The effect of cisapride on delayed colonic transit time in patients with idiopathic Parkinson's disease

Disorders of autonomic regulation are common in patients with Parkinson's disease (PD). Patients most frequently complain of dysphagia and therapy resistant constipation, as far as the gastrointestinal tract is concerned. These symptoms have to be attributed to a neuronal degeneration. In a pilot study we therefore investigated the effect of stimulation of the myenteric plexus by cisapride. 11 women and 13 men were examined, the average age was 67.3 years, the Webster rating 17 points. In 2 out of 24 patients, colonic transit was prolonged up to the limit, both with and without therapy. The other 22 patients showed an acceleration in transit on response to cisapride. On average the colonic transit of 130 hours was reduced to 79 hours. This objective improvement was associated with a subjective improvement. Central side effects or a worsening of Parkinsonian symptoms were not found. We conclude that cisapride is effective in the treatment of constipation in idiopathic PD.     

Salivary function in patients with reflux esophagitis: effect of cisapride

Saliva plays an important role in esophageal acid clearance. Reduction in salivary function has been considered in the pathogenesis of reflux esophagitis. Cisapride, a prokinetic agent, has been reported effective for treating mild-to-moderate grade gastroesophageal reflux disease. Some studies have shown that cisapride increases saliva volume and acid-buffering capacity. The aim of this study was to evaluate the effect of cisapride on salivary gland function by means of dynamic salivary scintigraphy. METHODS: Fifty-five patients with endoscopic reflux esophagitis (Savary-Miller Grades I-II) were enrolled in this study. In Group 1 (n = 29), patients were evaluated during the fasting state, both before and after cisapride treatment (5 mg, 3 times/day, before meals, for 2 wk). In Group 2 (n = 26), patients were evaluated during the postprandial state, both before and after cisapride treatment. Uptake ratio (UR) and excretion ratio (ER) of the salivary gland in each group were compared using the paired Student's t-test. RESULTS: In Group 1, no significant differences were found in UR or ER after cisapride treatment. However, in Group 2, ER increased significantly after treatment (p < 0.01), but UR did not show any significant change. CONCLUSION: Cisapride can increase the secretion function of salivary glands during the postprandial phase but not the fasting phase.     

Further evidence for central histamine H2-receptor involvement in the hypotensive effect of clonidine in the rat

Arteriosclerotic aneurysms of the abdominal aorta constitute a common clinical entity. Rarely are they associated with retroperitoneal fibrosis and ureteral obstruction requiring ureterolysis. Fifteen such cases have been reported, with resection successful in 5 of 7. A sixteenth case is presented complicated by the presence of a persistent left cardinal vein. It is the third aneurysm resected with such an anomaly, and to our knowledge the first to be associated with retroperitoneal fibrosis and ureteral obstruction. Ureterolysis with resection of the aneurysm was performed. The difficulties presented by these pathologic entities, as well as the anomalous venous pattern, are reviewed. Complete preoperative evaluation, including intravenous pyelogram, retrograde pyelography, aortography, and venacavography, for the definition of anatomic relationships and planning of the surgical approach is stressed.     

Ocular hypotensive effect of topical ketanserin in timolol users

This paper discusses some of the underlying reasons why health researchers have historically had difficulty working collaboratively across qualitative and quantitative research paradigms and argues why it is imperative that researchers move beyond traditional adherence to particular methods of inquiry. Chronic illnesses are prime examples of conditions that by their very nature need to be studied from a combination of perspectives, using both qualitative and quantitative methods. We suggest that the success of health research on managing these conditions lies in the shared application of both qualitative and quantitative research perspectives, methods and tools. In addition, we argue that effective research into long-term chronic illnesses requires not only combined research efforts but also longitudinal programs of study, so that the experience of managing chronic conditions can be captured over time.     

