Progressive dilated cardiomyopathy in a patient with longstanding and complete prednisone-induced hematological remission of idiopathic hypereosinophilic syndrome

Summary A female patient is described in whom the diagnosis of idiopathic hypereosinophilic syndrome (HES) with heart disease and peripheral neuropathy was made at the age of 32 years. Although prednisone induced a prompt and longstanding complete hematological remission, progressive and eventually intractable heart failure developed, and the patient died 6 years later. Endomyocardial biopsy at diagnosis showed infiltration with intact and disintegrated eosinophils and Charcot-Leyden crystals. Echocardiographic follow-up (including Doppler-Echocardiography) revealed mitral regurgitation with thickening and impaired motility of the posterior mitral leaflet, as well as progressive dilated cardiomyopathy. At autopsy, a diffuse interstitial fibrosis with patchy prominence in an eccentric hypertrophic and highly dilated heart was found. There were no significant endocardial thickening and no mural thrombi. In contrast to the findings of the initial endomyocardial biopsy, autopsy revealed no eosinophilic infiltrate.In this case, eosinophil-induced heart disease manifested as dilated cardiomyopathy, without endocardial fibrosis as originally described by Löffler. We speculate, that eosinophils have been deposited predominantly in the myocard at an early stage of disease, and — activated locally — secreted their granule proteins producing an initial damage to capillary endothelial cells and myocytes. After prednisone-induced clearance of eosinophils from blood and tissues, progressive, self-perpetuating interstitial fibrosis of the myocard and loss of myocytes eventually resulted in end-stage dilated cardiomyopathy.Abkürzungsverzeichnis HES idiopathic hypereosinophilic syndrome - UBBC unsaturated vitamin B₁₂ binding capacity - ECP eosinophil cationic protein - MBC major basic protein - EDD end-diastolic diameter of the left ventricle - LA left atrium diameter - LVEDP left ventricular end-diastolic pressure - NIH National Institutes of Health     

Combining capecitabine and gemcitabine in patients with advanced pancreatic carcinoma: a phase I/II trial.

PURPOSE: Preclinical studies indicate positive interactions between capecitabine, an oral fluorouracil precursor, and gemcitabine, the current standard treatment for advanced pancreatic carcinoma (APC). In this study, we investigated the addition of capecitabine to gemcitabine treatment for patients with APC. PATIENTS AND METHODS: This multicenter study included patients na?ve to chemotherapy who had histologically or cytologically confirmed, nonresectable or metastatic pancreatic carcinoma. Gemcitabine was given at a fixed dose of 1,000 mg/m(2) on days 1 and 8 of a 21-day cycle. Capecitabine was given in increasing doses orally bid for 14 days followed by a 1-week rest. The maximum-tolerated dose (MTD) was defined as one dose level below the dose causing dose-limiting toxicity (DLT) in >or= one third of a cohort of six patients. We included an additional 15 patients at the MTD. RESULTS: Thirty-six patients were included. DLT occurred at a dose of 800 mg/m(2) bid of capecitabine and consisted of myelotoxicity and mucositis. Hand-foot syndrome was not observed, and other toxic effects were mild. Thus, in this regimen, the recommended dose of capecitabine is 650 mg/m(2) bid. In 27 patients with measurable disease, we observed one complete and four partial remissions. In addition, significant drops (> 50% from baseline value) of the tumor marker CA 19-9 occurred in 14 of 24 assessable patients. CONCLUSION: The combination of capecitabine and gemcitabine is well tolerated, with apparent efficacy in patients with APC. Therefore, it is currently being compared with gemcitabine monotherapy in a phase III study.     

