Pathogenesis of Chagas disease cardiomyopathy

Chagas disease, or American trypanosomiasis, is a parasitic infection caused by the flagellate protozoan Trypanosoma cruzi. Chagas disease is mainly affecting rural populations in Mexico and Central and South America. The World Health Organization estimates that 300 000 new cases of Chagas disease occur every year and approximately 20 000 deaths are attributable to Chagas. However, this organisation classified Chagas disease as a neglected tropical disease. The economic burden of this disease is significant. In many Latin American countries, the direct and indirect costs, including the cost of health care in dollars and loss of productivity, attributable to Chagas disease ranges from $40 million to in excess of $800 million per nation per annum. So, it remains a contemporary public health concern. In chronic phase, mortality is primarily due to the rhythm disturbances and congestive heart failure that result from the chronic inflammatory cardiomyopathy (CCC) due to the persistence presence of parasites in the heart tissue. Mechanisms underlying differential progression to CCC are still incompletely understood. In the last decades immunological proteomic genetic approaches lead to significant results which help to disperse the veil covering the knowledge of the pathogenic process. Here, we reported these significant progresses.     

Prevalence of Chagas heart disease in dilated cardiomyopathy

Objectives:The main objective is to determine the prevalence of American trypanosomiasis in patients with dilated cardiomyopathy in a tertiary hospital in western Mexico.Methods:From January 1991 to February 2016, 387 consecutive patients with a confirmed diagnosis of dilated cardiomyopathy were included in the study. Cases with ventricular dilatation secondary to ischemic heart disease, valvular heart disease, hypertension, lung disease, pericardial disease, or congenital heart disease were excluded from the study. Diagnosis was made detecting antibodies against Trypanosoma cruzi with two different methods or parasite in blood.Results:Were included 387 patients with dilated cardiomyopathy, Chagas cardiomyopathy was confirmed in 6.9%, two patients in the acute phase (in one, suspected transfusion transmission was detected). Most patients were born in rural areas. About 96.2% showed congestive heart failure, only one patient with apical left ventricular aneurysm manifested palpitations. About 66% with right bundle branch block, left anterior fascicular block, or the association of both, in 14.8%, non-sustained ventricular tachycardia was found.Conclusions:Chagas cardiomyopathy is common in México, mainly in people who were born or lived during childhood in rural areas. It is a common cause of heart failure. Chagas’ heart disease should be suspected in patients receiving a blood transfusion, even without another epidemiological history.Key words: Chagas heart disease, Dilated cardiomyopathy, American trypanosomiasis     

Classification of diabetes in young adults: new concepts for an old disease

As clinicians, we are faced to difficult situations in young diabetic patients. The prevalence of type 2 diabetes increases in these patients due to a rising incidence of obesity. We present two clinical observations which both illustrate the insufficiencies of the present classifications. Modern tools are now available for diagnosis such as anti-GAD65 and IA-2 antibodies, genetic tools to investigate for specific mutations, but quantitative means of beta cell mass are lacking.

Clinical examination is still accurate to identify type 1 or type 2 diabetes, MODY and mitochondrial diabetes. Weight curve, lesions of acanthosis nigricans, criteria of metabolic syndrome, history of diabetes are critical factors. This problematic has important consequences in our daily practice: the right choice for rapid and good metabolic control.     

Current concepts in immunoregulation and pathology of human Chagas disease

PURPOSE OF REVIEW: Chagas disease is a complex ailment caused by infection with Trypanosoma cruzi. It afflicts millions in Latin America. Years of studies have focused on the development of pathology in Chagas disease and recent studies have helped us understand the cellular mechanisms behind differential clinical evolution of Chagas disease. RECENT FINDINGS: We discuss recent findings concerning the cellular immune response in human Chagas disease focusing on immunoregulation and the development of pathology. We seek to put several findings into the context of a disease that initially controls an extreme and patent infection, and later progresses to a chronic phase marked by the presence (cardiac and digestive forms), or not (indeterminate form), of associated pathology. SUMMARY: Several theories exist to explain differential clinical evolution of Chagas disease. A coherent understanding of these theories will certainly aid in determining what combination of them approximates the true development of chagasic pathology. For achieving the goal of developing a successful therapy or intervention, it is critical that no theory be excluded at this point, but. Rather, rather that a thoughtful analysis and assimilation of the best components of each system into a central theory that best fits the reality of human Chagas disease is desirable.     

