Sensitivity to vecuronium in myasthenia gravis: a dose-response study

A cumulative dose plus infusion technique and integrated EMG monitoring of the first dorsal interosseous muscle were used to determine the potency of vecuronium in 20 normal patients and in ten patients with myasthenia gravis under thiamylal, N2O, O2, fentanyl anaesthesia. The mean (+/- SEM) values for ED50, ED90, and ED95 in the normal patients were 19 +/- 1, 31 +/- 1 and 36 +/- 2 micrograms.kg-1, respectively. Myasthenic patients showed increased sensitivity to vecuronium, the mean values for ED50, ED90, and ED95 were 10 +/- 2, 17 +/- 2 and 20 +/- 3 micrograms.kg-1, being 50, 55 and 56 per cent of normal, respectively. We did not demonstrate a difference in sensitivity to vecuronium between those myasthenic patients who received pyridostigmine preoperatively and those who did not, nor among those chronically treated with corticosteroids, compared with those who were not.     

Multiple forms of anti-acetylcholine receptor antibody in myasthenia gravis

Sera of patients with myasthenia gravis (MG) contain anti-acetylcholine receptor (AChR) lgG antibodies (Ab) which have different antigenic specificities. Three Ab types were detected: (1) MG-I, which forms immune complexes with AChR; (2) MG-C, which decreases binding of AChR to concanavalin A; and MG-B, which blocks α-bungarotoxin binding to AChR. Sera from 152 MG patients were screened for the Ab types. Sixty-one percent contained MG-I, 26% contained MG-C, 10% contained MG-B, and 5% contained both MG-C and MG-B. The latter Ab types were associated with more severe forms of MG but showed no other clinical correlations. IgG antibodies of defined type were purified, and their interaction with unlabeled and toxin-prelabeled AChR from denervated rat muscle was studied in detail. Receptors are homogeneous with respect to determinants recognized by MG-I, but heterogeneous with respect to determinants recognized by MG-C (3 subpopulations, 22%, 28%, and 50% of AChR) and by MG-B (2 subpopulations, 30% and 70% of AChR). The stoichiometry of AChR interaction with the antibodies indicates that for each toxin-binding site, the receptor is divalent as an antigen for MG-I and MG-C but is tetravalent for MG-B. Denervated muscle AChR appears to be a mixture of at least 3 molecular forms of AChR, each of which has distinct immunological features as well as components common to all the receptor subpopulations.     

Association of clinical progression in classic Kaposi's sarcoma with reduction of peripheral B lymphocytes and partial increase in serum immune activation markers

OBJECTIVE: To evaluate various immunologic markers in the peripheral blood of patients with early and advanced classic Kaposi's sarcoma (CKS). DESIGN: Cross-sectional study. SETTING: A major referral center for skin and venereal diseases. PATIENTS: Sixty-eight patients with histologically confirmed CKS staged according to a modified version of the Mitsuyasu-Groopman classification in stage I-II (cutaneous involvement only) and stage IV (skin and systemic involvement). MAIN OUTCOME MEASURES: Concentrations of neopterin and beta2-microglobulin, titer of anti-human herpesvirus 8 antibodies, number of natural killer cells, and numbers of total lymphocytes, B lymphocytes, T lymphocytes, and their subsets in peripheral blood. RESULTS: The median values of beta2-microglobulin and neopterin were elevated in patients with CKS in stage IV (median, 3.679 microg/mL [312.72 nmol/L] and 14.0 nmol/L, respectively) compared with patients in stage I-II (median, 2.406 microg/mL [204.51 nmol/L] and 6.5 nmol/L, respectively). A statistically significant reduction in total lymphocyte and B-lymphocyte counts was observed in patients with advanced-stage CKS (1679/microL and 79/microL, respectively) compared with patients in earlier stages of the disease (2142/microL and 224/microL, respectively). The human herpesvirus 8 antibody titer, determined by latent immunofluorescent assay, decreased from stage I-II to stage IV, although not at a statistically significant level (P = .14). CONCLUSION: The evolution of CKS from the early stages of the disease to the more advanced may be associated with a partial activation of the immune system and a gradual decrease in the number of total and B lymphocytes.     

Prospective assessment of emotional distress, cognitive function, and quality of life in patients with cancer treated with chemotherapy

BACKGROUND: The current study sought to delineate prospectively the rates and clinical course of emotional distress, cognitive impairment, and quality of life (QOL) in chemotherapy-naive patients with cancer and to consider the determinants of global QOL. METHODS: Patients who consented to participate were administered the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire, the Mini-Mental State Examination (MMSE), and the Hospital Anxiety and Depression Scale before and at the end of treatment (EOT). RESULTS: Of the 102 patients initially assessed, 80 (78.4%) completed the study. Most aspects of QOL did not change considerably over time. At EOT, patients reported only significant increases in fatigue and significant decreases in sleep disturbance. Although no significant changes emerged in the rates of anxiety or depression throughout chemotherapy, nearly one-third of the patients experienced severe emotional distress at both points in time. In addition, the authors observed neither significant alteration in the cognitive performance over time nor reliable associations between scores on the MMSE and subjective cognitive function, emotional distress, or QOL. Finally, depression proved to be the leading predictor of global QOL at baseline and at EOT. CONCLUSIONS: The results indicated that a significant proportion of Greek patients with cancer experienced intense anxiety and depression throughout chemotherapy and confirmed the importance of depression as a strong predictor of global QOL. Routine screening of emotional distress across all phases of cancer is mandatory because it will contribute to the identification of patients who are in need of pharmaceutical and/or psychologic intervention.     

