High-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV +/- P) and autologous transplantation for patients with Hodgkin's disease who fail to enter a complete remission after combination chemotherapy

Patients with Hodgkin's disease (HD) who fail to enter a complete remission after an initial course of combination chemotherapy are usually considered to have an induction failure (IF); this subset of patients has an extremely poor outcome with further conventional therapy. Since 1985, we have entered 30 IF patients into protocols using conditioning with high-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV +/- P) followed by autologous stem cell transplantation (ASCT) with bone marrow (19 patients), peripheral blood stem cells (PBSCs; 8 patients), or both (3 patients). All except 2 patients had previously received chemotherapy regimens for HD that contained at least 7 drugs, and 9 had received prior radiotherapy (RT). After documentation of IF, the majority of patients received some cytoreductive therapy as specified by protocol (local RT in 9, two cycles of conventional chemotherapy in 2, both modalities in 2, or high-dose cyclophosphamide to enhance PBSC collection in 11) before CBV +/- P. Five treatment-related deaths occurred, all before day 150 posttransplant. Eleven patients have had progressive HD at a median of 6 months (range, 0.1 to 45 months) after ASCT. The actuarial progression-free survival (PFS) at a median follow- up of 3.6 years (range, 0.2 to 8.2 years) is 42% (95% confidence intervals, 21% to 61%). The statistical analysis identified only prior clinical bleomycin lung toxicity as an adverse risk factor for PFS, mainly because of the increased nonrelapse mortality seen in these patients. CBV +/- P and ASCT can produce durable remission in a substantial proportion of IF HD patients who otherwise have a poor survival, and we believed ASCT approaches represent the best therapy currently available for these patients. Additional measures are needed to reduce the primary problem of disease progression despite high-dose chemotherapy and stem cell transplantation.     

Schneiderian First Rank Symptoms and Gamma Oscillatory Activity in Neuroleptic Na?ve First Episode Schizophrenia: A 192 Channel EEG Study

Objective

Schneiderian first-rank symptoms (FRS) and abnormal EEG gamma activity in schizophrenia have been reported independently to have a neurodevelopmental basis. We aimed to investigate spontaneous gamma power in two groups of first episode schizophrenia patients (those who experience FRS and those who do not).

Methods

A comparative hospital based study having 37neuroleptic naïve male patients with schizophrenia divided into two groups-FRS(+) and FRS(-) groups based on the presence of FRS. Thirty age, sex, education and handedness matched individuals served as controls (N). All participants underwent a 192-channel resting Electroencephalography (EEG) recording. Gamma spectral power was calculated for low- (30-50 Hz) and high-gamma 1 & 2 (51-70 and 71-100 Hz) bands. Spectral power was compared between three groups using MANOVA and supplementary one-way ANOVA with Bonferroni test controlling for multiple comparisons. Linear regression was used to identifying predictor variables for FRS. Pearson correlation coefficient was computed between spectral power parameters and various clinical variables.

Results

Significantly higher high gamma band-1 power was observed over right frontal (p<0.05), parietal (p<0.05) and temporal (p<0.05) regions in FRS(+) than FRS(-) group and normal controls. Right parietal high gamma-1 power and paranoid cluster on PANSS significantly predicted number of FRS in total schizophrenia patients; paranoid cluster on PANSS showed significant correlation with number of FRS in FRS(+) group.

Conclusion

Findings of our study add to the evidence that areas contained within the hetero modal association cortex are associated with FRS. The study findings also strengthen the neurodevelopmental basis of FRS in schizophrenia.     

MR imaging of the breast with Gd-DTPA: use and limitations

Between August 1985 and November 1987, 150 patients with 167 biopsy-proved lesions were examined with magnetic resonance (MR) imaging enhanced with gadolinium diethylenetriaminepentaacetic acid, mammography, and palpation. Of these patients, 113 with 123 lesions were also examined with ultrasound. Enhancement above 300 normalized units (NU) on MR images was considered significant; between 250 and 300 NU, borderline; and below 250, nonsignificant. All 27 fibroadenomas and 70 of 71 carcinomas showed significant enhancement; one carcinoma showed borderline enhancement. Nonproliferative dysplasia showed nonsignificant enhancement in 15 of 16 cases and significant enhancement in one, whereas proliferative dysplasia showed usually diffuse enhancement varying from nonsignificant (five of 30 cases) to borderline (five of 30 cases) to significant (20 of 30 cases). In the nonblind evaluation of the modalities, MR imaging compared favorably. When limitations of the technique were considered, MR imaging seemed beneficial as a supplement in selected, diagnostically difficult cases.     

VX-166: a novel potent small molecule caspase inhibitor as a potential therapy for sepsis

Introduction  

Prevention of lymphocyte apoptosis by caspase inhibition has been proposed as a novel treatment approach in sepsis. However, it has not been clearly demonstrated that caspase inhibitors improve survival in sepsis models when dosed post-insult. Also, there are concerns that caspase inhibitors might suppress the immune response. Here we characterize VX-166, a broad caspase inhibitor, as a novel potential treatment for sepsis.     

Brainstem glioma progression in juvenile and adult rats

OBJECT： Brainstem gliomas are common in children and have the worst prognosis of any brain tumor in this age group. On the other hand, brainstem gliomas are rare in adults, and the authors of some clinical studies have suggested that this lesion behaves dif ferently in adults than in children. In the present study, the authors test an orthotopic C6 brainstem glioma model in juvenile and adult rats, and investigate the biological behavior of this lesion in the 2 age groups. METHODS： The C6 glioma cells were stereotacti eally implanted into the pons of juvenile or adult male rats. Neurological presentation and survival time were recorded.