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101.
- Kinins are believed to play a key role in many inflammatory conditions. Therefore, bradykinin antagonists are being developed for potential therapeutic applications. In the present investigation we describe the pharmacology, in vivo, of (E)-3-(6- acetamido- 3-pyridyl)- N-[N- [2,4- dichloro- 3-[(2- methyl-8- quinolinyl)oxymethyl]phenyl]- N-methylaminocarbonylmethyl]acrylamide (), a novel, non-peptide bradykinin antagonist. FR173657
- The hypotensive effects of i.v. injections of bradykinin (50 pmol) in captopril-pre-treated anaesthetized rats were significantly inhibited by 100 nmol kg−1 s.c., and completely abolished by 300 nmol kg−1. The full inhibitory effect developed within 60 min and remained unchanged for at least 4 h. However, the effect was reversible, since 24 h after an injection of 300 nmol kg−1 FR173657 no inhibitory effect could be observed. FR173657
- The plasma protein extravasation into the pancreas and duodenum induced by an i.v. infusion of bradykinin (11 nmol kg−1 within 20 min) in captopril-treated anaesthetized rats was completely abolished by at doses of 30 nmol kg−1 s.c. and above, given 60 min before bradykinin. FR173657 3 nmol kg−1 was ineffective, while a dose of 10 nmol kg−1 produced an intermediate effect. FR173657
- The paw oedema induced by the subplantar injection of bradykinin (30 nmol) in anaesthetized rats was inhibited slightly by s.c. injection of 0.3 μmol kg−1, whereas 1 and 3 μmol kg−1 produced significant inhibition of the bradykinin-induced oedema. The maximum inhibition amounted to about 50% and could not be increased even when the dose of FR173657 was increased to 30 μmol kg−1. FR173657 did not effect the oedema caused by histamine or 5-hydroxytryptamine. FR173657
- Bradykinin (20 nmol kg−1, i.v.) caused increases in pulmonary inflation pressure by 300–600 Pa in anaesthetized, respirated guinea-pigs. The effect was reduced to 58±9% of the initial value 60 min after the s.c. injection of 1 μmol kg−1, whereas only 9±7% remained after 10 μmol kg−1. The bronchoconstrictor actions of histamine remained unaffected by FR173657. FR173657
- In summary, is a highly potent and selective bradykinin antagonist. The inhibitory action in vivo lasts for longer than 4 h but is fully reversible. FR173657, or similar compounds, will be a useful tool for the pharmacological investigation of pathophysiological states and may possess a therapeutic potential in diseases involving the endogenous release of kinins. FR173657
102.
Methods
The possible association of brain tumour with headache was investigated in 100 patients seen for brain surgery. Preoperatively, 43 patients suffered from headache. These patients were thoroughly questioned about the nature of their pain. Investigation included the McGill Pain Questionnaire.Results
In only 11 of the patients was headache the primary symptom of a brain tumour. Pain intensity was found to be lower in patients with brain tumour then in those with extracranial tumours or headache of other origins. Female subjects, patients under 50 years of age and those with elevated intracranial pressure experienced more intensive pain. Diurnal variation in pain intensity was observed in 60% of patients with headache. There was no evidence, however, of an association with elevated intracranial pressure.Conclusions
Our investigations yielded new information concerning the epidemology of headache accompanying brain tumours. Headache is not an early cardinal symptom of brain tumours, as was generally believed earlier. With the help of the McGill Pain Questionnaire a fine quantitative and qualitative characterization of headache of different origins could be made. The connection between tumour localization and pain lateralization, as well as the possible mechanisms of intracranial pain projection was extensively analysed. The interpretations of the results are at best hypotheses and they do not help determine why more than half of the patients with brain tumour did not experience headache. 相似文献103.
104.
William A. Meier-Ruge Alois F. Schärli Franz Stoss 《Pediatric surgery international》1995,10(7):454-458
In a methodological survey, the technical prerequisites for optimal histopathological diagnosis of gut dysganglionosis are presented. To make a proper diagnosis, the pediatric surgeon or gastroenterologist and the pathologist must consider certain preconditions. The most important steps for the optimal biopsy diagnosis of an aganglionosis, an ultrashort Hirschsprung segment, a intestinal neuronal dysganglionosis (IND), a ganglioneuromatosis, a hypogenesis, or immaturity of the vegetative gut innervation are: (1) taking 3–4 biopsies the size of a peppercorn (3–5 mm3) with submucosa; (2) the best instruments for taking rectal mucosal biopsies are forceps and scissors or a conventional large biopsy forceps; and (3) biopsies may be taken 1 cm, 3–4 cm, 6–9 cm, and 9–12 cm (or from a preternatural anus) above the pectinate line. A biopsy containing mucosa, muscularis mucosae, and submucosa guarantees a satisfying histopathological diagnosis. The native biopsies can be transported on water-ice if the distance to the pathologist takes no longer than 4–6 h. For long distances, biopsies have to be frozen on dry ice (CO2 –80 °C) and transported in a sufficient amount of dry ice (adapted to the time of transportation). For biopsy processing, the following points are important: a total of 122 to 160 15-m-thick native cryostat serial sections have to be cut per biopsy and distributed on four microscope slides. Forty sections are used for lactic dehydrogenase reactions, 32 for succinic dehydrogenase reactions, and the rest for an acetylcholinesterase (AChE) reaction. An AChE reaction alone is sufficient for the diagnosis of Hirschsprung's disease (HD), but never for IND or other developmental malformations of the submucous and myenteric plexuses. Enzymehistotopochemical reactions allow the assessment of functional parameters. These reactions, in contrast to immunohistochemical staining, offer information about the functional activity of special gut structures, e. g., increased AChE activity in nerve fibers of the rectal wall in HD or a lack of dehydrogenase activity in immature ganglia. 相似文献
105.
