Preparation and biological activity of new substituted antimalarial diaminodiphenylsulfones

Starting from 4,4'-diamino-diphenylsulfone (DDS) as a lead structure, new 2-substituted analogues as well as new 2-substituted 4-alkylamino-4'-amino diphenylsulfones have been designed and synthetized in different ways. This has led to compounds the inhibitory activity of which against 7,8-dihydropteroic acid synthase of plasmodia and mycobacteria is clearly superior to that of sulfadoxine and in most cases to that of DDS. Of special interest is 4'-amino-4-n-propylamino-2-methyl-diphenylsulfone. Together with inhibitors of 7,8-dihydrofolate reductase in vitro and in vivo it possesses a marked synergistic inhibitory activity against plasmodia. In contrast to DDS in doses up to 200 mg/kg p.o. (cat) no methemoglobin formation is observed. The compound has been selected for further studies.     

Does Additional Doxorubicin Chemotherapy Improve Outcome in Patients with Hepatocellular Carcinoma Treated by Liver Transplantation?

The aim of this prospective randomized study was to determine whether additional doxorubicin chemotherapy improves outcome in patients with hepatocellular carcinoma (HCCA) treated by liver transplantation. Stratification parameters were tumor stage (UICC I-IVa), gender, age 50 years, α-fetoprotein 20 ng/mL, cirrhosis and HbsAg status. For pre-operative chemotherapy doxorubicin (15 mg/m²) was given biweekly, intra-operative chemotherapy was a single dose administered before surgical manipulation. Post-operative chemotherapy from day 10 was as given preoperatively for a total dosage of 300 mg/m². Outcome parameters were overall survival (OS) and disease-free survival. Of the 75 consecutive patients who received liver transplantation for treatment of HCCA, 62 patients were enrolled. Thirty-four patients were randomized in the chemotherapy group; 28 patients were in the control group and transplanted only. OS rates at 5 years were 38% in the chemotherapy group and 40% in the control group, disease-free survival rates at 5 years 43% and 53%, respectively. Tumor stage and vascular invasion were identified as independent risk factors for recurrence of disease. Doxorubicin chemotherapy did not improve organ survival and disease-free survival in patients undergoing liver transplantation for HCCA.     

The gene for the iron sulfur protein of succinate dehydrogenase (SDH-IP) maps to human chromosome 1p35-36.1

A partial human cDNA clone for the iron-protein (IP) subunit of succinate dehydrogenase (EC 1.3.99.1) was used in Southern analyses of restriction enzyme digests of genomic human and hamster DNA as well as hamster-human hybrids containing a limited number of human chromosomes. The gene for this protein was mapped to human chromosome 1. Digestion of genomic DNA with several restriction enzymes yielded two fragments detectable on a Southern blot, in contrast to the expectations based on the sequence of the cDNA clone. A preliminary analysis of a genomic clone with most of theIP gene has indicated the presence of several introns containing restriction sites detected by the Southern analysis. This genomic clone was also used for subregional mapping by fluorescence in situ hybridization (FISH) to human metaphase chromosomes. A single locus in the region 1p35-36.1 was identified.     

Case-control study of risk factors for cervical neoplasia in Denmark. II. Role of sexual activity,reproductive factors,and venereal infections

Sexual, reproductive and venereal risk factors for cervical neoplasia were investigated in a population-based case-control study of 586 women with histologically verified, cervical squamous-cell carcinoma in situ, and 59 women with invasive squamous-cell cervical cancer, diagnosed from 1985 to 1986 in Copenhagen. Cases were identified from the computerized Danish Cancer Registry. An age-stratified control group (n=614) was drawn at random from the female population in the study area by means of the Danish Central Population Register. A structured questionnaire was mailed to cases as well as controls. Increasing number of sexual partners exerted a significant effect on the risk both for carcinoma in situ, and invasive cancer, independently of age at first intercourse and other potential confounders. Conversely, the association with early age at first intercourse became statistically insignificant after allowance for other risk factors, although an increasing risk was still observed with decreasing age at sexual debut. Early age at first episode with genital warts was a significant risk factor for carcinoma in situ, perhaps indicating a possible increased susceptibility of the cervix epithelium during adolescence. A history of genital warts was a good predictor of risk for carcinoma in situ, whereas a history of previous gonorrhea was associated with an increased risk for invasive carcinoma. Women with multiple births had a significantly increased adjusted risk, especially for carcinoma in situ, although some association was also observed with invasive cervical cancer. The study supports the hypothesis of cervical neoplasia being a sexually transmitted disease, and that carcinoma in situ and invasive cervical carcinoma, to a high degree, have similar patterns of risk factors.Drs Kjaer, Engholm, and Lynge are with the Danish Cancer Registry. Dr Dahl is with the Department of Surgery, Slagelse Hospital, Denmark. Dr Bock is with the Department of Gynecology, Rigshospitalet, Copenhagen, Denmark. Dr Jensen, formerly with the Danish Cancer Registry, is deceased. Address correspondence to Dr Kjaer, Danish Cancer Registry, Institute of Cancer Epidemiology, Danish Cancer Society, Rosenvengets Hovedvej 35, Box 839, Copenhagen. Denmark. The Danish Cancer Society supported this study through grants.     

