scholarly journals Effect of nifedipine on anorectal sensorimotor functions in health and fecal incontinence

2011 ◽  
Vol 301 (1) ◽  
pp. G175-G180 ◽  
Author(s):  
Adil E. Bharucha ◽  
Jessica Edge ◽  
Alan R. Zinsmeister

The mechanisms of increased rectal stiffness in women with fecal incontinence (FI) and rectal urgency are not understood. Our hypothesis was that distention-induced activation of mechanosensitive L-type calcium channels in smooth muscle contributes to increased rectal stiffness in FI. Anal pressures, rectal distensibility (compliance, capacity, and contractile response to sinusoidal oscillation), and rectal sensation were assessed before and after oral nifedipine (30 + 10 mg) or placebo in 16 women with FI and 16 asymptomatic women. At baseline, FI patients had a lower anal pressure increment during squeeze (health, 66.9 ± 7.6: FI, 28.6 ± 5.9, mean ± SE, P ≤ 0.01), lower rectal capacity ( P = 0.052), and higher rectal pressures during sinusoidal oscillation (health, 13.7 ± 3.2: FI, 21.7 ± 1.4, mean ± SE, P = 0.02) than the healthy women, which suggests an exaggerated rectal contractile response to distention. Nifedipine decreased mean BP, increased heart rate ( P = 0.01 vs. placebo), and reduced anal resting pressure ( P ≤ 0.01) but did not significantly modify rectal distensibility in health or FI. Plasma nifedipine concentrations (health, 103 ± 21 ng/ml: FI, 162 ± 34 ng/ml) were correlated with increased rectal compliance ( r = 0.6, P = 0.02) in all study participants and, in healthy subjects, with decreased rectal pressures during sinusoidal oscillation ( r = 0.86, P = 0.01), indicative of reduced stiffness. No consistent effects on rectal perception were observed. These observations confirm that FI is associated with anal weakness and increased rectal stiffness. At therapeutic plasma concentrations, nifedipine reduced anal resting pressure but did not improve rectal distensibility in FI, outcomes that argue against a predominant contribution of myogenic L-type calcium channels to reduced rectal distensibility in FI.

2014 ◽  
Vol 5 (2) ◽  
pp. 47-50 ◽  
Author(s):  
Igor Alekseyevich Komissarov ◽  
Viktoriya Aleksandrovna Glushkova ◽  
Nadezhda Georgiyevna Kolesnikova

One of the reason of organic and neurogenic fecal incontinence in children is low resting pressure in the anal canal. In functional aspect, one of the main roles plays internal sphincter of the anal canal that provides 50-85 % of basal resting pressure and close of the anal canal. Purposes. The purpose of this article is to study the possibilities of using bulking agent «DAM+» to increase resting pressure in the anal canal in children with fecal incontinence, and evaluate the results of this treatment. Metods. The study has been performed in the Department of Pediatric Surgery in our university since 2007 for 2013. In total, 35 patients, aged 2-18 with organic or neurogenic fecal incontinence were underwent 57 procedure of introduction polyacrylamid gel «DAM+». Patients with overflow fecal incontinence were excluded. Before treatment and after, all patients were assessed clinical examination and anal manometry. Anal manometry was perfomed оn multifunctional apparatus «Menfis 2000». Results. The average quantity of resting pressure in the anal canal before operation is formed 20.98 ± 5.17 сm. (H2O), after operation 32.62 ± 6.63 сm. (H2O), in long-term period 28.07 ± 6.65 сm. (H2O) Conclusion. The clinical efficiency of procedure correlates with values of resting pressure in the anal canal before and after treatment. Implantation of «DAM+» into submucosal layer provides increasing of basal resting tone in the anal canal. Imitation of work of the internal anal sphincter and expansive vascular anal cushions on the other part, prevents patulous anus and provides a hermetic seal, that responds for close anal walls. Statistical data was shown, that the average quantity of resting pressure in the anal canal before operation and after operation has performed at the 5 % significance level. P-values < 0.05 was considered statistically significant.


