Juan Martinez

We have retrospectively analysed 344 multiple myeloma (MM) patients (202 de novo patients) treated in a non-uniform way in whom high-dose therapy and autologous stem cell transplantation (ASCT) response was simultaneously measured by both electrophoresis (EP) and immunofixation (IF). Patients in complete remission (CR) by EP were further subclassified as CR1 when IF was negative and CR2 when it remained positive. Partial responders (PR) were also subclassified as PR1 (very good PR, > 90% reduction in M-component) or PR2 (50–90% reduction). CR1 patients showed a significantly better event-free survival (EFS) [35% at 5 years, 95% confidence interval (CI) 17–53, median 46 months] and overall survival (OS) (72% at 5 years, CI 57–86, median not reached) compared with any other response group (univariate comparison P < 0·00000 to P = 0·004). In contrast, comparison of CR2 with PR1 and with PR2 did not define different prognostic subgroups (median EFS 30, 30 and 26 months respectively, P = 0·6; median survival 56, 44 and 42 months respectively, P = 0·5). The non-responding patients had the worst outcome (5-year OS 8%, median 7 months). Multivariate analysis confirmed both the absence of differences among CR2, PR1 and PR2 and the highly discriminatory prognostic capacity of a three-category classification: (i) CR1 (ii) CR2 + PR1 + PR2, and (iii) non-response (EFS P < 0·00000; OS P < 0·00000; both Cox models P < 0·00000). In the logistic regression analysis, the factors significantly associated with failure to achieve CR1 were the use of two or more up-front chemotherapy lines, status of non-response pre-ASCT and inclusion of total body irradiation (TBI) in the preparative regimen. Tandem transplants or the use of multiple agents (busulphan and melphalan) in the preparative regimen resulted in a higher CR1 level; none of the biological factors explored influenced the possibility of achieving CR1. These results confirm that, in MM patients undergoing ASCT, achieving a negative IF identifies the patient subset with the best prognosis; accordingly, therapeutic strategies should be specifically designed to achieve negative IF.

Abstract—A new single-stage high-power-factor electronic bal-last based on a flyback converter is presented in this paper. The ballast is able to supply a fluorescent lamp assuring a high-input power factor for the utility line. Other features are lamp power regulation against line ...

Objective: To determine the incidence and prognosis of candidemia in non-neutropenic critically ill patients, to define mortality-related factors, and to evaluate the results of systemic antifungal therapy. Design: A prospective multicenter survey in which medical and/or surgical intensive care units (ICUs) in 28 hospitals in Spain participated. Patients: All critically ill patients with positive blood cultures for Candida species admitted to the participating ICUs over a 15-month period were included. Interventions: Candidemia was defined as the presence of at least one positive blood culture containing Candida species. The follow-up period was defined as the time elapsed from the first positive blood culture for Candida species to discharge or death during hospitalization. Antifungal therapy was considered to be “early” when it was administered within 48 h of the date when the first positive blood culture was obtained and “late” when it was administered more than 48 h after the first positive blood culture. Measurements and main results: Candidemia was diagnosed in 46 patients (mean age 59 years), with an incidence of 1 critically ill patient per 500 ICU admissions. The species most frequently isolated were Candida albicans (60%) and C. parapsilosis (17%). Fluconazole alone was given to 27 patients, amphotericin B alone to 10, and sequential therapy to 6. Three patients did not receive antifungal therapy. The overall mortality was 56% and the attributable mortality 21.7%. In the univariate analysis, mortality was significantly associated with a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score at the onset of candidemia (p=0.04) and with the time elapsed between the episode of candidemia and the start of antifungal therapy 48 h or more later (p<0.02). Patients with an APACHE II score lower than 21 at the onset of candidemia had a higher probability of survival than patients who were more seriously ill (p=0.04). Patients with “early” antifungal therapy (≤48 h between the onset of candidemia and the start of antifungal therapy) had a higher probability of survival compared with patients with late therapy (p=0.06). No significant differences were noted between the two groups on different antifungal therapy. Conclusions: The incidence of candidemia in ICU patients was very low. An APACHE II score >20 at the time of candidemia was associated with a higher mortality. Further studies with a large number of patients are needed to assess the effect of early antifungal therapy on the decrease in mortality associated with candidemia and to determine the appropriate dosage of fluconazole and duration of treatment.

