HLA-DR7 predicts the response to alkylating agents in steroid-sensitive nephrotic syndrome

There is a lack of reliable predictors of the response to alkylating agents in children with idiopathic nephrotic syndrome (NS). HLA-DR7 is strongly associated with the frequency of relapses in steroid-sensitive NS before cytostatic therapy. We therefore examined retrospectively the time to the first relapse and the incidence of subsequent relapses in 54 HLA-typed children with frequently relapsing NS, after treatment with cyclophosphamide (n = 49) or chlorambucil (n = 5) for 8 or 12 weeks; 38 patients were HLA-DR7 positive and 16 negative with 80% in both groups being steroid dependent. HLA typing was performed using serological or DNA typing methods. Renal biopsy showed minimal glomerular changes. A lower proportion of HLA-DR7 positive than negative patients remained in remission after 3 years (36% vs. 81%, P<0.02) and 5 years (36% vs. 72%, P<0.03). In the first 3 years after cytostatic therapy the mean number of prednisone-treated relapses was 1.3/patient per year in HLA-DR7-positive patients compared with 0.4 in negative patients (P<0.025). There was no statistically significant difference in the proportion of relapse-free patients with and without steroid dependency. The HLA status predicts the response of NS patients to alkylating agents better than the rate of previous relapses. Received September 19, 1995; received in revised form and accepted April 16, 1996     

Growth modulation of hepatocytes and rat liver epithelial cells (WB-F344) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

Modulation of DNA synthesis by 2,3,7,8-tetrachlorodi-benzo-p-dioxin(TCDD) was studied in primary cultures of hepatocytes and inrat liver epithelial cells (WB-F344) to develop models for studieson the interactions between the activated Ah receptor and cellulargrowth control. In hepatocytes TCDD either positively or negativelymodulated EGF-stimulated DNA synthesis. In the presence of ethlnylestradiol10^–12 M TCDD moderately increased EGF-stimulated DNA synthyesis(     

Cardiac Surgery in Nonagenarians

A bstract Objectives and Background : The purpose of this study was to document our initial experience with patients 90 years of age and older and to determine whether cardiac surgery is justified in this age group. Cardiac surgery in octogenarians has proven to be a successful and worthwhile procedure. A small group of nonagenarians with severe coronary artery disease (CAD) and aortic valve disease refractory to medical therapy have been considered for surgery. Methods : Fourteen patients aged 90 or more underwent cardiac surgery for symptomatic CAD or aortic valvular disease refractory to medical therapy. Eight patients underwent isolated coronary artery bypass grafting (CABG) and six patients underwent aortic valve replacement (AVR). All patients were in NYHA Class IV preoperatively. Results : Hospital mortality occurred in one patient (7%). Hospital morbidity occurred in 10 patients (71%) and included 7 cardiac, 5 neurological, 1 gastrointestinal, 1 infectious, and 1 pulmonary event. All survivors left the hospital symptomatically improved. The mean length of stay was 26 days. Four CABG patients went on to die at a mean of 2 years and 2 months, and 3 remain alive at a mean of 2 years and 4 months. Three AVR patients expired at a mean of 3 years and 4 months, and 3 remain alive at 4 years and 1 month. Conclusions : Cardiac surgery in carefully selected nonagenarians is justified and can be performed with acceptable results.     

Selection of Streptococcus pneumoniae Mutants Having Reduced Susceptibility to Moxifloxacin and Levofloxacin

With Streptococcus pneumoniae, moxifloxacin was 4- and 10-fold more effective than levofloxacin at restricting selection of resistant mutants and at killing resistant mutants, respectively. The selection frequency for first-step topoisomerase mutants was 1,000 times lower for moxifloxacin than for levofloxacin; this difference was lost when second-step mutants were selected.     

Self management of oral anticoagulation with the IN Ratio system: impact of a structured teaching program on patient's knowledge of medical background and procedures.

BACKGROUND: Self management of oral anticoagulation (OAC) decreases complication rates and improves quality of life. Manual and cognitive abilities of patients and patient training in a structured format are a precondition for this concept. Up to now, there is no evidence about knowledge increase from teaching programs. METHODS: Seventy-six patients (mean age, 57.4 years, 71% male) who started long-term OAC were included in the prospective multi-center study at three teaching centers representing different populations of anticoagulation patients: a department of cardiovascular surgery, an inpatient rehabilitation center and an anticoagulation clinic. The patients were trained in a structured education program for two days. For the evaluation, the patients performed standardized tests including 16 questions prior to start (T0), after each training unit (T1/T2) and 6 weeks later (T3). The primary endpoint was the percentage of > or =75% of patients who could answer > or =50% of questions correctly at T3. Secondary endpoints were the overall and item-specific percentages of correct answers at the end of each training unit (T1, T2) and at T3. In addition, the teaching program was rated by the patients on a six-point rating scale. RESULTS: Seventy-four out of 76 patients gave at least 50% correct answers at T3 (97.4%; 95% confidence interval, 90.8-99.7%). The average rates of correct answers developed from 40% (T0), 86% (T1), 94% (T2) to 96% (T3). The greatest increase of knowledge was observed with blood components, interpretation of International Normalized Ratio (INR) value, and the interaction of anticoagulation with other variables (e.g. drugs or infection). Patients rated the teaching program between 1 (best rating) and 2 at all time points. At T3, the patients reported less fear of complications and less limitations in their daily life than in earlier evaluations. CONCLUSION: The structured training program INRatio appears to be an appropriate instrument for instruction of INR self management. In comparison with baseline knowledge, the percentage of correctly answered questions was twice as high directly after the end of training and remained at a high level of >90% for at least 6 weeks.     

Multilevel surgery for obstructive sleep apnea: short-term results.

OBJECTIVE: To determine the efficacy of a new multilevel surgical protocol for obstructive sleep apnea (OSA). STUDY DESIGN AND SETTING: Sixty patients with moderate to severe OSA because of multilevel pharyngeal obstruction were enrolled into this prospective, controlled clinical trial after clinical examination, endoscopy, and polysomnography. Surgery included uvulaflap, tonsillectomy, hyoid suspension, and radiofrequency treatment of the tongue base (group A). A second group did not receive hyoid suspension (group B). In both groups, nasal surgery was performed if necessary. Polysomnography and Epworth Sleepines Scale (ESS) were recorded at baseline and 2 to 15 months after surgery. RESULTS: In group A, the mean apnea-hypopnea index (AHI) decreased significantly after surgery (38.9 +/- 20.0 vs 20.7 +/- 20.6, P < 0.0001), whereas in group B the AHI did not. All secondary variables (minimal oxygen saturation, mean oxygen saturation, arousal index), and the ESS significantly improved in group A with only changes in arousal index and ESS reaching levels of significance in group B. CONCLUSION: The presented protocol including the hyoid suspension proved to be effective in the treatment of OSA, whereas surgery without hyoid suspension was less successful. EBM rating: B-2b.