2017 ◽  
Vol 4 (6) ◽  
pp. 1861
Author(s):  
Ahmed M. S. M. Marzouk

Background: Fecal incontinence is a difficult and debilitating problem with various nonsurgical and surgical modes of treatment. Biofeedback is among the most considerable nonoperative strategies. This study is to review of the short-term effectiveness of the use of biofeedback therapy in management of fecal incontinence.Methods: A retrospective review of 14 patients with fecal incontinence were included and completed the planned biofeedback sessions regarding clinical response and change in anorectal manometric parameters.Results: 14 incontinent patients (9 males and 5 females), mean age 38.0 ± 21.4 years, 6 patients (42.8%) showed excellent response (cured), 5 patients (35.7%) showed good response (improved) and 3 patients (21.5%) showed poor response. There were a highly significant decrease in the grade with mean 3.8±1.4 to 2.4±1.7 (P value =0.003) and a score mean 11.8±5.9 to 6.1±7.1 (P value = 0.002). increase in anal resting pressure by mean 33.6±18.1 mmHg (P value = 0.004) and anal squeeze pressure by mean 75.4±35.2 mmHg (P value = 0.002). Also increase in anal resting pressure from 36.2±13.4 mmHg to 46.0±19.7 mmHg (P value = 0.046) and the anal squeeze pressure 89.3±21.8 mmHg to 106.7±21.0 mmHg (P value = 0.026). the volume required for 1st sensation mean 34.6±10.8 cc. decreased to 29.3±9.4 cc. (P value = 0.048) and the maximum tolerable volume increases from 221.4±55.9 cc to 235.7±54.9 cc (P-value = 0.022).Conclusions: Biofeedback therapy has an effective role in short term efficacy in management of fecal incontinence.


2007 ◽  
Vol 21 (2) ◽  
pp. 309-314 ◽  
Author(s):  
J. Miholic ◽  
M. Hoffmann ◽  
J.J. Holst ◽  
J. Lenglinger ◽  
M. Mittlböck ◽  
...  

2003 ◽  
Vol 98 (5) ◽  
pp. 1057-1062 ◽  
Author(s):  
Cyrus Motamed ◽  
Riad Menad ◽  
Robert Farinotti ◽  
Krassen Kirov ◽  
Xavier Combes ◽  
...  

Background Mivacurium is potentiated by pancuronium to a much greater extent than other relaxants. In a previous investigation we suggested that this potentiation could be due to the ability of pancuronium to inhibit plasma cholinesterase activity, but we did not measure plasma concentrations of mivacurium. In the current study we performed a pharmacokinetic analysis by measuring the plasma concentration of mivacurium when preceded by administration of a low dose of pancuronium. Methods After induction of general anesthesia with propofol and fentanyl and orotracheal intubation, 10 patients (pancuronium-mivacurium group) received 15 microg/kg pancuronium followed 3 min later by 0.1 mg/kg mivacurium, whereas 10 other patients (mivacurium group) received saline followed by 0.13 mg/kg mivacurium 3 min later. Plasma cholinesterase activity was measured before and 3 and 30 min after pancuronium dosing in the pancuronium-mivacurium group and was measured before and after administration of saline in the mivacurium group. Arterial plasma concentrations of mivacurium and its metabolites were measured at 0.5, 1, 1.5, 2, 4, 10, 20, and 30 min after injection. Neuromuscular blockade was assessed by mechanomyography. Results Plasma cholinesterase activity decreased by 26% in the pancuronium-mivacurium group 3 min after injection of pancuronium (P &lt; 0.01) and returned to baseline values 30 min later; however, no significant variation was observed in the mivacurium group. The clearances of the two most active isomers (Cis-Trans and Trans-Trans) were lower in the pancuronium-mivacurium group (17.6 +/- 5.1, 14.7 +/- 5.3 ml. min-1. kg-1, respectively) than in the mivacurium group (32.4 +/- 20.2, 24.8 +/- 13.5 ml. min-1. kg-1; P &lt; 0.05). Conclusions A subparalyzing dose of pancuronium decreased plasma cholinesterase activity and the clearance of the two most active isomers of mivacurium. Pancuronium potentiates mivacurium more than other neuromuscular blocking agents because, in addition to its occupancy of postsynaptic acetylcholine receptors, it slows down the hydrolysis of mivacurium.


