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TREATMENT OF AUTONOMIC NEUROPATHY
TREATMENT OF AUTONOMIC DYSFUNCTION
OF THE GASTROINTESTINAL TRACT (Part Three)
The autonomic control of the gastrointestinal tract is mediated by the extrinsicparasympathetic and sympathetic nervous systems and the intrinsic enteric nervoussystem. The parasympathetic input to the gut originates from the vagus and pelvicnerves from second through fourth sacral segments. The post−synaptic cholinergicneurons provide excitatory input to the gastrointestinal tract. The sympathetic nervoussystem provides inhibitory input to the gastrointestinal tract. Extrinsic sympatheticefferents arising in the intermediolateral grey column synapse in the celiac, superior,and inferior mesenteric ganglia and ramify throughout the gastrointestinal tract in thedistribution of their respective arterial trunks. The upper gastrointestinal tract isinnervated by the greater splanchnic nerve which synapses in the celiac ganglion andtravels with the celiac artery; the small intestine (mid−gut) is innervated by the lessersplanchnic nerve which synapses in the superior mesenteric ganglion and travels withthe superior mesenteric artery; and the large intestine is innervated by the lumbarsplanchnic nerve which synapses in the inferior mesenteric ganglion and travels withthe inferior mesenteric ganglion.1−3
The enteric nervous system is comprised of a myenteric plexus located between theinner−circular and outer−longitudinal smooth muscle layers (Auerbach’ s plexus) and asubmucosal plexus (Meissner’s plexus). At least five types of intrinsic enteric neuronhave been identified, and any individual neuron may contain multiple neuropeptides.2Motor excitation is mediated by the cholinergic−substance P neurons and inhibition ismediated by the dynorphin−vasoactive intestinal polypeptide neurons. Even in theabsence of extrinsic autonomic nervous system influences, the enteric nervous systemgoverns basic gut functions.2 The myoelectrical activity of gastrointestinal smoothmuscle thus may be influenced by neural input intrinsic to the gut (the enteric nervoussystem),
gastrointestinal neuropeptides acting either as neurotransmitters or as circulatinghormones.
anatomically discrete areas of the gastrointestinal tract. For example, the internal analsphincter is under autonomic control, particularly tonic sympathetic excitation while thestriated muscle sphincters, both at the anus (external anal sphincter) and at the level ofthe esophagus, are also subject to extrinsic autonomic nervous system influences.
Disorders of bowel motility and peripheral neuropathy
Peripheral autonomic neuropathy may affect motility at any level of the gastrointestinal
tract. Diabetic neuropathy is the most common of the peripheral dysautonomias; and,
given its various gastrointestinal manifestations, it is not surprising that a great
experience has accrued in its management, and that therapies in diabetics have
become paradigms for trials in other diseases. Feldman reported that 76% of a random
sampling of diabetic outpatients reported one or more gastrointestinal symptoms, of
which constipation was the most common.4 Among asymptomatic patients, radiologic
evidence for gastric retention was observed in 22% in one prospective study.5
Gastric emptying is delayed in 30−50% of both type I and type II diabetics.6, 7 The termgastroparesis diabeticorum was first introduced by Kassander to describe the alteredgastrointestinal motility in diabetics.5 Food residue is retained in the stomach due toabsent or decreased gastric peristalsis compounded by lower intestinal dysmotility.8Diabetic gastroparesis may manifest as nausea, post−prandial vomiting, bloating,abdominal distension and pain, belching, loss of appetite, and early satiety. Manypatients, however, are asymptomatic despite impaired gastric motility.7 A gastric splashmay be elicited on clinical examination. Gastroparesis is also associated with thedevelopment of bezoars9 and bacterial overgrowth of stomach and small intestine,esophagitis, gastric ulcers, and gastritis.10 Gastroparesis may impair the establishmentof adequate glycemic control by mismatching plasma glucose and insulin levels. Theabsorption of orally administered drugs may also be affected.5, 11
Impaired gastric emptying is frequently associated with cardiovagal neuropathy andsmall−fiber dysfunction.12 Morphological changes in the vagus nerve are reported insome,13, 14 but not all studies.15 Recent studies have implicated hyperglycemia as acause of impaired gastric and small intestinal motility during fasting and after foodintake. Hyperglycemia, delays gastric emptying in healthy and diabetic subjects.16−19
Diarrhea and other lower gastrointestinal tract symptoms may also occur. Diabeticdiarrhea manifests as a profuse, watery, typically nocturnal diarrhea, which can last forhours or days and frequently alternates with constipation.20−22 Abdominal discomfort iscommonly associated.
