A multicentre phase II trial of bryostatin-1 in patients with advanced renal cancer

Protein kinase C (PKC) has a critical role in several signal transduction pathways, and is involved in renal cancer pathogenesis. Bryostatin-1 modulates PKC activity and has antitumour effects in preclinical studies. We conducted a multicentre phase II clinical trial in patients with advanced renal cancer to determine the response rate, immunomodulatory activity and toxicity of bryostatin-1 given as a continuous 24 h infusion weekly for 3 out of 4 weeks at a dose of 25 mug m(-2). In all, 16 patients were recruited (11 males and five females). The median age was 59 years (range 44-68). Patients had been treated previously with nephrectomy (8) and/or interferon therapy (9) and/or hormone therapy (4) and/or radiotherapy (6). Eight, five and three patients had performance statuses of 0, 1 and 2, respectively. A total of 181 infusions were administered with a median of 12 infusions per patient (range 1-29). Disease response was evaluable in 13 patients. Three patients achieved stable disease lasting for 10.5, 8 and 5.5 months, respectively. No complete responses or partial responses were seen. Myalgia, fatigue, nausea, headache, vomiting, anorexia, anaemia and lymphopenia were the commonly reported side effects. Assessment of biological activity of bryostatin-1 was carried out using the whole-blood cytokine release assay in six patients, two of whom had a rise in IL-6 levels 24 h after initiating bryostatin-1 therapy compared to pretreatment values. However, the IL-6 level was found to be significantly lower at day 28 compared to the pretreatment level in all six patients analysed.     

Assessing the information management requirements for behavioral health providers

Behavioral health agencies will soon implement automated information-management systems to support their administrative, financial, and clinical care functions. Assessing current information-management capabilities and delineating future needs are prerequisite to recommending a specific information technology solution. Quantifying the discrepancy between current information-management capabilities and future requirements highlights the areas of greatest unmet need for information management. Selecting an information system that addresses the most critical areas of unmet need is a prudent purchase decision. This article describes the results of a process to assess the information-management requirements for agencies that were considering implementation of an integrated behavioral health information-management system. The assessment revealed that these agencies already employed automated systems to manage most financial functions and many administrative functions. Few agencies, however, utilized automated systems to manage clinical care functions. Selection of a behavioral health electronic medical record (EMR) effectively addressed clinical care information-management needs without duplicating existing financial and administrative management functions. Also, the EMR included features that addressed some administrative functions for which a discrepancy between current capabilities and future needs was found. Selecting an EMR instead of an integrated behavioral health information system was associated with a significant reduction in information system acquisition costs.     

Comparison of the performance of selenite cystine and mannitol selenite enrichment broths in the isolation of Salmonella spp. from faeces

Over a four-month period, 4,658 routine faecal samples were examined in four laboratories and the isolation rates of Salmonella spp. from mannitol selenite (MS) and selenite cystine (SC) broths plated to xylose lysine desoxycholate agar (XLD) compared. The isolation rate by MS was 1.55% and by SC was 1.48%, a small difference which is not statistically significant. Significantly fewer colonies were selected for supplementary testing from SC than MS (p = 0.029), thus reducing confirmatory work. In laboratories where SC is already used for food and environmental work, an opportunity exists to limit stocked salmonella enrichment broths to SC alone.     

Relative lack of cognitive effects of methylphenidate in elderly male volunteers

Rationale Methylphenidate, a dopaminergic and noradrenergic reuptake inhibitor, has been shown in young, healthy adult volunteers to produce pronounced effects on working memory and sustained attention. We were interested in assessing whether similar improvements could be conferred upon elderly volunteers in order to gain a more complete understanding of the effects of age on monoaminergic manipulations of working memory and attention, as well as to explore the potential for pharmacological intervention in attention and executive dysfunction disorders in this age group. Objectives The main aim of the study was to characterise the dose-related effects of methylphenidate on a range of neuropsychological functions in elderly healthy volunteers. Methods Sixty healthy elderly adult male volunteers received either a single oral dose of placebo, 20 mg or 40 mg methylphenidate prior to performing a variety of tasks designed to assess memory, attention and executive function. A randomised double-blind, between-subjects design was used. Results Methylphenidate had significant cardiovascular and subjective effects. However, unlike in younger volunteers, no significant effects of drug on working memory (spatial span and spatial working memory), response inhibition (stop-signal) or sustained attention (rapid visual information processing) were seen. Subtle effects on latency similar to those in younger volunteers were identified: both doses of methylphenidate resulted in a slowing in response time during set-shifting and decision-making. Conclusions The results of this study demonstrate that, in elderly subjects, the cognitive effects of methylphenidate are grossly attenuated and distinct from the profile previously described in younger volunteers. It is suggested that methylphenidate may not be appropriate as a pharmacological intervention in elderly patient groups, such as those reporting age-related cognitive decline.     