Albert J. Augustin Manfred Spitznas Nahid Kaviani Daniel Meller Frank H. J. Koch Franz Grus Martin J. Göbbels 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》1995,233(11):694-698
Purpose: To evaluate whether products of oxidative and inflammatory reactions are detectable in the tear fluid of patients suffering from dry eyes. Methods: The tear fluid of 217 patients (397 eyes) was sampled. Criteria for grouping of the patients were (1) basic secretion test (sicca l: BST = 0–5 mm, n = 78 eyes; sicca 2: BST = 6–10 mm, n = 109 eyes) and (2) subjective symptoms (normal BST, burning, foreign body sensations, tearing, dryness of the eyes: n = 78 eyes). One group of healthy patients (normal BST, n = 132 eyes) served as controls. Lipid peroxide levels and myeloperoxidase activity, as parameters for oxidative tissue damage and inflammatory activity, were determined in the tear fluid. Those patients whose consent could be obtained were subjected to the rose bengal test (sicca 1: 56 eyes; sicca 2: 97 eyes; subjective symptoms: 44 eyes; controls: 49 eyes). The correlation between BST and rose bengal test results was calculated. Results: Lipid peroxides were significantly (P < 0.05) higher in the groups sicca 1 and subjective symptoms than in healthy controls, as was the inflammatory activity in groups sicca 1, sicca 2 and subjective symptoms. Additionally, the inflammatory activity in the group sicca 1 was significantly (P < 0.05) higher than in the groups sicca 2 and subjective symptoms. No evidence of a significant correlation between BST and rose bengal test results was observed. Conclusions: Both oxidative tissue damage and polymorphonuclear leukocytes indicating an oxidative potential occur in the tear film of patients suffering from dry eyes. These reactions lead to severe damage of the involved tissue. Free radicals and inflammation may be involved in the pathogenesis or in the self-propagation of the disease. 相似文献
106.
BACKGROUND: The goal of our investigation was to facilitate research on clinical negotiation between patients and physicians by developing a reliable and valid classification system for patients' requests in office practice. METHODS: We developed the Taxonomy of Requests by Patients (TORP) using input from researchers, clinicians, and patient focus groups. To assess the system's reliability and validity, we applied TORP to audiotaped encounters between 139 patients and 6 northern California internists. Reliability was assessed with the kappa statistic as a measure of interrater agreement. Face validity was assessed through expert and patient judgment of the coding system. Content validity was examined by monitoring the incidence of unclassifiable requests. Construct validity was evaluated by examining the relationship between patient requests and patient health status; patient request fulfillment and patient satisfaction; and patient requests and physician perceptions of the visit. RESULTS: The 139 patients made 772 requests (619 requests for information and 153 requests for physician action). Average interrater agreement across a sample of 40 cases was 94% (kappa = 0.93; P <.001). Patients with better health status made fewer requests (r = -0.17; P = .048). Having more chronic diseases was associated with more requests for physician action (r = 0.32; P = .0002). Patients with more unfulfilled requests had lower visit satisfaction (r = -0.32; P <.001). More patient requests was also associated with physician reports of longer visit times (P = .016) and increased visit demands (P = .006). CONCLUSIONS: Our study provides evidence that TORP is a reliable and valid system for capturing and categorizing patients' requests in adult primary care. Further research is needed to confirm the system's validity, expand its applicability, and explore its usefulness as a tool for studying clinical negotiation. 相似文献
107.
The theoretical background of the present investigation was the decoupling hypothesis of alexithymia, which presumes for alexithymic individuals a dissociation of psychophysiological indicators of emotion from verbal cognitive awareness of one's emotional state. To study alterations in reactivity to emotionally distressing stimuli in alexithymic individuals, 12 high-alexithymic and 14 low-alexithymic subjects (separated by TAS) out of a general sample of 54 were investigated. All subjects were exposed to cognitive (CPT) and affect inductive (film sequences) distress. During stimulus exposition electrodermal activity (spontaneous fluctuations) was recorded. After stimulus exposition the subjects assessed their emotional reaction towards the film sequences (DAS). Concerning electrodermal activity no differences were found between high and low alexithymics under cognitive distress. In any case a significant autonomous arousal was registered. However, only the low alexithymic subjects but not the high alexithymics showed a significant increase of spontaneous fluctuations as expression of autonomous arousal during presentation of affect inductive stimuli. The altered psychophysiological reactivity found in high alexithymics in contrast to low alexithymic subjects was revealed specifically for the processing of emotional qualified stimuli. However, there was no difference between the groups in cognitive self assessment of emotional response towards the film sequences. The findings are discussed with reference to neurophysiological and psychodynamic models and the decoupling hypothesis of alexithymia. 相似文献
108.