The pathogenesis of diabetic diarrhea includes reduced
gastrointestinal motility23 abnormalities in gut transit time24, 25 reduced alpha−2adrenergic receptor mediated fluid absorption26 bacterial overgrowth27 pancreaticinsufficiency, co−existent celiac disease28 and abnormalities in bile salt metabolism.29Fecal incontinence, due to anal sphincter incompetence or reduced rectal sensation isanother manifestation of diabetic intestinal neuropathy.26,30 Incontinence is oftenexacerbated by diarrhea.
Constipation is the most frequently reported gastrointestinal autonomic symptom and isfound in up to 60% of diabetics.4 The pathophysiology of diabetic constipation is poorlyunderstood but may reflect intestinal denervation and loss of the post−prandialgastrocolic reflex.31
Pharmacotherapy of bowel hypomotility
An increase in dietary fibre (up to 25 g/day), with water (10 ounces four times per day)
and exercise is the first line of therapy for most patients. The use of psyllium (up to 30
g/day) or methylcellulose (up to 6 g/day) with a concomitant increase in fluid intake will
further increase stool bulk. Appropriate caution must be exercised with these agents for
example high fiber may be disadvantageous in diabetic gastroparesis, because of
distension and cramping pain that can be associated with its use or because of the
potential of bezoar formation.
Stool softeners (e.g. docusate sodium 100−500 mg/day) or lubricants (e.g. mineral oil)together with an osmotic laxative (e.g. lactulose 15−60 ml/day) may be used if theabove measures are ineffective. Glycerin suppositories or sodium phosphate enemasstimulate evacuation by promoting fluid retention in the rectum. (See Table 1)
The contact cathartics such as the diphenylmethane derivatives (phenolphthalein andbisacodyl), the anthraquinones (senna and cascara) should be used sparingly −although the use of these agents cannot be avoided in patients with constipation due toautonomic failure. Extensive use of these agents may damage the myenteric plexusproducing cathartic bowel.
One or more of three general mechanisms of action have been described for thelaxatives a group. First, a given drug may increase intestinal bulk because of itshydrophilic or osmotic properties; second, it may decrease the net absorption ofelectrolytes and water by the intestinal mucosa by damaging the enterocytes orweakening intercellular junctions; third, it may have its effects by enhancing intestinalmotility and thus reducing fluid and electrolyte absorption.
The individual agents may be classified by their response latency and clinical effects.
Softening of feces over one to three days occurs with the bulk forming preparations anddocusates;
diphenylmethane and anthraquinone laxatives; and a watery evacuation in one to threehours occurs with the saline cathartics, such as magnesium citrate and milk ofmagnesia.32−38
The benzamide, metoclopramide (5−20 mg orally, 30 minutes before meals and atbedtime), accelerates gastric emptying and has a central antiemetic action.
Metoclopramide action is inhibited by atropine and is not affected by vagotomy,suggesting that its mode of action, which is primarily on antral motor activity, involvesrelease of acetylcholine from intramural cholinergic neurons or direct stimulation ofantral muscle by intact postganglionic cholinergic neurons.39−43 A dopaminergicmechanism has been inferred from studies demonstrating that levodopa−relatedinhibition of gastric emptying is reversed by metoclopramide.41, 44
In diabetics with concurrent gastroparesis and constipation, metoclopramide wasassociated with improvement in both symptoms.42 Battle, et al.45 have observed thatmetoclopromide has a dose−related stimulatory effect on colonic myoelectrical and
motor activity in normal and diabetic patients, although other authors have noted nomajor effect on colonic motility.39, 46
Tolerance to metoclopramide therapy has been described.44 Patients maintained in thelong term on metoclopramide theoretically may be at risk for the development of tardivedyskinesia and other dopamine−antagonist−related side effects. Concurrent renalfailure may increase risk for acute toxicity.47 The cholinomimetic bethanecol has beenused in combination with metoclopramide and in cases of metoclopramide resistance.4, 48
Erythromycin and related macrolide compounds exhibit strong in vitro affinity for motilinreceptors and have agonist properties that mimic the prokinetic action of exogenousmotilin, a gastrointestinal polypeptide.49, 50 Infusions of motilin in diabetics withgastroparesis result in accelerated gastric emptying, but therapeutic use of the agent islimited by its need for intravenous administration and by its short half−life.51 In humanstudies52 single intravenous doses of erythromycin shortened post−prandial, gastric−emptying time for both liquids and solids to normal levels in diabetics withgastroparesis. After four weeks of treatment with oral erythromycin (250 mg threetimes per day), gastric emptying continued to exhibit improvement, though not to thedegree noted after a single parenteral administration.
