Evaluation of the results of cleft lip and palate surgical treatment: preliminary report

We have analysed randomized controlled studies which reported the incidence of postoperative nausea and vomiting (PONV) after propofol anaesthesia compared with other anaesthetics (control). Cumulative data of early (0-6 h) and late (0-48 h) PONV were recorded as occurrence or non-occurrence of nausea or vomiting. Combined odds ratio and number-needed-to-treat were calculated for propofol as an induction or maintenance regimen, early or late outcomes, and different emetic events. This was performed for all control event rates and within a range of 20-60% control event rates. We analysed 84 studies involving 6069 patients. The effect of propofol on PONV was dependent mainly on the method of administration, time of measurement and range of control event rates. When all studies were included the number-needed-to-treat to prevent PONV with propofol was more than 9 when used for induction of anaesthesia and at best 6 when used for maintenance. Within the 20-60% control event rate range, best results were achieved with propofol maintenance to prevent early PONV: the number-needed-to-treat to prevent early nausea was 4.7 (95% confidence interval 3.8-6.3), vomiting 4.9 (4-6.1) and any emetic event 4.9 (3.7-7.1). Within the 20-60% control event rate, of five patients treated with propofol for maintenance of anaesthesia, one will not vomit or be nauseated in the immediate postoperative period who would otherwise have vomited or been nauseated. This may be clinically relevant. In all other situations the difference between propofol and control may have reached statistical significance but was of doubtful clinical relevance. Treatment efficacy should be established within a defined range of control event rates for meaningful estimates of efficacy and for comparisons.     

Continuous infusional topotecan in advanced breast and non-small-cell lung cancer: no evidence of increased efficacy

Two open, phase II studies were performed to evaluate the activity and toxicity of infusional topotecan in patients with advanced non-small-cell lung carcinoma (NSCLC) and advanced breast cancer who had not received previous chemotherapy for metastatic disease. Twenty-five patients with an ECOG performance score < 2 were treated with infusional topotecan administered as a daily, continuous intravenous infusion starting at 0.6 mg m(-2) day(-1) (NSCLC) and 0.5 mg m(-2) day(-1) (breast cancer) for 21 days every 4 weeks. Three patients achieved a partial response as defined by WHO criteria: one with NSCLC (8%; 95% CI 0-39%) and two with advanced breast cancer (15%; 95% CI 2-45%). The major toxicities were neutropenia and thrombocytopenia, with one episode of neutropenic sepsis. These data suggest that topotecan delivered as a continuous intravenous infusion over 21 days as single-agent therapy does not appear to offer a clinical advantage over conventional 5-day schedules against advanced NSCLC and advanced breast cancer.     

Pulmonary surfactant concentration during transition from high frequency oscillation to conventional mechanical ventilation

OBJECTIVE: To test the hypothesis that conventional mechanical ventilation (CV) provides a greater stimulus to secretion of pulmonary surfactant than high frequency oscillatory ventilation (HFO). METHODOLOGY: Sequential examination of surfactant indices in lung lavage fluid in a group of six infants with severe lung disease (group 1), ventilated with HFO and then converted back to CV as their lung disease recovered. A similar group of 10 infants (group 2) ventilated conventionally throughout the course of their illness were studied for comparison. In groups 1 and 2, two sequential tracheal aspirate samples were taken, the first once lung disease was noted to be improving, and the second 48-72 h later. Group 1 infants had converted from HFO to CV during this time. RESULTS: A marked increase in concentration of total surfactant phospholipid (PL) and disaturated phosphatidylcholine (DSPC) was seen in group 1 after transition from HFO to CV; the magnitude of this increase was significantly greater than that sequentially observed in group II (total PL: 9.4-fold increase in group 1 vs 1.8-fold in group 2, P = 0.006; DSPC: group 1 6.4-fold increase vs. group 2 1.7-fold, P = 0.02). CONCLUSION: These findings suggest that intermittent lung inflation during CV produces more secretion of surfactant phospholipid than continuous alveolar distension on HFO, and raise the possibility that conservation and additional maturation of surfactant elements may occur when the injured lung is ventilated with HFO.     