The success of coronary revascularization for ischemic cardiomyopathy (left ventricular ejection fraction of 0.25 or less) has been unpredictable. We and others have demonstrated that the hospital operative mortality rate for these operations has been surprisingly low, particularly if evidence of ischemia is present. We subsequently liberalized our selection criteria based on our hypothesis that coronary artery bypass grafting is safe in this subset of patients regardless of the status of their distal coronary vasculature.To examine this hypothesis, we studied retrospectively our patients undergoing coronary artery bypass grafting from 1983 to 1993. Ninety-six patients with ejection fractions of 0.25 or lower underwent this operation, with 88 hospital survivors (mortality 8%). All of the patients had clinical symptoms of heart failure. The male to female ratio was 4.6:1. The average age was 63.1 ± 0.9 years (mean ± standard error of the mean). Patients were excluded if they had valvular heart disease other than mild to moderate mitral regurgitation, required resection of a ventricular aneurysm, or required an emergency operation for acute coronary occlusion. Possible predictors of death were examined retrospectively. The catheterization films were reviewed retrospectively by a cardiovascular surgeon who was blinded to patient outcome and was never involved in the clinical management of any of the patients. Vessel quality was described as good, fair, or poor.Increased age and poor vessel quality were the only significant predictors of poor outcome. Sex, presence or absence of angina, preoperative angina, preoperative ejection fraction, preoperative arrhythmia disorder, aortic cross-clamp time, and the number of bypass grafts had no significant effect on outcome in the perioperative period.These results demonstrate that poor vessel quality and older age are predictors of poor outcome in patients with low ejection fractions undergoing myocardial revascularization. We conclude that poor distal coronary vasculature is a contraindication to coronary artery bypass grafting in patients with an ejection fraction of 0.25 or less, even if angina is present.

Recent experimental studies and one clinical case have suggested that grafting tissue from the adrenal medulla into the brain may ameliorate the signs of Parkinson&amp;#39;s disease. We describe the treatment of two young patients (35 and 39 years old) with intractable and incapacitating Parkinson&amp;#39;s disease, in whom fragments of the adrenal medulla were autotransplanted to the right caudate nucleus. Clinical improvement was noted in both patients at 15 and 6 days (respectively) after implantation and has continued in both. Rigidity and akinesia had virtually disappeared in the first patient at 10 months after surgery, and his tremor was greatly reduced. A similar degree of improvement was present in the second patient at three months. We conclude that autografting of the adrenal medulla to the right caudate nucleus was associated with a marked improvement in the signs of Parkinson&amp;#39;s disease in two patients, but our results are preliminary and further work is necessary to see whether this procedure will be applicable over the long term in other types of patients with Parkinson&amp;#39;s disease.

Invasive techniques such as amniocentesis and cordocentesis are used for diagnosis and treatment in fetuses at risk for anemia due to maternal red-cell alloimmunization. The purpose of our study was to determine the value of noninvasive measurements of the velocity of blood flow in the fetal middle cerebral artery for the diagnosis of fetal anemia. We measured the hemoglobin concentration in blood obtained by cordocentesis and also the peak velocity of systolic blood flow in the middle cerebral artery in 111 fetuses at risk for anemia due to maternal red-cell alloimmunization. Peak systolic velocity was measured by Doppler velocimetry. To identify the fetuses with anemia, the hemoglobin values of those at risk were compared with the values in 265 normal fetuses. Fetal hemoglobin concentrations increased with increasing gestational age in the 265 normal fetuses. Among the 111 fetuses at risk for anemia, 41 fetuses did not have anemia; 35 had mild anemia; 4 had moderate anemia; and 31, including 12 with hydrops, had severe anemia. The sensitivity of an increased peak velocity of systolic blood flow in the middle cerebral artery for the prediction of moderate or severe anemia was 100 percent either in the presence or in the absence of hydrops (95 percent confidence interval, 86 to 100 percent for the 23 fetuses without hydrops), with a false positive rate of 12 percent. In fetuses without hydrops that are at risk because of maternal red-cell alloimmunization, moderate and severe anemia can be detected noninvasively by Doppler ultrasonography on the basis of an increase in the peak velocity of systolic blood flow in the middle cerebral artery.

Agri-environment schemes are an increasingly important tool for the maintenance and restoration of farmland biodiversity in Europe but their ecological effects are poorly known. Scheme design is partly based on non-ecological considerations and poses important restrictions on evaluation studies. We describe a robust approach to evaluate agri-environment schemes and use it to evaluate the biodiversity effects of agri-environment schemes in five European countries. We compared species density of vascular plants, birds, bees, grasshoppers and crickets, and spiders on 202 paired fields, one with an agri-environment scheme, the other conventionally managed. In all countries, agri-environment schemes had marginal to moderately positive effects on biodiversity. However, uncommon species benefited in only two of five countries and species listed in Red Data Books rarely benefited from agri-environment schemes. Scheme objectives may need to differentiate between biodiversity of common species that can be enhanced with relatively simple modifications in farming practices and diversity or abundance of endangered species which require more elaborate conservation measures.