Autoimmune autonomic ganglionopathy is a form of acquired autonomic failure affecting parasympathetic, sympathetic functions, usually affecting healthy young people. The disorder affects both sympathetic and parasympathetic nervous systems, with acute onset, monophasic course, and partial recovery with relative preservation of motor and sensory function. We experienced a case of young man with acute autoimmune autonomic ganglionopathy who developed voiding difficulty, sudden blurred vision and gastrointestinal discomfort without motor or sensory dysfunction. Fever developed 5 days earlier and persisted until onset of autonomic failure. Patient complained voiding difficulty and urodynamic study revealed detrusor are flexia with failure to initiate and sustain adequate detrusor contraction. Sympathetic skin response and several autonomic function tests showed abnormalities. Intravenous immunoglobulin was applied for 5 days but symptoms persisted. Thus, 5 days of plasmapheresis treatment was followed showing improvements in most of the symptoms. However bladder dysfunction persisted at 6 months follow-up, showing partial recovery at bethanechol administration.
Bethanechol ; Fever ; Follow-Up Studies ; Humans ; Immunoglobulins ; Parasympathetic Nervous System ; Plasmapheresis ; Primary Dysautonomias ; Sensation ; Skin ; Urinary Bladder ; Urinary Bladder, Neurogenic* ; Urodynamics

Malakoplakia is a rare granulomatous disease that occurs commonly in the urinary tract and secondarily in the gastrointestinal tract. Most reported cases of malakoplakia are associated with immunosuppressive diseases or chronic prolonged illness. Here, we report a rare case of malakoplakia in a young healthy adolescent without any underlying disease. A 19-year-old female was referred to our hospital following the discovery of multiple rectal polyps with sigmoidoscopy. She had no specific past medical history but complained of recurrent abdominal pain and diarrhea for 3 months. A colonoscopy revealed diverse mucosal lesions including plaques, polyps, nodules, and mass-like lesions. Histological examination revealed a sheet of histiocytes with pathognomonic Michaelis-Gutmann bodies. We treated the patient with ciprofloxacin, the cholinergic agonist bethanechol, and a multivitamin for 6 months. A follow-up colonoscopy revealed that her condition was resolved with this course of treatment.
Anti-Bacterial Agents/therapeutic use ; Bethanechol/therapeutic use ; Biopsy ; Ciprofloxacin/therapeutic use ; *Colon/drug effects/pathology ; *Colonic Diseases/diagnosis/therapy ; Colonoscopy ; Drug Therapy, Combination ; Female ; Humans ; *Intestinal Mucosa/drug effects/pathology ; *Malacoplakia/diagnosis/therapy ; Muscarinic Agonists/therapeutic use ; Treatment Outcome ; Vitamins/therapeutic use ; Young Adult

Intestinal pseudo-obstruction is a massive colonic dilation with signs and symptoms of colonic obstruction, but without a mechanical cause. A 49-year-old female patient complained of nausea, vomiting, and abdominal distension 1 month after a massive brainstem hemorrhage. No improvement was seen with conservative treatments. An extended-length rectal tube was inserted to perform glycerin enema. In addition, bethanechol (35 mg per day) was administered to stimulate colonic motility. The patient's condition gradually improved over a 2-month period without any surgical intervention. Extended length rectal tube enema and bethanechol can be used to improve intestinal pseudo-obstruction in stroke patients.
Bethanechol ; Brain Stem ; Colon ; Enema ; Female ; Glycerol ; Hemorrhage ; Humans ; Intestinal Pseudo-Obstruction ; Middle Aged ; Nausea ; Stroke ; Vomiting

OBJECTIVEDiagnosing asthma in infancy is largely made on the basis of the symptoms of cough and wheezing. A similar presentation can be seen in neurologically normal infants with excessive gastroesophageal reflux (GER). There are no randomized placebo controlled studies in infants using proton pump inhibitors (PPI) alone or in addition to prokinetic agents. The primary objective was to confirm the presence of excessive GER in a population of infants that also had respiratory symptoms suggestive of asthma. Second, in a randomized placebo-controlled fashion, we determined whether treatment of GER with bethanacol and omeprazole could improve these respiratory symptoms.