Riesgo de enfermar y morir por cáncer de mama en Castilla-La Mancha (1975–1998)

Background. To know the temporary tendency in the mortality due to breast cancer in Castilla-La Mancha (CLM, Spain) between 1975 and 1998. Patients and methods. The mortality data are from the Registry of Mortality of CLM. Crude and standardized mortality rates are calculated. In order to evaluate the tendency, we use the Poisson’s log- linear model. We have calculated the accumulated rate to die and the accumulated risks to die and to become ill. Results. Between 1975 and 1998, 2.44% of all deaths in CLM women were consequence of a breast cancer. The crude rate increased from the 14.55 by 100,000 in 1975 to 25.23 by 100,000 in 1998, with an annual average increase of 1.49%. The average age of death increased until the 67 years old in 1998 as opposed to the 59 years old of 1975. The risk of dying of a breast cancer increased in the period from 1.4% in 1975 to 2.34% in 1998. Conclusion. Mortality by breast cancer has raised until 1993, when it begun to decrease. In general, women with breast cancer die elderly, and young women have increased risk to fall ill.     

Epidemiologic aspects of pediatric multiple trauma in a Spanish urban population

BACKGROUND/PURPOSE: Trauma is still the most frequent cause of mortality and disability in childhood and adolescence. An epidemiologic prospective study on children under 16 years of age with multiple trauma (MT) was conducted in a large Spanish urban university hospital over a 6-year period. METHODS: Of 1,937 children admitted at the pediatric trauma unit for musculoskeletal injuries from March 1988 until March 1994, 56 patients including 37 boys and 19 girls had MT. MT was considered when at least 2 long bones were fractured or there was a fracture of 1 long bone combined with an injury of 4 other major anatomic regions (face and neck, thorax, abdomen, or neural system). The severity of injuries was evaluated according to the modified injury severity score (MISS). RESULTS: Injury to pedestrians was the most frequent cause of MT (54%). The overall mortality rate of the series, including those children dying during transport to the hospital was 11.5%. The average MISS for the whole group was 15 (range, 5 to 59). Head trauma was the most frequent associated injury (52%), two thirds of which were considered minor injuries (Glasgow Coma Scale >15). Seventy-seven fractures were registered, 10% of which were open fractures. External fixation was the most common surgical technique among operated fractures. The average hospitalization period was 16 (median, 13; range, 1 to 150) days. Children with a MISS above 18 points showed a significant longer hospitalization period (mean, 31 +/- 45 days) as compared with those with MISS below 18 points (mean, 10 +/- 7 days; P < .05). There was a strong correlation between the MISS and both the period of hospitalization at the pediatric intensive care unit and the total length of hospital stay. CONCLUSIONS: Pedestrian accidents caused by motor vehicles in children playing at the street contributed most significantly to MT in the urban pediatric population. Special care for prevention must be taken in the age group of 6 to 10 years. Head injury was the main cause of death in children with multiple trauma. MISS was found to be a good predictor of survival and duration of hospital stay in pediatric MT.     

Contribution of mitral valve leaflet length and septal wall thickness to outflow tract obstruction in patients with hypertrophic cardiomyopathy

We sought to examine whether elongation of the mitral valve leaflets in patients with hypertrophic cardiomyopathy (HCM) is synergistic to septal wall thickness (SWT) in the development of left ventricular outflow tract obstruction (LVOTO). HCM is a common genetic cardiac disease characterized by asymmetric septal hypertrophy and predisposition towards LVOTO. It has been reported that elongation of the mitral valve leaflets may be a primary phenotypic feature and contribute to LVOTO. However, the relative contribution of this finding versus SWT has not been studied. 152 patients (76 with HCM and 76 non-diseased age, race and BSA-matched controls) and 18 young, healthy volunteers were studied. SWT and the anterior mitral valve leaflet length (AMVLL) were measured using cine MRI. The combined contribution of these variables (SWT × AMVLL) was described as the Septal Anterior Leaflet Product (SALP). Peak LVOT pressure gradient was determined by Doppler interrogation and defined as “obstructive” if?≥?30 mmHg. Patients with HCM were confirmed to have increased AMVLL compared with controls and volunteers (p?<?0.01). Among HCM patients, both SWT and SALP were significantly higher in patients with LVOTO (N?=?17) versus without. SALP showed modest improvement in predictive accuracy for LVOTO (AUC?=?0.81) among the HCM population versus SWT alone (AUC?=?0.77). However, in isolated patients this variable identified patients with LVOTO despite modest SWT. Elongation of the AMVLL is a primary phenotypic feature of HCM. While incremental contributions to LVOTO appear modest at a population level, specific patients may have dominant contribution to LVOTO. The combined marker of SALP allows for maintained identification of such patients despite modest increases in SWT.     

