Evidence for an association between hairy cell leukemia and renal cell and colorectal carcinoma.

BACKGROUND. Hairy cell leukemia (HCL) has been associated with several disease states. In this study, a possible association is reported between HCL and renal cell carcinoma (RCC) and colorectal carcinoma (CRC). METHODS. A retrospective study of the case records of 50 patients with HCL in a study of alpha-interferon (alpha-IFN) treatment of HCL. RESULTS. Three of 50 patients with HCL studied had RCC, and 2 of these also had CRC. In addition, two other patients had CRC. The other malignant lesions developed either before or after the diagnosis of HCL. In all patients, the HCL responded to alpha-interferon (alpha-IFN), but in four patients, the second lesion was diagnosed during IFN treatment. CONCLUSIONS. These findings could indicate that IFN does not correct a possible common basic etiologic defect and shows that even early CRC and RCC do not respond to the IFN doses administered. These findings should be considered in future trials of IFN treatment of these diseases. The authors also recommend a reevaluation of the frequency of second malignant lesions in HCL; this may be important particularly with the increased survival in patients with HCL who receive alpha-IFN treatment.     

Reversal of granulocyte adherence to nylon fibers using local anesthetic agents: possible application to filtration leukapheresis

The effects of the cationic anesthetic agents tetracaine and lidocaine on granulocyte function, morphology, and adherence to nylon fibers were studied in an attempt to improve current methods of granulocyte collection by filtration leukapheresis (FL). When dissolved in acid- citrate-dextrose (ACD) plasma, these drugs significantly increased granulocyte elution from the fibers in a dose-related fashion. Granulocytes exposed to tetracaine and lidocaine remained more than 95% viable, retained normal bactericidal capacity after the drugs were washed from the cells, and had preserved membrane integrity, as evidenced by the normal ultrastructural appearance of tetracaine- exposed cells and an absence of leakage of lysozyme or lactic dehydrogenase. Granulocytes eluted with the anesthetic agents were rounded in shape with a reduction in the number of filopodial cytoplasmic projections and a relative absence of cytoplasmic vacuolization when compared to granulocytes eluted with ACD plasma alone. Dose-related inhibition of phagocytosis and adherence, which was largely reversible after washing the granulocytes, was noted. Greater than 95% of the lidocaine could be removed from the eluate with a single centrifugation and resuspension, indicating that granulocytes prepared by FL with anesthetic-enhanced elution could be potentially transfusable.     

Platelets inhibit the induction of nitric oxide synthesis by interleukin-1 beta in vascular smooth muscle cells

We have investigated the role of platelets in regulating the hemostatic and vasomotor properties of vascular smooth muscle. Experiments were performed to examine the effect of the releasate from activated platelets on the production of nitric oxide from interleukin-1 beta (IL- 1 beta)-treated cultured rat aortic smooth muscle cells. Treatment of vascular smooth muscle cells with IL-1 beta resulted in significant accumulation of nitrite in the culture media and in marked elevation of intracellular cyclic guanosine monophosphate (GMP) levels. The releasate from collagen-aggregated platelets blocked the IL-1 beta- mediated production of nitrite and the accumulation of cyclic GMP in smooth muscle cells in a platelet number-dependent manner. In functional assays, the perfusates from columns containing IL-1 beta- treated smooth muscle cells relaxed detector blood vessels without endothelium and the addition of IL-1 beta-treated smooth muscle cells to suspensions of platelets inhibited their thrombin-induced aggregation. The simultaneous treatment of smooth muscle cells with IL- 1 beta and the platelet releasate abolished both the vasorelaxing activities of the perfusates and the inhibition of platelet aggregation. Platelet releasates treated with a neutralizing antibody to platelet-derived growth factor (PDGF) failed to block IL-1 beta- induced nitric oxide production by the smooth muscle cells, as measured by both biochemical and functional assays. The platelet releasate from a patient with gray platelet syndrome likewise failed to block IL-1 beta-induced nitrite release by smooth muscle cells. These results demonstrate that platelets downregulate the production of nitric oxide by IL-1 beta-treated vascular smooth muscle cells through the release of PDGF. This effect may represent a novel mechanism by which platelets regulate vasomotor tone and thrombus formation at sites of vascular injury.     

APOC's strategy of community-directed treatment with ivermectin (CDTI) and its potential for providing additional health services to the poorest populations. African Programme for Onchocerciasis Control

Since its inauguration in 1995, the African Programme for Onchocerciasis Control (APOC) has made significant progress towards achieving its main objective: to establish sustainable community-directed treatment with ivermectin (CDTI) in onchocerciasis-endemic areas outside of the remit of the Onchocerciasis Control Programme in West Africa (OCP). In the year 2000, the programme, in partnership with governments, non-governmental organizations and the endemic communities themselves, succeeded in treating 20,298,138 individuals in 49,654 communities in 63 projects in 14 countries. Besides the distribution of ivermectin, the programme has strengthened primary healthcare (PHC) through capacity-building, mobilization of resources and empowerment of communities. The community-directed-treatment approach is a model that can be adopted in developing other community-based health programmes. The approach has also made it possible to bring to the poor some measure of intervention in some other healthcare programmes, such as those for malaria control, eye care, maternal and child health, nutrition and immunization. CDTI presents, at all stages of its implementation, a unique window of opportunity for promoting the functional integration of healthcare activities. For this to be done successfully and in a co-ordinated manner, adequate funding of CDTI within PHC is as important as an effective sensitization of the relevant policy-makers, healthworkers and communities on the value of integration (accompanied by appropriate training at all levels). Evaluation of the experiences in integration of health services, particularly at community level, is crucial to the success of the integration.     

