Phase I dose escalation study of carboplatin to a fixed dose of irinotecan as first-line treatment of small cell lung cancer

BACKGROUND: Superiority of irinotecan (CPT-11) plus cisplatin over etoposide plus cisplatin in small cell lung cancer (SCLC) has recently been demonstrated. This study determines dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of escalating doses of carboplatin to a fixed dose of irinotecan in Caucasians with small cell lung cancer. PATIENTS AND METHODS: Patients with extensive small cell lung cancer received 50 mg/m(2) irinotecan on day 1, 8, and 15. Dose escalation of carboplatin on day 1 started in dose level 1 at an AUC of 5 mg x min/ml and was escalated to AUC 6 in level 2. Cycles were repeated on day 29. Dose escalation was evaluated after 3 consecutive patients. If no grade IV neutropenia lasting for > or =7 days or thrombopenia or non-hematologic toxicity > or = grade III occurred, treatment was continued in the next dose level. RESULTS: 16 patients were treated. DLT was reached in dose level 2 with 2 grade IV neutropenias and 1 grade IV thrombopenia and diarrhea. Toxicity was further investigated at dose level 1 in a total of 10 patients, which revealed 2 grade III neutropenias and 1 grade III diarrhea. Of 15 evaluable patients, 10 had a partial response, 3 had disease stabilization and 2 progressed. CONCLUSION: Dose level 1 was found to be MTD, this dose is currently compared to the combination of etoposide plus carboplatin within a randomised phase II/III trial.     

Robotic technology and stroke rehabilitation: translating research into practice

Research on the effectiveness of robotic therapy for the paretic upper limb after stroke has shown statistically significant reductions in motor impairment during both acute and chronic phases of recovery. Despite growing empirical support for this technology and a stronger focus on optimizing rehabilitation outcomes and productivity, there continues to be a disconnect between research and clinical practice. We review studies on the use of robot-aided neurorehabilitation for the paretic arm after stroke and discuss ways in which this technology may provide opportunities for intensive training that complement more conventional therapy methods.     

Working memory deficits in adult rats after prenatal disruption of neurogenesis

We investigated the cognitive consequences of a prenatal injection of the mitotic inhibitor methylazoxymethanol (MAM) into pregnant rats at embryonic day 15 (E15) or 17 (E17). The male offspring were tested when adult on a version of the radial-arm maze task that assesses spatial working memory with an extended delay, where performance is dependent, in part, on the hippocampal-prefrontal circuit. A major impairment of spatial learning was observed in E15 MAM rats. However, the E17 MAM rats did learn the rule but were impaired selectively in the 30-min delay-interposed task. Morphologically, the E15 MAM rats exhibited dramatic gross brain abnormalities, whereas the E17 MAM animals displayed aberrant cell migration in the hippocampus and a disrupted laminar pattern in the neocortex. These results suggest that late gestational MAM injection (E17) causes a cognitive impairment in a prefrontal cortex-hippocampus-dependent working memory task. This approach could provide a new developmental model of disorders associated with working memory deficits, such as schizophrenia.     

Disease severity at time of referral for pediatric failure to thrive and obesity: time for a paradigm shift?

The percent of ideal body weight at first visit to pediatric referral clinics was compared by chart review between patients with failure to thrive and obese patients. Results indicated that underweight children were mildly underweight, whereas the overweight children were severely so. In primary care settings, underweight children may be referred more aggressively than overweight children.     

Clonal T cell-mediated cyclic thrombocytopenia

Cyclic thrombocytopenia is a rare disorder characterized by periodic platelet count fluctuations of unknown aetiology. We report on a female patient with cyclic changes of platelet counts ranging from 6 x 10(9)/l to 753 x 10(9)/l in 4-week intervals. Platelet counts were inversely correlated to thrombopoietin levels suggesting production failure. Reticulocyte counts and neutrophil counts showed similar, but less prominent, fluctuations. Clonal T-cell receptor rearrangement was detected in bone marrow samples as well as in peripheral blood. Cell typing of blood lymphocytes revealed a relative increase in CD3+ T cells. Treatment with cyclosporine A resulted in a substantial improvement of platelet counts. Taken together, we provide evidence for clonal T-cell mediated bone marrow failure with cyclic impairment of thrombopoiesis responsive to cyclosporine therapy.     

Degradation of hydroxyapatite coating on a well-functioning femoral component

We carried out a histological study of a proximally hydroxyapatite (HA)-coated femoral component, retrieved after 9.5 years of good function. The HA coating had completely degraded. Bone was in direct contact with the titanium surface in all the areas which had been coated, with no interposing fibrous tissue. There were no signs of particles, third-body wear, adverse tissue reactions or osteolysis. Bone remodelling was evident by the presence of resorption lacunae; tetracycline labelling showed bone laid down six years after implantation. The loss of the HA-coating had no negative effect on the osseo-integration of the stem. We conclude that the HA coating contributes to the fixation of the implant and that its degradation does not adversely affect the long-term fixation.     

Jail-based substance user treatment: an analysis of retention

Many jail inmates have a history of substance use and "abuse"; few, however, receive comprehensive treatment for substance use disorders while in jail. The authors offer a longitudinal reanalysis of data from five jail-based substance user treatment programs. Survival analysis was used to identify client characteristics associated with length of time in treatment. Survival curves for the five programs were compared, indicating which ones retained inmates the longest. Results from a model stratified by jail site revealed that inmates over 25 years of age and those already sentenced had significantly longer treatment stays. The Substance Abuse Intervention Division (SAID) program, a modified therapeutic community in a New York jail, and the Deciding, Educating, Understanding, Counseling, and Evaluation (DEUCE) program, a curriculum-based intervention, had the longest survival curves and were, therefore, most effective at retaining inmates in treatment.     

Neurological soft-signs and minor physical anomalies in schizophrenia: differential transmission within families

Markers of vulnerability have been identified in schizophrenia, and among them, neurological soft-signs (NSS) and minor physical anomalies (MPAs) also seem to occur in biological relatives. The similarities of these developmental markers within families may depend on either genetic or non-genetic factors. The aim of the study was to investigate the intra-familial similarities of NSS and MPAs within 18 nuclear families (18 probands with schizophrenia and 36 of their non-psychotic parents). A general linear model showed similarities within families for NSS (intra-class coefficient [ICC] = 0.64; F = 2.6; df = 17.17; p = 0.02) but not for MPAs (ICC = -0.10; F = 0.7; df = 17.17; ns). We thus found a direct evidence for the intra-familial transmission of NSS but not of MPAs, suggesting that this morphological phenotypic trait could be more dependent on epigenetic influences.