The role of patient selection and patient description in clinical pharmacological studies

1980 ◽  
pp. 242-249
Author(s):  
Roland Gugler ◽  
Andrew Somogyi
1996 ◽  
Vol 271 (6) ◽  
pp. C1963-C1972 ◽  
Author(s):  
D. J. Culp ◽  
W. Luo ◽  
L. A. Richardson ◽  
G. E. Watson ◽  
L. R. Latchney

We investigated the role of M1 and M3 receptors in regulating exocrine secretion from acini isolated from rat sublingual glands. In secretion experiments, we derived affinity values (KB) from Schild regression analysis for the antagonists pirenzepine (61.0 nM) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP; 1.06 nM). The KB for 4-DAMP is similar to its affinity value [equilibrium dissociation constant from competition studies (Ki); 1.81 nM] determined from radioligand competition experiments. In contrast, the KB for pirenzepine is between its high-affinity (17.6 nM) and low-affinity (404 nM) Ki values. In separate secretion experiments, we found that the M1 receptor antagonist, M1-toxin, induces a rightward shift in the concentration-response curve to muscarinic agonist and inhibits maximal secretion by 40%. The inhibitory effect of M1-toxin appears specific for M1 receptor blockade, since the toxin abolishes acinar high-affinity pirenzepine-binding sites and does not inhibit secretion induced by nonmuscarinic agents. Additional pharmacological studies indicate muscarinic receptors do not function through putative neural elements within isolated acini. Our combined results are consistent with both M1 and M3 receptors directly regulating mucous acinar exocrine secretion and indicate M3 receptors alone are insufficient to induce a maximal muscarinic response.


Author(s):  
Daniel H Clarke ◽  
Stephen J Banks ◽  
A.Roger Wiederhorn ◽  
John W Klousia ◽  
Jeanne M Lissy ◽  
...  

2012 ◽  
Vol 7 (1) ◽  
Author(s):  
Wilson L Costa ◽  
Felipe JF Coimbra ◽  
Ricardo C Fogaroli ◽  
Héber SC Ribeiro ◽  
Alessandro L Diniz ◽  
...  

Author(s):  
André Moreira de Assis ◽  
Airton Mota Moreira ◽  
Francisco Cesar Carnevale ◽  
Antonio Sergio Zafred Marcelino ◽  
Alberto Azoubel Antunes ◽  
...  

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Dulka Manawadu ◽  
Shankranand Bodla ◽  
Laszlo Sztriha ◽  
Josef Jarosz ◽  
Lalit Kalra

Background: The role of CT perfusion (CTP) in thrombolysis decisions remains controversial and there are no studies that compare outcomes of thrombolysis in patients with or without mismatch on CT perfusion imaging. Methods: We analysed registry data between Jan 2009 and December 2010 for patients thrombolysed within 0-4.5 hours of stroke onset in whom CTP studies were performed prior to thrombolysis. The centre followed thrombolysis guidelines but patients >80 years were included. CTP was not obligatory in the treatment protocol and failure to demonstrate a mismatch was not a contraindication to thrombolysis. We retrospectively analysed data for estimated CTP mismatch of ≥ 100% according to pre-defined criteria and compared outcomes of thrombolysed patients showing perfusion mismatch with those showing no mismatch. Findings: The sample included 160 patients aged between 32-95 years of whom 63 had no mismatch and 97 had a significant mismatch. The two groups were comparable for mean age (73 v 70 years, p=0.18), sex (49% v 54% male, p=0.75), premorbid Rankin Score (mRS) 0-2 (81% v 92%, p=0.77), vascular risk factors profile, mean baseline BP (148/87 v 148/79 mm Hg, p=0.92), mean blood glucose (6.6 v 6.6 mmols/L, p=0.98) and mean National Institute of Health Stroke Scale (NIHSS) score (14.0 v 12.6,p=0.12). Patients who had mismatch prior to thrombolysis showed lower mean 24 hour NIHSS score (7.6 v 11.8, p=0.002) and greater mean 24 hour improvement in NIHSS score (5.1 v 2.0, p=0.010). A higher proportion of patients with mismatch achieved mRS 0-1 and mRS 0-2 at 3 months (36% v 18%, p= 0.012 and 51% v 32%, p=0.015 respectively) but there were no differences in symptomatic sICH rates (1.1% v 0%). Mortality (29% v 18%) and any intracranial haemorrhages (19% v 13%) were lower in mismatch patients but did not achieve significance. Regression analyses showed that PCT mismatch prior to thrombolysis was an independent predictor of both early improvement and functional outcomes at 3 months. Conclusion: Stroke patients who have perfusion mismatch on CTP imaging prior to thrombolysis within the 4.5 hour time window show better early and 3 month outcomes compared with those in whom mismatch cannot be demonstrated. Patient selection using multimodal CT may improve the effectiveness of thrombolysis.


Neurosurgery ◽  
2014 ◽  
Vol 75 (5) ◽  
pp. 491-499 ◽  
Author(s):  
Shawn L. Hervey-Jumper ◽  
Mitchel S. Berger

Abstract Optimal treatment for recurrent high-grade glioma continues to evolve. Currently, however, there is no consensus in the literature on the role of reoperation in the management of these patients. In this analysis, we reviewed the literature to examine the role of reoperation in patients with World Health Organization grade III or IV recurrent gliomas, focusing on how reoperation affects outcome, perioperative complications, and quality of life. An extensive literature review was performed through the use of the PubMed and Ovid Medline databases for January 1980 through August 2013. A total 31 studies were included in the final analysis. Of the 31 studies with significant data from single or multiple institutions, 29 demonstrated a survival benefit or improved functional status after reoperation for recurrent high-grade glioma. Indications for reoperation included new focal neurological deficits, tumor mass effect, signs of elevated intracranial pressure, headaches, increased seizure frequency, and radiographic evidence of tumor progression. Age was not a contraindication to reoperation. Time interval of at least 6 months between operations and favorable performance status (Karnofsky Performance Status score ≥70) were important predictors of benefit from reoperation. Extent of resection at reoperation improved survival, even in patients with subtotal resection at initial operation. Careful patient selection such as avoiding those individuals with poor performance status and bevacizumab within 4 weeks of surgery is important. Although limited to retrospective analysis and patient selection bias, mounting evidence suggests a survival benefit in patients receiving a reoperation at the time of high-grade glioma recurrence.


2020 ◽  
Vol 14 ◽  
Author(s):  
Diana Carolina Esquivel-Franco ◽  
Sietse F. de Boer ◽  
Marcel Waldinger ◽  
Berend Olivier ◽  
Jocelien D. A. Olivier

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