Review of dilated cardiomyopathies. Dilated cardiomyopathies and altered prothrombotic state: a point of view of the literature

Heart failure is an enormously important clinical problem that, if not faced, may overwhelm health care resources. Primary and secondary cardiomyopathies cause the majority of cases of clinical heart failure, which is thus better approached from the utility point of view of myocardial failure. Furthermore, the risk of thromboembolic complications presenting in such disease may be higher than in ischemic cardiomyopathy. Intracardiac thrombi and mural endocardial plaques (from the organization of thrombi) are present at necropsy in more than 50% of patients with dilated cardiomyopathy (DCM). Several studies have shown that systemic and pulmonary emboli are more frequent in patients with ventricular thrombi or plaques. Dilated cardiomyopathy has been associated with left ventricular thrombosis which leads to substantial morbidity and mortality as a site for peripheral emboli. There are some studies on patients with dilated cardiomyopathy showing altered hemostasis and platelet behavior despite sinus rhythm. Platelet activation, thrombin activation and fibrinolytic activity are increased in patients with DCM compared to normal subjects. However, these markers reflecting coagulation activation in patients with left ventricle thrombus are comparable to those in patients without thrombus in the left ventricle. The pathophysiology and clinical issues concerning the susceptibility to develop left ventricular (LV) thrombosis and its complications like cerebrovascular disease in patients with DCM are summarized and the most recent articles present in the medical literature are reviewed.     

Reconstruction of the medial patellofemoral ligament for patellar instability using a semitendinosus autograft

Between 1999 and 2001 thirty knees underwent a semitendinosus tendon plasty to recreate the medial patellofemoral ligament for recurrent patellar dislocation. The mean follow-up was 38 months. The mean improvement of the patellofemoral congruence angle after surgery was 14 +/- 7 degrees. All patients ended up with a full range of motion, except one patient, whose flexion was limited to 120 degrees due to superficial wound infections. Dislocation did not recur. According to the Larsen and Lauridsen outcome score the clinical results were excellent in 27 patients, good in 2 and fair in one. In conclusion this procedure is indicated for the chronic dislocation and cases of severe femoral dysplasia with marked laxity. The procedure assures the stabilisation of the patella, although it doesn't restore the patellofemoral congruence angle to normal values.     

Breastfeeding and concentrations of HCB and p,p'-DDE at the age of 1 year

Exposure to organochlorine compounds (OCs) occurs both in utero and through breastfeeding. Levels of hexachlorobenzene (HCB) in the cord serum of newborns from a population located in the vicinity of an electrochemical factory in Spain are among the highest ever reported. We aimed to assess the degree of breast milk contamination in this population and the subsequent exposure of children to these chemicals through breastfeeding. A birth cohort including 92 mother-infant pairs (84% of all births in the study area) was recruited between 1997 and 1999 in five neighboring villages. OCs were measured in cord serum, colostrum, breast milk, and children's serum at 13 months of age. Concentrations of OCs were detected and quantified in all colostrum and milk samples. The concentrations in mature milk were lower than those encountered in colostrum. At 13 months of age the highest concentration of OC was found for dichlorodiphenyl dichloroethane (p,p'-DDE), in contrast to what these children presented at birth, where HCB was the highest compound. Those infants who were breastfed had higher concentrations at the age of 1 than those who were formula fed (2.13 ng/mL of HCB among formula feeders vs 4.26 among breast feeders, and 1.95 of p,p'-DDE vs 6.00 (P<0.05)). Long-term breastfeeding leads to a dose-response increase of the concentrations in children's serum during the first year of life.     

Dealing with euthanasia

This article leads to reflection and debate about such a difficult and delicate question which requires a multidisciplinary focus and due attention paid to all the agents implicated in euthanasia. This debate remains open and what is fundamental is to maintain the capacity for dialogue and receptiveness in hopes of achieving a social and political consensus regarding this topic.     

2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency: an X-linked inborn error of isoleucine metabolism that may mimic a mitochondrial disease

We describe three patients, from two Spanish families, with 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency, a recently described X-linked neurodegenerative inborn error of isoleucine metabolism. Two of them are males with severe lactic acidosis suggestive of a mitochondrial encephalopathy, and the third is a female who was less severely affected, suggesting skewed X-inactivation. Molecular studies revealed a new missense mutation, 740A-->G, in one family and a previously described mutation, 388C-->T, in the other, causing the amino acid substitutions N247S and R130C, respectively. Both male patients died, one of them despite treatment with an isoleucine-restricted diet, but the disease has remained stable in the female patient after 1 y of treatment.     

