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91.
The circadian timekeeping system exhibits many functional changes with aging, including a loss of sensitivity to time cues such as systemic injections of the serotonergic agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). In order to elucidate the neurochemical mechanisms responsible for this age-related loss of sensitivity of the circadian pacemaker to serotonin agonists, the present study used quantitative autoradiography to determine whether aging decreases serotonin receptor populations in male Syrian hamsters. Four neuroanatomical regions that regulate circadian timekeeping were studied (the suprachiasmatic nuclei [SCN], the lateral geniculate nuclei [LGN], and the median raphe nucleus [MRN] and dorsal raphe nucleus [DRN]). The specific binding of [3H]8-OH-DPAT to serotonin7 (5-HT7) and serotonin1A (5-HT1A) receptors was investigated by competitive inhibition with ritanserin and pindolol, respectively. The results showed that the SCN, IGL, MRN, and DRN of the male Syrian hamster exhibited specific binding of [3H]8-OH-DPAT to both the 5-HT7 and 5-HT1A receptors, and that the latter receptor subtype is more abundant in all of these regions. At 17-19 months of age, a 50% decrease in 5-HT7 receptors was found in the DRN but not in any other regions. No significant age-related changes in 5-HT1A receptors were observed in any regions examined. The finding that a marked decrease in 5-HT7 receptors occurs in the DRN at the age previously characterized by loss of sensitivity to 8-OH-DPAT suggests that this region and this receptor subtype play important roles in 8-OH-DPAT induction of circadian phase shifts in vivo and that they constitute an important locus of aging in the circadian timing system.  相似文献   
92.
Women in the United States, particularly African-Americans and Hispanics, are at increased risk for HIV. The female condom now offers women a potentially important option for HIV prevention, yet few efforts have been made to increase its use. To elucidate strategies to promote the use of the female condom, we conducted in-depth interviews with 62 women recruited from the four major racial/ethnic groups of the U.S. (African-American, Asian-American, Hispanic, and white). Subject recruitment took place at a family planning clinic in San Francisco during 1996-97. We identified four major types of facilitators and barriers to use of the female condom: mechanical, psychosexual, interpersonal, and situational. Specifically, the mechanical facilitators and barriers included positive and negative aspects of the device, and difficulty with insertion. The psychosexual factors were female empowerment, more options for contraception and disease prevention, discomfort with vaginal insertion, and condom use norms. The interpersonal factors included: enhanced communication, relationship status, partner preferences, and partner objections. Finally, the situations that made women disinclined to use the device were: no access to the female condom when having sex and using other forms of contraceptives. The implications of these findings for HIV prevention and future research are discussed.  相似文献   
93.
· Background: To investigate the potential of high-resolution ultrasound biomicroscopy (UBM) for studying the zonular apparatus of human beings in vivo. · Methods: Using transducer frequencies of 34 MHz and 50 MHz, criteria were developed to identify transcorneal and transscleral sections that allowed reproducible identification of the different fiber groups of the zonular architecture. For that purpose, 10 volunteers between the ages of 14 and 41 years underwent high-resolution ultrasound biomicroscopy under conditions of consensual far- and near-accommodation. The online video recordings of the respective UBM investigations were afterwards analyzed image by image. Good visibility of zonular fibers was obtained when the ultrasound wave propagation comprised an angle close to 90° with the fiber orientation and when the oscillations of the UBM scan had a strict radial orientation towards the limbus and avoided, simultaneously, the ciliary processes. · Results: In all the volunteers, high-resolution ultrasound biomicroscopy imaged the zonular fiber groups known from histology. In addition, it detected fibers that do not follow the course of the inner ciliary body surface but take a direct route from the ora serrata to the lens. It also demonstrated that fibers that seem to change direction at crossings with other fibers. Under conditions of near-accommodation, the zonular fibers showed signs of relaxation. · Conclusions: High-resolution ultrasound biomicroscopy seems well suited for in vivo investigations of the zonular apparatus and of accommodation in man. The results support the fundamental features of the Helmholtz theory on accommodation. Received: 8 June 1998 Revised version received: 7 September 1998 Accepted: 14 September 1998  相似文献   
94.
We have investigated the role of coagulation and fibrinolysis during the metastatic lung colonization of F3II mouse mammary carcinoma cells. The selective synthetic urokinase inhibitor B623 significantly enhanced lung colonization and blocked the antimetastatic effect of heparin when administered i.p. during the first stages of metastasis formation. In B623-treated mice the overall activity of the fibrinolytic system was reduced and circulating urokinase was specifically inhibited by this agent. In vitro studies demonstrated that B623 induces the aggregation of F3II cells in the presence of mouse plasma and facilitates the entrapment of tumor cells in a fibrin gel matrix. Our data suggest that imbalances of fibrin deposition and removal may dramatically influence metastatic lung colonization.  相似文献   
95.
Summary Taurine, a putative inhibitory neurotransmitter, was injected in various doses intracerebroventricularly to conscious rats via pre-implanted polythene cannulas. The formation of DOPA and 5-hydroxytryptophan (5-HTP) in various brain regions was investigated by measuring the accumulation of these monoamine precursors induced within 30 min by the intraperitoneal injection of 3-hydroxybenzyl hydrazine HCl (NSD 1015, 100 mg/kg), an inhibitor of the aromatic L-amino acid decarboxylase readily penetrating into the brain. DIPA formation, but not 5-HTP formation was significantly enhanced by taurine in dose-related manner in all brain regions studied, indicating an increased synthesis of both dopamine and noradrenaline. Dopamine depletion induced by -methyltyrosine was significantly retarded by taurine, whereas noradrenaline depletion tended to be enhanced. Endogenous levels of dopamine were increased, whereas the following brain constituents were unchanged: tyrosine, tryptophan, noradrenaline, 5-HT and 5-hydroxyindoleacetic acid. In the exoeriments with NSD 1015, a dose-related decrease in rectal temperature and in motility was observed after taurine treatment, as compared to treatment with the decarboxylase inhibotor alone. Systemic parenteral administration of taurine caused no significant changes in brain monoamines, body temperature or behaviour but decreased the heart noradrenaline levels. The data indicate that taurine, which apparently has to be given intracerebroventricularly in order to reach the brain in sufficient amounts, causes inhibition of firing in central dopamine neurons but has the opposite effect on noradrenaline neurons, perhaps also peripherally, whereas 5-HT neurons appear to be unaffected. In addition, taurine appears to interfere with motor behaviour and temperature regulation, possibly via effects on catecholaminergic systems.  相似文献   