131I-Anti CD20 radioimmunotherapy of relapsed or refractory non-Hodgkins lymphoma: a phase II clinical trial of a nonmyeloablative dose regimen of chimeric rituximab radiolabeled in a hospital

In order to increase the availability and affordability of radioimmunotherapy of refractory or relapsed non-Hodgkins lymphoma, we developed and evaluated radioiodinated rituximab in an ongoing physician-sponsored Phase II Clinical Trial. The chimeric 1gG(1) anti CD 20 monoclonal antibody rituximab was radiolabeled with iodine-131 using a modified Chloramine T method with high radiochemical purity (98% +/- 0.82) and preservation of immunoreactivity. All patients received therapeutic loading doses of unlabeled rituximab (375 mg/m(2)) immediately prior to administration of tracer (200 MBq (131)I) or therapy (1.7-4.3 GBq (131)I) activities of (131)I-rituximab to provide additive immunotherapy and enhance tumor uptake of the radiolabeled antibody. Objective response rate (ORR) was 71% in 35 patients with a median follow-up of 14 months (range 4-28 months). Complete remission (CR) was achieved in 54% of patients, with median duration 20 months. Toxicity evaluation included an additional 7 patients followed for at least 3 months. Tracer dosimetry studies were performed in each patient and the whole body radiation absorbed dose was limited to a mean prescribed dose (MPD) of 0.75 Gy. Myelosuppression was reversible and in only 2 of 42 patients was grade IV hematological toxicity observed. No hemopoietic support was required in any patient. There was no instance of hemorrhage or infection in this group of patients in each of whom individual prospective dosimetry was performed prior to (131)I rituximab radioimmunotherapy for relapsed or refractory non-Hodgkins lymphoma.     

Plasmablastic lymphoma of the lung: report of a unique case and review of the literature

Non-Hodgkin lymphomas associated with acquired immunodeficiency syndrome are heterogeneous. Recently, a novel subtype of non-Hodgkin lymphoma occurring mostly in patients with acquired immunodeficiency syndrome has been described and designated as plasmablastic lymphoma. The histomorphologic and immunophenotypic findings of this distinct subtype of non-Hodgkin lymphoma have been characterized previously. Most patients present with oral cavity involvement. We report a case of plasmablastic lymphoma presenting as a lung tumor. To our knowledge, this is the first case report of this unusual subtype of diffuse large B-cell lymphoma in this location.     

Communication between members of the cardiac arrest team--a postal survey

Aims: Effective communication enhances team building and is perceived to improve the quality of team performance. A recent publication from the Resuscitation Council (UK) has highlighted this fact and recommended that cardiac arrest team members make contact daily. We wished to identify how often members of this team communicate prior to a cardiopulmonary arrest. Method: A questionnaire on cardiac arrest team composition, leadership, communication and debriefing was distributed nationally to Resuscitation Training Officers (RTOs) and their responses analysed. Results: One hundred and thirty (55%) RTOs replied. Physicians and anaesthetists were the most prominent members of the team. The Medical Senior House Officer is usually nominated as the team leader. Eighty-seven centres (67%) have no communication between team members prior to attending a cardiopulmonary arrest. In 33%, communication occurs but is either informal or fortuitous. The RTOs felt that communication is important to enhance team dynamics and optimise task allocation. Only 7% achieve a formal debrief following a cardiac arrest. Conclusion: Communication between members of the cardiac arrest team before and after a cardiac arrest is poor. Training and development of these skills may improve performance and should be prioritised. Team leadership does not necessarily reflect experience or training.