46. Erfahrungen systematisch kombinierter Chemotherapie und operativer Behandlung maligner Tumoren im Kindesalter

Zusammenfassung Anfang 1969 wurde in Österreich eine Arbeitsgemeinschaft zum Studium maligner Tumoren im Kindesalter gegründet. Es wurde zunächst ein zentrales Tumorregister errichtet, an dem die Krankengeschichten, die Operations-berichte und die pathologisch-histologischen Befunde von allen kindlichen Tumoren in ganz Österreich gesammelt werden.Es ist beabsichtigt, neben der Feststellung der Häufigkeit der einzelnen Geschwulsttypen und der Bestimmung ihrer Prognose, auch die derzeit verschieden gehandhabten Operationstaktiken, sowie die auch z. T. verschieden durchgeführten cytostatischen Nachbehandlungen zu beurteilen, um weiterhin in prospektiven, kooperativen Studien eine Optimierung des therapeutischen Vorgehens erreichen zu können.Die bisher bereits an 173 Fällen mit Erfolg erprobte Methodik der Dokumentation besteht darin, daß an jeder chirurgischen Kinderstation die Krankengeschichte, der Operationsbericht und der pathologisch-anatomische und histologische Befund von Tumorpatienten photokopiert wird und davon zentral am Register alle relevanten Daten mittels eines ausführlichen Erhebungsblattes lochkartengerecht dokumentiert werden. Ferner wird von jedem Operationspräparat ein Makrophoto und Tumormaterial an die Zentrale übersandt und gesammelt. Die von dem Material angefertigten histologischen Präparate dienen als Grundlage für eine von allen beteiligten Pathologen gemeinsam zu erarbeitende Klassifikation kindlicher Tumoren.Es wird außerdem der weitere beobachtete Krankheitsverlauf festgehalten, so daß unter Berücksichtigung des internationalen TNM-Systems von prognosegleichen Gruppen Absterbekurven errechnet und beurteilt werden können.

---

Experiences in adjuvant chemotherapy and operative treatment of malignant tumours in children

Summary Starting 1969 a cooperative study of malignant tumours in children was initiated. First of all a central tumour register was established and the medical histories, reports of operation and pathological-histological findings of all children treated for malignant tumours in the whole country were collected.The incidence of different types of tumours and estimation of their prognosis after different kinds of operation and/or different adjuvant chemotherapy would be estimated to aime thereafter in prospective cooperative trials the optimal therapeutic procedure.The method of documentation is established on 173 cases and consists of a procedure as follows: on each surgical department copies of the medical history, operation report and pathological-anatomical-histological reports of each patient are done by photography.From these all relevant data are documented at the register by extented forms using punch cards. Additionally a photogramm and samples for histology are collected at the register from each tumour specimen. These histological slides would be the basis for histological classification developed in cooperation with the pathologists involved.Follow-up studies will be done and life-tables of groups of patients equal in prognosis will be calculated.

     

A randomized, double-blind, close-ranging, pilot study of intravenous granisetron in the prevention of postoperative nausea and vomiting in patients abdominal hysterectomy

BACKGROUND AND OBJECTIVE: Postoperative nausea and vomiting (PONV) is a frequent and unpleasant experience that may increase postoperative complications and costs. For surgical procedures with a high risk of PONV, prevention is preferable to treatment. In this study, the authors explore the dose-response relationship between granisetron administered just prior to the end of surgery and post-operative nausea and vomiting in patients undergoing abdominal hysterectomy. METHODS: This was a randomized, double-blind, placebo-controlled, pilot study of post-operative nausea and vomiting prevention. Patients undergoing elective open abdominal hysterectomy requiring general anaesthesia received a single dose of granisetron 0.1, 0.2 or 0.3 mg or placebo administered approximately 15 min prior to the end of surgery. The primary efficacy end-point was the proportion of patients with no vomiting in the 0--6 h interval following medication administration. No inferential statistics were planned. RESULTS: The proportion of patients with no vomiting episode in the 0--6 h interval after administration of study medication was higher in each granisetron treatment group (>90%) than in the placebo group (77%). Proportions of patients with no vomiting episodes in the 0--24 h interval were similar across treatment groups. Results of analyses of proportions of patients with no moderate or severe nausea episodes, proportions of those requiring rescue medication and times to first use of rescue medication suggested a treatment effect of granisetron relative to placebo in both the 0--6 and 0--24 h intervals. Similar proportions of patients in each treatment group reported at least one adverse event. CONCLUSIONS: Granisetron at doses of 0.1, 0.2 and 0.3 mg administered just prior to the end of surgery suggested a trend of improved efficacy compared to placebo in preventing postoperative nausea and vomiting in the first 6 h after abdominal hysterectomy. This pilot study did not identify a dose-response relationship.     

Percutaneous coronary intervention to anomalous right coronary artery and retained piece of guidewire in the coronary vasculature

The incidence of anomalous origin of the coronary arteries varies between 0.2% and 1.2%; the anomalous right coronary artery accounting for 6--27% of all the cases. To date technical experience on angioplasty in patients with anomalous coronary arteries reported in the literature is limited. A major factor is the selection of the guiding catheter to access the anomalous origin and also to give good support during angioplasty. We report the details of angioplasty in a patient with a similar problem and the dilemma following a fractured segment of the guidewire retained in the coronary vasculature.     

