Synthesis and antitumor activity of novel C-7 paclitaxel ethers: discovery of BMS-184476.

The preparation of C-7 paclitaxel ethers is described. Various substituted ethers were prepared via activation of the corresponding methylthiomethyl ether followed by alcohol addition. Variation of the C-7 ether group as well the 3' side chain position led to the discovery of a novel taxane, BMS-184476 (4), with preclinical antitumor activity superior to paclitaxel.

Synthesis of metabolically blocked paclitaxel analogues.

The stereospecific syntheses of the metabolically blocked 6-alpha-F, Cl, Br paclitaxel, and 6-alpha-F-10-acetyldocetaxel are described and in vitro and in vivo activity is presented.

Synthesis and antitumor activity of novel paclitaxel-chlorambucil hybrids.

The syntheses and antitumor activity of three paclitaxel-chlorambucil hybrids are presented. Hybrid 3 showed significant in vivo efficacy.

Self-interference patterns and their application to inertial-fusion target characterization.

The sphericity and wall-thickness uniformity requirements of direct-drive inertial-fusion targets are of the order of less than 1%. These shells display self-interference patterns (SIP's) when irradiated with a spatially incoherent, narrow-bandwidth light source and viewed with a compound microscope. These patterns are distinct concentric fringes when the target is uniform, whereas faint, distorted, or discontinuous fringes indicate a nonuniform target. We determined the wall thickness to within +/-0.5 microm by counting the number of fringes in the SIP, independent of the outside diameter. Thickness uniformity is verified to an accuracy better than 0.05 microm. The wall thickness of gas-filled targets can be determined to this accuracy without knowledge of the type of gas or its pressure. The SIP fringe technique is used to select polymer shells typically of 800- to 1000-microm diameter and 5- to 12-microm wall thickness. The fringe locations have been modeled by use of ray tracing and agree well with actual measurements of well-characterized shells. Details of the formation of the SIP fringes, a theoretical model, and the method used for quantitative measurement of the shell-wall thickness with the SIP are presented with validation examples.

A description of general health risks in adult liver transplant recipients.

The focus of posttransplant care and clinical research has been on the management of rejection and short-term side effects associated with immunosuppressive therapy. Long-term side effects have only recently been recognized as potential health problems in liver transplant recipients. The aim of this pilot study was to determine the feasibility of using the Healthier People Version 4.0 Health Risk Appraisal as a tool for identifying existing and potential risk factors for premature disease and death among asymptomatic liver transplant recipients and to describe health risks in adult liver transplant recipients. The sample consisted of 50 adult first-time liver transplant recipients. It was found that this tool highlights health risks affecting life expectancy and pinpoints risks that an individual can control. It also provides practitioners with information necessary to design appropriate prevention and health promotion strategies to assure better health and quality of life for patients following liver transplantation.

Chorionic villi sampling: laboratory experience with 4,000 consecutive cases.

Experience with 4,000 consecutive CVS cases shows that 1) the combination of both the direct and culture methods greatly reduces false diagnoses and maternal cell contamination; 2) the time interval between the sampling procedure and processing of villus specimens influences the quality of direct preparations; 3) maternal cell contamination (MCC) can be minimized with dissection of CVS specimens. We have compiled a large volume of confined placental mosaicism (CPM) cases to serve as a resource in interpreting mosaic cytogenetic findings. It was noted that, in up to 92% of the mosaic cases, the abnormal cell line was confined to the placenta. The frequency of true chromosomal mosaicism was 0.2%, and is not different from that for amniocentesis.

Early absorption of enteral ranitidine after major laparotomy.

Thirty-six patients were studied following abdominal aortic surgery to determine if a commonly used medication could be absorbed from the gastrointestinal (GI) tract in the early postoperative period. Patients were randomized into two groups: Group I received ranitidine elixir 3 mg/kg via nasogastric tube every 12 hours; Group II received intravenous (IV) ranitidine 1 mg/kg every 8 hours. Ranitidine serum levels were measured with high performance liquid chromatography 1 hour after administration of the first three doses. Gastric pH was measured every 4 hours. It was found that serum ranitidine levels generally regarded as clinically effective were achieved in both groups. Although the levels were significantly higher following intravenous (IV) administration (Group II), there were no differences in average gastric pH. The authors conclude that within 24 hours of aortic surgery enterally administered ranitidine is effectively absorbed and provides prophylaxis equivalent to IV administration of the drug at lower cost. Other medications might be deliverable via the GI tract in the early postoperative period.

New method for monitoring pulmonary artery catheter location.

OBJECTIVE: To test the ability of a modified pulmonary artery (PA) monitoring catheter to detect distal catheter migration. DESIGN: Prospective nonrandomized trial. PATIENTS: Surgical ICU patients requiring invasive hemodynamic monitoring. INTERVENTIONS: Eight patients received PA catheters modified to include a right ventricular (RV) pressure monitoring port located 7 cm from the tip. Fifteen patients received catheters with an RV port located 10 cm from the tip. Guided by the RV port pressure waveform, catheters were initially positioned so that the RV port was located just proximal to the pulmonic valve. MEASUREMENTS AND MAIN RESULTS: Pulmonary capillary occlusion pressure (PAOP) could not be obtained in six of the eight patients receiving the 7-cm RV port catheter unless the RV port was advanced into the PA. PAOP was consistently obtained in all 15 patients receiving the 10-cm RV port catheter, with the RV port positioned in the RV. Chest radiographs confirmed a central PA catheter position. In this group, distal migration of the catheter occurred 14 times in eight patients, as detected by appearance of a PA pressure waveform at the RV port. Distal migration was corrected by withdrawal of the catheter until an RV waveform reappeared at the RV port. CONCLUSIONS: We conclude that distal catheter migration occurs frequently with PA monitoring catheters, but can be detected at the bedside with a catheter modified to include an RV port 10 cm from the tip. This new catheter may add a margin of safety to PA monitoring and lower its overall cost by eliminating the need for chest radiographs ordered solely to confirm catheter tip location.

Preventive mental health work with the elderly: With special reference to Asian/Pacific populations.

With the emergence of primary prevention as a major concern in health and mental health it becomes important to assess the possibilities for application of knowledge from this field to improve the quality of life for vulnerable populations such as elderly Asian/Pacific Islanders. It is necessary to address such aspects of special need as language, life styles, cultural practices, and poverty, among others, if preventive measures are to be of value. Recent legislation offers some prospect (if not vitiated by reductionist national policy) for expanding preventive services to older people who are most in need of community services oriented to their special needs.

Application of knowledge about prevention in social work education and practice.

The status of preventive social work in the United States is reviewed, as are the three knowledge sources used in the teaching and practice of prevention: public health, mental health, and social work. The integration of concepts of prevention in social work curricula and practice are discussed, and new directions for its use are projected.