Thrombin--an effective treatment for gastric variceal haemorrhage.

The optimum treatment of gastric varices has still to be defined. Lesser curve gastric varices may be treated by injection sclerotherapy, but this has a limited role in the treatment of fundal gastric varices. Surgical intervention is commonly needed but carries a high mortality in patients with advanced liver disease. This study evaluated the use of thrombin for the treatment of gastric varices in 11 consecutive patients (nine with fundal, two with high lesser curve varices), identified as having bled from this site. Bovine thrombin (1000 U/ml) was injected intravariceally (mean volume 5.5 ml, range 2-10 ml) producing initial haemostasis in all 11 cases. Varices were considered thrombosed or obliterated in all patients after a median of two injection episodes (range 1-3). After a median follow up of nine months only one patient had rebled from a gastric varix. Thrombin may represent a valuable alternative injectate for the treatment of gastric varices.     

Resting discharge and sensitivity of ampullary electroreceptors in Clarias gariepinus related to convergence ratio during ontogeny

The ampullary electroreceptor organs of the teleost fish Clarias gariepinus converge to single afferent neurons. During the first 4 months of ontogeny the convergence ratio (CR) increases from 1 to 3. Extracellular single-unit recordings show that a 3-fold increase in CR results on average in a 3.6-fold increase in sensitivity measured at stimulus frequencies of 2, 8 and 20 Hz, and in a small but significant 1.1-fold increase in resting discharge. Adaptation of the primary afferents could account for the differences between changes in sensitivity and resting discharge.     

A phase II study of sulofenur,a novel sulfonylurea,in recurrent epithelial ovarian cancer

Summary A total of 16 patients with recurrent epithelial ovarian cancer were treated with sulofenur (LY 186641), a novel oral sulfonylurea. All subjects had received previous chemotherapy. Anaemia occurred in all 16 patients, 14 of whom required a blood transfusion, and 2/16 patients received methylene blue for breathlessness due to methaemaglobinaemia. Treatment was discontinued in 2/16 cases due to rising liver enzyme values, which reverted to normal on cessation of the drug. There was no nausea or alopecia. Only two minor responses were seen. Plasma drug levels were insufficient to result in antitumour activity as extrapolated from animal data. Further studies that attempt to increase the bioavailability and improve the therapeutic index are warranted.     

Stimulation of ovarian tumor cell proliferation with monocyte products including interleukin-1, interleukin-6, and tumor necrosis factor-alpha.

OBJECTIVE: We investigated whether monocyte-derived factors could stimulate the growth of ovarian cancer cells. STUDY DESIGN: Human peripheral blood monocytes or human monocyte-like cell lines THP-1 and U-937 were cultured with or without macrophage colony-stimulating factor, lipopolysaccharide, or phorbol myristate acetate. Culture supernatants or recombinant cytokines were assayed for growth stimulation of ovarian cancer cell lines by tritium-thymidine incorporation and direct cell counts followed by statistical analysis with Student t test. RESULTS: Conditioned medium from peripheral blood monocytes or from THP-1 or U-937 cells stimulated ovarian cancer cell growth. Interleukin-1 alpha, tumor necrosis factor-alpha, and interleukin-6 also stimulated ovarian cancer cell growth, whereas macrophage, granulocyte, and granulocyte-macrophage colony-stimulating factor did not. Concentrations of tumor necrosis factor, interleukin-1, and interleukin-6 in conditioned medium could not account for all the growth stimulation, and activity remained after neutralization of tumor necrosis factor, interleukin-1, and interleukin-6 with antibodies. CONCLUSIONS: Interleukin-1, interleukin-6, tumor necrosis factor, and additional monocyte factor(s) could provide paracrine growth stimulation when monocytes are attracted to ovarian cancers that produce macrophage colony-stimulating factor.     

Relation of 5'-nucleotidase and phosphatase activities with immunophenotype, drug resistance and clinical prognosis in childhood leukemia.