METHODSInfants (n=22) with a history of chronic cough and wheeze were enrolled, if they had evidence of GER by history and an abnormal pH probe or gastric emptying scan. Infants were randomly allocated to four treatment groups: placebo/placebo (PP), omeprazole plus bethanacol (OB), omeprazole/placebo (OP), bethanacol/placebo (BP). Evaluations by clinic questionnaire and exam, home diary, and pH probe data were done before, after study-medication and after open label of OB.

RESULTSNineteen children were studied. PP did not affect GER or respiratory symptoms, and did not decrease GER measured by pH probe. In contrast, OB decreased GER as measured by pH probe indices and parental assessment. In association, OB significantly decreased daytime coughing and improved respiratory scores. No adverse effects were reported.

CONCLUSIONSIn infants with a clinical presentation suggestive of chronic GER-related cough, the use of omeprazole and bethanacol appears to be viable therapeutic option.

Bethanechol ; therapeutic use ; Cough ; drug therapy ; Double-Blind Method ; Female ; Gastroesophageal Reflux ; complications ; Humans ; Hydrogen-Ion Concentration ; Infant ; Male ; Omeprazole ; therapeutic use ; Pilot Projects ; Respiratory Sounds ; etiology

The aim of the present study was to elucidate the direct effects of melatonin on bladder activity and to determine the mechanisms responsible for the detrusor activity of melatonin in the isolated rat bladder. We evaluated the effects of melatonin on the contractions induced by phenylephrine (PE), acetylcholine (ACh), bethanechol (BCh), KCl, and electrical field stimulation (EFS) in 20 detrusor smooth muscle samples from Sprague-Dawley rats. To determine the mechanisms underlying the inhibitory responses to melatonin, melatonin-pretreated muscle strips were exposed to a calcium channel antagonist (verapamil), three potassium channel blockers [tetraethyl ammonium (TEA), 4-aminopyridine (4-AP), and glibenclamide], a direct voltage-dependent calcium channel opener (Bay K 8644), and a specific calcium/calmodulin-dependent kinase II (CaMKII) inhibitor (KN-93). Melatonin pretreatment (10(-8)~10(-6) M) decreased the contractile responses induced by PE (10(-9)~10(-4) M) and Ach (10(-9)~10(-4) M) in a dose-dependent manner. Melatonin (10(-7) M) also blocked contraction induced by high KCl ([KCl]ECF; 35 mM, 70 mM, 105 mM, and 140 mM) and EFS. Melatonin (10(-7) M) potentiated the relaxation response of the strips by verapamil, but other potassium channel blockers did not change melatonin activity. Melatonin pretreatment significantly decreased contractile responses induced by Bay K 8644 (10(-11)~10(-7) M). KN-93 enhanced melatonin-induced relaxation. The present results suggest that melatonin can inhibit bladder smooth muscle contraction through a voltage-dependent, calcium-antagonistic mechanism and through the inhibition of the calmodulin/CaMKII system.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; 4-Aminopyridine ; Acetylcholine ; Animals ; Benzylamines ; Bethanechol ; Calcium Channels ; Contracts ; Melatonin ; Muscle, Smooth ; Muscles ; Nocturia ; Phenylephrine ; Phosphotransferases ; Potassium Channel Blockers ; Quaternary Ammonium Compounds ; Rats ; Rats, Sprague-Dawley ; Relaxation ; Sulfonamides ; Urinary Bladder ; Urinary Bladder, Overactive ; Verapamil

Background: Postoperative urinary retention is a commonly encountered problem after anal surgery particularly under spinal anesthesia. Bethanchol chloride, a muscarinic cholinergic receptor agonist was used to determine whether it could prevent this problem. Methods: One hundred six patients with mean age of 37+ 9 who underwent anal surgery under spinal anesthesia from January to August 2007 were included in this nonblinded randomized prospective experimental study. Forty- six patients were given bethanechol chloride 25mg/tab 1 hour post- op then another dose after 4-6 hours. Those with the urge to void but unable to do so within the hour or had hypogastric pain (VAS > 8) were immediately catheterized and the amount drain recorded. Conclusion: Although bethanechol chloride did not completely prevent the development of postoperative urinary retention, it use was associated with reduced need for the catheterization.
Human ; Adult ; BETHANECHOL ; URINARY RETENTION ; ANESTHESIA, SPINAL

