Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper. 相似文献
An N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer carrier containing doxorubicin and human immunoglobulin as an actively/passively targeting moiety was used in four patients with generalized breast cancer resistant to standard cytotoxic chemotherapy. The dose and time schedule were deduced from a Phase I clinical trial in which doxorubicin bound to HPMA copolymer carrier (PK1) was tested. It was confirmed that the Dox-HPMA-HuIg conjugate is stable and doxorubicin remains in the peripheral blood with a small amount also in the urine, mostly in its polymer-bound form. More than 116 biochemical, immunological and hematological parameters were determined for blood samples taken from patients 24 h, 48 h, 72 h and 1 to 11 weeks after treatment. Depending on the patient, some parameters decreased permanently or temporarily to the normal level (CRP, C3, CA 72-4, beta(2)-microglobulin, ferritin, CEA, CA 125, CD4, CD8, CE19, CD16(+)56(+), leu, ery) and some moved markedly towards physiological values (AST, ALT, ALP, GMT, CA 15-3, NSE, AFP). While the number of peripheral blood reticulocytes was significantly decreased after treatment with the classical free drug, their number was not affected or was even elevated after treatment with Dox-HPMA-HuIg. Increased absolute numbers of CD16(+)56(+) and CD4(+) cells in the peripheral blood and activation of NK and LAK cells in all patients support data obtained in experimental animals, pointing to a dual, i.e. cytostatic and immunomobilizing character of Dox-HPMA conjugates containing a targeting immunoglobulin moiety. 相似文献
Abuse liability and acute subjective and psychomotor effects of flunitrazepam were assessed in ten methadone-maintained males
with history of benzodiazepine and alcohol use, who voluntarily participated in a double-blind, controlled, cross-over, randomized
clinical trial. There were six experimental sessions in which a single oral dose of flunitrazepam 1, 2, and 4 mg; triazolam
0.5 and 0.75 mg; and placebo was given. Evaluations included physiological measures; psychomotor performance tasks (simple
reaction time, Digit Symbol Substitution Test, balance task, Maddox-wing device); and self-administered subjective effects
questionnaires [Addiction Research Center Inventory (ARCI), Profile of Mood States (POMS), a series of visual analog scales
(VAS)]. All drugs but flunitrazepam 1 mg caused an impairment of psychomotor tasks. Effects were more evident with the highest
doses of both drugs. Only flunitrazepam 4 mg produced a significant decrease in balance time. Triazolam 0.75 mg induced increases
in sedation measured by ARCI-PCAG, depression in POMS, and VAS-drowsiness scores. Flunitrazepam 4 mg caused euphoria-related
effects as measured by increases in ARCI-MBG and “high” scores in the VAS. Our findings of flunitrazepam-induced euphoria
in methadone-maintained subjects together with epidemiological evidence of flunitrazepam abuse by opioid dependents, suggest
that it may be included in the group of benzodiazepines with a relatively high abuse potential.
Received: 13 February 1998/Final version: 1 May 1998 相似文献
A high-performance liquid chromatographic (HPLC) method is described for the assay of the active metabolite [1-(2-pyrimidinyl)piperazinel of buspirone, an anxiolytic agent, in rat plasma.
The method is based on the use of ion-pair HPLC coupled to a liquid—solid extraction scheme. Samples of rat plasma (2 ml) with internal standard (1-phenylpiperazine), adjusted to pH 10.5 with borate buffer, were loaded on to a preactivated C-18 cartridge. The metabolite and the internal standard were eluted with 5 ml of methanol and injected on to a reversed-phase 10-μm Spherisorb ODS-2 column. The column was eluted with a mobile phase of 0.005 M sodium lauryl sulphate in citrate buffer (pH 3.6)-acetonitrile (65:35, v/v) at 2 ml min−1. Detection was carried out at 248 nm. The recovery of the metabolite was 55%. The method was applied to the determination of the metabolite in rat plasma after oral dosing (25 mg kg−1) of the parent compound. 相似文献
Using a system that allows transfection of resting peripheral blood lymphocytes (PBLs) two questions were addressed: the kinetics of HIV replication from the state of proviral latency, and the impact of different parameters on the efficacy of protease inhibitors to control HIV replication. PBLs were transfected with an infectious full length HIV-DNA harboring a luciferase reporter gene and activated thereafter. Ritonavir was added at different times at doses ranging from to 0.06 to 1 microM. Viral expression was assessed by quantifying luciferase activity in cell extracts and levels of p24 HIV antigen in culture supernatants. After transfection and cell activation, intracellular expression of HIV proteins, as assessed by luciferase detection, occurred within 2 hr. HIV-gag p24 antigen was detected in culture supernatants between 6 and 8 hr post-activation. Ritonavir was effective in blocking viral replication when given within 4 hr following HIV reactivation, but a delay in ritonavir administration or breaches in ritonavir levels after 6 hr from transfection resulted in viral escape. HIV reactivation from proviral latency in PBLs is an extremely rapid process, faster than estimated from previous models. These data stress the need for maintaining effective antiretroviral concentrations to block completely viral replication. 相似文献