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1.
AIMS: To investigate the pharmacokinetic profile of the ACE-inhibitor imidapril in 10 hypertensive patients after a first single dose (10 mg) and after 28 days therapy with imidapril 10 mg once daily. METHODS: Cmax, tmax, t1/2 and AUC of imidapril and imidaprilat were obtained. ACE-activity and arterial blood pressure during imidapril were corrected by a preceding placebo-investigation. RESULTS: The AUC of imidapril was 140 (43 s.d.) ng ml(-1) h after the first dose and 123 (34 s.d.) ng ml(-1) h at steady state. AUC of the active moiety imidaprilat averaged 211 (101 s.d.) ng ml(-1) h after the first dose and 240 (55 s.d.) ng ml(-1) h at the steady state investigation. Maximal ACE-inhibition was 75% after the single dose as well as at steady state. ACE inhibition before drug intake at day 28 (i.e. trough) was 50%. The (placebo-corrected) maximal drop in diastolic blood pressure after imidapril was 22 mm Hg after the first dose and 25 mmHg at steady state. Exploratory analysis of imidaprilat plasma concentration vs effect profiles suggests a hyperbolic concentration effect relationship where data of the single dose contribute to the ascending part of an Emax-curve, whereas the plateau around Emax is maintained at steady state. CONCLUSIONS: In this group of hypertensive patients, the pharmacokinetic profile and the drop in ACE-activity as well as in blood pressure seen after a single dose of imidapril and at steady state were similar. The initial response to a test dose might therefore predict the response during chronic dosing.  相似文献   

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OBJECTIVES: To evaluate the incidence and severity of vesical neck strictures and urinary incontinence after radical retropubic prostatectomy (RRP) for prostate cancer. METHODS: Between August 1983 and December 1991, 481 consecutive patients underwent RRP by 1 of 2 senior surgeons. Strictures were treated by passing a urethral sound. Incontinence was measured by asking patients for a daily "pad count" of pads required to control urinary leakage. Results were compared to patient age, tumor volume, number of neurovascular bundles spared, preoperative urinary complaints, and previous transurethral resection of the prostate. RESULTS: Of 456 patients with adequate follow-up to determine stricture formation, 82.5% had no strictures, 6.8% required a single dilation, 3.7% required 2 dilations, 3.1% required 3 dilations, and 3.9% required more than 3 dilations. Risk of stricture formation was unrelated to every variable studied. Of 458 patients with adequate follow-up to determine recovery of continence, 80.1% required no pads, 8.1% required 1 to 2 pads a day, 6.6% required 3 to 5 pads a day, and 5.2% were totally incontinent 1 year or more after surgery. Incontinence was closely associated with postoperative urinary urgency. CONCLUSIONS: Strictures are a common but easily managed complication of RRP for prostate cancer. Despite substantial surgical experience, we report a somewhat higher rate of postoperative incontinence than other recently reported series. Our experience is more closely matched by published surveys of patient-reported complications after RRP.  相似文献   

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Oxytocin analogues which combine high oxytocic activities with negligible antidiuretic and pressor activities have been studied. [4-Threonine,7-glycine]oxytocin, [1-(L-2-hydroxy-3-mercaptopropionic acid),4-threonine,7-glycine]oxytocin, and [1-(L-2-hydroxy-3-mercaptopropionic acid)]oxytocin were found to possess the following specific biological activities respectively: rat uterotonic, 270 +/- 10, 337 +/- 23, 1542 +/- 0.4; rat antidiuretic, 0.002 +/- 0.0008, 0.048 +/- 0.005, 40.3 +/- 2.4. The results are analyzed from a conformation-activity viewpoint in a continued attempt to evaluate the scope and limitations of this approach in comparison to structure-activity studies.  相似文献   