96.
The purpose of these experiments was to study the incidence of stress ulcers in restrained rats and to correlate it with hypothalamic and adrenal cortical and medullary activity, with and without vagotomy. A total of 217 adult rats were used, grouped into 56 sets, and distributed at random in 5 experimental groups. Restraint was followed by a 79% incidence of ulceration in the glandular portion of the gastric mucosa. Vagotomy made these worse (p<0.01). Hypothalamic levels of catecholamines and serotonin showed no significant changes. Urinary measurements revealed decreased excretion of 17-ketosteroids (p<0.001), increased excretion of uropepsinogen (p<0.01), and no significant changes in vanillylmandelic acid among the rats submitted to immobilization. In the adrenal glands of stressed animals, there was a decreased level of catecholamines (p<0.01) and no significant changes in corticosteroid content (17-ketosteroids). These results suggest that hypothalamic stimulation and the participation of the adrenal glands are not essential factors in the pathogenesis of restraint-induced experimental stress ulcer.  相似文献   
97.
Percutaneous dilatational tracheostomy (PDT) is being increasingly used. Concerns have been raised as to its safety, especially when it is done at the bedside. A prospective evaluation was conducted of 100 consecutive, unselected critically ill patients with PDT. The mean intensive care unit (ICU) stay before PDT was 12 days. One surgeon performed PDT alone (5 cases) or assisted residents (95 cases) in all operations; 84 were performed at the ICU bedside. Only the first six patients were taken to the operating room solely for tracheostomy. A modified technique was used: (1) the endotracheal tube was left in place during sequential dilations; (2) dilators were inserted in a 60-degree cephalad orientation to the skin and directed caudally after penetration of the anterior tracheal wall; (3) a digit was inserted through the tracheal opening to guide withdrawal of the endotracheal tube to the level of the vocal cords; and (4) size 8 tracheostomy cannulas were inserted over 28F dilators. The average time from skin incision to insertion of the tracheostomy tube was 12 minutes (< 10 minutes, 41 patients; 10 to 15 minutes, 37 patients; > 15 minutes, 22 patients). Sixty-five percent had unfavorable anatomic conditions due to spinal precautions or diffuse neck edema. Postoperative complications occurred in four patients; surgical emphysema after tracheal lacerations in three, cannula dislodgment in one. All complications were successfully managed without an operation by tube exchange (n= 3) or observation (n= 1); there was no procedure-related mortality. Forty patients were available for long-term follow-up (6–18 months after tracheostomy) by telephone; one had persistent hoarseness without respiratory difficulty. We concluded that bedside PDT is safe and easy to teach when performed with a technique that ensures correct instrumentation.  相似文献   
98.
PURPOSE: To assess the efficacy of the marine-derived alkaloid ecteinascidin 743 (ET-743) in patients with soft tissue sarcomas that progressed despite prior conventional chemotherapy and to characterize the pharmacokinetic profiles of ET-743 in this patient population. PATIENTS AND METHODS: Thirty-six previously treated soft tissue sarcoma patients from three institutions received ET-743 as a 24-hour continuous intravenous (IV) infusion at a dose of 1,500 microg/m(2) every 3 weeks. Pharmacokinetic studies were also performed. Patients were restaged every two cycles for response by objective criteria. RESULTS: Objective responses were observed in three patients, with one complete response and two partial responses, for an overall response rate of 8% (95% CI, 2% to 23%). Responses were durable for up to 20 months. Two minor responses (43% and 47% tumor reduction) were observed, for an overall clinical benefit rate of 14%. The predominant toxicities were neutropenia and self-limited transaminitis of grade 3 to 4 severity in 34% and 26% of patients, respectively. The estimated 1-year time to progression and overall survival rates were 9% (95% CI, 3% to 27%) and 53% (95% CI, 39% to 73%), respectively. The maximum observed plasma concentration and total plasma clearance of ET-743 (mean +/- standard deviation), 1.04 +/- 0.48 ng/mL and 35.6 +/- 16.2 L/h/m(2), respectively, were consistent with previously reported values from phase I studies of the drug given as a 24-hour IV infusion. CONCLUSION: ET-743 is a promising new option for the management of several histologic subtypes of sarcoma. Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy. Additionally, the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent.  相似文献   
99.
OBJECTIVE: To assess the association between changes in nutritional status in hospitalized patients and the occurrence of infections, complications, length of stay in hospital, and hospital charges. DESIGN: A prospective observational study with a retrospective component was conducted over a 7-month interval at a university hospital. SUBJECTS: A total of 404 adults (> or = 18 years old) admitted to the inpatient service for more than 7 days who were not pregnant or lactating and not a psychiatric patient were included. MAIN OUTCOME MEASURES: Major outcome variables included changes in nutritional status as assessed by subjective global assessment (SGA) at hospital admission and discharge, length of stay, hospital charges, complications, and infections. STATISTICAL ANALYSIS PERFORMED: Analysis of variance with a Tukey adjustment for multiple comparisons was used to examine the impact of changes in nutritional status between nutrition change categories for continuous variables (charges and length of stay). Discrete variables were assessed using chi 2 analysis. Logistic regression was used to calculate odds ratios with 95% confidence intervals for the development of complications and infections when compared with the reference group. RESULTS: Compared with the reference group (normally nourished at admission and discharge), patients who declined nutritionally, regardless of nutritional status at admission, had significantly higher hospital charges ($28,631 +/- 1,835 vs $45,762 +/- 4,021). Odds of complications were significantly greater for patients who declined nutritionally, regardless of nutritional status at admission, compared with the reference group. APPLICATIONS/CONCLUSIONS: Declines in patients' nutritional status while they are hospitalized, regardless of their nutritional status at admission, were associated with significantly higher hospital charges and a higher likelihood of complications. Practicing clinicians should make reducing declines in patients' nutritional status a priority regardless of patients' nutritional status at admission.  相似文献   
100.
Purpose: To compare the efficacy of concomitant irradiation with mitomycin C and bleomycin in patients with inoperable head and neck carcinoma with radiotherapy alone.

