Treatment of senile maculopathy with etaretin

The results of parenteral treatment with Etaretin in 40 patients (79 eyes) suffering from senile maculopathy are reported. In 84% of the cases there was a degeneration of the dry type and in 16% a disciform exudative maculopathy. The cases of dry maculopathy responded well within a floow-up period of 8 to 18 months.     

Anästhesiologische Risikoevaluation und rechtssichere Aufklärung per Telemedizin – Sind wir bereit für einen Paradigmenwechsel?

Die Anaesthesiologie - In Deutschland werden pro Jahr 17 Millionen Narkosen und damit auch ungefähr so viele Narkosevorgespräche durchgeführt. Bis dato finden diese praktisch...     

Patients at lower risk of arrhythmia recurrence: a subgroup in whom implantable defibrillators may not offer benefit. Antiarrhythmics Versus Implantable Defibrillator (AVID) Trial Investigators

OBJECTIVES: The goal of this study was to identify subgroups of arrhythmia patients who do not benefit from use of the implantable cardiac defibrillator (ICD). BACKGROUND: Treatment of serious ventricular arrhythmias has evolved toward more common use of the ICD. Since estimates of the cost per year of life saved by ICD therapy vary from $25,000 to perhaps $125,000, it is important to identify patient subgroups that do not benefit from the ICD. METHODS: Data for 491 ICD patients enrolled in the Antiarrhythmics Versus Implantable Defibrillators Study were used to create a hazards model relating baseline factors to time to first recurrent arrhythmia. The model was used to predict the hazard for recurrent arrhythmia among all trial patients. A priori cut points provided lower and higher recurrent arrhythmia risk strata. For each stratum the incremental years of life due to ICD versus antiarrhythmic drug therapy were calculated. RESULTS: Factors that predicted recurrent arrhythmia were: ventricular tachycardia as the index arrhythmia, history of cerebrovascular disease, lower left ventricular ejection fraction, a history of any tachyarrhythmia before the index event and the absence of revascularization after the index event. Survival times (over a follow-up of three years) were identical in each arm of the lowest risk sextile (survival advantage 0.03 +/- 0.12 [se] years), while the survival advantage for patients above the first sextile was 0.27 +/- 0.07 (se) years (two-sided p = 0.05). CONCLUSIONS: Patients presenting with an isolated episode of ventricular fibrillation in the absence of cerebrovascular disease or history of prior arrhythmia who have undergone revascularization or who have moderately preserved left ventricular function (left ventricular ejection fraction > 0.27) are not likely to benefit from ICD therapy compared with amiodarone therapy.     

HIV infection-associated immune activation occurs by two distinct pathways that differentially affect CD4 and CD8 T cells

HIV infection is characterized by a brisk immune activation that plays an important role in the CD4 depletion and immune dysfunction of patients with AIDS. The mechanism underlying this activation is poorly understood. In the current study, we tested the hypothesis that this activation is the net product of two distinct pathways: the inflammatory response to HIV infection and the homeostatic response to CD4 T cell depletion. Using ex vivo BrdU incorporation of PBMCs from 284 patients with different stages of HIV infection, we found that CD4 proliferation was better predicted by the combination of CD4 depletion and HIV viral load (R² = 0.375, P < 0.001) than by either parameter alone (CD4 T cell counts, R² = 0.202, P < 0.001; HIV viremia, R² = 0.302, P < 0.001). Interestingly, CD8 T cell proliferation could be predicted by HIV RNA levels alone (R² = 0.334, P < 0.001) and this predictive value increased only slightly (R² = 0.346, P < 0.001) when CD4 T cell depletion was taken into account. Consistent with the hypothesis that CD4 T cell proliferation is driven by IL-7 as a homeostatic response to CD4 T cell depletion, levels of phosphorylated STAT-5 were found to be elevated in naive subsets of CD4 and CD8 T cells from patients with HIV infection and in the central memory subset of CD4 T cells. Taken together these data demonstrate that at least two different pathways lead to immune activation of T cells in patients with HIV infection and these pathways differentially influence CD4 and CD8 T cell subsets.     