Defensins, cysteine-rich cationic polypeptides released from neutrophils, are known to have powerful antimicrobial properties. In this study, we sacrificed 30 rats to investigate the effects of alpha-defensin 1 on detrusor muscle contractions in isolated rat bladder. From the experiments we found relaxing effects of alpha-defensin 1 on the contractions induced by phenylephrine (PE) but not by bethanechol (BCh) in the detrusor smooth muscles. To determine the mechanisms of the effects of alpha-defensin 1, the changes of effects on PE-induced contraction by alpha-defensin 1 pretreatment were observed after pretreatment of Rho kinase inhibitor (Y-27632), protein kinase C (PKC) inhibitor (Calphostin C), potent activator of PKC (PDBu; phorbol 12,13-dibutyrate), and NF-kappaB inhibitors (PDTC; pyrrolidinedithiocarbamate and sulfasalazine). The contractile responses of PE (10(-9) ~ 10(-4) M) were significantly decreased in some concentrations of alpha-defensin 1 (5x10(-9) and 5x10(-8) M). When strips were pretreated with NF-kappaB inhibitors (PDTC and sulfasalazine; 10(-7) ~ 10(-6) M), the relaxing responses by alpha-defensin 1 pretreatment were disappeared. The present study demonstrated that alpha-defensin 1 has relaxing effects on the contractions of rat detrusor muscles, through NF-kappaB pathway. Further studies in vivo are required to clarify whether alpha-defensin 1 might be clinically related with bladder dysfunction by inflammation process.
Animals ; Bethanechol ; Contracts ; Defensins ; Inflammation ; Muscle Contraction ; Muscle, Smooth ; Muscles ; Neutrophils ; NF-kappa B ; Peptides ; Phenylephrine ; Phorbols ; Protein Kinase C ; Pyrrolidines ; Rats ; rho-Associated Kinases ; Thiocarbamates ; Urinary Bladder

PURPOSE: Our study was undertaken to investigate changes in the bladder according to duration of diabetes mellitus in the Otsuka Long Evans Tokushima Fatty (OLETF) rat model, which is similar to type 2 diabetes. MATERIALS AND METHODS: OLETF rats (n=14) and Long Evans Tokushima Otsuka (LETO, n=14) rats were used. LETO is a normal control of OLETF. The animals were assigned to 4 groups: L-40 group, LETO rats 40 weeks after birth (n=7); O-40 group, OLETF rats 40 weeks after birth (n=7); L-60 group, LETO rats 60 weeks after birth (n=7); and O-60 group, OLETF rats 60 weeks after birth (n=7). At 40 weeks or 60 weeks after birth, blood glucose, cystometry, bladder weight, detrusor contractility, and mRNA expression of nerve growth factor (NGF) were assessed. RESULTS: Cystometry showed that diabetic bladders had increased compliance compared with the control groups at 40 and 60 weeks, and the O-60 group had greater compliance than the O-40 group. Contractile responses to electrical stimulation, bethanecol (250microM), and ATP (10 mM) were decreased in the experimental groups compared with the control groups at 40 and 60 weeks, and the O-60 group had a lower contractile response than the O-40 group. The mRNA expression of NGF was decreased in the experimental groups compared with the control groups, and the O-60 group had lower expression than the O-40 group. Changes in NGF were identified through immunohistochemical staining. CONCLUSIONS: The degree of diabetic cystopathy in OLETF rats was changed by duration of type 2 diabetes mellitus. Our results showed that the changes in the bladder in type 2 diabetes mellitus can be identified through a new rat model.
Adenosine Triphosphate ; Animals ; Bethanechol ; Blood Glucose ; Compliance ; Dextrans ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Drug Combinations ; Electric Stimulation ; Nerve Growth Factor ; Parturition ; Rats ; Rats, Inbred OLETF ; RNA, Messenger ; Sodium Chloride ; Urinary Bladder ; Urinary Bladder, Neurogenic

