Evolving short-term and long-term mechanical assist for cardiac-failure -- a decade of experience in Münster

Technological advances and growing expertise has lead to referral of much sicker patients with a greater incidence of heart failure prior to and after cardiac surgical procedures. The diversity of the heart failure patient cohort mandates a differentiated protocol for mechanical support adapted to the clinical requirements. It is desirable to have appropriate mechanical support available for different circumstances of heart failure. In this paper, we review the first decade of the Muenster University Hospital experience with the use of intra-aortic ballon pump, extracorporal membrane oxygenators, short term uni- and biventricular assist systems such as Thoratec and Medos devices, as well as long term left ventricular assist systems such as the TCI Heartmate and the Novacor system. The patient profiles, indications, contraindications, and future trends are reviewed within the framework of a contemporary university hospital Servive.     

Role of bone marrow examination in staging Hodgkin's disease: experience in México

We assessed the value of bone marrow biopsy prospectively in a group of 91 individuals with Hodgkin's disease. The median age of our population was 29 years (range 4-87 years); 59 were males. Most patients (45%) had nodular sclerosing disease and most patients (44%) were in pathological stage II at diagnosis. The bone marrow biopsy showed infiltration by Hodgkin's disease in only three individuals (3.3%); two of these patients displayed constitutional symptoms and had been assigned to stage III before the biopsy. In one case, bone marrow biopsy was the diagnostic procedure, which was performed as part of the investigation of fever of unknown origin. Follow-up periods ranged between 1 and 117 months (median 16 months). All patients achieved complete remission, seven patients relapsed and four were given autologous stem cell transplants. The median survival of the whole group was 117 months, while the 3500-day survival was 76%. As bone marrow biopsy was the diagnostic procedure in one case, bone marrow biopsy was a useful staging procedure in only 2.2% of patients (two out of 90 patients). We suggest that bone marrow biopsy should be only be performed as a staging procedure in a selected subset of patients with Hodgkin's disease (clinical stage III, B symptoms, etc.).     

Risk for diabetes mellitus in middle-aged Caucasian male participants of the PROCAM study: implications for the definition of impaired fasting glucose by the American Diabetes Association. Prospective Cardiovascular Münster

The criteria of the American Diabetes Association and the WHO for the diagnosis of diabetes mellitus are controversially discussed. In a prospective population study, we evaluated the data of 3,737 men, aged 36-60 yr, without diabetes mellitus and with fasting serum glucose levels less than 7 mmol/L at entry into the study who had at least 1 repeat examination during a follow-up of 4-10 yr. During a mean follow-up of 6.3 yr, 200 men developed diabetes mellitus. They differed significantly from 3,537 men by body mass index, fasting serum levels of glucose, high density lipoprotein cholesterol, and family history positive for diabetes mellitus. Receiver operating curve analysis revealed that a glucose level of 5.72 mmol/L was the best discriminatory cut-off. Upon global risk estimation by multiple logistic function (MLF) analysis, 69.6% of all diabetes mellitus incidences occurred in the highest quintile as defined by the MLF algorithm. The relative risk of a men in this quintile was 8.7 compared to that in the residual population. The performance of risk assessment by MLF as estimated by the area under the receiver operator characteristic curve was similar to fasting glucose levels. Global risk estimation by multiple risk factors does not improve the prediction of diabetes mellitus by fasting glucose in middle-aged men. The lower discriminatory cut-off of 5.72 mmol/L glucose may help to reduce the previously reported discordance between impaired fasting glucose (American Diabetes Association) and impaired glucose tolerance (WHO) in diagnosis of the prediabetic state.     

Mechanisms of disease: is osteoporosis the obesity of bone?

Osteoporosis and obesity, two disorders of body composition, are growing in prevalence. Interestingly, these diseases share several features including a genetic predisposition and a common progenitor cell. With aging, the composition of bone marrow shifts to favor the presence of adipocytes, osteoclast activity increases, and osteoblast function declines, resulting in osteoporosis. Secondary causes of osteoporosis, including diabetes mellitus, glucocorticoids and immobility, are associated with bone-marrow adiposity. In this review, we ask a provocative question: does fat infiltration in the bone marrow cause low bone mass or is it a result of bone loss? Unraveling the interface between bone and fat at a molecular and cellular level is likely to lead to a better understanding of several diseases, and to the development of drugs for both osteoporosis and obesity.     

Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: results of a nested case-control analysis of the Prospective Cardiovascular Münster (PROCAM) study

BACKGROUND AND AIM: Sitosterolemia, a rare genetic disorder characterized by profoundly elevated plasma sitosterol concentrations, is associated with premature atherosclerosis in some individuals. This study was conducted to evaluate if the modest sitosterol elevations seen in the general population are also associated with the occurrence of coronary events. METHODS AND RESULTS: A nested case-control study using stored samples from male participants in the Prospective Cardiovascular Münster (PROCAM) study was performed. Each of 159 men who suffered a myocardial infarction or sudden coronary death (major coronary event) within 10 years of follow-up in PROCAM was matched with 2 controls (N = 318) by age, smoking status, and date of investigation. Analysis was performed using conditional logistic regression. Plasma sitosterol concentrations were elevated in cases compared with controls (4.94 +/- 3.44 micromol/L versus 4.27 +/- 2.38 micromol/L; P = 0.028). The upper quartile of sitosterol (>5.25 micromol/L) was associated with a 1.8-fold increase in risk (P < 0.05) compared with the lower three quartiles. Among men with an absolute coronary risk > or = 20% in 10 years as calculated using the PROCAM algorithm, high sitosterol concentrations were associated with an additional 3-fold increase in the incidence of coronary events (P = 0.032); a similar, significant relationship was observed between a high sitosterol/cholesterol ratio and coronary risk (P = 0.030). CONCLUSIONS: Elevations in sitosterol concentrations and the sitosterol/cholesterol ratio appear to be associated with an increased occurrence of major coronary events in men at high global risk of coronary heart disease. Further evaluations are warranted to confirm these preliminary findings.     

Highly active antiretroviral therapy in resource-poor settings: the experience of Médecins Sans Frontières

We describe the short-term results of highly active antiretroviral therapy (HAART) in seven projects in low and middle income countries. A total of 743 adults were included, and clinical, immunological and virological responses were analysed. At 6 months, outcomes were similar to those observed in western countries, and the probability of remaining on treatment was 94%. The challenge now is to extend access to HAART to the millions in urgent need.     

Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy: A report of the Berlin-Frankfurt-Münster Group Trial NHL-BFM 90.

In study NHL-BFM 90, we investigated whether the serum lactate dehydrogenase (LDH) concentration and early response are useful markers for stratification of therapy for childhood B-cell neoplasms in addition to stage, if the outcome of patients with abdominal stage III and LDH >/=500 U/L can be improved by high-dose (HD) methotrexate (MTX) at 5 g/m(2) instead of intermediate-dose (ID) MTX at 500 mg/m(2) in the preceding study 86; whether 2 therapy courses are enough for patients with complete resection; and whether combined systemic and intraventricular chemotherapy is efficacious for central nervous system-positive (CNS(+)) patients. After a cytoreductive prephase, treatment was stratified into 3 risk groups: patients in R1 (completely resected) received 2 5-day courses (ID-MTX, dexamethasone, oxazaphorins, etoposide, cytarabine, doxorubicin, and intrathecal therapy), patients in R2 (extra-abdominal primary only or abdominal tumor and LDH <500 U/L) received 4 courses containing HD-MTX, and patients in R3 (abdominal primary and LDH >/=500 U/L or bone marrow/CNS/multilocal bone disease) received 6 courses. Incomplete responders after 2 courses received an intensification containing HD-cytarabine/etoposide. Patients with no or necrotic tumor thereafter received 3 more courses; 6 patients with viable tumor received autologous bone marrow transplantation. From April 1990 through March 1995, 413 evaluable patients were enrolled (R1, 17%; R2, 40%; and R3, 43%). The 6-year event-free survival (pEFS) was 89% +/- 2% for all and 100%, 96% +/-2%, and 78% +/- 3% in R1, R2, and R3, respectively. The pEFS of patients with abdominal stage III and LDH >/=500 U/L was 81% +/- 4% as compared with 43% +/- 10% in study 86. Of 26 CNS(+) patients, 5 died early, but only 3 relapsed.