Cisapride is a cholinomimetic agent which increases motility in esophagus, stomach,and bowel by enhancing release of acetylcholine from neurons of the myenteric plexus.
In contrast to metoclopramide, cisapride lacks dopamine blocking activity. It has beentried with some success in several clinical conditions including idiopathic gastric stasis53intestinal pseudo−obstruction54−56 chronic constipation associated with laxative use57 indiabetics with constipation58 and in diabetic gastroparesis.59 In a comparison ofintravenously administered doses of cisapride and metoclopromide, cisaprideaccelerated post−prandial emptying to a slightly greater degree.59 Unfortunately, due toan increased incidence of ventricular arrhythmias, this agent is no longer available forgeneral use.60
The somatostatin analogue, octreotide, may stimulate intestinal motor complexes andthis agent has been used to treat sclerodermatous pseudo−obstruction.61 Somatostatin,however, is known to impair motor responses to feeding62 and treatment with octreotidein other conditions has been associated with hypomotility and bacterial overgrowth.63Clinical experience to date with octreotide suggests that its various side effects maypotentially limit therapeutic use.
Nausea and abdominal cramping pain occur with
Fat malabsorption and cholelithiasis have been
Domperidone, a peripheral antidopaminergic agent, may provide symptomatic relief inpatients with gastroparesis64−66 although it is not clear that the medication improvesobjective measures of gastric emptying.67, 68 Koch69 observed that gastric "dysrhythmias,"as determined by electrogastrogram, normalized in six patients treated withdomperidone over six months, although only minimal improvement was noted in gastricemptying over the same period.
The synthetic prostaglandin E1 analog, misoprostol, enhances intestinal motility andaffects intestinal fluid and electrolyte secretion. Preliminary studies suggest that thisagent may be of benefit in refractory constipation.70
Rare patients who do not respond to medical therapy may require colonic surgery.
Such patients should have documented slow colonic transit time and intact rectalsphincter function.
Pharmacotherapy of bowel hypermotility
Diabetic diarrhea best exemplifies the diagnostic subtleties that are involved in the
evaluation and treatment of neurogenic diarrheal conditions. Prior to the diagnosis of
neurogenic diarrhea, other causes must systematically be excluded. Diarrhea as a
result of bacterial overgrowth has been a subject of some controversy. One theory
regarding the pathogenesis of diabetic diarrhea holds that gastric and small bowel
hypomotility may predispose to the proliferation of bacteria, which deconjugate bile
salts and thus inhibit micelle formation. Steatorrhea and diarrhea result indirectly as a
consequence of neurogenic dysmotility.4
A trial of antibiotic therapy (tetracyclines, metronidazole, or cephalosporin) is thereforeconducted in most patients with unexplained chronic diarrhea, especially whensteatorrhea is present. Bile acid malabsorption may be treated with cholestyramine.