Indomethacin does not attenuate the hypotensive effect of trandolapril

This is a randomised, double-blind, placebo-controlled, four-way crossover study to determine if indomethacin attenuates the hypotensive effect of trandolapril. Twenty-three hypertensive patients (diastolic blood pressure (DBP) 95-115) requiring NSAID were recruited. Seventeen completed the study. Three week treatment periods: trandolapril 2 mg od and indomethacin 25 mg tds, trandolapril 2 mg and placebo, indomethacin and placebo, placebo and placebo. Clinic and ambulatory BP after 3 weeks of each treatment. Study had 85% power to detect a 5 mm Hg difference in BP (s.d. 7 mm Hg). End of treatment clinic BPs were: 152.9/98 mm Hg (95% CI 147.2, 158.6/95.8, 101.4) with placebo and placebo; 150.4/94.9 mm Hg (95% CI 144.7, 156.1/92.1, 97.7) with trandolapril and indomethacin; 148.2/96.5 mm Hg (95% CI 142.5, 153.9/93.7, 99.3) with trandolapril and placebo; and 156.6/97.4 mm Hg (95% CI 150.9, 162.3/94.6, 100.2) with indomethacin and placebo. There were no significant interactions between trandolapril and indomethacin for clinic systolic BP (SBP) (P = 0.79) or clinic DBP (P = 0.87). When trandolapril treatments (placebo or with indomethacin) were compared to treatments without trandolapril (placebo or indomethacin), trandolapril lowered clinic SBP by 5.4 mm Hg (P = 0.047) and DBP by 2.3 mm Hg (P = 0.08). Mean ambulatory BP was: 140.6/88.2 mm Hg (trandolapril and placebo); 142.8/89.7 mm Hg (trandolapril and indomethacin); 149.6/95.0 mm Hg, (indomethacin and placebo); 147.7/94.0 mm Hg (placebo and placebo). Compared with placebo, trandolapril and placebo lowered BP by 6.5/7.5 mm Hg (P < 0.001, SBP; P < 0.001, DBP). Compared with indomethacin, trandolapril and indomethacin lowered BP by 5.0/5.5 mm Hg (P = 0.001, SBP; P < 0.001, DBP). In the present study trandolapril 2 mg lowered clinic SBP and ambulatory BP, but indomethacin did not attenuate this. Indomethacin had no significant effect on either clinic or ambulatory BP. The antihypertensive effects of trandolapril in this study were modest. Patient selection factors may have contributed to the observed responses, but it seems unlikely from these data that a clinically important drug interaction has occurred.     

Sulfhydryl group donors potentiate the hypotensive effect of acetylcholine in rats

Nitric oxide mediates the vasodilator and hypotensive responses of acetylcholine infusion. It has been reported that nitric oxide could be protected from free radical destruction by forming an S-nitrosothiol compound. Furthermore, sulfhydryl donors such as N-acetylcysteine or thiosalicylic acid enhance nitric oxide production from nitroglycerin. Consequently, the hypotensive effect of intravenous acetylcholine infusion might be potentiated during the simultaneous administration of sulfhydryl donors. The objective of the present study was to test in Okamoto spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (1) whether the hypotensive effect of acetylcholine (10 micrograms/kg per minute) was affected by the simultaneous administration of N-acetylcysteine (10 micrograms/kg per minute) or thiosalicylic acid (10 micrograms/kg per minute), and (2) whether NG-nitro-L-arginine-methyl ester (100 micrograms/kg per minute) administration was able to reverse the changes induced by acetylcholine plus N-acetylcysteine or acetylcholine plus thiosalicylic acid. The administration of acetylcholine reduced (P < .05) mean arterial pressure in WKY rats (13 +/- 2%) and SHR (14 +/- 2%) without affecting urine flow rate, urinary sodium excretion, and glomerular filtration rate. In the presence of N-acetylcysteine, the acetylcholine-induced reduction in mean arterial pressure was potentiated (P < .05) in WKY rats (24 +/- 4%) and SHR (20 +/- 2%). These changes in mean arterial pressure were accompanied by significant reductions in urine flow rate and urinary sodium excretion in WKY rats, as well as in glomerular filtration rate in SHR.2     

The involvement of medullary reticular formation in the hypotensive effect of extracts from seeds of Cassia tora

In pentobarbital anesthetized rats, the medial portion of the medullary reticular formation has been identified to be directly involved in the hypotensive effect of extracts from the seeds of Cassia tora. This conclusion was drawn from the observed decrease in arterial blood pressure following local injection of extracts of this herb into this reticular site and from its inability to promote hypotension when the same reticular site has been electrolytically lesioned. The role of the medullary reticular formation in the Cassia tora-induced hypotension was suggested to be one which modulates the basic cardiovascular reflexes, favoring a decrease in vasomotor tone.     