Effect of atrioventricular synchrony on stroke volume during ventricular tachycardia in man.

The hemodynamic consequences of atrioventricular (AV) synchrony during ventricular tachycardia were evaluated during cardiac electrophysiologic testing. The relationship between stroke volume and the AV interval was investigated on a beat-by-beat basis in six patients during induced monomorphic ventricular tachycardia. Stroke volume was calculated either (1) in the right ventricle using impedance catheter method (four patients) or (2) in the left ventricle using Doppler measurement of aortic blood velocity (two patients). The impedance catheter method underestimated stroke volume by a factor of 4.2 +/- 2.4 compared with the thermodilution cardiac output method. However, there was a highly linear relationship between both methods for computing stroke volume (r greater than 0.9). Five patients had complete AV dissociation during ventricular tachycardia, and different AV intervals spanned the entire tachycardia cycle lengths. Largest stroke volumes were associated with optimal AV intervals within 120 and 230 msec, resulting in a 97 +/- 59% increase in stroke volume over ventricular tachycardia cycles not associated with atrial activity. Customized atrial pacing during ventricular tachycardia may provide a valuable means for artificially establishing the hemodynamically optimal AV interval and eliminating the ventricular tachycardia cycles not preceded by atrial activity.     

Experiences of taking neuroleptic medication and impacts on symptoms,sense of self and agency: a systematic review and thematic synthesis of qualitative data

Purpose

Neuroleptic (antipsychotic) drugs reduce psychotic symptoms, but how they achieve these effects and how the drugs’ effects are experienced by people who take them are less well understood. The present study describes a synthesis of qualitative data about mental and behavioural alterations associated with taking neuroleptics and how these interact with symptoms of psychosis and people’s sense of self and agency.

Methods

Nine databases were searched to identify qualitative literature concerning experiences of taking neuroleptic medication. A thematic synthesis was conducted.

Results

Neuroleptics were commonly experienced as producing a distinctive state of lethargy, cognitive slowing, emotional blunting and reduced motivation, which impaired functioning but also had beneficial effects on symptoms of psychosis and some other symptoms (e.g. insomnia). For some people, symptom reduction helped restore a sense of normality and autonomy, but others experienced a loss of important aspects of their personality. Across studies, many people adopted a passive stance towards long-term medication, expressing a sense of resignation, endurance or loss of autonomy.

Conclusions

Neuroleptic drugs modify cognition, emotions and motivation. These effects may be associated with reducing the intensity and impact of symptoms, but also affect people’s sense of self and agency. Understanding how the effects of neuroleptics are experienced by those who take them is important in developing a more collaborative approach to drug treatment in psychosis and schizophrenia.

     

Mortality attributable to tobacco consumption in the years 1987 and 1997 in Castilla la Mancha, Spain

BACKGROUND: Smoking is an important public health problem and is one of the main avoidable causes of morbidity and early mortality. The aim of this work was to describe the mortality attributable to tobacco consumption in Castilla la Mancha between 1987 and 1997. METHOD: Deaths in relation to age, sex and cause of death were obtained from the Death's Register of Castilla la Mancha. From the National Health Surveys of 1987 and 1997, the percentages of non-smokers, smokers and ex-smokers in the population in relation to age and sex were recorded. The relative risks of death were obtained from the Cancer Prevention Study II, carried out in the United States. The proportion of deaths attributable to smoking was calculated for each year, and according to sex and age group, from the etiological fraction of the population. Likewise, loss of potential life in years and the mean number of years of potential life lost were also calculated. RESULTS: During the study period, 18% of all the deaths in Castilla la Mancha can be attributed to tobacco consumption. Mortality is higher in males than in females, and the most important diagnostic categories were tracheobronchopulmonary cancer (24.3%) in males and diseases of the cardiovascular system (24.28%) in females. These were also the conditions most responsible for years of potential life lost. CONCLUSIONS: Every day, in Castilla la Mancha, 8 people die from smoking-related conditions. The measures currently in practise to control tobacco consumption are insufficient.