Effect of amifostine on toxicities associated with radiochemotherapy in patients with locally advanced non-small-cell lung cancer

PURPOSE: Radiochemotherapy (RCT) is an effective treatment for locally advanced non-small-cell lung cancer (NSCLC), but can be limited by acute and late toxicities (esophagitis, pneumonitis, and myelosuppression). This trial investigated whether pretreatment with amifostine, a radioprotector, could reduce the incidence of radiochemotherapy-induced acute and late toxicities. METHODS AND MATERIALS: Between October 1997 and August 1999, 73 patients with previously untreated Stage IIIa-IIIb NSCLC were randomized to treatment with RCT alone (n = 36) or RCT plus amifostine (300 mg/m(2) daily i.v. infusion, n = 37). RCT consisted of either paclitaxel (60 mg/m(2)) or carboplatin (AUC 2) once weekly during a 5- to 6-week course of conventional radiotherapy given as 2 Gy/5 days/week to a total dose of 55 to 60 Gy. Blood cell counts were measured weekly; esophagitis and acute lung toxicity were evaluated during the treatment course. Treatment efficacy was assessed following World Health Organization criteria for response. Late lung toxicity was assessed at 3 and 6 months after RCT and was graded from 0 to 4 according to the Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer criteria. RESULTS: A total of 68 patients were evaluable for toxicity analysis (RCT group, n = 32; RCT + amifostine, n = 36). There was no significant difference between treatment arms in patient baseline characteristics. The incidence of Grade >or=3 esophagitis during RCT was significantly lower for patients receiving amifostine than for patients receiving RCT alone (38.9% vs. 84.4%%, p < 0.001). Furthermore, the incidence of Grade >or=3 acute pulmonary toxicity was significantly reduced in patients treated with RCT plus amifostine compared to patients who received RCT alone (19.4% vs. 56.3%, p = 0.002). At 3 months after RCT, patients treated with amifostine had a significantly lower incidence of pneumonitis than patients who received RCT alone (p = 0.009). Combined response rates (complete plus partial responses) were 82.2% in the RCT group and 88.8% in the RCT plus amifostine group (p = 0.498).Amifostine is effective in reducing the incidence of both acute and late toxicities associated with RCT in patients with locally advanced NSCLC without compromising antitumor efficacy.     

Human leukocyte antigen mismatches predispose to the severity of bronchiolitis obliterans syndrome after lung transplantation

BACKGROUND: Obliterative bronchiolitis (OB) is the most important cause of long-term morbidity and mortality in lung transplant recipients, and probably results from alloimmune airway injury. Bronchiolitis obliterans syndrome (BOS), defined as a staged decline in pulmonary function, is the clinical correlate of OB. OBJECTIVE: Evaluation of the risk and severity of BOS on the basis of the incompatibility of donor and recipient human leukocyte antigen (HLA) molecules. DESIGN: Retrospective cohort study. SETTING: Large university hospital. PARTICIPANTS: Lung transplant recipients between January 1990 and January 2000. MEASUREMENTS: We determined the BOS stage using internationally promulgated guidelines with a minor modification on all recipients at their 4-year transplant anniversary. Recipients whose graft function had deteriorated or who died due to causes other than BOS were excluded from the study. HLA loci mismatches and other covariables, including recipient age, donor age, cytomegalovirus (CMV) mismatch, cold ischemic time, use of cardiopulmonary bypass, ventilatory days, episodes of acute rejection and CMV pneumonitis, mean trough cyclosporin A (CsA) level, episodes of subtherapeutic CsA levels, and histopathology of OB and diffuse alveolar damage were entered into the analysis of BOS predictors. RESULTS: Sixty-four patients met the inclusion and exclusion criteria of the study at the 4-year posttransplant time point. In univariate analyses, the number of combined HLA-A and HLA-B mismatches was strongly associated with the stage of BOS at 4 years (p = 0.002). This association remained significant after the inclusion of other potential risk factors for BOS in multiple linear regression models. Pretransplant and posttransplant proportional odds models confirmed that the increasing number of combined HLA-A and HLA-B mismatches increased the overall severity of BOS (adjusted odds ratio, 1.84 [p = 0.035] vs 1.69 [p = 0.067], respectively). A trend toward significance was seen with HLA-DR mismatching (p = 0.17). CONCLUSIONS: The degree of HLA class I mismatching between donors and recipients predisposes lung transplant recipients to the development and severity of BOS.     