Quality-adjusted survival: a rigorous assessment of cure after cancer during childhood and adolescence

Survivors of cancer in childhood and adolescence, while increasing gratifyingly in number with ever more effective therapy, have a life expectancy that is compromised all-too-often in both duration and value as a result of adverse treatment-related sequelae. Accounting for this burden of morbidity and mortality is essential for a proper appreciation of cure. Adjusting estimates of survival by measures of its quality affords a means of accomodating this requirement. It can be accomplished by "weighting" the length of survival according to preference-based assessments of health-related quality of life (HRQL), which allow the calculation of quality-adjusted life years. Inclusion of measures of HRQL in clinical trials is imperative as we reach to the ultimate objective; the truly cured child restored to normal health.     

Prevalence and correlates of advanced retinopathy in a large selected hypertensive population. The Evaluation of Target Organ Damage in Hypertension (ETODH) study

OBJECTIVE: To describe the prevalence of advanced retinal microvascular lesions and their associations with cardiac and extracardiac signs of target organ damage (TOD) in a large selected hypertensive population. METHODS: A total of 2172 non-diabetic untreated and treated uncomplicated essential hypertensives consecutively attending for the first time our hospital outpatient hypertension clinic and included in the Evaluation of Target Organ Damage in Hypertension (ETODH), an observational ongoing registry of hypertension-related TOD, were considered for this analysis. Advanced hypertensive retinopathy was defined by the presence of any of the following lesions: flame-shaped haemorrhages, soft exudates or cotton wool spots and papilloedema. Left ventricular hypertrophy (LVH), carotid structural abnormalities, such as plaques and intima media (IM) thickening, and microalbuminuria were diagnosed according to the 2003 ESH/ESC guidelines criteria. RESULTS: Among the whole study population, 33 patients (1.5%) were found to have advanced hypertensive retinopathy. Patients with these retinal lesions were similar to those without for age, body mas index, known duration of hypertension, smoking habit, total serum cholesterol, fasting blood pressure and prevalence of antihypertensive treatment; whereas mean systolic and diastolic blood pressures were higher in the former group. The prevalence rates of LVH, carotid plaques, carotid IM thickening and microalbuminuria in patients with and without retinopathy were 57%, 67%, 69%, 19% and 25%, 47%, 44%, 12%, respectively. In a multivariate logistic regression analysis, advanced retinopathy was significantly associated with LVH (OR = 4.0), carotid IM thickening (OR = 2.9), carotid plaques (OR = 2.8), but not with microalbuminuria. CONCLUSIONS: Our study indicated that: (i) advanced retinopathy is a rare finding in non-diabetic hypertensive patients seen in a specialist setting; (ii) a strong relation exists between retinal microvascular lesions and cardiac and macrovascular markers of TOD.     

Cerebrospinal fluid interferon-gamma-inducible protein 10 (IP-10, CXCL10) in HIV-1 infection

Interferon-gamma-inducible protein (IP-10 or CXCL10) is a potent chemoattractant and has been suggested to enhance retrovirus infection and mediate neuronal injury. In order to assess this chemokine in central nervous system (CNS) HIV infection, we measured the cerebrospinal fluid (CSF) and plasma concentrations of CXCL10 by immunoassay in samples derived from 97 HIV-infected subjects across a spectrum of immunological progression and CNS complications and from 16 HIV seronegative control subjects studied at three clinical centers between 1994 and 2001. We also examined changes in the CSF and plasma CXCL10 concentrations in 30 subjects starting and three stopping antiretroviral therapy. CSF CXCL10 concentrations: (1) correlated with CSF HIV RNA and white blood cell (WBC) counts, but not with blood CXCL10, HIV RNA, or CD4 counts; (2) were increased in subjects with primary and asymptomatic HIV infections and AIDS dementia complex, but less frequently in those with more advanced infection, with or without CNS opportunistic diseases except cytomegalovirus encephalitis; (3) decreased in subjects starting antiretroviral in association with decreases in CSF and plasma HIV RNA and CSF WBCs; and (4) conversely, increased in subjects stopping treatment in parallel with CSF HIV RNA and WBCs. These results confirm that CSF CXCL10 associates closely with both CSF HIV and WBCs and suggest that this chemokine may be both a response to and contributing determinant of local infection. High CSF levels may be useful in the diagnosis of ADC in subjects with advanced immunosuppression in whom CMV encephalitis has been ruled out, though this issue requires further study.