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BACKGROUND: The biologic aggressiveness of squamous cell carcinoma of the oral cavity is reflected in its ability to metastasize to regional cervical lymph nodes. Patients with clinically negative cervical lymph nodes are believed to have a good prognosis; however, the prognosis of patients with lymph node metastasis occurring after excision or radiotherapy of the primary tumor is poor. METHODS: Univariate and multivariate analyses for occult lymph node metastasis (ONM) in 172 patients with clinically negative cervical lymph nodes were performed by the authors to elucidate the clinical and histologic tumor risk factors to enhance their ability to predict ONM. A multivariate Cox proportional hazards model and Hayashi's quantification theory type II were used to analyze prognostic factors and to determine the probability of ONM. RESULTS: Using Cox's proportional regression model, the factors linked to cancer specific survival were selected: tumor differentiation (P = 0.0330), mode of carcinoma invasion (P = 0.0175), and ONM (P = 0.0433). Pathologically identified metastatic lymph nodes were found in 21.5% of the cases studied (37 of 172 cases). The 5-year cancer specific survival was 94.0% for patients without lymph node metastasis, and 51.0% for patients with ONM (P < 0.0001, log rank test). The most significant predictors for ONM of each of the clinical and histologic factors, in descending order, were: mode of carcinoma invasion, intensity of lymphocytic infiltration, degree of differentiation, number of mitotic figures, and type of growth by means of Hayashi's quantification theory type II. The presence or absence of ONM in 147 of 172 patients (85.5%) was correctly predicted by the score at the point of intersection of the two curves, which was -0.03. Further investigation revealed that 28 of 32 new cases were differentiated accurately by means of this diagnostic system. CONCLUSIONS: The results of the current study suggest that this method of analysis can establish a reliable predictor of ONM, thereby facilitating correct choices for surgical procedures to enhance the survival rates of patients with clinically negative cervical lymph nodes.  相似文献   

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Four patients with lateral sinus thrombosis were studied by radionuclide (RN) dynamic studies and RN static brain scans. Findings included: (a) abrupt termination of RN activity in the midportion of a lateral sinus ("stump sign"); (b) nonvisualization on dynamic, increased visualization on static images ipsilateral to a prominent sinus groove on a plain skull radiograph; and (c) increased activity on static images with nonfilling on angiography. RN demonstration of the "stump sign" is pathognomonic of lateral sinus occlusion; the latter two patterns require radiographic demonstration of an ipsilateral sinus groove or angiography for significance.  相似文献   

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Lateral rostrotentorial and caudal suboccipital approaches to the brain were performed on six beagles. Intracranial pressure (ICP) was measured as the two craniectomies were connected by removing the bone of the nuchal crest and occluding the transverse venous sinus. Intracranial pressure remained constant after acute occlusion of the sinus with bone wax and there was no gross evidence of brain edema. All six dogs survived the surgery and five dogs survived for a minimum of 3 months. One dog died acutely during the postoperative period. The exact cause of the cerebellar hemorrhage and infarction found at necropsy in the latter dog was not evident. Anemia occurred in three of the six dogs as a result of intraoperative hemorrhage. All dogs surviving the perioperative period had mild, transient hypermetria and conscious proprioceptive deficits, but were neurologically normal 72 hours after surgery. Results of this study indicate that acute, unilateral transverse sinus occlusion is possible without an increase in ICP. The ability to do this allows access to the rostral aspect of the ipsilateral cerebellum and brain stem.  相似文献   

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Meta-analyses of gender differences in the consequences of unilateral brain lesions have reported a positive correlation between the percentage of men in studies and the magnitude of the difference between Verbal (V) and Performance (P) IQ. Such findings are limited by both the indirectness of the methodology and the focus on V–P differences rather than on the separate effects of brain lesions on VIQ and PIQ. A repeated-measures analysis was conducted of studies that reported separate VIQ and PIQ means for men and women with unilateral lesions. Women showed lower IQ scores following lesions to the hemisphere thought to be nondominant for each function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

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The effects of 10 antiallergic drugs (astemizole, azelastine, ebastine, emedastine, epinastine, ketotifen, oxatomide, terfenadine, pemirolast and tranilast) on neuronal dopamine uptake were examined. Some drugs examined showed a concentration-dependent inhibition of [3H]dopamine uptake into synaptosomal preparations of the rat striatum. The inhibition constant (Ki) values were 231-876 nM for ebastine, terfenadine, oxatomide and astemizole. The specific binding of [3H] (1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine) (GBR12935) to the rat striatal membranes was also inhibited by these antiallergic drugs. There was a good correlation between the degrees of inhibition of [3H]dopamine uptake and [3H]GBR12935 binding. Then, the behavioral excitement induced by L-DOPA (100 mg/kg, s.c.) plus pargyline hydrochloride (80 mg/kg, i.p.) in mice was significantly enhanced by i.p. treatment with ebastine (10 mg/kg) and astemizole (5 mg/kg). These results suggest that the neuronal dopamine uptake is inhibited by some antiallergic drugs, especially ebastine.  相似文献   

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In a prospective study of patients admitted to a coronary care unit, the incidence of isotopically diagnosed deep venous thrombosis was found to be related to the severity of illness rather than to the duration of bed rest. In addition, no negative correlation was found between cigarette smoking and deep venous thrombosis.  相似文献   

