Summary— Recent clinical studies have reported a beneficial effect of fluoxetine, a serotonin reuptake inhibitor, in patients with severe refractory orthostatic hypotension. The present study was undertaken to investigate the effect of fluoxetine in orthostatic hypotension occurring during Parkinson's disease on both blood pressure values and number of clinical symptoms during orthostatic procedure evaluated using a validated clinical rating scale. In a pilot study performed in fourteen patients with idiopathic Parkinson's disease plus orthostatic hypotension, fluoxetine hydrochloride (20 mg orally daily during one month) significantly reduced the fall in systolic blood pressure [-33 ± 21 (SD) mmHg before fluoxetine vs -22 ± 19 mmHg after fluoxetine, P = 0.03] elicited by standing without modifying heart rate. The drug also significantly reduced the number of postural symptoms occurring during the orthostatic procedure [2.9 ± 1.5 (SD) before fluoxetine vs 1.2 ± 1.3 after fluoxetine, P = 0.006]. A similar pattern of response was obtained in an experimental model of neurogenic orthostatic hypotension obtained in chronically sino-aortic denervated dogs submitted to an 80° head-up tilt test procedure under chloralose anaesthesia. Fluoxetine did not change plasma noradrenaline levels. This pilot study suggests a slight but clinically significant effect of fluoxetine on both hemodynamic parameters and clinical symptoms in parkinsonian patients suffering from orthostatic hypotension. 相似文献
Following a cryopreservation step, short-term cultures of circulating leukemic blasts from a patient with acute myeloid leukemia (AML) were performed. Because cultured tumor cells became susceptible to natural killer (NK) activity, in vitro alteration of the blasts was studied. Immediately after thawing, cell suspensions consisted of a relatively homogeneous population of undifferentiated blasts. In culture, tritiated thymidine uptake by the leukemic cells was low during the first 24 hours and then increased (X20) to a peak on day 7. The cell concentration started to increase on day 4. On day 8, less than 10% of the cultured cells still appeared as undifferentiated blasts, whereas up to 60% were granular and 30% to 40% had a monocytoid morphology. Prior to being cultured, the blasts were resistant to resting and IL2- activated natural killing. When the kinetics of in vitro acquired susceptibility were studied, it was found that maximum cytotoxicity against these leukemic cells was reached within 24 hours. Thus, the blasts had become NK-sensitive prior to increase in DNA synthesis, proliferation, and differentiation based on morphological and cytochemical criteria. In contrast, there was a positive correlation between acquired susceptibility and surface expression of an activation antigen, termed TNKtar. To dissect further the mechanisms of acquired susceptibility, a series of six NK clones representing four distinct phenotypes of NK active lymphocytes were tested against the leukemic cells. Immediately after thawing, blasts were essentially resistant to all clones, whereas they were strongly killed by 5 of 6 clones when cultured for 24 hours. Cold target inhibition assays indicated that resistance of fresh blasts was likely to be due to a binding defect. These results suggested that tumor cells became susceptible because they surface-expressed NK target structure(s) in the early phase of an activation process leading to their proliferation and/or differentiation. This hypothesis was substantiated for one clone, termed JT9, because the anti-TNKtar antibody blocked cytotoxicity of JT9 cells against the cultured blasts. 相似文献
The current research examined the capability of materialism, pain of paying, social anxiety, social support, and loneliness to predict compulsive buying. A sample of students attending a public university located in the northeast USA were surveyed. A multiple regression indicated materialism, pain of paying, anhedonia, coping with substances, and social support received from family were predictors of compulsive buying. Pain of paying was the strongest predictor of compulsive buying. Understanding factors that affect compulsive buying aids the identification of compulsive buying and informs the treatment of compulsive buying. Treatment models may be more effective if additional attention is given to addressing and developing social support networks of compulsive buyers. Such social support may act as a buffer against the social anxiety compulsive buyers experience and may help reduce feelings of anhedonia and use of substances to control social anxiety.