The effects of cisapride on the topography of oesophageal peristalsis

BACKGROUND: Topographic analysis of oesophageal motility in humans demonstrates sequential pressure regions in the peristaltic wave. This study was designed to see if cisapride preferentially affects any of the topographic regions. METHODS: Fifteen asymptomatic volunteers received placebo, 10 mg or 20 mg of cisapride orally in a double-blind, single-dose trial. Topographic plots of oesophageal peristalsis through the oesophageal body and lower sphincter were analysed before and after drug administration for each subject. RESULTS: Four sequential contraction segments through the oesophageal body and lower sphincter, separated by amplitude troughs, were again identified on contour plots in normal subjects. Dose-related increases from cisapride were found in the contraction volume of the first smooth-muscle segment (P < 0.0001), in total contraction volume (P = 0.005) and in the amplitude of the trough separating smooth-muscle segments of the oesophageal body (P = 0.005). Within the distal smooth-muscle segment, significant drug effects were seen only in the cephalad half (P = 0.03). Significant effects on conventional manometric parameters could not be demonstrated. CONCLUSIONS: Cisapride enhances contraction in the proximal smooth-muscle segment of the oesophageal body and partially obliterates the pressure trough separating the adjacent smooth-muscle segment. Considering the known effects of this agent on neural function, our findings support a gradient in cholinergic influence on peristalsis through the human smooth-muscle oesophagus. Topographic analysis is a novel and sensitive way of examining the effects of pharmacological manipulations on oesophageal peristalsis.     

The hypotensive effect of fusaric acid: the results of long-term administration of fusaric acid in elderly hypertensive patients

The hypotensive effect of fusaric acid calcium salt (Calcium salt of 5-butylpicolinic acid) was examined clinically in 10 elderly hypertensive patients by the long-term administration of this agent and the following results were obtained. 1) The means of the systolic and/or diastolic blood pressures of each patient were significantly lower during the first year of the trial period than those during the one year's control period in all patients. 2) The means of the systolic and/or diastolic blood pressures of each patient were significantly lower during the second year of the trial period than those during the one year's control period in whom administration of fusaric acid calcium salt was continued throughout two years. A significant reduction of the systolic blood pressure was observed in 3 out of 6 patients and that of the diastolic blood pressure was observed in 5 out of 6 patients. 3) Comparison was made between the means of the systolic and diastolic blood pressures during the one year's control period and those during the six month's placebo period after two year's administration of fusaric acid calcium salt. During the placebo period, both systolic and diastolic blood pressures showed a tendency of returning to the levels during the control period confirming the hypotensive effect of this agent. 4) Laboratory findings after one year's administration of fusaric acid calcium salt showed no adverse effect of this agent.     

Effects of cisapride on QTc interval in neonates

AIM: Prospective survey of the effects of cisapride on QTc interval in neonates given cisapride. METHODS: QTc interval was determined just before and 2.9 (0.9) days after outset of the treatment in 49 neonates treated with cisapride between 1 August 1995 and 29 February 1996. RESULTS: Cisapride significantly increased QTc interval (p = 0.0001), and this was higher when birthweight or gestational age were lower. The prolongation of QTc interval above the arbitrary value of 0.450 (n = 7) was clinically asymptomatic and was significantly more common in the infants born with a gestational age < or = 33 weeks (n = 6). CONCLUSION: The findings indicate that cisapride accumulates in less mature neonates. Further pharmacokinetic studies are needed.     

Functional characterization of adenosine receptors in the nucleus tractus solitarius mediating hypotensive responses in the rat

1. The aim of this study was to characterize adenosine receptors located in the nucleus tractus solitarius (NTS) that mediate decreases in blood pressure in the anaesthetized rat. To determine the adenosine receptor subtype involved, a range of selective agonists and antagonists were studied and their relative potencies evaluated. 2. The rank order of agonist potency in inducing decreases in diastolic blood pressure was N6-cyclopentyladenosine (CPA) > N6-cyclohexyladenosine (CHA) > N-ethyl-carboxamidoadenosine (NECA) > or = 2-phenylaminoadenosine (CV1808) > 2-p-(carboxyethyl)phenethylamino-5' N-ethylcarboxamidoadenosine (CGS 21680) > N6-(2-(4-aminophenyl)ethyl)-adenosine (APNEA). 3. The hypotensive action of CPA following microinjection into the NTS was antagonized by i.v. infusions (50 micrograms kg-1 min-1) of adenosine receptor antagonists, 8-cyclopentyl-1,3 dipropylxanthine (DPCPX), 8-phenyltheophylline (8-PT), 8-(p-sulphophenyl)theophylline (8-SPT), and 1,3-dipropyl-8-N-(2-diethylamino)ethyl)-N methyl-4-(2,3,6,7-tetrahydro-2,6-dioxo) benzenesulphonamidexanthine (PD 115199). The antagonist potency order was DPCPX > PD115199 > or = 8-PT. Intravenous infusion of 8-SPT had no effect on blood pressure responses to microinjection of CPA into the NTS. 4. The results suggest that adenosine A1 receptors in the NTS mediate hypotensive responses in the anaesthetized rat preparation.     