Diminished and erratic absorption of ergocalciferol in adult cystic fibrosis patients

BACKGROUND: Osteoporosis diminishes the quality of life in adults with cystic fibrosis (CF). Vitamin D deficiency resulting from malabsorption may be a factor in the etiology of low bone mineral density (BMD) in patients with CF. OBJECTIVE: Absorption of oral ergocalciferol (vitamin D2) and the consequent response of 25-hydroxyvitamin D in 10 adults with CF and exocrine pancreatic insufficiency was compared with that of 10 healthy control subjects. DESIGN: In this pharmacokinetic study, CF patients and control subjects were pair-matched on age, sex, and race. Each subject consumed 2500 microg oral vitamin D2 with a meal. The CF group also took pancreatic enzymes that provided > or = 80000 U lipase. Blood samples were obtained at baseline and at 5, 10, 24, 30, and 36 h after vitamin D2 consumption to measure serum vitamin D2 and 25-hydroxyvitamin D concentrations. RESULTS: Vitamin D2 concentrations in all subjects were near zero at baseline. CF patients absorbed less than one-half the amount of oral vitamin D2 that was absorbed by control subjects (P < 0.001). Absorption by the CF patients varied greatly; 2 patients absorbed virtually no vitamin D2. The rise in 25-hydroxyvitamin D in response to vitamin D2 absorption was significantly lower over time in the CF group than in the control group (P = 0.0012). CONCLUSIONS: Vitamin D2 absorption was significantly lower in CF patients than in control subjects. These results may help explain the etiology of vitamin D deficiency in CF patients, which may contribute to their low BMD.     

Setting characteristics and cavity adaptation of low-shrinking resin composites

ObjectivesThe aim of this study was to evaluate the setting characteristics of low-shrinking resin composites and examine the possible interactions with curing efficiency and marginal adaptation in dentin cavities.MethodsThe materials tested were Ceram X Mono/CM, Premise/PR, Clearfil Majesty/CM, ELS/EL, and Filtek Silorane/FS. Polymerization shrinkage strain (%S), strain rate (%S_r) and time at maximum strain rate (t_max) were measured using the bonded disk method. Curing efficiency was measured on the top and bottom surfaces of composites with ATR-FTIR spectroscopy. Marginal adaptation was measured in unbonded (%VVF) and bonded (%XVF) specimens by computerized X-ray microtomography (micro-XCT). The % linear length of the interfacial gaps along the cavity margins (%LD) and the maximum gap width (WD_max) were calculated under optical microscopy on sectioned specimens. Statistical analysis was performed with one- and two-way ANOVA, Bonferroni's post hoc test and Pearson's correlation coefficient.ResultsThe %S values ranged from 1.34% (FS) to 2.29% (CX), while %S_r ranged from 0.06%s^?1 (FS) to 0.15%s^?1 (CX). %VVF values extended from 1.9% (FS) to 5.3% (CX) and for %XVF from 1.98% (FS) to 3.35% (CX). The values for %LD ranged from 36.52% (FS) to 81.28% (CX). Linear regression showed strong positive correlation for %S_r and t_max with %VVF (r² = 0.884 and r² = 0.927) and also for %S_r and t_max with %LD (r² = 0.823 and r² = 0.869).Significance%S_r and t_max are more representative than %S in determining the setting pattern of the materials and are strongly correlated to marginal adaptation. The silorane material showed better behavior than the dimethacrylate materials in setting shrinkage and marginal adaptation.     