The aims of this study are to examine the characteristics of compulsive buying among college students at an American public university. More specifically we explored how irrational beliefs impact compulsive buying among this population; and, to investigate the types and frequency of consumer goods purchased by college students at an American public university. The study is based on data collected from a self-administered survey of 175 American college women. The results of this study showed that the prevalence of women are compulsive buyers was consistent with an earlier estimate using the Richmond Compulsive Buying Scale (27 %); irrational beliefs were associated with and predicted compulsive buying; and compulsive and non-compulsive buyers did not differ in the types of consumer goods purchased but in the frequency with which consumer goods are purchased. The study has significance by replicating the impact irrational beliefs have on compulsive buying. Such beliefs should be addressed in any preventative program targeting compulsive buying. 相似文献
We have investigated the effect of deletions of a postsynaptic density, disc large and zo-1 protein (PDZ) motif at the end of the COOH-terminus of the rat A2B adenosine receptor on intracellular trafficking following long-term exposure to the agonist 5′-(N-ethylcarboxamido)-adenosine.
Experimental approach:
The trafficking of the wild type A2B adenosine receptor and deletion mutants expressed in Chinese hamster ovary cells was studied using an enzyme-linked immunosorbent assay in combination with immunofluorescence microscopy.
Key results:
The wild type A2B adenosine receptor and deletion mutants were all extensively internalized following prolonged treatment with NECA. The intracellular compartment through which the Gln325-stop receptor mutant, which lacks the Type II PDZ motif found in the wild type receptor initially trafficked was not the same as the wild type receptor. Expression of dominant negative mutants of arrestin-2, dynamin or Eps-15 inhibited internalization of wild type and Leu330-stop receptors, whereas only dominant negative mutant dynamin inhibited agonist-induced internalization of Gln325-stop, Ser326-stop and Phe328-stop receptors. Following internalization, the wild type A2B adenosine receptor recycled rapidly to the cell surface, whereas the Gln325-stop receptor did not recycle.
Conclusions and implications:
Deletion of the COOH-terminus of the A2B adenosine receptor beyond Leu330 switches internalization from an arrestin- and clathrin-dependent pathway to one that is dynamin dependent but arrestin and clathrin independent. The presence of a Type II PDZ motif appears to be essential for arrestin- and clathrin-dependent internalization, as well as recycling of the A2B adenosine receptor following prolonged agonist addition. 相似文献
Health-care case management places pressure on decision makers to adopt treatment strategies that promote economic efficiency and hence profitability. Traditional costeffectiveness analysis (CEA), where the objective is to calculate cost-effectiveness ratios, can better inform decision making in markets where prices and efficacy vary widely. However, the threshold at which a given therapy becomes economically efficient relative to competing therapies is not evident from cost-effictiveness ratios alone. OBJECTIVE: To illustrate the use of spatial techniques for identifying efficient treatment options, using statin therapy in secondary prevention of coronary heart disease (CHD) as a case study. METHODS: We used a Markov model of CHD epidemiology and treatment to estimate cost-effectivness of 13 statin regimens versus no therapy in secondary prevention of CHD. Comparative efficacy was assessed using data from a recent trial (CURVES) that included these regimens. Patients were assumed to have a history of CHD with risk factors similar to those observed in the trial. CHD event risk was estimated using new subsequent-event risk equations from the Framingham Heart Study. Effectiveness was measured alternatively as gain in life expectancy and CHD events averted. RESULTS: At usual starting doses, atorvastatin therapy provided the largest life expectancy gain and CHD event avoidance at the lowest cost per life-year gained ($12,900 and $23,400 for men and women, respectively), followed by simvastatin ($17,700 and $31,700), lovastatin ($18,800 and $33,700), pravastatin ($22,600 and $40,200), and fluvastatin ($23,800 and $42,000). Any desired level of effectiveness can be obtained at lowest cost with atorvastatin. CONCLUSION: Economic efficiency is enhanced when atorvastatin is used to treat some or all patients requiring statin therapy in secondary prevention of CHD. 相似文献