工作作为药物及酒精滥用者有效的干预策略和治疗方法

1Introduction Substanceabusecontinuestobeamongthemostsevereso cialandcostlyhealthproblemsdevastatingindividualsandtheir familiesintheUnitedStates.Initssimplestdefinition,sub stanceabuseisthecontinueduseofalcoholorotherdrugsde spiteknowledgeofhavingapersistentsocial,vocational,psy chologicalorphysicalproblemthatiscausedorexacerbatedby theuseofalcoholorotherdrugs(DSMIV TR,1994).All drugsofabuse,includingalcohol,aretoxicandcannegatively impacteverysysteminthehumanorganism.Protractedsub stance…     

Closed versus open mitral commissurotomy in pure noncalcific mitral stenosis: hemodynamic studies before and after operation

Controversy persists regarding whether the efficacy of closed instrumental mitral commissurotomy compares well enough with that of open commissurotomy to warrant its continued use. The purpose of this study was to compare the results of operation as determined by catheterization studies in 63 patients with pure, severe, and noncalcified mitral stenosis. The patients were randomly assigned to one of two groups: thirty-two patients were operated on by the closed technique (group I) and 31 by the open technique (group II). All patients underwent left-sided and right-sided catheterization before and 4 months after operation. Preoperatively the two groups were statistically similar with regard to major clinical data and hemodynamic findings. There were no deaths at operation or systemic embolism in the two groups. The prevalence of surgically induced mitral regurgitation was similar in the two groups (12.4% versus 12.9%). Pulmonary arterial pressure and arteriolar and total pulmonary vascular resistance decreased significantly in the two groups. Pulmonary capillary wedge pressure decreased from 23.3 +/- 8.5 to 15.8 +/- 7 mm Hg in group I (p less than 0.001) and from 23.7 +/- 6 to 14 +/- 5.8 mm Hg in group II (p less than 0.001). Cardiac index increased from 2.86 +/- 0.84 to 3.14 +/- 0.78 L/min/m2 in group I, but this increase did not reach statistical significance. In group II cardiac index increased from 2.89 +/- 0.6 to 3.6 +/- 0.6 L/min/m2 (p less than 0.005). The mean and end-diastolic transmitral pressure gradients decreased significantly in the two groups, but the decrease was statistically greater in the open mitral commissurotomy group (p less than 0.001). Mitral valve area increased from 0.82 +/- 0.18 to 1.4 +/- 0.40 cm2 in group I (p less than 0.01) and from 0.84 +/- 0.15 to 2.14 +/- 0.53 cm2 in group II (p less than 0.001). The mean increase in mitral valve area was 0.61 cm2 in group I and 1.34 cm2 in group II (p less than 0.001). At exercise, in patients with resting pulmonary capillary wedge pressures of 18 mm Hg or less, cardiac index increased by 36% in group I (23 patients) and 48% in group II (24 patients), because of a smaller mitral valve area in group I (1.61 +/- 0.39 cm2) than in group II (2.45 +/- 0.65 cm2). Thus open commissurotomy improved hemodynamic values to a greater extent than closed commissurotomy at both rest and exercise.(ABSTRACT TRUNCATED AT 400 WORDS)     

Selective homing of phenotypically lytic cells within nasopharyngeal carcinoma biopsies: numerous CD8- and CD16-positive cells in the tumor.

We present a comparative analysis of cell-mediated immunity between circulating lymphocytes and tumor-infiltrating lymphocytes (TIL) from patients with nasopharyngeal carcinoma (NPC). Phenotypic analysis using a panel of monoclonal antibodies (MAbs) to define lymphocytic subsets has revealed a selective homing of phenotypically lytic cells such as CD8- and CD16-positive cells, but a low percentage of macrophages when compared to PBL of NPC patients. Also, PBL and TIL contain an equivalent percentage of activated T-lymphocytes expressing HLA-DR molecules and IL-2 receptors. Functionally, TIL exhibit an abolished NK-cell activity and concomitant decrease of proliferative response to phytohemagglutinin (PHA) and concanavalin A (ConA) stimulation when compared with PBL.     

Tumor necrosis factor-alpha in whole blood cultures of preeclamptic patients and healthy pregnant and nonpregnant women.

OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) is recognized as a likely mediator of the excessive endothelial activation and injury that is a key pathogenetic mechanism of preeclampsia. We used whole blood cell cultures from 12 patients with severe preeclampsia and from 12 healthy pregnant and nonpregnant women to determine the release of TNF-alpha by unstimulated leukocytes as a measure of their state of activation, and their response to stimulation with lipopolysaccharide (LPS) as an indicator of their state of priming. METHODS: Blood was cultivated without and with LPS, and TNF-alpha release was measured after six and 24 hours of cultivation by enzyme-linked immunoassays. Differential leukocyte counts were performed, and TNF-alpha values calculated per 10(5) monocytes. RESULTS: In unstimulated whole blood cultures, TNF-alpha release after six hours of cultivation was similar in all three groups; but after 24 hours, TNF-alpha concentrations in culture supernatants from preeclamptic patients were significantly higher than were values obtained in blood from normotensive pregnant women. In LPS-stimulated blood cultures with a maximum of TNF-alpha release at six hours cultivation time, TNF-alpha concentrations were significantly lower in preeclamptic women than they were in both control groups. We showed in an additional experiment that a strong LPS challenge following preactivation with high doses of LPS resulted in reduced release of TNF-alpha compared with release of TNF-alpha following preactivation with low doses of LPS. CONCLUSIONS: The observed high capacity for spontaneous TNF-alpha release by leukocytes in preeclampsia indicates activation of TNF-alpha producing leukocytes by the disease process. Preactivation and exhaustion of leukocytes by leakage of TNF-alpha could lead to the reduced response to TNF-alpha inducer LPS as observed in blood cultures from preeclamptic patients.     

A novel cubic phase of medium chain lipid origin for the delivery of poorly water soluble drugs.

The existence of a novel cubic liquid crystalline phase is described within the pseudo-ternary system comprising lauric acid, monolaurin, and simulated endogenous intestinal fluid (SEIF). This phase behaviour has been characterized using cross-polarizing light microscopy (CPLM), and the structure of the cubic phase identified by small angle X-ray scattering (SAXS). The presence of the cubic phase was found to be temperature sensitive within the 20-37 degrees C range making it putative material for in situ gelation purposes. The cubic phase was shown to have a high capacity to solubilise a model poorly water-soluble drug, cinnarizine, and initial in vitro release data highlight the potential of this phase to provide sustained release. Absorption of cinnarizine from the cubic phase was studied in an unconscious rat model via duodenal administration and blood sampling via the carotid artery. The rate of absorption was significantly reduced when compared to a simple suspension formulation, a likely combination of retarded erosion of the cubic phase together with hindered drug release from the cubic matrix. The results of this study suggest that this cubic phase may potentially be of benefit in the delivery of poorly water-soluble compounds due to its high loading capacity and potential for sustained release. The ability to manipulate this system using temperature may warrant further interest in delivery applications via other routes of administration.