PURPOSE: Bethanechol enhances detrusor contraction and alpha1-blockers reduce bladder outlet resistance. We evaluated the effects of bethanechol with doxazosin in patients with impaired detrusor contractility. MATERIALS AND METHODS: Fifty-six patients that had confirmed detrusor underactivity with at least 150ml of postvoid residual urine volume(PVR) based on a urodynamic study were enrolled. The initial dosage of bethanechol given was 75mg/day, and the dosage was gradually increased to 150mg/day if necessary. Doxazosin gastro-intestinal therapeutic system(GITS)(4mg) was also given. The effect of the treatment was evaluated by a urine flow test, the amount of PVR, and frequency of clean intermittent catheterization(CIC). RESULTS: The mean follow-up period was 6 months(range, 1 to 9 months). After treatment, the mean PVR decreased from 251.8+/-149.6ml to 136.4+/-153.2ml(p<0.001) and was less than 100ml in 22(39%) of the 38 patients that showed a decrease. The maximum flow rate(Qmax) increased from 8.7+/-4.7ml/s to 11.1+/-5.6ml/s(p=0.024) and was more than 5ml/s in 13 patients(23%). Five of the 18 patients that previously required CIC could discontinue this treatment and another nine patients showed a decrease in the frequency. The mean daily frequency of CIC was reduced from 3.2 to 1.5(p=0.004). Ten of the 12 patients that were not able to void became capable of voluntary voiding. Five patients(9%) complained of adverse reactions and four of them were taken off the medication. CONCLUSIONS: The combination therapy of bethanechol with doxazosin improved emptying ability in patients with impaired detrusor contractility.
Adrenergic alpha-Antagonists ; Bethanechol* ; Doxazosin ; Follow-Up Studies ; Humans ; Urinary Bladder ; Urinary Bladder, Neurogenic ; Urodynamics

PURPOSE: Botulium toxin-A (BoTx A) is useful in treating detrusor-sphincter dyssynergia, detrusor hyperreflexia, and refractory overactive bladder. Only the blocking action of acetycholine (ACh) release from nerve endings is the well known aspect of the action mechanism. The aim of this study is to investigate the effects of BoTx A on the detrusor muscle itself. MATERIALS AND METHODS: Sprague-Dawley rats were divided into 3 groups: the control group, the low dose injection group (1unit/ml of BoTx A, 0.5cc), and the high dose injection group (5units/ml of BoTx A, 0.5cc). All rats were either injected with normal saline (control group) or BoTx A (injection groups). Ten days after injection, a strip of the detrusor muscle was harvested. Contraction and relaxation responses of the strips were measured by an isometric force transducer. Contractions were induced by various concentrations of ACh, bethanechol, phenylephrine (PE), high concentrations of potassium (35, 70, 105, 140mM), tetraethylammonium (TEA, 0.1, 1, 10mM), 4-aminopyridine (4-AP, a delayed rectifier K+ antagonist, 0.1, 1, 10mM), and Bay K8644 (a L-type voltage dependent calcium channel opener, 0.1, 1, 10mM). The results were analyzed by ANOVA and the Student's t test. RESULTS: Contractions of the strips were noted when concentrations were above 1mM for TEA and above 0.1mM for 4-AP. A high dose injection as well as a low dose injection of BoTx A had no significant effects on the Ach or bethanechol-induced contractions of the strips compared to the control group. Denervation supersensitivity was not found in the injection groups after the Ach and bethanechol treatments, but the contractility was decreased in high concentrations of potassium (70, 105, 100mM), TEA (10mM), 4-AP (10mM), and Bay K8644 in both the high and low dose injection groups. There was no significant difference in the decrease of contractility between the high and low dose groups with the exception of the Bay K8644 1M treatment. CONCLUSIONS: BoTx seems to have some direct effects on decreasing the contractility of the detrusor muscle by increasing the delayed rectifier K+ channel activity and decreasing the L-type voltage dependent calcium channel activity.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; 4-Aminopyridine ; Animals ; Ataxia ; Bethanechol ; Botulinum Toxins, Type A ; Calcium Channels* ; Calcium* ; Denervation ; Nerve Endings ; Phenylephrine ; Potassium ; Rats* ; Rats, Sprague-Dawley ; Reflex, Abnormal ; Relaxation ; Tea ; Tetraethylammonium ; Transducers ; Urinary Bladder* ; Urinary Bladder, Overactive