Modulation of adenosine-induced responses in the guinea-pig trachea during long-term caffeine treatment: possible role of epithelium.

The responses to adenosine were studied on isolated, methacholine-precontracted tracheal strips of guinea pigs in the course of long-term caffeine or solvent treatment. Guinea pigs were fed caffeine for 10 weeks (average serum caffeine concentration: 39.1 +/- 3.9 microM). In epithelium-intact tracheal preparations (EITPs), sensititization to adenosine-induced relaxation (AIR) developed. It attained a maximum in week 1 of caffeine treatment, and then its level diminished and disappeared completely by weeks 4 - 6. In epithelium-denuded tracheal preparations (EDTPs), an increase in the sensitivity to adenosine was observed from week 1 to week 10 (a 4 - 6-fold reduction in EC50). Use of a coaxial bioassay system confirmed the role of epithelium in this process. The enhancement of the AIR of the EITPs was not modified by inhibitors of cyclooxygenase and lipoxygenase. Following depletion of the neuropeptides by acute capsaicin pretreatment, the AIR of the EITPs was strongly enhanced after caffeine treatment for 6 weeks. In chronically caffeine-treated EITPs, the inhibition of neutral endopeptidase led to dramatic reduction of the AIR. On the basis of the results by inhibiting nitric oxide synthase, it can be supposed that nitric oxide released from EITPs of long-lasting caffeine-treated animals operated as a constrictor agent. Our results show that chronic caffeine treatment gives rise to an initial sensitization to adenosine of the EITPs, this being followed by the development of a specific adaptive process in the epithelial cells, which counterbalances the increased tracheal sensitivity to adenosine.

[Results in 42 non-resectable NSCLC IIA-B patients with initial concurrent Taxotere-Cisplatin chemoradiotherapy]. / IIIA-B stádiumú NSCLC elsovonalbeli Taxotere-Cisplatin konkuráló kemo-radioterápiájának eredményei 42 irreszekábilis daganatos beteg vizsgálata alapján.

GOALS: A prospective multicenter study to treat non-small cell lung cancer (NSCLC) with inductive chemoradiotherapy for improving chances of operability. If used as first-line therapy, combined treatment improves survival and it is well tolerated with a low rate of side effects. PATIENTS: 42 patients with stage IIIA-B NSCLC from which 36 could be followed. METHODS: A full dose Taxotere-Cisplatin chemotherapy was given to patients with concurrent radiotherapy in 2 Gy fractions up to 60 Gy via conformal irradiation. RESULTS: Local response was very high and 40.47% of patients became operable while in inoperable cases consolidation chemotherapy showed similar results as other protocols. We also found a low rate of side effects. The high rate of brain metastasis suggests that prophylactic cranial irradiation (PCI) should be considered.

Adenosine inhibits the release of interleukin-1beta in activated human peripheral mononuclear cells.

The effects of adenosine and subtype-specific activators of adenosine receptors (A1, A2A, A2B and A3) were studied on the release of interleukin-1beta (IL-1beta) from peripheral mononuclear cells, monocytes and lymphocytes. In the cells activated by the protein kinase C specific phorbol ester (phorbol 12-myristate 13-acetate) and Ca(2+) ionophore (A23187) both adenosine and the subtype-specific receptor agonists, CPA (A1), CGS 21680 (A2A) and IB-MECA (A3) induced a concentration-dependent inhibition of IL-1beta release. The rank order of potency in the inhibition of IL-1beta release was CPA=CGS 21680>IB-MECA>adenosine>NECA (in the presence of A1, A2A and A3 receptor inhibitors). The inhibitory actions of CPA, CGS 21680 or IB-MECA were significantly reduced in the presence of DPCPX, ZM 243185 or MRS 1191 as subtype-specific antagonists on A1, A2A and A3 adenosine receptors, respectively. It can be concluded that adenosine inhibits the release of IL-1beta from the activated human peripheral mononuclear cells. In this process A1, A2A and A3 receptors are involved.

[Bronchoscopy in intensive care units]. / Bronchoszkópia az intenzív osztályokon.

The authors report their 1535 urgent bronchoscopic examinations performed between 1998-2002. The examinations/interventions were requested mostly by surgical and internal medicine intensive care units. The main indications were: postoperative excretion removal, stump control, suspicion of fistula, foreign body, injury of a large bronchus, tracheal stenosis, specimen taking and bronchoscopic local drug treatment. The authors mention the most important contraindications for urgent bronchofiberscopy too: missing written consent of the patient (except the cases of unconsciousness), size discrepancy between the tool and tracheal lumen, and asthmatic attack. The authors also underline the emerging importance of both diagnostic and therapeutic bronchoscopy performed on emergency wards and intensive care units. They conclude: it's necessary for the anesthetists to get a basic level ability to work with bronchofiberscope and for pulmonologist-bronchologists to be experienced to answer the questions of other specialists.