes and surrounding cells. This excess of NO production, associated with anion superoxide synthesis, limits the inotropic properties of catecholamines and exert proapoptotic effects. The role of NO donors in heart failure treatment is still controversial but by reducing preload they improve patient's symptoms. Beside blockade of the renin-angiotensin system, the angiotensin converting enzyme inhibitors act via the inhibition of bradykinin degradation which increase NO levels. Finally, vascular endothelial NO expression is improved by exercise training and participates in the improvement of exercise capacity in patients with chronic heart failure involved in cardiac readaptation program.

Supraomohyoid neck dissection in the treatment of head and neck tumors. Survival results in 212 cases.

Elective supraomohyoid neck dissection is considered part of standard treatment of oral and oropharyngeal cancer in most institutions, but its role in the treatment of clinically positive neck cancer remains a subject of controversy. The main object of this study is to report the results of 212 consecutive patients who underwent supraomohyoid neck dissections from 1954 to 1990. Most patients had squamous cell carcinoma of the oral cavity. Eighty-six patients (40.6%) had histologically positive lymph nodes in the surgical specimen (sensitivity, 0.55; specificity, 0.53). At the study closing date there were 58.8% actuarial 10-year overall survival rates. Forty-five patients (21.2%) had 50 tumor recurrences (32 local, 13 regional, five distant), and in 40 patients (18.8%) a second primary tumor was diagnosed. A multivariate regression technique based on Cox's proportional hazards model was used, and age (65 years or younger vs older than 65 years) represented the variable with the highest predictive strength with respect to overall survival (relative risk, 2.3). Tumor site, sex, and histologically proved metastasis were also associated with overall survival rates. The same variables were also related to the risk of recurrence. In conclusion, the death rate is mainly related to the control of the primary site tumor and the occurrence of a second primary tumor rather than to neck recurrences. It confirms that supraomohyoid neck dissection is an adequate elective procedure and possibly sufficient in the treatment of a selected group of patients with lip cancer with positive nodes at level 1.

New Jersey's health care system reforms.

As New Jersey grappled with the huge burden of uncompensated hospital care, a diverse group of organizations banded together to develop a unique private sector response to the immediate crisis and a long-term strategy for comprehensive reform of the state's health care system.