Native atherosclerosis and vein graft arterialization: association with increased urokinase receptor expression in vitro and in vivo

Persistent chlorinated hydrocarbons assimilated through the diet may, as a result of their carcinogenic, immunotoxic, and, at least in regard to certain of these substances, estrogenic properties, play a role in the etiology of human breast cancer. As a consequence, increased concentrations of these ubiquitous environmental contaminants may be found in breast tissue of women suffering from malignant breast disease. To examine this possibility, surgically removed breast tissue samples from 65 women in Hesse, Germany were examined by capillary gas chromatography for p, p'-dichloro(diphenyl)trichloroethane (p,p'-DDT), p, p'-dichloro(diphenyl)-dichloroethane (p,p'-DDD), p, p'-dichloro(diphenyl)dichloroethene (p,p'-DDE), hexachlorobenzine (HCB), alpha-, beta-, and gamma-hexachlorocyclohexane (HCH) as well as the polychlorinated biphenyls (PCB) no. 28, 31, 49, 52, 101, 105, 118, 138, 153, 156, 170, and 180. Of the 65 patients, 45 were diagnosed with breast cancer. The control group of 20 women suffered from benign breast disease such as mastopathy. After statistical adjustment for age differences, higher concentrations of p,p'-DDT, p, p'-DDE, HCB as well as PCB-congeners no. 118, 138, 153, and 180 were detected in tissue from women with breast cancer than in tissue from control persons. These differences were weakly significant for p, p'-DDE (p = 0.017), for PCB 118 (p = 0.042) and for PCB no. 153 barely not significant (p = 0.083). On an average, a 62% higher concentration of p,p'-DDE was found in cancer tissue (cancer patients: 805 microg/kg fat; controls: 496 microg/kg fat) and 25% higher concentration of PCB no. 118 (81 microg/kg fat; 65 microg/kg fat). The concentrations of beta-HCH, PCB no. 156 and 170 were lower (not significant) in cancer tissue than in tissue from women with benign disease. PCB-congeners no. 105 and 149 as well as gamma-HCH could only be detected in individual tissue samples; congeners no. 28, 31, 49, 52, and 101 as well as alpha-HCH and p,p'-DDD were not detected in any of the samples. To rule out the possibility that the concentrations of chlorinated hydrocarbons measured were influenced by the surgical procedure, 20 samples of tissue that were at a distance (minimum 1 cm and maximum 3 cm) from the tumor, tissue that was in direct proximity to the tumor (no more than 5 mm from the tumor), and tumor tissue itself (center of tumor) were separately prepared and analyzed. The average concentrations of chlorinated hydrocarbons varied to differing degrees and only minimally in tumor and surrounding breast tissue, indicating that the surgical procedure did not influence the results.     

Magnetic resonance imaging features of pituitary yttrium-90 rod implantation

Intersellar implantation of yttrium-90 rods was a common treatment for a variety of pituitary tumours in the 1960s and 1970s. The magnetic resonance (MR) imaging features in three patients with implants (two for growth hormone-secreting and one for prolactin-secreting pituitary adenomas) are presented: the implants appeared as low signal cylinders with no image distortion, in contradistinction to CT where the implants generate beam hardening and back projection artefacts. Confident evaluation of the pituitary fossa for residential tumour and sequelae of therapy could be made on MR. It is the imaging technique of choice in the follow-up of patients treated with yttrium-90 implants.     

Temperature-sensitive Gbeta mutants discriminate between G protein-dependent and -independent signaling mediated by serpentine receptors

Deletion of the single gene for the Dictyostelium G protein beta-subunit blocks development at an early stage. We have now isolated temperature-sensitive alleles of Gbeta to investigate its role in later development. We show that Gbeta is directly required for adenylyl cyclase A activation and for morphogenetic signaling during the entire developmental program. Gbeta was also essential for induction of aggregative gene expression by cAMP pulses, a process that is mediated by serpentine cAMP receptors (cARs). However, Gbeta was not required for cAR-mediated induction of prespore genes and repression of stalk genes, and neither was Gbeta needed for induction of prestalk genes by the differentiation inducing factor (DIF). cAMP induction of prespore genes and repression of stalk genes is mediated by the protein kinase GSK-3. GSK-3 also determines cell-type specification in insects and vertebrates and is regulated by the wingless/wnt morphogens that are detected by serpentine fz receptors. The G protein-dependent and -independent modes of cAR-mediated signaling reported here may also exist for the wingless/wnt signaling pathways in higher organisms.     

Risk factors for drug-related problems in elderly ambulatory patients

Medication use among elderly patients in ambulatory care, home health care, and long-term care settings has become increasingly complicated during the past decade. Home intravenous therapy, multiple drug regimens to treat multiple chronic diseases, increased acuity of nonhospitalized patients, and increased longevity have placed elderly patients at increased risk for drug-related problems.