Control of T helper 2 cell function and allergic airway inflammation by PKCzeta

Asthma is a disease of chronic airway inflammation in which T helper (Th) 2 cells play a critical role. The molecular mechanisms controlling Th2 differentiation and function are of paramount importance in biology and immunology. PKCzeta has been implicated in the regulation of apoptosis and NF-kappaB, as well as in the control of T-dependent responses, although no defects were detected in na?ve T cells from PKCzeta-/- mice. Here, we report that PKCzeta is critical for IL-4 signaling and Th2 differentiation. Thus, PKCzeta levels are increased during Th2 differentiation, but not Th1 differentiation, of CD4+ T cells, and the loss of PKCzeta impairs the secretion of Th2 cytokines in vitro and in vivo, as well as the nuclear translocation and tyrosine phosphorylation of Stat6 and Jak1 activation, essential downstream targets of IL-4 signaling. Moreover, PKCzeta-/- mice display dramatic inhibition of ovalbumin-induced allergic airway disease, strongly suggesting that PKCzeta can be a therapeutic target in asthma.     

Fetoplacental vascular tone is modified by magnesium sulfate in the preeclamptic ex vivo human placental cotyledon

OBJECTIVE: The purpose of this study was to evaluate fetoplacental vascular tone and response to a vasoconstrictor in placentas of preeclamptic and normotensive pregnancies with and without the presence of magnesium sulfate. STUDY DESIGN: Two cotyledons from each placenta were selected from preeclamptic (n=8) and normotensive (n=7) pregnancies. In one cotyledon from each pair, the maternal circuit was perfused with magnesium sulfate. The fetal arteries were injected sequentially with angiotensin II (10(-10)mol and 10(-11.5) mol). Perfusion pressures and response to angiotensin II were compared, with regard to preeclampsia and exposure to magnesium sulfate. RESULTS: Perfusion pressure was higher in preeclamptic placentas, compared with normotensive placentas (30.4 mm Hg vs 24.4 mm Hg, P=.02). There was a decrease in perfusion pressure with exposure to magnesium sulfate in preeclamptic placentas (22.5 mm Hg, P<.01), but not in normotensive placentas. Fetoplacental vascular response to angiotensin II was not affected by preeclampsia or magnesium sulfate. CONCLUSION: In placentas from preeclamptic pregnancies there is increased fetoplacental perfusion pressure, which decreases with exposure to sulfate.     

The effect of fetal acidemia on fetal-placental vascular tone and production of the inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha

OBJECTIVE: Our purpose was to determine the effects of fetal acidemia on placental vascular tone and production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). STUDY DESIGN: With use of an ex vivo placental perfusion model, the maternal and fetal circulation of two cotyledons from five human placentas were perfused for 4 hours. The fetal circulation of one cotyledon was perfused with acidemic (pH 6.90) Hanks' balanced salt solution (HBSS), whereas the fetal circulation of the other cotyledon was perfused with physiologic (pH 7.35) HBSS. Fetal venous effluents were collected hourly, and IL-6 and TNF-alpha concentrations were determined by enzyme-linked immunosorbent assay. Cotyledon perfusion pressures were recorded every 10 minutes. Paired t tests were used to compare differences in cytokine production and perfusion pressure between the cotyledons. RESULTS: Fetal-placental vascular perfusion pressure was consistently reduced from baseline under acidemic, but not physiologic, conditions with statistical significance achieved from 20 minutes onward (P <.05). IL-6 and TNF-alpha increased exponentially over time for both conditions (P <.05). There was no difference in cytokine production when acidemic conditions were compared with physiologic conditions (P <.05). CONCLUSION: Fetal-placental vasodilation may be a compensatory mechanism to improve acidemic conditions. Unlike fetal hypoperfusion or fetal hyperoxia, fetal acidemia does not result in elevated placental cytokine levels.     

GPs facing reluctant and demanding patients: analysing ethical justifications

BACKGROUND: Several studies have explored the physicians' preferred actions when facing a reluctant or a demanding patient, but only a few studies have explored the physicians' justifying reasons. OBJECTIVE: The aim of this study was to assess how GPs would act and how they would justify their choice. METHOD: A postal questionnaire with questions about preferred actions and justifying reasons was sent to a random sample of GPs in Slovenia (n = 160) and Sweden (n = 200) using four vignettes: (i). a healthy patient reluctant to quit smoking; (ii). a healthy patient demanding an X-ray; (iii). a pulmonary cancer patient reluctant to quit smoking; and (iv). a pulmonary cancer patient demanding immunotherapy. RESULTS: The majority of GPs would bring up the question about smoking with the patients reluctant to quit. They justified their choice by referring to promotion of medical benefit and to protection from harm. Swedish GPs were less inclined to bring up smoking than were their Slovenian colleagues. Those who would not bring up the question referred to respect for self-determination and an enhanced relationship as their justifying reasons. With reference to the demanding patients, a minority of GPs would grant the healthy patient's request for an X-ray that was not medically motivated. The answers were similar with respect to the seriously ill patient requesting non-medically motivated immunotherapy. Slovenian GPs were much more inclined to grant the request than were their Swedish colleagues. Enhancing the relationship and respect for self-determination were the most important reasons for granting the demands. When the demands were denied, the GPs mostly referred to promotion of fair distribution of resources. CONCLUSION: Many of the GPs considered their patients' right to self-determination less important than other values, e.g. the obligation to promote medical benefit, to protect from harm, to distribute public resources fairly and to enhance the patient-physician relationship.