Huntington's disease: current concepts of therapy.

Huntington's disease (Huntington's chorea), a degenerative disorder of the central nervous system, is inherited in an autosomal dominant pattern. Since there is no cure for this genetic disorder, therapy has been focused on pharmacologic manipulation of the involved neurotransmitter systems. In Huntington's disease, there is a functional predominance of striatal dopaminergic activity over antagonist cholinergic and possibly GABA-minergic systems. Many dopaminergic antagonists and cholinergic and GABA-minergic agonists are currently used in treatment. Supportive psychiatric care for affected persons and their families is an important therapeutic adjunct in the management of Huntington's disease. The eventual therapy will depend upon accurate identification of the primary genetic defect.     

Specific treatment of Chagas disease: current status and new developments

The current situation regarding specific chemotherapy for Chagas disease (American trypanosomiasis), and new developments in this field, are reviewed. Despite previous controversy on the autoimmune origin of Chagas disease pathology, available knowledge supports the notion that this condition should be treated as a parasitic, not an autoimmune, disease. Currently available drugs (nitrofurans and nitroimidazoles) are active in acute or short-term chronic infections, but have very low antiparasitic activity against the prevalent chronic form of the disease, and toxic side-effects are frequently encountered. The nitroimidazole benznidazole has also shown significant activity in the treatment of reactivated Trypanosoma cruzi infections in patients with acquired immune deficiency syndrome and in other immunosuppressed patients with underlying chronic Chagas disease. Although the etiological agent, T. (Schizotrypanum) cruzi, requires specific endogenous sterols for cell viability and proliferation, the currently available antifungal sterol biosynthesis inhibitors are not powerful enough to induce parasitological cures of human or experimental infections. However, new triazole antifungal compounds, which are potent inhibitors of the sterol C14alpha demethylase of the parasite and have special pharmacokinetic properties, are capable of inducing parasitological cures in murine models of both acute and chronic Chagas disease. They are currently the most advanced candidates for clinical trials in patients with Chagas disease. Other potential chemotherapeutic agents against T. cruzi currently in development include antiproliferative lysophospholipid analogs (already in clinical trials as the first oral treatment for visceral leishmaniasis), cysteine proteinase (cruzipain) inhibitors, and compounds that interfere with purine salvage and inositol metabolism.     

Nitroglycerin: New concepts about an old drug

Increasing evidence has profoundly challenged previously accepted concepts about the actions and clinical uses of nitroglycerin. Traditionally, use of this agent has been contraindicated in patients with acute myocardial infarction because of its hypotensive effects, and it has had no place in the therapeutic armamentarium of heart failure or arrhythmias. Recent investigations, however, suggest that nitroglycerin's usefulness may far transcend the role it has had for more than a century [1] in alleviating symptoms of angina pectoris. Nitroglycerin appears to be a potentially important addition to the treatment of both chronic heart failure and heart failure due to acute myocardial infarction. In addition, several reports have suggested that nitroglycerin decreases infarct size, has antiarrhythmic effects and reverses localized contraction abnormalities (asynergy) when due to ischemic dysfunction. This evidence is rapidly accumulating despite the fact that nitroglycerin's basic mechanisms of action have remained controversial.     

Immunosuppressive therapy in patients with thyroid eye disease: an overview of current concepts

Thyroid eye disease (TED) is a debilitating disease impairing the quality of life of affected patients. Treatment is often not satisfactory. This review summarizes the existing literature and discusses the most widely used forms of treatment for TED such as glucocorticoids (GCs), and other immunosuppressive agents. GCs are the most commonly used treatment in patients with TED. Other immunosuppressive agents such as cyclosporin A, azathioprin, cyclophosphamide and ciamexone have been used, but the results are modest at best and indicate an unfavorable benefit-risk relationship. Limited experience indicates that methotrexate may be effective even in patients with refractory TED. Somatostatin analogs, octreotide and lanreotide, may provide a valuable, although costly, therapeutic alternative to GCs. Orbital radiotherapy has been used in the management of TED for almost 60 years. However, its beneficial effects have been questioned recently by several studies, the details of which have not yet been published. Other studies have argued in favor of orbital radiotherapy; however, the benefits appear to be limited to improvement of extraocular muscle dysfunction.     