Treatment with prokinetic agents (see above) may also improve diarrhea. Should thesemeasures fail, opioid agonists should be used. These agents decrease peristalsis andincrease rectal sphincter tone. The synthetic opioids (diphenoxylate and loperamide)are preferable to alcohol solutions of opium. In the individual case, empiricmanagement with antibiotics, opiates, prokinetic agents, psyllium, anticholinergics, andothers is often required.32
An alternative theory implicates a dysregulation of alpha−2 adrenoreceptor mediatedintestinal ion transport in diabetic diarrhea. Clonidine, a specific alpha−2−adrenergicreceptor agonist, may be used to treat diarrhea in doses of up to 1.2 mg per day.26
The somatostatin analogue, octreotide, has been studied as a potential antidiarrhealagent in small numbers of patients with various conditions.71 As noted above, it mayhave a prokinetic action, but somatostatin has also been shown to inhibit stimulatedwater secretion in gut. 4
Studies of idiopathic fecal incontinence have found delayed conduction in pudendal
nerves supplying the external sphincter and denervation changes in pelvic muscles.
Impaired rectal sensation may be responsible for incontinence in such cases, since
detecting the presence of stool in the anal canal is essential to normal continence.
Other authors have argued that the neuropathy is secondary to prolonged straining at
stool and traction on pudendal nerves.
Medical treatments generally attempt to rectify conditions that are either associatedwith or predispose to fecal incontinence. Use of high−fiber diets and bulking agentsmay be beneficial, since a semi−formed stool is more easily controlled than liquid feces.
Fecal disimpaction is indicated in some cases. Daily tap water enemas aid in clearingresidua in the rectum between evacuations and may allow for functional continence.
Antidiarrheal agents may benefit patients for whom incontinence and diarrhea coexist.
Biofeedback based on the patient’s perception of a distensible balloon in the rectumand training to increase external sphincter pressure has met with success in somereports, although the response to biofeedback is likely dependent on the state ofafferent pathways from the rectum.
A majority of patients who undergo surgical sphincter repair may regain continence forsolid stool, although the presence of pelvic floor neuropathy is associated with pooreroutcome. Other surgical interventions, including colostomy, artificial anal sphincters,and creation of a reconstructed with muscle grafts may be necessary in treatment−resistant cases.30, 72
Pharmacotherapy of bowel hypomotility
Laxatives and Cathartics:
LactuloseSorbitolMagnesium SaltsSodium PhosphatePolyethylene glycol−saline solutionsGlycerin suppositories
PhenolphthaleinBisacodyl tablets or suppositories
Stool Softeners and Lubricants:
1. Wingate DL. Autonomic dysfunction and the gut. In: Bannister R, Mathias CJ,
editors. Autonomic failure
. Oxford: Oxford University Press. 1992; 510−528.
2. Wood JD. Physiology of the enteric nervous system. In: Johnson LR,
Christensen J, Jackson MJ, Jacobson ED, Walsh JH, editors. Physiology of thegastrointestinal tract
. New York: Raven Press, 1987;67−109.
3. Camilleri M. Disorders of gastrointestinal motility in neurologic diseases. Mayo
. 1990; 65:825−846.
4. Feldman M, Schiller LR. Disorders of gastrointestinal motility associated with
diabetes mellitus. Ann Intern Med
. 1983; 98:378−384.
5. Kassander P. Asymptomatic gastric retention in diabetics (gastroparesis
diabeticorum). Ann Intern Med
. 1958; 48:797−812.
6. Wegener M, Borsch G, Schaffstein J, Luerweg C, Leverkus F. Gastrointestinal
transit disorders in patients with insulin treated diabetes mellitus. DigestiveDiseases
. 1990; 8:23−36.
7. Horowitz M, Harding PE, Maddox AF, et al. Gastric and oesophageal emptying
in patients with Type 2 (non−insulin−dependent) diabetes mellitus. Diabetologia
8. Vogelberg KH, Rathmann W, Helbig G. Sonographic examination of gastric
motility in diabetics with autonomic neuropathy. Diabetes Research
9. Brady PG, Richardson R. Gastric bezoar formation secondary to gastroparesis
diabeticorum. Arch Intern Med
. 1977; 137:1729.
associated with diabetic gastroparesis. Arch Intern Me
d. 1987; 147:1477−1480.
11. Loo FD, Palmer DW, Soergel KH, Kalbfleisch JH, Wood CM. Gastric emptying in
patients with diabetes mellitus. Gastroenterology
. 1984; 86:485−495.