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INTRODUCTION AND OBJECTIVE: Massive usage of new neuroimaging techniques has produced an increase in the number of patients with cerebral venous thrombosis. Our aim has been to evaluate this shift in our county through the clinico-radiologic characteristics of the patients admitted to our unit. MATERIAL AND METHODS: Over the last 7 years a total of 12 patients suffering from cerebral venous thrombosis were attended in our department. We have analyzed retrospectively their clinical records. RESULTS: There were 11 women 1 man with a range of ages from 13 to 60 years old. The main associated factor was oral contraceptives intake. Most of them presented with symptoms of benign intracranial hypertension. Magnetic resonance imaging was the most sensitive diagnostic tool. Outcome was good in general. Most of them were treated with intravenous heparin during the acute phase and received oral anticoagulation for 6 months. More than half were diagnosed all over the last three years. CONCLUSIONS: Our data seem to confirm this tendency towards a larger number of cases with the application of new diagnostic tools. In these cases, clinical course is more benign than reported in classical series.  相似文献   

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Diagnostic evaluation in the patient with suspected deep vein thrombosis (DVT) and pulmonary embolism (PE) includes a clear correlation between clinical probability, test selection and test interpretation. Real-time B-mode ultrasound with color Doppler remains the imaging technique of choice in suspected DVT. The ventilation/perfusion (V/Q) lung scan is the preferred diagnostic modality in suspected PE. The D-dimer assay may be useful in excluding PA. New diagnostic techniques, including spiral computerized tomography may further modify the diagnostic algorithm.  相似文献   

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This paper describes the role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism. Inability to compress the common femoral or popliteal vein is usually diagnostic of a first episode of deep venous thrombosis in symptomatic patients (positive predictive value of about 97%). Full compressibility of both of these sites excludes proximal deep venous thrombosis in symptomatic patients (negative predictive value of about 98%). In patients with suspected deep venous thrombosis or in those who present with suspected pulmonary embolism but have a nondiagnostic lung scan, the subsequent risk for symptomatic venous thromboembolism is very low (<2% during 6 months of follow-up) provided that ultrasonography of the proximal veins remains normal in the course of 1 week (suspected deep venous thrombosis) or 2 weeks (suspected pulmonary embolism). Anticoagulation and further diagnostic testing can usually be safely withheld in these situations. Venous ultrasonography is much less reliable for the diagnosis of asymptomatic, isolated distal, and recurrent deep venous thrombosis than for the diagnosis of a first episode of proximal deep venous thrombosis in symptomatic patients. Clinical evaluation of the probability of deep venous thrombosis or pulmonary embolism, preferably by using a validated clinical model, complements venous ultrasonographic findings and helps to identify patients who would benefit from additional (often invasive) diagnostic testing. Thus, venous ultrasonography is thought to be a very valuable test for the diagnosis and management of patients with suspected deep venous thrombosis or pulmonary embolism.  相似文献   

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HM Spinelli  S Falcone  G Lee 《Canadian Metallurgical Quarterly》1994,33(4):377-83; discussion 384
Carotid-cavernous fistulas are abnormal communications between the internal carotid artery and the cavernous sinus produced by a rupture of the wall of the carotid artery or one of its branches into the sinus. Extradural branches of the internal or external carotid arteries may communicate with the cavernous sinus, producing proptosis, progressive glaucoma, and ocular vascular engorgement. Various approaches to obliterate these fistulas have evolved, many of which carry high morbidity or are precluded by anatomical considerations. Analysis of the venous anatomy of the orbit and face, including human cadaver dissections, reveals a new and safe approach to the cavernous sinus, requiring microsurgical isolation and cannulation of the superior ophthalmic vein through an anterior orbital approach. Selective embolization of a carotid-cavernous fistula can be performed successfully through this route. We present pertinent anatomy and technical considerations and the successful clinical application of these principles. Surgeons familiar with craniofacial anatomy and microvascular techniques can apply these principles and play an active role in the treatment of these complex problems.  相似文献   

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Fifty consecutive unselected patients with infiltrating carcinoma of the breast underwent radical mastectomy in two consecutive stages. The initial operation was a modified radical mastectomy, with preservation of the pectoral muscles, and the second stage, a procedure to transform the initial operation into a standard radical mastectomy. An analysis of the location and the number of the lymph nodes recovered in the two stage operation shows that a so-called modified radical mastectomy is inadequate to ensure the clearing of the axilla. Lymph nodes were recovered at the second stage of the operation in 36 patients, and seven of these patients had metastasis. Modified radical mastectomy was effective in erradicating the lymph nodes of the lower part of the axilla but inadequate for lymph nodes at levels II and III and, especially, the interpectoral lymph nodes.  相似文献   

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