Chagas cardiomyopathy and captopril.

Chagas disease is a leading cause of heart failure in Latin America. Sudden death occurs in approximately 40% of patients with heart failure due to Chagas disease. We report a single blind, cross-over trial of prolonged treatment with captopril and placebo in 18 Chagas disease patients with class IV NYHA heart failure. Ventricular dimensions, neurohormones, electrolytes and ventricular arrhythmias were analysed in 11 men and seven women receiving stable doses of digoxin and frusemide who were randomly divided into two intervention groups. Group I patients were given increasing doses of captopril up to 150 mg.day-1 maintained for 6 weeks, group II received the placebo. A 24 h Holter, 2-D echocardiogram, urinary catecholamines, plasma renin and electrolyte determinations were performed at the end of each phase. After a 2-week washout period, the two groups crossed over and another period of 6 weeks was observed. Ventricular arrhythmias were analysed by either Mann-Whitney or the Wilcoxon test. Remaining data were assessed by the Student t-test. A significant reduction in heart rate and urinary catecholamine levels, and enhanced plasma levels of renin, together with a reduction in ventricular couplets was found in the captopril-treated group. We conclude that captopril has a beneficial effect on neurohormones with a subsequently reduced heart rate and diminished incidence of ventricular arrhythmias in patients with Chagas disease. This effect might result in a reduction of mortality caused by the disease, suggesting the need for further investigations.     

Silent ischaemia: an update on current concepts

Angina pectoris is the cardinal symptom of coronary heart disease and is a symptom with which physicians are very familiar. The clinical diagnosis of ischaemic heart disease is often based largely on a history of typical chest or arm pain, and the major therapeutic endeavour in such patients is directed towards abolition or amelioration of angina. Indeed physicians have, at least up until recently, been confident in assuming that angina is a reliable marker of ongoing ischaemia and that success of medical or surgical treatment of coronary heart disease can be accurately gauged according to improvement or disappearance of anginal symptoms (Cohn & Braunwald, 1988). However, the results of a number of important clinical studies, reported over that last 10 to 15 years, appear to challenge these traditional medical assumptions. In many patients with coronary heart disease, acute episodes of myocardial ischaemia are frequently unaccompanied by angina, often referred to as "silent myocardial ischaemia" (Epstein et al., 1988; Fox, 1988; Cohn, 1985; Maseri, 1985). It has to be pointed out that not all painless ischaemic episodes are truly silent. Instead of experiencing pain during some episodes of acute myocardial ischaemia, patients may, on occasion, instead report symptoms such as dyspnoea or palpitations (these symptoms being known as "anginal equivalents") (Cohn & Braunwald, 1988). Nevertheless, the great majority of painless ischaemic episodes are, truly silent and not accompanied by "anginal equivalents", which has led to the trend in the recent literature to regard the terms "silent" and "painless" myocardial ischaemia as synonymous.     

Kidney disease and psoriasis: novel evidences beyond old concepts

Psoriasis is an immune-mediated inflammatory disease for a long time considered as a type of pathology characterized by an exclusive skin involvement. Recently it has been shown that patients affected by this disease have a higher risk of developing comorbidities such as cardiovascular diseases, arterial hypertension, diabetes mellitus, and metabolic syndrome. Even the kidneys can be affected by psoriasis through three different mechanisms: immune-mediated renal damage, drug-related renal damage and chronic renal damage. Renal function should be monitored periodically to minimize the risk of renal adverse events.     