12. Westerman RA, Delaney C, Ivamy−Phillips A, Horowitz M, Roberts A.
Concordance between different measures of small sensory and autonomic fibreneuropathy in diabetes mellitus. Clinical & Experimental Neurology
13. Guy RJ, Dawson JL, Garrett JR, et al. Diabetic gastroparesis from autonomic
neuropathy: surgical considerations and changes in vagus nerve morphology. JNeurol Neurosurg Psychiatry
. 1984; 47:686−691.
14. Britland ST, Young RJ, Sharma AK, Lee D, Ah−See AK, Clarke BF. Vagus nerve
morphology in diabetic gastropathy. Diabetic Medicine
. 1990; 7:780−787.
15. Yoshida MM, Schuffler MD, Sumi SM. There are no morphologic abnormalities
of the gastric wall or abdominal vagus in patients with diabetic gastroparesis.Gastroenterol
. 1988; 94:907−914.
16. Fraser R, Horowitz M, Dent J. Hyperglycaemia stimulates pyloric motility in
normal subjects. Gut
. 1991; 32:475−478.
17. Bjornsson ES, Urbanavicius V, Eliasson B, Attvall S, Smith U, Abrahamsson H.
Effects of hyperglycemia on interdigestive gastrointestinal motility in humans.Scand J Gastroenterol
. 1994; 29(12):1096−1104.
18. Horowitz M, Fraser R. Disordered gastric motor function in diabetes mellitus [see
comments]. [Review] [60 refs] Diabetologia
. 1994; 37(6):543−551.
19. Jones KL, Horowitz M, Wishart MJ, Maddox AF, Harding PE, Chatterton BE.
Relationships between gastric emptying, intragastric meal distribution and bloodglucose concentrations in diabetes mellitus. J Nucl Med
. 1995; 36(12):2220−2228.
20. Ogbonnaya KI, Arem R. Diabetic diarrhea. Pathophysiology, diagnosis, and
management [see comments]. Arch Intern Med
. 1990; 150:262−267.
21. Valdovinos MA, Camilleri M, Zimmerman BR. Chronic diarrhea in diabetes
mellitus: mechanisms and an approach to diagnosis and treatment. Mayo ClinProc
. 1993; 68(7):691−702.
22. Lysy J, Israeli E, Goldin E. The prevalence of chronic diarrhea among diabetic
patients. Am J Gastroenterol
. 1999; 94(8):2165−2170.
23. Whalen GE, Soergel KH, Geenen JE. Diabetic diarrhea: A clinical and
pathophysiological study. Gastroenterol
. 1969; 56:1021−1032.
24. Keshavarzian A, Iber FL. Intestinal transit in insulin−requiring diabetics. Am J
25. Scarpello JHB, Greaves M, Sladen JE. Small intestinal transit in diabetics. Br
26. Fedorak RN, Field M, Chang EB. Treatment of diabetic diarrhea with clonidine.
Ann Intern Med
. 1985; 102:197−199.
27. Scarpello JHB, Hague RV, Cullen DR, Sladen GE. The 14C−glycocholate test in
diabetic diarrhea. Br Med J
. 1976; ii:673−675.
28. Walsh CP, Cooper BT, Right AD, Malin JM, Cooke WT. Diabetes mellitus in
coeliac disease: a clinical study. Q J Med
. 1978; 47:89−92.
29. Molloy AM, Tomkin GH. Altered bile in diabetic diarrhea. Br Med J
30. Schiller LR, Santa Ana CA, Schmulen AC, Hendler RS, Harford WV, Fordtran
JS. Pathogenesis of fecal incontinence in diabetes mellitus: evidence forinternal−anal−sphincter dysfunction. N Engl J Me
d. 1982; 307:1666−1671.
31. Feldman M, Corbelt DB, Ramsey EJ. Abnormal gastric function in longstanding
insulin−dependent diabetic patients. Gastroentero
l. 1979; 77:12−17.
32. Brunton LL. Agents affecting gastrointestinal water flux and motility, digestants,
and bile acids. In: Gilman AG, Rall TW, Nies AS, Taylor P, editors. ThePharmacological Basis of Therapeutics
. New York: Pergamon Press, 1990:914−932.
33. Camilleri M, Thompson WG, Fleshman JW, Pemberton JH. Clinical management
of intractable constipation. Ann Intern Med
. 1994; 121(7):520−528.