Pharmacology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Alex Guazzi Rodrigues ◽  
Helton Oliveira Campos ◽  
Lucas Rios Drummond ◽  
Umeko Marubayashi ◽  
Cândido Celso Coimbra

<b><i>Aim:</i></b> The aim of this study was to assess the influence of adrenomedullary secretion on the plasma glucose, lactate, and free fatty acids (FFAs) during running exercise in rats submitted to intracerebroventricular (i.c.v.) injection of physostigmine (PHY). PHY i.c.v. was used to activate the central cholinergic system. <b><i>Methods:</i></b> Wistar rats were divided into sham-saline (sham-SAL), sham-PHY, adrenal medullectomy-SAL, and ADM-PHY groups. The plasma concentrations of glucose, lactate, and FFAs were determined immediately before and after i.c.v. injection of 20 μL of SAL or PHY at rest and during running exercise on a treadmill. <b><i>Results:</i></b> The i.c.v. injection of PHY at rest increased plasma glucose in the sham group, but not in the ADM group. An increase in plasma glucose, lactate, and FFAs mobilization from adipose tissue was observed during physical exercise in the sham-SAL group; however, the increase in plasma glucose was greater with i.c.v. PHY. Moreover, the hyperglycemia induced by exercise and PHY in the ADM group were blunted by ADM, whereas FFA mobilization was unaffected. <b><i>Conclusion:</i></b> These results indicate that there is a dual metabolic control by which activation of the central cholinergic pathway increases plasma glucose but not FFA during rest and exercise, and that this hyperglycemic response is dependent on adrenomedullary secretion.


Open Medicine ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. 509-517 ◽  
Author(s):  
Silvia Marola ◽  
Alessia Ferrarese ◽  
Enrico Gibin ◽  
Marco Capobianco ◽  
Antonio Bertolotto ◽  
...  

AbstractConstipation, obstructed defecation, and fecal incontinence are frequent complaints in multiple sclerosis. The literature on the pathophysiological mechanisms underlying these disorders is scant. Using anorectal manometry, we compared the anorectal function in patients with and without multiple sclerosis.136 patients referred from our Center for Multiple Sclerosis to the Coloproctology Outpatient Clinic, between January 2005 and December 2011, were enrolled. The patients were divided into four groups: multiple sclerosis patients with constipation (group A); multiple sclerosis patients with fecal incontinence (group B); non-multiple sclerosis patients with constipation (group C); non-multiple sclerosis patients with fecal incontinence (group D). Anorectal manometry was performed to measure: resting anal pressure; maximum squeeze pressure; rectoanal inhibitory reflex; filling pressure and urge pressure. The difference between resting anal pressure before and after maximum squeeze maneuvers was defined as the change in resting anal pressure calculated for each patient.ResultsGroup A patients were noted to have greater sphincter hypotonia at rest and during contraction compared with those in group C (p=0.02); the rectal sensitivity threshold was lower in group B than in group D patients (p=0.02). No voluntary postcontraction sphincter relaxation was observed in either group A or group B patients (p=0.891 and p=0.939, respectively).ConclusionsThe decrease in the difference in resting anal pressure before and after maximum squeeze maneuvers suggests post-contraction sphincter spasticity, indicating impaired pelvic floor coordination in multiple sclerosis patients. A knowledge of manometric alterations in such patients may be clinically relevant in the selection of patients for appropriate treatments and for planning targeted rehabilitation therapy.