Concentric needle single fiber electromyography: comparative jitter on voluntary-activated and stimulated Extensor Digitorum Communis.

OBJECTIVE: To compare the jitter values in voluntarily activated (v-CNE) and stimulated (s-CNE) techniques for Extensor Digitorum Communis muscle using a disposable concentric needle electrode (CNE). Quantifying jitter using a CNE in conjunction with a stimulated technique has not been reported previously. METHODS: Forty-one normal subjects were studied, 15 male and 26 female with a mean age of 34.1+/-10.7 years (19-55). The jitter values were expressed as the mean consecutive difference (MCD) of 20 analyzed potential pairs using v-CNE and 30 isolated potentials using s-CNE. RESULTS: The mean MCD (n=41) was 23.0+/-2.8 micros for v-CNE and 18.2+/-2.2 micros for s-CNE. The mean jitter of all recorded potentials was 22.9+/-6.7 micros for v-CNE (n=820) and 18.3+/-5.2 micros for s-CNE (n=1230). Upper limits for the 18th (v-CNE) and 27th highest (s-CNE) MCD were 38.9 and 30 micros, respectively (95% confidence limit). The jitter decrease in s-CNE compared to v-CNE was 1:0.79. CONCLUSIONS: Our findings of the jitter values using CNE were similar to other published reports using the voluntarily activated technique; however, these are the first described for the stimulated technique using CNE. SIGNIFICANCE: The present study confirms that CNE can be used for the stimulated jitter acquisition and measurement, although certain precautions must be taken regarding signal quality, e.g., observing minimal summation.     

Lung transplantation for cystic fibrosis patients with Burkholderia cepacia complex. Survival linked to genomovar type.

The number of cystic fibrosis (CF) patients undergoing lung transplant has risen over the past decade, because of a clear-cut survival benefit. However, patients with Burkholderia cepacia complex are often excluded from transplantation because of increased mortality. To determine the influence of B. cepacia complex genomovar type on transplant outcome, we undertook a retrospective study in 121 CF patients transplanted at UNC. Twenty-one and three patients, respectively, were infected pre- or postoperatively with B. cepacia complex. All posttransplant acquisitions were successfully treated. However, excess mortality occurred over the first 6 postoperative months in those infected preoperatively with B. cepacia complex compared with those not infected (33% versus 12%, p = 0.01). The 1-, 3-, and 5-yr survival were significantly lower in the B. cepacia complex cohort. Of the patients infected preoperatively, genomovar III patients were at the highest risk of B. cepacia complex-related mortality (5 of 12 versus 0 of 8, one isolate not typed; p = 0.035). Each of the B. cepacia complex-related deaths was caused by a unique genotype as determined by pulsed-field gel electrophoresis. All isolates were negative for the cable pilin gene. These results warrant a multicenter analysis of B. cepacia complex-infected patients with genomovar-typing to confirm that genomovar III patients are at highest risk for post-transplant complications.     

Survival time of patients with acquired immune deficiency syndrome: experience with 274 patients in Dar-es-Salaam

To determine the survival time once acquired immune deficiency syndrome (AIDS) has developed, we analysed case records of 274 patients confirmed to have died of the disease. Of the 274 patients 193 were males and 81 females (M:F 2:1). The duration of symptoms ranged from a few weeks to two years but over 70% had apparently enjoyed good health until 2-3 months before diagnosis. Weight loss, severe weakness, chronic diarrhoea, prolonged fevers and oro-pharyngeal candidosis were the commonest features. Kaposi's sarcoma (KS) was the presenting feature in 2 (0.7%) patients. Frequent concurrent illnesses included tuberculosis (19%), unspecified (23%) and skin lesions other than KS (24%). In 31 (11.3%) patients no concurrent illness was detected. The survival after one week was 63.5% and 7.5% at the end of three months. These results indicate that due to a combination of factors survival of AIDS patients in developing countries is much shorter than in developed countries.