34. Soffer EE. Constipation: an approach to diagnosis, treatment, referral. Cleve
Clin J Med
. 1999; 66(1):41−46.
35. Moriarty KJ, Irving MH. ABC or colorectal disease. Constipation. BMJ
36. Wrenn K. Fecal impaction [see comments]. N Engl J Med
. 1989; 321(10):658−
37. Romero Y, Evans JM, Fleming KC, Phillips SF. Constipation and fecal
incontinence in the elderly population. Mayo Clin Proc
. 1996; 71(1):81−92.
38. Prather CM, Ortiz−Camacho CP. Evaluation and treatment of constipation and
fecal impaction in adults. Mayo Clin Proc
. 1998; 73(9):881−886.
39. Jacoby HI, Brodie DA. Gastrointestinal actions of metoclopramide. An
experimental study. Gastroenterol
. 1967; 52:676−684.
40. Perkel MS, Moore C, Hersh T, Davidson ED. Metoclopramide therapy in patients
with delayed gastric emptying a randomized, double−blind study. Dig Dis Sci
41. Schulze−Delrieu K. Metoclopramide. Gastroentero
l. 1979; 77:768−779.
42. Snape WJ, Jr., Battle WM, Schwartz SS, Braunstein S, Goldstein HH, Alavi A.
Metoclopramide to treat gastroparesis due to diabetes mellitus: A double−blind,controlled trial. Ann Intern Med
. 1982; 96:444−446.
43. Longstreth GF, Malagelada JR, Kelly KA. Metoclopramide stimulation of gastric
motility and emptying in diabetic gastroparesis. Ann Intern Me
d. 1977; 86:195−196.
44. Ricci DA, McCallum RW. Diagnosis and treatment of delayed gastric emptying.
Adv In Intern Med
. 1988; 33:357−384.
45. Battle WM, Snape WJ, Jr., Alavi A, Cohen S, Braunstein S. Colonic dysfunction
in diabetes mellitus. Gastroenterol
. 1980; 79:1217−1221.
46. Eisner M. Effect of metoclopramide on gastrointestinal motility in man. A
manometric study. Dig Dis
. 1992; 16:409−419.
47. Sirota RA, Kimmel PL, Trichtinger MD, Diamond BF, Stein HD, Yudis M.
Metoclopramide−induced Parkinsonism in hemodialysis patients: Report of twocases. Diabetes Spectrum
. 1992; 5:165−166.
48. Malagelada JR, Rees WDW, Mazzotta LJ, Go VLW. Gastric motor abnormalities
in diabetic and postvagotomy gastroparesis: Effect of metoclopramide andbethanechol. Gastroentero
l. 1980; 78:286−293.
49. Kondo Y, Torii K, Omura S, Itoh Z. Erythromycin and its derivatives with motilin−
like biological activities inhibit the specific binding of 125I−motilin to duodenalmuscle. Biochemical and Biophysical Research Comm
. 1988; 150:877−882.
50. Depootere I, Peeters TL, Matthijs G, Vantrappen G. Macrolide antibiotics are
motilin receptor agonists. Hepato−Gastroenterol
. 1988; 35:198.
51. Schmid R, Schusdziarra V, Allescher HD, Bofilias J, Buttermann G, Classen M.
Effect of motilin on gastric emptying in patients with diabetic gastroparesis.Diabetes Care
. 1991; 14:65−67.
52. Janssens J, Peeters TL, Vantrappen G, Tack J, Urbain JL, De Roo M et al.
Improvement of gastric emptying in diabetic gastroparesis by erythromycin:preliminary studies. N Engl J Med
. 1990; 322:1028−1031.
53. Jian R, Ducrot F, Piedeloup C, Mary JY, Najean Y, Bernier JJ. Measurement of
gastric emptying in dyspeptic patients: effect of a new gastrokinetic agent(cisapride). Gut
. 1985; 26:352−358.
54. Camilleri M, Brown ML, Zinsmeister AR, Malagelada JR. Cisapride corrects the
impaired small bowel transit of chyme in chronic intestinal pseudo−obstruction.Gastroenterol
. 1985; 88,1340.
55. Camilleri M, Malagelada JR, Abell TL, Hench V, Zinsmeister AR. Effect of six
. 1989; 96:704−712.