Dose verification in clinical IMRT prostate incidents

PURPOSE: In view of the need for dose-validation procedures on each individual intensity-modulated radiation therapy (IMRT) plan, dose-verification measurements by film, by ionization chamber, and by polymer gel-MRI dosimetry were performed for a prostate-treatment plan configuration. Treatment planning system (TPS) calculations were evaluated against dose measurements. METHODS AND MATERIALS: Intensity-modulated radiation therapy (IMRT) treatments were planned on a commercial TPS. Kodak EDR-2 films were used for the verification of two-dimensional (2D) dose distributions at 1 coronal and 5 axial planes in a water-equivalent phantom. Full three-dimensional (3D) dose distributions were measured by use of a novel polymer gel formulation and a 3D magnetic resonance imaging (MRI) readout technique. Calculations were compared against measurements by means of isocontour maps, gamma-index maps (3% dose difference, 3-mm distance to agreement) and dose-volume histograms. RESULTS: A good agreement was found between film measurements and TPS predictions for points within the 60% isocontour, for all the examined plans (gamma-index <1 for 96% of pixels). Three-dimensional dose distributions obtained with the polymer gel-MRI method were adequately matched with corresponding TPS calculations, for measurements in a gel phantom covering the planning-target volume (PTV). CONCLUSIONS: Measured 2D and 3D dose distributions suggest that, for the investigated prostate IMRT plan configuration, TPS calculations provide clinically acceptable accuracy.     

Bioequivalence evaluation of 2 brands of cefuroxime axetil 250 mg tablets in healthy human volunteers

OBJECTIVE: To assess the bioequivalence of 2 oral cefuroxime axetil (250 mg) tablets formulation. The reference preparation was Zinadol/Glaxo Wellcome, England, while the test preparation was cefuroxime axetil/Pharmathen, Athens, Greece. SUBJECTS, MATERIAL AND METHODS: The study was an open, randomized, 2-period, 2-sequence, 2-treatment crossover, involving 24 healthy male and female volunteers. All volunteers completed the study. Cefuroxime axetil plasma concentrations were measured utilizing a sensitive, reproducible and accurate HPLC method. Care was taken through the collection and analysis of the samples due to instability of cefuroxime axetil in light. Pharmacokinetic parameters used to assess bioequivalence were AUC(0-last), AUC(0-inf) for the extent of absorption and Cmax and tmax for the rate of absorption. Statistical evaluation of Cmax, AUC(0-last), and AUC(0-inf) was done using 2-way analysis of variance (ANOVA) after semilogarithmic transformation. Tmax values were tested using the distribution-free Hodges-Lehman interval. RESULTS: The parametric 90% confidence intervals for ratio T/R ranged from 98.91-111.65% (point estimate 105.09%) for AUC(0-last), 99.41-111.78% (point estimate 105.41%) for AUC(0-inf) and 87.61-102.89% (point estimate 94.95%) for Cmax, respectively. Based on the results of tmax, K(el) and t(1/2) there were no statistically significant differences. CONCLUSION: The 2 cefuroxime axetil preparations, examined in accordance with the European Union bioequivalence requirements, are equivalent with respect to rate and extent of absorption.     

Prognostic significance of the deleted in colorectal cancer gene protein expression in high-risk resected gastric carcinoma

The deleted in colorectal cancer (DCC) gene is a candidate tumor suppressor gene that may be associated with differentiation and proliferation of normal cells. Loss of heterozygosity (LOH) of 18q, where the gene is located, and absence of DCC protein expression have been associated with worse prognosis in certain subgroups of patients with colorectal adenocarcinoma. We studied the prognostic significance of loss-of-protein expression in 66 patients with resected gastric cancer with a high probability of relapse (T3, T4, N+). The DCC protein was detected with immunohistochemistry using an anti-DCC monoclonal antibody on paraffin-embedded sections. The DCC protein expression was present in 51 cases (77.3%) and absent in 15 cases (22.7%). Poorly differentiated and signet ring carcinomas had significantly lower expression than more differentiated tumors (p < 0.05) as did diffuse-type tumors compared to intestinal and mixed (p < 0.01). There was no correlation with proliferation rate, estimated immunohistochemically using an anti-proliferating cell nuclear antigen (PCNA) monoclonal antibody. Absence of DCC protein was an independent favorable prognostic factor (median survival 57 months vs. 18 months, p = 0.0176). The DCC protein expression was correlated with relapse site: all patients with distant metastases were positive for DCC staining, while one-third of patients with local/peritoneal relapse were negative (p < 0.01). In conclusion, DCC protein expression seems to be a significant prognostic factor in high-risk resected gastric cancer. Our results support previous data associating the DCC gene with differentiation and indicate that this gene may play a role in the metastatic potential of these tumors. These findings need to be confirmed by future larger studies.