Ecto-5'-nucleotidase (ecto-5'NT) catalyzes the extracellular dephosphorylation of nucleotides like IMP. Cytoplasmic 5'NT (cyto-5'NT) and non-specific (e.g. acid- and alkaline) phosphatases (AP) regulate the intracellular degradation of nucleotides. High NT and AP activities might cause a resistance to the thiopurines 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). We studied the relation between these enzymes and immunophenotype, drug resistance and prognosis in 77 children with acute lymphoblastic leukemia (ALL). Enzyme activities were assessed radiochemically; in vitro drug resistance was measured with the MTT assay. AP activities were higher in T-ALL and B-ALL than in precursor B-ALL. Cyto-5'NT activity was very low in all phenotypes and accounted for a significant proportion of total IMPase activity only in the very immature CD10- c mu- precursor B-ALL. CD10+ ALL cases with high ecto-5'NT activities showed a trend (p = 0.065) for a lower probability of continuous complete remission than those with a low activity. Ecto-5'NT activity was not related to in vitro drug resistance to 6-TG. A weak correlation was found between in vitro 6-TG resistance and cyto-5'NT and AP activities. We conclude that high ecto-5'NT activities do not cause a resistance to 6-thiopurines in childhood ALL. Some patients have high cyto-5'NT and AP activities associated with 6-thiopurine resistance.     

Amphotericin B serum levels in pediatric bone marrow transplant recipients

We studied amphotericin B (AMB) serum levels (n = 590) in 41 pediatric patients, who underwent allogeneic (21) or autologous (20) bone marrow transplantation (BMT). All patients received AMB orally as part of a total gut decontamination; 30/41 patients (73%) had AMB i.v. either for prophylaxis or therapy of fungal infections. Rapid initial dose escalation of AMB and the infusion over 1 h only were well tolerated by the children. Serum level monitoring allowed AMB long-term treatment safely to be administered in children suffering from transplantation-related complications (veno-occlusive disease of the liver, graft-versus-host disease of the liver). An h.p.l.c. method was used for monitoring AMB serum trough levels to avoid levels exceeding 2 mg/l. One lethal fungal infection was observed in 41 pediatric BMT recipients (2.4%). Rapidly increasing doses of AMB at start of therapy and drug monitoring by h.p.l.c. might help to reduce fungal mortality and renal toxicity by a dose sparing effect in BMT recipients.     

Effects of chronic ethanol consumption and pair feeding on rates of protein synthesis and nucleic acid composition in rat tibia.

An investigation was made into the chronic effects of ethanol feeding on bone (represented by the tibia). Treated rats were fed a liquid diet containing ethanol as 36% of total calories, and controls were pair-fed identical amounts of the same diet in which ethanol was substituted by isocaloric glucose. Bone DNA and RNA contents in ethanol-fed rats were not significantly different from glucose-fed controls at days 3, 7, 14, 28 and 42 of treatment. Fractional rates of bone protein synthesis were measured with [43H]-phenylalanine. At 3, 7, 14, 28 and 42 days, ethanol feeding had no effect on free and protein-bound specific radioactivities, nor on fractional or absolute rates of protein synthesis. Synthesis rates relative to RNA (RNA activities) and DNA (cellular efficiencies) were also not significantly altered by ethanol feeding at these time points. Comparisons were made between rats fed a standard solid laboratory diet ad libitum (i.e. normal rats), and those fed restricted amounts of glucose-containing liquid diet (i.e. dietary-restricted rats) for 42 days. In normal rats, there was an increase in tibial mass and accretion of total collagen content, but in dietary-restricted rats, this accretion was markedly impaired. Furthermore, whilst RNA and DNA contents were increased in tibia of normal rats, the contents of these nucleic acids were reduced in bones of dietary restricted rats. Fractional rates of bone protein synthesis in normal rats were unaltered after 42 days, but reduced by feeding the control liquid diet in restricted amounts.(ABSTRACT TRUNCATED AT 250 WORDS)