Eingeladener Kommentar zu: „Einmal- versus wiederverwendbare Instrumente in der laparoskopischen Cholezystektomie — Kostenkalkulation und Nutzwertbestimmung”

Schlu?folgerungen Unser Motto in der Chirurgie sollte hei?en: „An erster Stelle steht die Qualit?t, erst sekund?r kommen die Kosten.“ In diesem Sinne verstehen wir auch die vorgelegte Arbeit vonKriwanek et al. (1). Durch den Gebrauch von wiederverwendbaren Instrumenten (oder Kombinationen davon) konnten die Kosten der LC um 50 bis 70% reduziert werden. Die Qualit?t für den Chirurgen litt jedoch unter dem reinen Gebrauch von wiederverwendbaren Instrumenten. Deshalb erachten es die Autoren für sinnvoll, eine Kombination zwischen Wegwerfinstrumenten und wiederverwendbaren Instrumenten anzuwenden. Damit entsteht unter leichter Erh?hung der Kosten keine Qualit?tseinbu?e und demzufolge ein maximaler Nutzen für die Patienten (nicht jedoch für die Spital?konomen). Jede Kosten-Nutzen-Analyse unterliegt jedoch einem stetigen Flu? und ver?ndert sich demzufolge auch mit der Einführung neuer Produkte und Technologien von Seite der Industrie. Interessant für die gesamte Laparoskopie wird es jedoch dann, wenn solche Kosten-Nutzen-Analysen auf andere Gebiete wie z. B. die Therapie der Leistenhernie oder der Gallengangssteine übertragen werden. Diese Ergebnisse werden die weitere Zukunft der laparoskopischen Chirurgie wesentlich beeinflussen. Deshalb gilt es für uns Chirurgen, eine Sensibilit?t für ?konomische Aspekte zu entwickeln und Kosten-Nutzen-Analysen für das eigene Spital (wie hier gezeigt) zu erarbeiten.     

Social-Emotional Predictors of Preschoolers'' Responses to Adult Negative Emotion

The study examined predictors of children's prosocial responses to adult negative emotions. An adult displayed anger, sadness and pain during play sessions with 39 preschoolers (mean age = 43 months). Older children responded more prosocially to all three emotions, whereas children with greater emotion knowledge responded more prosocially to the adult's sadness. Children who behaved prosocially in response to peers' negative emotions also were prosocial after the adult's negative emotions, even with effects of age and emotion knowledge held constant. Assertive children responded more prosocially to the adult's anger, even with effects of other variables held constant. Both theoretical and practical implications are discussed.     

U.K. Limited – eine Rechtsform für Ärzte?

Ohne Zusammenfassung     

Hip arthroplasty after failed internal fixation of the trochanteric fractures in aged patients with co-existent osteoporosis]

The authors present the results of hip arthroplasty of 67 patients treated after failed internal fixation of the osteoporotic, trochanteric fractures of the femur, which were primary stabilised with angular plate AO in 39 patients and with dynamic hip screw (DHS) in 28 patients. In the discussed material 16 persons were male and 51 female, in the age between 51 and 83 years old. According to the Evans classification in 4 cases we diagnosed type I of fracture, in 10--type II, 31--type III and in 22--type IV. Hip arthroplasty was made from the 3rd to the 39th week after primary fixation of the fracture. In 42 patients we made total hip arthroplasty, in 14 cases Austin-Moore hemiarthroplasty, and in 11 patients bipolar arthroplasty. According to the Postel and Merle d'Aubigne classification there were obtained 29 very good, 21 good and 17 satisfactory results.