Celiac disease: current concepts in diagnosis and treatment

Celiac disease is a complex autoimmune enteropathy that affects the small bowel in genetically predisposed individuals. It is thought that celiac disease is the result of an inappropriate T cell-mediated immune response against ingested gluten protein. The characteristic lesion of the small intestinal mucosa includes loss of absorptive villi and infiltration of the lamina propria with inflammatory cells. The clinical presentation of celiac disease varies greatly depending on patient's age, duration and extent of the disease, and the presence of extraintestinal manifestations. Unfortunately, most patients with celiac disease have either silent or atypical presentations, thus escaping diagnosis for several years. Medical nutrition therapy with lifelong adherence to a strict gluten-free diet is the only accepted treatment of celiac disease. Individuals at risk for this entity should undergo appropriate serologic testing, but there is no evidence to support mass screening.     

Cardiovascular disease in diabetes type 2: current concepts

Type 2 diabetes is a major and accelerating public health challenge. Between 1980 and 2014, a period of just 35 years, the number of adults with diabetes globally is estimated to have increased from 108 to 422 million, due not only to sharply rising obesity rates, but also to increasing population size, longer life expectancy, and rising prevalence of diabetes worldwide. Overall, worldwide age‐standardized adult diabetes prevalence doubled from 4.3% to 9.0% in men and from 5.0% to 7.9% in women. The largest increases in diabetes type 2 have been demonstrated in low‐ and middle‐income countries, whilst rises in high‐income countries have been less marked, or even flat. Diabetes type 2 rates in low‐ and middle‐income countries now in many instances surpass those in high‐income countries, in response to changes in lifestyle. One factor of particular concern are the large relative increases in type 2 diabetes amongst young individuals observed in many countries, their higher overall risk factor burden, long exposure to hyperglycaemia and greater risk of complications over the life course. Type 2 diabetes is increasingly found to be a heterogeneous condition, where risk of cardiovascular disease that traditionally has been estimated at 2–4 times that of the nondiabetic population varies substantially with diabetes phenotype and accordingly diabetes does not confer the same increase in relative or absolute risk in all people. New research shows that excess risk varies substantially with type of outcome, age, glycaemic control, the presence of renal complications and other factors. Heart failure, previously less recognized that other cardiovascular conditions, is increasingly coming into focus, because of strong links with poor glycaemic control and obesity. The knowledge about risk of cardiovascular disease in diabetes is almost entirely derived from high‐income countries, whereas there is comparatively very little data from low‐ and middle income countries, where the majority of persons with type 2 diabetes live, and where management in many cases is far from optimal. The reductions in cardiovascular disease incidence and mortality now observed in high‐income countries are encouraging, because this reinforces the fact that improvement is possible and that a near‐normal, or even normal life‐expectancy can be achieved in subtypes of type 2 diabetes.     

Laparoscopic surgery for inflammatory bowel disease: current concepts

BACKGROUND: The aim of a laparoscopic approach is reduced pain scores, early mobilization, virtual absence of wound sepsis, rapid return of gastrointestinal function, early discharge from hospital and return to normal activity and improved cosmetics. Potential advantages are fewer complications due to adhesion formation, viz. small-bowel obstruction, infertility and chronic abdominal pain-advantages that are of particular importance to patients with inflammatory bowel disease (IBD) since they are young and in the middle of building up their socio-economic life. This review highlights the current status of laparoscopic surgery for patients with IBD. METHODS: Virtually all abdominal procedures carried out in patients with IBD can be done laparoscopically, and vary from stoma formation to restorative proctocolectomy. RESULTS: Conversion rates and operating times depend on the surgical expertise and patient-related factors, viz. prior laparotomy, the presence of intestinal fistula or inflammatory masses. Morbidity rates are similar to those of open surgery provided that the procedures are done by expert laparoscopic surgeons. The observed earlier recovery contributed to laparoscopic surgery has not been proved in well-conducted trials; however, an advantage can be expected. A very obvious feature of laparoscopic surgery is the improved cosmetics, which might turn out to be the most important advantage of the laparoscopic approach in this relatively young patient group. CONCLUSION: The laparoscopic approach can be considered the procedure of first choice in patients with IBD provided the surgery is done by expert laparoscopists ensuring low conversion rates, acceptable operating times and low morbidity.