Phase I trial of sequential high-dose chemotherapy with escalating dose paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer

A single high-dose cycle of chemotherapy with stem cell support can produce disease-free survival of 15-20% for at least 3 years in women with responding stage IV breast cancer. North American Autologous Bone Marrow Transplant Registry data suggest that a complete response (CR) is the single most important prognostic factor associated with prolonged disease-free survival. Therefore, if sequential high-dose chemotherapy can increase the CR rate, then perhaps an increased proportion of patients will remain disease free. Women with at least a partial response (PR) to induction chemotherapy received three separate high-dose cycles of chemotherapy with peripheral blood progenitor support and granulocyte colony-stimulating factor. The first intensification was a dose escalation of paclitaxel (400-825 mg/ m2), the second intensification was melphalan (180 mg/m2), and the third intensification consisted of 6000 mg/m2 cyclophosphamide (1500 mg/m2/day), 500 mg/m2 thiotepa (125 mg/m2/day), and 800 mg/m2 carboplatin (200 mg/m2/day; CTCb). Thirty-six women were enrolled and 31 completed all three cycles. After the paclitaxel infusion most patients developed reversible predominantly sensory neuropathy. Of the 19 patients with measurable disease, 6 converted to CR, 7 converted to a PR* (the complete resolution of all soft tissue or visceral disease with sclerosis of prior lytic bone lesions), and 2 had a further PR for an overall response rate of 79%. Two patients had no further response and disease in two patients progressed, and thus they were taken off the study before CTCb. Seventy-eight percent are progression-free at a median follow-up of 14 months (range, 3-24+). Three sequential cycles of high-dose chemotherapy are feasible and were administered in this study with no mortality. Single agent paclitaxel at doses up to 825 mg/m2 were well tolerated with moderate reversible toxicity.     

Combined treatment of acute EAE in Lewis rats with TNF-binding protein and interleukin-1 receptor antagonist

Experimental autoimmune encephalomyelitis (EAE) is a term given to describe a collection of animal models representing the human disease multiple sclerosis (MS). Although not fully understood, the involvement of cytokines and the immune system in either EAE or human MS is well established. Past efforts have shown that inhibition of proinflammatory cytokines tumor necrosis factor (TNF-alpha) or interleukin-1 (IL-1) result in amelioration of acute EAE in Lewis rats. The present study examined this model for the effect of concomitant inhibition of both TNF-alpha and IL-1, which resulted in a modest but significant therapeutic effect that was superior to inhibition of either single agent alone with respect to four of the five variables used to follow the progression of disease in this model, i.e., clinical severity, frequency of disease, loss of body weight, and day of onset. These results are in accordance with the idea that combination treatments are likely to prove superior to single agent therapy in the treatment of autoimmune inflammatory disease.     

Cable properties of dendrites in hippocampal neurons of the rat mapped by a voltage-sensitive dye

Dendrites of pyramidal neurons from embryonic rat hippocampus are investigated in culture using a voltage-sensitive fluorescent dye. The electrical response to somatic stimulation is observed as a time-resolved map with a resolution of 0.9 microm at a time constant of 0.4 ms without signal averaging. The data are interpreted in terms of a tapering cable with Hodgkin-Huxley parametrization. The spread of short hyperpolarizing transients is damped by capacitive shunting. The invasion of an action potential is boosted by voltage-gated conductances of a low density. No irregularity is observed at a bifurcation. The passive cable parameters of internal resistance and membrane resistance at resting voltage are Ri = 300 omega cm and Rm = 40 (k)omega cm2 respectively, at a maximum sodium conductance of approximately 4.4 mS/cm2. The electrotonic length constant and the dynamic length constant at 1 kHz are 580 and 90 microm respectively. These results are compatible with electrophysiological data of dendrites in slices of adult hippocampus and with optical data of narrow processes of leech neurons in culture. The functional implications of boosting an action potential by voltage-gated channels of low density are considered.     

On not being rational

Summary A Bayesian decision-theoretic approach appears to me as a sensible idealization of a guide to behaviour. At the same time I would like to understand why my behaviour is not always of this form: I sometimes use randomization and I sometimes find confidence intervals acceptable. Not all of my problems have an explicit cost function. Am I lazy or irrational? Do I use non-Bayesian conventions to help communicate? Is the cost of rationality-computation missing from the Bayesian model?     

A novel class of antitumour agents. III. Morphological findings in treated cells

The findings of intracellular light-reflecting droplets and clotted mitoses after incubation of Walker and HeLa cells, human lymphocytes and rat fibroblasts with the synthetic amino steroid, 2beta, 16beta-dipiperidino-5alpha-androstane-3-alpha,17beta-diol dipivalate (DAP) were examined in detail. An interaction of DAP with the cellular membranes in all stages of cell life, with the exception of the Go-phase, is postulated.     

A high-power CH3F laser for plasma diagnostics

A high-power, optically pumped, methyl fluoride laser operating at 496 μm has been developed for plasma diagnostic applications. An output power of 100 mW has been measured directly on a calorimeter. The high-pump power utilized in this experiment has also allowed the first observation of saturation in far-infrared output power resulting from severe vibrational bottlenecking. The effect of buffer gases in relieving this bottlenecking is described and compared to a simple rate-equation model     

Traumatic rupture of duodenal diverticulum. Report of a case and literature review

Duodenal diverticulum is a common anatomic abnormality. Its inflammatory perforation is a rare complication, with less than 100 cases reported in the available literature. Traumatic perforation is exceedingly rare (only 3 cases reported). In this report one more case of traumatic perforation is presented, and the literature is reviewed focusing on the pathogenic, diagnostic and therapeutic aspects of this severe disease.     

Detection of free malignant cells in the peritoneal cavity before and after resection of colorectal cancer

PURPOSE: This study was designed to select the best monoclonal antibody to stain malignant cells in peritoneal wash fluid, and to investigate the incidence of free malignant cells in preresection and postresection colorectal cancer peritoneal washings using a combination of conventional cytology and immunocytochemistry. METHODS: Peritoneal washings were taken from 35 consecutive patients undergoing colorectal cancer resection. RESULTS: Malignant cells were isolated on a density gradient and identified by conventional cytology and an indirect immunoperoxidase stain. Malignant cells were identified in peritoneal washings from 15 patients (preresection only n = 3, postresection only n = 4, both n = 8). The origin of free malignant peritoneal cells in 11 preresection-positive washings must be the serosa. The origin of these cells in the four postresection-positive patients is uncertain: serosal and luminal spillage were considered unlikely and no circulating cells were found in the mesenteric vessels near the tumor. CONCLUSION: Tumor cells may have leaked out from lymphatics cut during the dissection.