56. Camilleri M, Brown ML, Malagelada JR. Impaired transit of chyme in chronic
intestinal pseudoobstruction. Gastroentero
l. 1986; 91:619−626.
57. Muller−Lissner SA. Cisapride in chronic constipation and laxative abuse.
. 1985; 88,1510. Abstract
58. Lederer PC, Ellermann A, Ludwig S, Lux G. Effects of cisapride (c) and
metoclopramide (m) on antroduodenal motor activity in man. Gastroenterol
59. Feldman M, Smith HJ. Effect of cisapride on gastric emptying of indigestible
solids in patients with gastroparesis diabeticorum. Gastroenterol
. 1987; 92:171−174.
60. Evans AJ, Krentz AJ. Should cisapride be avoided in patients with diabetic
gastroparesis? J Diabetes Complications
. 1999; 13(5−6):314−315.
61. Soudah HC, Hasler WL, Owyang C. Effect of octreotide on intestinal motility and
bacterial overgrowth in scleroderma. N Engl J Med
. 1991; 325:1461−1467.
62. Peeters TL, Janssens J, Vantrappen GR. Somatostatin and the interdigestive
migrating motor complex in man. Regulatory Peptides
. 1983; 5:209−217.
63. Witt K, Pedersen NT. The long−acting somatostatin analogue SMS 201−995
causes malabsorption. Scan J Gastroll
. 1989; 24:1248−1252.
64. Patterson D, Abell T, Rothstein R, Koch K, Barnett J. A double−blind multicenter
comparison of domperidone and metoclopramide in the treatment of diabeticpatients with symptoms of gastroparesis. Am J Gastroenterol
. 1999; 94(5):1230−1234.
65. Farup CE, Leidy NK, Murray M, Williams GR, Helbers L, Quigley EM. Effect of
domperidone on the health−related quality of life of patients with symptoms ofdiabetic gastroparesis. Diabetes Care
. 1998; 21(10):1699−1706.
66. Barone JA. Domperidone: a peripherally acting dopamine2−receptor antagonist.
. 1999; 33(4):429−440.
67. Horowitz M, Harding PE, Chatterton BE, Collins PJ, Shearman DJ. Acute and
chronic effects of domperidone on gastric emptying in diabetic autonomicneuropathy. Dig Dis Sci.
68. Watts GF, Armitage M, Sinclair J, Hill RD. Treatment of diabetic gastroparesis
with oral domperidone. Diabetic Med
. 1985; 2:491−492.
69. Koch KL, Stern RM, Stewart WR, Vasey MW. Gastric emptying and gastric
myoelectric activity in patients with diabetic gastroparesis: Effects of long−termdomperidone treatment. Am J Gastroenterol
. 1989; 84:1069−1075.
70. Soffer EE, Metcalf A, Launspach J. Misoprostol is effective treatment for patients
with severe chronic constipation. Dig Dis Sci
. 1994; 39(5):929−933.
71. Nakabayashi H, Fujii S, Miwa U, Seta T, Takeda R. Marked improvement of
diabetic diarrhea with the somatostatin analogue octreotide. Arch Intern Med
1994; 154(16): 1863−1867.
72. Madoff RD, Williams JG, Caushaj PF. Fecal incontinence. N Engl J Med
Minutes of the Board of Directors Meeting American Mosquito Control Association, Sparks, Nevada March 6, 2008 AMCA Board Members in Attendance Major S. Dhillon, President Doug Carlson, President-Elect Janet McAllister, Vice-President Allan Inman, Treasurer Stephanie Whitman, Industry Director William Reinert, North Atlantic Stanton Cope, Mid-Atlantic Roxanne Connelly, South Atlantic Tom Wilmot,
Not Reported in S.E.2d, 2008 WL 703810 (Va.App.) Briefs and Other Related Documents Only the Westlaw citation is currently available. UNPUBLISHED OPINION. CHECK COURT RULES BEFORE CITING. From the Circuit Court of the City of Virginia Beach, William R. O'Brien, Judge. Tanya Bullock (Meggan B. Sullivan; Bullock & Cooper, on brief), for appellant. Alice T. Armstrong, Assistant Attorney General