176. Kryochirurgische Therapie des Rectumcarcinoms

Zusammenfassung Die kryochirurgische Therapie wurde von uns bei 45 Patienten mit inop. Rectumcarcinom angewandt. Todesfälle traten nicht auf. Wir fanden: Eine Narkose ist nicht unbedingt nötig. Kleine Tumoren lassen sich destruieren. Stenosen bleiben stationär. Die Passage bleibt erhalten. Lokale Beschwerden (Tenesmen, Schmerzen) klingen ab. Größere Komplikationen wie Blutungen und Infektionen traten nicht auf. Da aber die Kryochirurgie rein lokal wirksam ist und keine sichere Radikalentfernung erzielt, kann these Methode nur als palliative Maßnahme angesehen werden.     

Medicinal plants used by Luo mothers and children in Bondo district,Kenya

In a follow-up to studies of school-children's medical knowledge among the rural Luo of western Kenya, seven mothers were asked for their knowledge of plant medicine, and the 91 plant remedies mentioned by them were collected, 74 of these remedies were identified as 69 different species (in 13 cases, the material did not allow identification of the species, in two cases, only the family could be identified, and in two, not even this was possible). The results of this survey and some comments on Luo illness concepts are presented below and briefly discussed in relation to the earlier work on school-children and to another survey of Luo plant medicine in the same district. The article concludes that the consensual core of Luo plant medicine is known by ordinary mothers and their children as well as by recognised healers. It is a shared resource, that is used by women, mainly in the care for their children, and it is not an expert domain of knowledge, as is often, in studies of herbal or 'traditional' medicine are studied. The medicinal plants, upon which many mothers as well as healers agree should be examined further pharmacologically in order to assess their efficacy against the common infectious and parasitic diseases found in this area of western Kenya.     

Alterations in intestinal permeability following the intensified polydrug-chemotherapy IFADIC (ifosfamide,Adriamycin, dacarbazine)

PURPOSE: The aim of this study was to investigate the severity and time-course of alterations in gastroduodenal and intestinal permeability in relation to nausea/emesis following administration of the highly emetogenic polydrug regimen IFADIC (ifosfamide, Adriamycin, dacarbazine) using a differential lactulose/mannitol absorption (SLM) test. We also assessed the ease of administration and patients' tolerance of the SLM test. METHODS: The SLM test was performed in seven patients with soft tissue sarcomas on days 1, 3 and 14 of cycle I and cycle III of chemotherapy; seven healthy volunteers served as controls. The degree of correlation between the clinical grade of nausea/emesis according to WHO criteria and gastroduodenal permeability, expressed in terms of urinary sucrose excretion, and intestinal permeability, expressed in terms of the permeability index (urinary lactulose to mannitol permeability ratio), was also assessed. RESULTS: The permeability index values were significantly different (P < or =0.01) on days 1, 3 and 14 during both cycles of chemotherapy. The median permeability index on day 3 was higher (P < =0.01) in patients with nausea/emesis than in those without symptoms. Additionally, the permeability index when nausea was present (day 3) was higher (P < or =0.01) than when nausea/emesis was absent (days 1 and 14). In 59% of patients the increased permeability index on day 3 was accompanied by nausea/emesis of WHO grade 3. Gastroduodenal permeability did not alter consistently following chemotherapy. CONCLUSIONS: Our study confirms an acute, transient increase in intestinal permeability following the polydrug regimen IFADIC, accompanied by nausea/emesis of WHO grade 3 in the majority of patients. Normal intestinal permeability was achieved on day 14 in all patients, thus allowing intensified 2-weekly treatment administration. The SLM test may be recommended as a feasible test for the objective assessment of alterations in intestinal permeability following chemotherapy administration.     

Phase I/II trial of weekly epidoxorubicin and docetaxel (wED) in the neoadjuvant and palliative treatment of patients with breast cancer

PURPOSE: Anthracyclines and taxanes are the most active cytotoxic agents in the treatment of breast cancer. Based on observations with weekly administration of paclitaxel which results in better tolerability and higher dose intensity as compared with 3-weekly schedules, we designed a phase I/II trial with weekly epidoxorubicin and docetaxel (wED) for the preoperative and palliative treatment of patients with breast cancer. PATIENTS AND METHODS: A group of 33 female patients (20 neoadjuvant and 13 palliative) were treated with weekly epidoxorubicin (25-35 mg/m(2)) as a short i.v. infusion followed by docetaxel (25-40 mg/m(2)) as a 1-h i.v. infusion once a week for 6 weeks followed by 1 week off therapy, without G-CSF support. Sequential cohorts of patients were treated with epirubicin and docetaxel at the following dose levels: 25/25, 25/30, 30/30, 30/35, 35/35, and 35/40 mg/m(2). RESULTS: Patients received a total of 74 courses (median 2, range 1-4 courses) of this therapeutic regimen. The maximum tolerated dose occurred at the dose level combining 35 mg/m(2) of epidoxorubicin and 40 mg/m(2) of docetaxel, with the dose-limiting toxicity being neutropenic fever in two patients at dose level 6. CONCLUSIONS: The wED regimen is a feasible, safe, and highly active combination chemotherapy for advanced breast cancer. We recommend epidoxorubicin 30 mg/m(2) and docetaxel 35 mg/m(2) for further trials because of the high incidence of neutropenic fever and lymphocytopenia of WHO grade IV at dose levels 5 and 6.     

Flavonoids with epidermal growth factor-receptor tyrosine kinase inhibitory activity stimulate PEPT1-mediated cefixime uptake into human intestinal epithelial cells

We have tested 33 flavonoids, occurring ubiquitously in foods of plant origin, for their ability to alter the transport of the beta-lactam antibiotic cefixime via the H+-coupled intestinal peptide transporter PEPT1 in the human intestinal epithelial cell line Caco-2. Of the flavonoids tested, quercetin, genistein, naringin, diosmin, acacetin, and chrysin increased uptake of [14C]cefixime dose dependently by up to 60%. All other flavonoids were either without effect or decreased the absorption of cefixime. Quercetin was shown to increase the Vmax of cefixime influx without changing the apparent Km for transport. However, the expected concomitant increase in intracellular acidification due to PEPT1-mediated cefixime/H+-cotransport was less pronounced in the presence of quercetin. This suggested that pH regulatory systems such as apical Na+/H+-exchange could be activated by quercetin and maintain the proton-motive driving force for cefixime uptake. Since quercetin and genistein have been shown to inhibit epidermal growth factor (EGF)-receptor tyrosine kinases, we applied tyrphostin 25 to prove whether such an inhibition could explain the stimulatory effects seen on cefixime uptake. It was found that tyrphostin 25 simulated the effects of quercetin by increasing cefixime absorption due to maintenance of the transmembrane pH gradient. In conclusion, our studies show that flavonoids with EGF-receptor tyrosine kinase inhibitory activities enhance the intestinal absorption of the beta-lactam antibiotic cefixime in Caco-2 cells by activation of apical Na+/H+-exchange and a concomitant increase of the driving force for PEPT1.