Trofosfamide as salvage therapy for anaplastic large cell lymphoma relapsing after high-dose chemotherapy

Patients with relapsed aggressive lymphoma after high dose chemotherapy have a very poor prognosis and long-term survival is rare. Most patients are not eligible for allogeneic stem cell transplantation in this setting and treatment, therefore, becomes palliative. A few studies have shown that trofosfamide, an oral alkylating agent, may be effective as palliative treatment in non-Hodgkin's lymphoma. Trofosfamide therapy is considered rather non-toxic with an overall response rate from 50 to 80%. Most responses are, however, partial and their duration is short. We report a patient with a very aggressive ALK + anaplastic large cell lymphoma (ALCL), relapsing shortly after high dose chemotherapy. Unrelated allogeneic transplantation was hot possible. After several radio/chemotherapy regimens trofosfamide was started as palliative treatment. This therapy resulted in a complete remission, still ongoing, 27 months after termination of intravenous cytotoxic therapy and 16 months after withdrawal of trofosfamide. Thus, in this particular case, trofosfamide turned out to be an unexpectedly effective salvage therapy for an otherwise very aggressive relapsing ALCL.     

Angiotensin‐converting enzyme inhibition increases glucose‐induced insulin secretion in response to acute restraint

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GROWTH HORMONE ATTENUATES MYOCARDIAL FIBROSIS IN RATS WITH CHRONIC PRESSURE OVERLOAD-INDUCED LEFT VENTRICULAR HYPERTROPHY

• 1 The role of growth hormone (GH) in cardiac remodelling and function in chronic and persistent pressure overload‐induced left ventricular hypertrophy has not been defined. The aim of the present study was to assess short‐term GH treatment on left ventricular function and remodelling in rats with chronic pressure overload‐induced hypertrophy.
• 2 Twenty‐six weeks after induction of ascending aortic stenosis (AAS), rats were treated with daily subcutaneous injections of recombinant human GH (1 mg/kg per day; AAS‐GH group) or saline (AAS‐P group) for 14 days. Sham‐operated animals served as controls. Left ventricular function was assessed by echocardiography before and after GH treatment. Myocardial fibrosis was evaluated by histological analysis.
• 3 Before GH treatment, AAS rats presented similar left ventricular function and structure. Treatment of rats with GH after the AAS procedure did not change bodyweight or heart weight, both of which were higher in the AAS groups than in the controls. After GH treatment, posterior wall shortening velocity (PWSV) was lower in the AAS‐P group than in the control group. However, in the AAS‐GH group, PWSV was between that in the control and AAS‐P groups and did not differ significantly from either group. Fractional collagen (% of total area) was significantly higher in the AAS‐P and AAS‐GH groups compared with control (10.34 ± 1.29, 4.44 ± 1.37 and 1.88 ± 0.88%, respectively; P < 0.05) and was higher still in the AAS‐P group compared with the AAS‐GH group.
• 4 The present study has shown that short‐term administration of GH to rats with chronic pressure overload‐induced left ventricular hypertrophy induces cardioprotection by attenuating myocardial fibrosis.

     

Antihepatotoxic biochemical effects of kolaviron,a biflavonoid of Garcinia kola seeds

Male rats (200–220 g) were treated with toxic doses of carbon tetrachloride (2 mL/kg per day i.p., for 3 days) to induce liver damage. Another group of rats received kolaviron, a biflavonoid extract from seeds of Garcinia kola (500 mg/kg, i.p.) 1 h prior to receiving carbon tetrachloride. Tests for liver function were performed on all animals. The activities of glutamic oxaloacetatetransaminase (GOT), glutamic pyruvate transaminase (GPT), sorbitol dehydrogenase (SDH) and glutamic dehydrogenase (GLDH) in serum were determined, as were the concentrations of hepatic glutathione (GSH) and triglyceride in liver. Hepatic lipid peroxidation was assessed by measuring hepatic malondialdehyde (MDA) formation in the liver. Carbon tetrachloride induced marked depletion of GSH and increased the formation of MDA and triglyceride in the liver, as well as causing significant increases in activities of the serum enzymes assessed. Pretreatment with kolaviron significantly attentuated all the alterations caused by carbon tetrachloride. The antihepatotoxic action of kolaviron was clearly demonstrated in the model of hepatitis employed in this study.     

A requirement for low concentration of hepatic glutathione for induction of gammaglutamyltransferase by phenobarbitone

The effect of low concentration of hepatic glutathione on the induction of GGT by phenobarbitone was investigated. Rats were treated with diethyl maleate to decrease the hepatic concentration of GGT and with cysteine to increase glutathione concentration in the liver. All animals were then treated with phenobarbitone. The study shows that the induction of GGT is promoted by low concentration of hepatic glutathione.