Franz M Lieberz K Schmitz N Schepank H 《Social psychiatry and psychiatric epidemiology》1999,34(12):651-656
Background: Our epidemiological study demonstrates the spontaneous long-term course of predominantly psychosocially influenced (“psychogenic”)
disorders (neurotic spectrum disorders, personality disorders, stress reactions and somatoform disorders) in a representative
community sample of the normal adult population of Mannheim, an industrial and university town in Germany. The natural spontaneous
course of these disorders in a population sample over a long period remains largely unknown. Method: Beginning in 1979 (n
t1 = 600) a random population sample was investigated three times over a mean period of approximately 11 years. The last follow-up
study ended in 1994 (n
t3 = 301). The follow-up sample was representative of the t1 sample. Psychodynamically trained and clinically experienced interviewers
used a semi-structured interview and standardized clinical and psychometric instruments. Psychogenic impairment was assessed
using a standardized expert rating (Impairment Score, IS). Results: The mean sum-score of psychogenic impairment after 11 years exceeded the value at t1. The case rate (point prevalence, ICD
diagnosis + clinical cut-off/IS) increased from 21.6% at t1 to 26.2% at t3 in the investigated follow-up sample. Intra-individual
correlation of psychogenic impairment between t1 and t3 was high (r = 0.55). We found strong evidence for an unfavorable long-term course of psychogenic impairment and only a weak tendency
(23.1%) for spontaneous remission of clinically relevant psychogenic impairment. Within a regression model clinical variables,
childhood development conditions and personality traits at t1 predicted psychogenic impairment at t3. Conclusion: All clinical variables conclusively indicate an unfavorable spontaneous long-term course of psychogenic impairment. Together
with the well-known high prevalence of psychogenic disorders in the normal population, this underlines the need for early
therapeutic and preventive intervention.
Accepted: 20 August 1999 相似文献
109.
X K Liu W Wang S N Ebert M R Franz A Katchman R L Woosley 《Journal of cardiovascular pharmacology》1999,34(2):287-294
Recent clinical observations indicate that female gender is associated with a higher risk of developing torsades de pointes (TdP) cardiac arrhythmia. In this study, we used the Langendorff technique in isolated perfused rabbit hearts and the whole-cell patch-clamp technique in ventricular myocytes to examine the gender difference in TdP incidence and gain insight into the underlying mechanisms. Isolated rabbit hearts were perfused by using the Langendorff technique. TdP was induced by abrupt changes of cycle length (deltaCL) in the presence of Tyrode's solution containing 1 mM 4-aminopyridine (4AP) and 50% reduced Mg2+ and K+ (low K/Mg). The effects of 1 mM 4AP on cardiac potassium currents were characterized by using the patch-clamp technique. Results demonstrated that (a) no significant gender difference was observed in the absolute QT interval before or after 4AP perfusion in the presence of low K/Mg; (b) 4AP caused marked QT prolongation in the ECG; (c) a significantly higher TdP incidence (nine of 12) was found in female hearts compared with male hearts (three of 12; p < 0.05); (d) 1 mM 4AP primarily inhibited Ito, although a slight inhibition of IKr also occurred in low-K/Mg Tyrode's solution. (e) No inhibition of IK1 was observed. (f) No gender difference was found in the potassium current block produced by 4AP. Female gender is associated with a higher incidence of TdP in an experimental isolated heart model and mechanisms subsequent to QT prolongation may contribute to such a gender difference. 相似文献
110.
Helmuth Adelsberger Nicolas von Beckerath Franz Parzefall Josef Dudel 《Pflügers Archiv : European journal of physiology》1996,431(5):680-689
Single-channel measurements were performed with the aim of constructing a detailed molecular scheme for the reaction between -aminobutyric acid (GABA) and a chloride channel of crayfish deep extensor abdominal muscle (DEAM). GABA was applied in pulses to outside-out patches of muscle membrane, and, based on the dose-response of the peak currents and of their rise times, a linear model with five binding steps has been proposed. Evaluation of the single-channel kinetics indicated at least three open states. Two of them originate most probably from the fully liganded receptor state and are grouped in mixed bursts due to their different life times. The third one appears independently, outside the bursts, and originates from a lower liganded receptor state. Simulations of the dose-responses and the open time distributions with this model led to a set of rate constants which generated relatively optimal fits. 相似文献