2007 ◽  
Vol 292 (1) ◽  
pp. G282-G289 ◽  
Author(s):  
Christopher Andrews ◽  
Adil E. Bharucha ◽  
Barb Seide ◽  
A. R. Zinsmeister

The rate and pattern of rectal distension affect rectal distensibility, perception, and anal relaxation in health. Because rectal urgency is a prominent symptom in fecal incontinence (FI), we assessed rectal distensibility, contractions, perception, and anal pressures during rectal distention in 21 healthy, asymptomatic women (age 61 ± 2 yr, mean ± SE) and 51 women with FI (60 ± 2 yr). Rectal staircases (0–32 mmHg, 4-mm steps) and ramp distensions [0–200 ml at 25, 50, and 100 ml/min with a phase of sustained distension (SD), lasting 1 min, between inflation and deflation]. The rectum was stiffer during rapid than slow ramp distention. This effect was more prominent at a lower volume (50 ml) and was also more pronounced in older subjects and in FI. A rectal contractile response was observed not only during inflation but also during SD and during deflation. During inflation, this contractile response was rate dependent in controls but not in FI. During staircase but not ramp distentions, the threshold for the desire to defecate was lower in FI. During ramp distentions, the duration of perception was significantly longer in FI. The rate of distention did not affect rectal perception (i.e., sensory thresholds or duration of perception) during ramp distentions. Baseline anal pressures and the magnitude of anal relaxation during rectal distention were also reduced in FI. In addition to reduced rectal capacity and compliance, women with FI had an exaggerated rate-dependent reduction in rectal distensibility, lower sensory thresholds, and more prolonged perception, indicative of rectoanal dysfunctions.


1996 ◽  
Vol 270 (3) ◽  
pp. E477-E482 ◽  
Author(s):  
J. W. Rhee ◽  
L. D. Longo ◽  
W. J. Pearce ◽  
N. H. Bae ◽  
G. J. Valenzuela ◽  
...  

Mechanisms involving the timing of normal parturition are not well understood in most animal species. To gain a greater understanding of the mechanisms, we employed hypoxia to perturb the normal system of parturition. The present study was designed to investigate the effects of chronic hypoxia on myometrial contractility in the near-term pregnant rat. Rats were exposed to room air (control) or to continuous hypoxia (10.5% O2) either from experimental days 19 through 21 (2-day exposure) or from experimental days 15 through 21 (6-day exposure). On day 21, blood was collected for hormone assays, and the uterine horns were collected from each dam. One horn was snap-frozen in liquid nitrogen for oxytocin (OT) receptor analysis, and the other was used for in vitro assessment of myometrial contractile responses to cumulative doses of OT or arginine vasopressin (AVP). Hypoxic exposure resulted in approximately 60% reduction of the maximal myometrial contractile response to OT and a significant reduction in OT binding sites from 256.9 +/- 34.9 to 84.9 +/- 21.3 fmol/mg protein (P<0.01). In contrast, the contractile response to AVP was unaffected after exposure to chronic hypoxia (P> 0.05). Additionally, we observed no difference in the plasma concentrations of estrogen, progesterone, and corticosterone. We conclude that chronic hypoxia decreased the effectiveness of OT-specific contractile mechanisms, at least partially through a decrease in OT binding sites.


2014 ◽  
Vol 54 (2) ◽  
pp. 187 ◽  
Author(s):  
I. Zulkifli ◽  
Y. M. Goh ◽  
B. Norbaiyah ◽  
A. Q. Sazili ◽  
M. Lotfi ◽  
...  