No evidence for central histamine-receptor involvement with the hypotensive effect of clonidine in cats

The serum half-life of phenytoin in rabbits after a single intravenous dose was significantly shortened by pretreating the rabbits with daily oral doses of phenytoin. This suggests that in vivo phenytoin induces its own metabolism.     

The effect of stevioside on glucose metabolism in rat

This study was conducted to determine the effect of stevioside (SVS) on glucose metabolism. The experiments were performed in male Wistar rats treated with SVS either by intravenous infusion or feeding. SVS infusion (150 mg/mL) was carried out in doses of 0.67, 1.00, and 1.33 mL.kg-1 body weight.h-1. The plasma glucose level significantly increased both during and after SVS infusion, whereas it was not affected by SVS feeding (13.3 mL.kg-1 body weight). The glucose turnover rate (GTR) of [14C(U)]glucose and [3(-3)H]glucose was not significantly different between control and SVS infusion animals. Percent glucose carbon recycling and glucose clearance were reduced from 28.7 +/- 1.3 to 23.0 +/- 1.6% (p < 0.05) and from 6.46 +/- 0.34 to 4.99 +/- 0.20 mL.min-1.kg-1 body weight (p < 0.01), respectively. The plasma insulin level did not change, whereas the plasma glucose level significantly increased from 120.3 +/- 5.9 to 176.8 +/- 10.8 mg% (p < 0.01) during SVS infusion. Animals pretreated with angiotensin II and arginine vasopressin showed no significant effect, while animals pretreated with prazosin had an attenuated hyperglycemic effect of SVS infusion. Pretreatment with indomethacin or N omega-nitro-L-arginine methyl ester (L-NAME) alleviated the plasma glucose level during the second period of SVS infusion. Pretreatment with the combination infusion of indomethacin and L-NAME reduced the plasma glucose level from 117.0 +/- 1.8 to 109.0 +/- 1.7 mg% (p < 0.001), and normalized the plasma glucose level in the second period of SVS infusion. Insulin infusion inhibited the hyperglycemic effect of SVS infusion. The present results show that the elevation of the plasma glucose level during SVS infusion is not due to the reduction of the insulin level. It is probably the effect of SVS on glucose transport across the cell. Insulin response to a high plasma glucose level is suppressed during SVS infusion. Several interactions among norepinephrine, prostaglandin, and nitric oxide are involved in modulating the hyperglycemia during SVS infusion.     

The effect of propionate on lipid synthesis in rat lymphocytes

1. The effect of propionate on lipid synthesis in lymphocytes cultured for 24 hr and incubated for 2 hr was investigated. 2. [1-14C]-propionate was incorporated mainly into phospholipids in both control and concanavalin A (Con A) stimulated cultured lymphocytes. 3. The content of free coenzyme A markedly decreased in 2 hr incubated lymphocytes when propionate was added to the medium at concentrations from 10 to 100 mmol/l. 4. Propionate at 40 mmol/l decreased the incorporation of [1-14C]-palmitate into phospholipids (86%), triacylglycerol (87%) and cholesterol ester (98%) and increased in cholesterol (133%) of cultured lymphocytes. 5. Addition of propionate into the culture medium at 2.5 and 5.0 mmol/l concentrations markedly increased the activity of hydrolases of various acylCoA derivatives. 6. The results suggest that propionate may reduce the content of acylCoA and so its esterification and this might be important for the regulation of lymphocytes proliferation.     

The effect of deferoxamine on ciprofibrate-induced hepatocarcinogenesis in the rat

A 74-year-old woman was hospitalised for pleuro-pneumonia of the right base. The chest x-ray showed the presence of a right paratracheal opacity which persisted during the course of the infectious episode. A computed tomographic scan of the thorax showed a voluminous anterior mediastinal mass which compressed the trachea without invading it. Surgical excision enabled the ablation of a tumour which was haemorrhagic and the histological examination established a diagnosis of cystic parathyroid adenoma. At anytime did the patient present either clinical symptoms or biochemical signs suggesting primary hyperparathyroidism.