Regression analysis based on pairwise ordering of patients' clinical histories

When a medical treatment influences a variety of outcomes, describing the global effect of treatment can be difficult. Traditional approaches specify how treatment affects each separate outcome. This can be done with separate models for each outcome, or by using a combined multivariate model. Describing the overall effect of a treatment thus requires combining these separate effects in some fashion and can be difficult to explain. In this paper, I specify a regression model for use with multiple outcomes where the outcome histories for each pair of patients are ranked. Pairs of patients with different lengths of follow-up are evaluated solely over the common follow-up interval. The logit of the probability that the outcome for patient i is better than that of patient j is assumed to depend on a linear function of the difference of the covariate vectors (for example, treatment indicators) for persons i and j. Thus covariates directly affect the entire clinical history, rather than directly affecting specific outcomes that comprise the history. The idea is that ranking outcomes is more relevant and interpretable than statistically combining separate effects. An estimating equations approach for estimation is described and an example of a clinical trial involving patients with heart failure is provided.     

Variance imputation for overviews of clinical trials with continuous response.

Overviews of clinical trials are an efficient and important means of summarizing information about a particular scientific area. When the outcome is a continuous variable, both treatment effect and variance estimates are required to construct a confidence interval for the overall treatment effect. Often, only partial information about the variance is provided in the publication of the clinical trial. This paper provides heuristic suggestions for variance imputation based on partial variance information. Both pretest-posttest (parallel groups) and crossover designs are considered. A key idea is to use separate sources of incomplete information to help choose a better variance estimate. The imputation suggestions are illustrated with a data set.     

Molecular and flow cytometric characterization of the CD4 and CD8 T-cell repertoire in patients with myelodysplastic syndrome

We studied 18 patients with myelodysplastic syndrome (MDS), measuring clonality and T-cell receptor Vbeta (TCRBV) expression of CD4 and CD8 T cells by polymerase chain reaction and by flow cytometric analysis of TCRBV families. The CD4 and CD8 T-cell repertoire in most MDS patients is characterized by an abnormal TCRBV-restricted expansion of T cells in CD4 and CD8 cells, and increased expression of the CD8 effector marker CD57 of multiple TCRBV in CD8 cells. Clonality analysis of CD4 and CD8 cells showed that seven of 10 patients analysed had a major clone in the CD8 cells but not in CD4 cells. Furthermore, in one patient we found that both the CD57- and CD57+ fraction contained the clone (which was absent from the TCRBV-negative fraction). These data suggest that, in MDS, multiple T-cell expansions can be found in both helper and cytotoxic T cells, and that, in the CD8 cells, T cells functionally differentiate in vivo from memory to effector T cells. Together, these data support the hypothesis of the involvement of T cells in the pathogenesis of MDS.     

G-CSF-induced spleen size changes in peripheral blood progenitor cell donors

BACKGROUND: PBPC donors given G-CSF experience splenic enlargement and, rarely, spontaneous rupture of the spleen. This study evaluated the incidence and time course of splenic enlargement in PBPC concentrate donors and assessed factors affecting size changes. STUDY DESIGN AND METHODS: Twenty healthy adults were given G-CSF (10 microg/kg/day) for 5 days and a PBPC concentrate was collected by apheresis. Ultrasound was used to assess craniocaudal spleen length before giving G-CSF, on the day of apheresis and 3 or 4 days after apheresis. The effects of donor age, gender, race, and changes in blood chemistries, blood counts, and CD34+ cell counts on spleen length change were assessed. RESULTS: Spleen length increased in 19 of 20 donors. Mean length changed from 10.9 +/- 2.0 cm before G-CSF to 12.3 +/- 2.1 cm on the day of apheresis (p < 0.001). The mean increase in length was 1.5 +/- 0.9 cm or 13.8 +/- 9.1 percent. Spleen length increased 20 percent or more in six subjects. The spleen length fell to 11.3 +/- 1.8 cm (p < 0.001) 3 or 4 days after apheresis, but it remained greater than baseline levels (p = 0.03). Spleen length change was not affected by donor gender, race, or age. There was no relationship between changes in spleen length and 1) baseline and apheresis-day blood counts and chemistries, or 2) changes in blood counts and chemistries. CONCLUSIONS: Spleen size increases in almost all PBPC donors. Enlargement is transient but may be marked in some donors and may place them at risk for splenic rupture.