Methods and materials: Between March 1991 and December 1993, 64 patients with inoperable head and neck carcinoma (41 with oropharyngeal site) were randomized to radiotherapy alone (group A) or radiotherapy combined with simultaneous application of mitomycin C and bleomycin (group B). In both groups patients were irradiated five times weekly with 2 Gy to a total dose of 66–70 Gy. The planned concomitant treatment in group B was: bleomycin 5 units twice a week IM, total dose 70 units, mitomycin C 15 mg/m2 IV after delivery of 10 Gy, and 10 mg/m2 IV on the last day of radiotherapy. To enhance the effect of these two drugs, patients received also nicotinamide, chlorpromazine, and dicoumarol.

Because significantly better results were achieved in arm B for patients with inoperable oropharyngeal carcinoma, the study was closed and such patients were after December 1993 routinely treated with the combined therapy (as in arm B). Until October 1996, we treated and followed up 48 such consecutive patients.

Results: Median follow-up of our study patients is 42 months. Complete remission (CR) rate in group A was 31% and in group B 59% (p = 0.04); disease-free survival (DFS) in group A was 8% and in group B 37% (P = 0.01); and overall survival (OS) was 7% in group A and 26% in group B (p = 0.08). CR rate for patients with oropharyngeal carcinoma was 29% in group A (N = 21) and 75% in group B (N = 20) (p = 0.007); DFS in group A was 10% and in group B 48% (p = 0.001); and the OS was 10% in group A and 38% in group B (p = 0.019). In patients with inoperable oropharyngeal carcinoma treated after December 1993, complete remission was achieved in 32/48 (67%, 95% CI: 52%–80%). DFS at the median follow-up of 14 months was 60% (95% CI 43–77%) and OS 58% (95% CI 42–74%).

Conclusion: From the results of our study it seems that the concomitant treatment significantly improves CR rate, DFS, and OS in patients with inoperable oropharyngeal carcinoma in comparison with radiotherapy alone.  相似文献   

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