The present study aimed to provide a comparative analysis of the effects of penetrative stunning, non-penetrative stunning and post-slaughter stunning on biochemical parameters and electroencephalogram (EEG) associated with stress in heifers and steers. Ten animals were assigned to each of the following four treatment groups: (1) animals were subjected to conventional halal slaughter (a clean incision through the structures on the ventral neck at the approximate level of vertebrae C2–C3 – the trachea, oesophagus, carotid arteries and jugular veins) and post-cut penetrating mechanical stun within 10–20 s of the halal cut (U); (2) high-power non-penetrating mechanical stunning using a mushroom-headed humane killer, followed by conventional halal slaughter (HPNP); (3) low-power non-penetrating mechanical percussive stunning using a mushroom-headed humane killer, followed by conventional halal slaughter (LPNP); and (4) penetrative stunning using a captive-bolt pistol humane killer, followed by conventional halal slaughter (P). For each animal, blood samples and electroencephalogram recordings were taken before stunning, post-stunning (if applicable) and post-slaughter, and plasma concentrations of cortisol, adrenocorticotrophic hormone (ACTH), adrenaline, noradrenaline and β-endorphin were determined. Irrespective of the stunning method, except for percentage change in plasma concentrations of noradrenaline, the values of blood parameters attained before and after stunning were not significantly different. The plasma noradrenaline concentration of the HPNP animals was significantly elevated following stunning. Following slaughter, the percentage change of plasma ACTH concentration in the P animals was significantly elevated. Neither stunning method nor sampling time had a significant effect on plasma β-endorphin concentration. On the basis of the EEG results, penetrative stunning seemed to be better in maximising the possibility of post-stunning insensibility, whereas U animals appeared to demonstrate an evident increase in EEG activity which is consistent with the presence of post-slaughter noxious stimuli associated with tissue cut and injury. The U animals had consistently higher, if not the highest, RMS values than did other stunned animals. This indicates a degree of EEG changes associated with stress and pain. On the basis of EEG data, our results suggested that penetrative stunning would be the most reliable method of ensuring insensibility and minimising pain. However, at slaughter, the P animals showed a dramatic elevation in the percentage change of circulating ACTH, suggesting physiological stress response. On a cautionary note, the results are not unequivocal, and it may be that the range of analyses available to researchers at this point of time are not sufficiently specific to allow definitive conclusions to be drawn.


2021 ◽  
Vol 8 ◽  
Author(s):  
Carine Farkh ◽  
Syrine Ellouze ◽  
Louis Gounelle ◽  
Mama Sad Houari ◽  
Jérôme Duchemin ◽  
...  

Background: Direct oral factor Xa (FXa) inhibitors interfere with lupus anticoagulant (LA) assays challenging antiphospholipid syndrome diagnosis in treated patients. We evaluated a new device, called DOAC Filter, and its usefulness in this setting. It is a single-use filtration cartridge in which FXa inhibitor compounds are trapped by non-covalent binding while plasma is filtered through a solid phase. Patient samples were analyzed before and after filtration: 38 rivaroxaban, 41 apixaban, and 68 none. Anticoagulant plasma concentrations were measured using specific anti-Xa assays and HPLC-MS/MS. LA testing was performed using dilute Russell Viper Venom Time (dRVVT) and Silica Clotting Time (SCT). Baseline median [min–max] concentrations were 64.8 [17.6; 311.4] for rivaroxaban and 92.1 ng/mL [37.1; 390.7] for apixaban (HPLC-MS/MS). They were significantly correlated with anti-Xa assay results (r = 0.98 and r = 0.94, respectively). dRVVT was positive in 92% rivaroxaban and 72% apixaban and SCT in 28 and 41% of samples, respectively. Post-filtration, median % of neutralization was 100% with rivaroxaban and apixaban concentrations of, respectively, &lt;2 [&lt;2–2.4] and &lt;2 ng/mL [&lt;2–9.6] using HPLC-MS/MS. No significant effect of DOAC Filter was observed on LA testing in controls (n = 31) and LA-positive (n = 37) non-anticoagulated samples. dRVVT and SCT remained positive in, respectively, 16 and 8% of rivaroxaban and 41 and 18% of apixaban samples. DOAC Filter would be an easy-to-use device allowing FXa inhibitor removal from plasma samples, limiting their interference with LA testing in treated patients.


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