Phase II study of vinorelbine (Navelbine) in previously treated small cell lung cancer patients. EORTC Lung Cancer Cooperative Group

26 previously treated patients with progressive recurrent small cell lung cancer (SCLC) were given vinorelbine (Navelbine), 30 mg/m2 weekly. All patients had responded to first-line chemotherapy and were off therapy for at least 3 months. Partial response was observed in 4 out of 25 eligible patients (16%; 95% confidence interval 4-36%), stable disease in 7 patients and progression in 12 patients. The limiting toxicity was a non-cumulative leucopenia (80%, 32% WHO grade 3-4). Reaction at the site of injection was observed in 5 patients, causing treatment discontinuation in 2 cases. Other non-haematological toxicities were moderate. These results suggest acceptable toxicity and some antitumour activity of vinorelbine in pretreated SCLC patients.     

Effects of ketotifen on human lymphocytes in vitro and in vivo

The effects of the antiasthmatic drug ketotifen (CAS 34580-13-7) on human mononuclear leukocytes were studied in vitro and in vivo. In vitro ketotifen concentration-dependently inhibited mitogen-stimulated lymphocyte proliferation. High ketotifen concentrations also inhibited T-lymphocyte mitogen- and adenosine triphosphate stimulated increases in intracellular Ca2+ in lymphocytes and the U937 human monocyte precursor cell line, respectively; this involved inhibition of both Ca2+ influx and intracellular mobilization. In in vivo experiments, treatment of healthy volunteers with 1 mg ketotifen b.i.d. for 7 d did not alter the number or subset composition of circulating lymphocytes. Moreover, the mitogen-stimulated in vitro proliferation of lymphocytes obtained before and after ketotifen treatment in vivo was similar. It is concluded that high ketotifen concentrations can inhibit the activation of resting lymphocytes in vitro but standard ketotifen treatment does not notably affect the number of function of circulating lymphocytes in vivo.     

Psoriasis of the nails associated with disability in a large number of patients: results of a recent interview with 1,728 patients

We present the first case of esophagogastric devascularization and esophagogastric transection using a stapler through laparoscopic surgery. The procedure was performed in a 71-year-old diabetic woman with alcoholic liver cirrhosis (Child-Pugh B class), portal hypertension, bleeding grade III esophageal varices, and a previous bleeding episode. The surgical technique was carried out without problems, and the patient had an excellent postoperative condition. Esophagogastric devascularization with esophageal transection using a stapler through laparoscopic surgery is a feasible technique that accomplishes the same and all objectives of the open procedure. Operative time in both methods is the same, whereas surgical trauma, inmunologic depletion, amount of transfused blood, pain, use of analgesics, and hospital stay are reduced in the laparoscopic technique.     

Correlates of alcohol use and misuse in fourth-grade children: psychosocial, peer, parental, and family factors

To determine level of alcohol use/misuse and to examine correlates of these behaviors, 1,314 fourth-grade students were surveyed. The questionnaire included 55 items concerning tolerance of deviance, deviant self-image, self-efficacy, susceptibility to peer pressure, personal and peer approval of alcohol use, peer adjustment, parent nurturance and monitoring, family adjustment, parental permissiveness, peer use of alcohol, and exposure to alcohol. The items were factor analyzed and indices constructed. The indices generally had acceptable alpha coefficients (alpha = .61-.91); two exceptions were peer adjustment (alpha = .51) and parental permissiveness (alpha = .42). Tolerance of deviance, deviant self-image, susceptibility to peer pressure, personal and peer approval, peer use and exposure by peers, and parental permissiveness were positively correlated with alcohol use/misuse. Self-efficacy, child-parent interactions, family adjustment, and peer adjustment were negatively correlated with alcohol use/misuse. Implications for the design of family-based alcohol use/misuse prevention programs are discussed.     

The use of low-osmolar contrast agents: technological change and defensive medicine

The escalating cost of medical care in the United States, especially in the past decade, has resulted in efforts to identify the factors contributing to rising costs. One factor often assumed to cause higher medical costs is the physician's fear of liability for not using the latest available technology. In this article, we report the results of a case study we conducted to better understand the relationship between the introduction and use of one particular technology, low-osmolar contrast agents, and liability concerns. Our study suggests that both clinicians and administrators are primarily guided by the medical benefits of low-osmolar contrast agents, and that liability concerns, although widespread, are of secondary importance. The inability to control this and similar technologies is likely to put a far greater strain on the nation's health care resources than is the practice of defensive medicine. These findings may be helpful to health policy makers, physicians, administrators, and legislators considering choices for health care reform in general and for medical liability reform in particular.     

In vitro degradation of dermal sheep collagen cross-linked using a water-soluble carbodiimide

Bacterial collagenase was used to study the susceptibility of dermal sheep collagen (DSC) cross-linked with a mixture of the water-soluble carbodiimide 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide hydrochloride and N-hydroxysuccinimide (E/N-DSC) towards enzymatic degradation. Contrary to non-cross-linked DSC (N-DSC), which had a rate of weight-loss of 18.1% per hour upon degradation, no weight loss was observed for E/N-DSC during a 24 h degradation period. The tensile strength of the E/N-DSC samples decreased during this time period, resulting in partially degraded samples having 80% of the initial tensile strength remaining. The susceptibility of E/N-DSC samples towards enzymatic degradation could be controlled by varying the degree of cross-linking of the samples. Ethylene oxide sterilization of E/N-DSC samples made the material more resistant against degradation compared with non-sterilized E/N-DSC samples. This may be explained by a decrease of the adsorption of bacterial collagenase onto the collagen owing to reaction of ethylene oxide with remaining free amine groups in the collagen matrix.     

Evolution of the serum amyloid A (SAA) protein superfamily

The serum amyloid A (SAA) superfamily comprises a number of genes and proteins characterized from a range of mammalian species. The majority of members described to date are dramatically induced during the acute-phase response, suggesting an important short-term beneficial role in the response to tissue injury and inflammation. However, important disease associations have also been proposed for certain SAAs during chronic inflammation. The nomenclature of many of the superfamily members has been the result of comparisons with previously reported sequences implying disease association and/or functional relatedness between such members. The evolutionary relationships of the SAA superfamily members have been investigated by comparisons at both the amino acid and the nucleotide level. The results indicate that all members of the superfamily within a species have been undergoing concerted evolution. This has important implications in ascribing functions and disease associations to individual SAA superfamily members and indicates that designations should not be based on the extent of amino acid identity alone but should be made only following direct experimental observation of the proteins themselves.     

Impurity Distribution Behavior in Caprolactam Extraction with Environmentally Benign Mixed Solvents

In a previous study a solvent mixture of heptane containing 40 mass % heptanol was selected as an alternative in the industrial extraction of caprolactam to replace benzene, toluene, or chlorinated hydrocarbons. This work reports the equilibrium distribution ratio of caprolactam and four model impurities of organic nature, namely, cyclohexanone, aniline, n‐methylcaprolactam, and cyclohexane‐carboxamide, comparing the mixed solvents with toluene as a reference. The resulting phase equilibria were interpreted using the equilibrium stage model. Based on these calculations it was found that, compared to toluene, the co‐extracted fraction of cyclohexanone and aniline was higher, that of n‐methylcaprolactam was comparable, and that of cyclohexane‐carboxamide was lower using the mixed solvent. Overall, the mixed solvent reduced the fraction of co‐extracted impurities by almost 10 %.