Ischemic colitis associated with pseudoephedrine: four cases.

OBJECTIVE: There is one previously reported case linking ischemic colitis and orally administered nasal decongestants containing pseudoephedrine (MEDLINE 1974-1998). We aimed to document an association between pseudoephedrine ingestion and ischemic colitis. METHODS: We reviewed the cases of four women (ages, 37-50 yr) who presented with the sudden onset of colicky abdominal pain followed by hematochezia. Three patients had used medicine containing pseudoephedrine daily for approximately 1 wk before admission. The fourth patient had used pseudoephedrine chronically for 6 months. Two patients had no significant past medical history. One woman had presented 6 months earlier with ischemic colitis while taking both pseudoephedrine and hormone replacement therapy. This time she presented with ischemic colitis while not taking hormone replacement therapy, but still taking decongestants. Another woman had a history of ulcerative colitis, which had been quiescent for 10 yr. One patient had been a smoker; however, like the other patients she had no evidence of systemic vascular disease. On colonoscopy, all four patients had colitis, primarily affecting the splenic flexure in the anatomical watershed area. Other causes of segmental colitis, including infectious colitides, pseudomembranous colitis, and Crohn's disease, were not evident. Colonoscopic biopsies were consistent with ischemic injury. RESULTS: All cases responded to abstinence from pseudoephedrine and medical supportive therapy. None has had a relapse since discontinuing the pseudoephedrine (8-12 months). CONCLUSIONS: The vasoconstrictive action of pseudoephedrine may predispose susceptible patients to develop ischemic colitis in the watershed area of the splenic flexure. Perimenopausal women may be especially susceptible because of irregular ovulation. This may result in relative vasoconstriction when estrogen levels are low or a hypercoagulable state when estrogen levels are excessive.

Regional quantitation of preprodynorphin mRNA in guinea pig gastrointestinal tract.

The endogenous opioid peptide dynorphin has been shown by immunochemical studies to be widely distributed in the gastrointestinal tract. The aim of this study was to determine basal levels of preprodynorphin (ppDyn) mRNA in different regions of the gastrointestinal tract of the guinea pig. A modified sensitive and specific solution hybridization RNase protection assay was used to quantitate ppDyn mRNA, with confirmation by gel analysis of the RNase protected hybrids and PCR amplified cDNA. This method combines high sensitivity and sufficient throughput to analyze large number of samples in a single assay. Low but measurable amounts of ppDyn mRNA were detected in fundus, duodenum, jejunum, ileum, cecum, and rectum. The rectum contained significantly more ppDyn mRNA than the stomach, small bowel, and cecum. The muscularis/myenteric plexus layer of both ileum and rectum contained a higher concentration of ppDyn mRNA per microg total RNA compared to the mucosa/submucosa/submucosal plexus. However, a greater absolute amount of ppDyn mRNA (80-85%) localized to the mucosal layer. The greater absolute amount of ppDyn mRNA in the mucosal layer may indicate the presence of dynorphin in the endocrine cells of the mucosa.

Hypothalamic-pituitary-adrenal axis hypersensitivity to naloxone in opioid dependence: a case of naloxone-induced withdrawal.

A case of opioid withdrawal precipitated in an opioid-dependent person by low plasma levels of naloxone is presented. In this patient, changes were observed in the hypothalamic-pituitary-adrenal (HPA) axis that preceded the clinical symptoms and adrenergic signs of withdrawal. Plasma naloxone levels were strongly correlated with plasma cortisol levels (P < .0001, R2 = .73, r = .85). In addition, these neuroendocrine changes persisted after adrenergic changes and clinical symptoms had been ameliorated by administration of a short-acting opioid agonist. It is suggested that the HPA axis is a more sensitive indicator of opioid withdrawal than the adrenergic system.

Orally administered opioid antagonists reverse both mu and kappa opioid agonist delay of gastrointestinal transit in the guinea pig.

Kappa(kappa) opioid agonists slow gastrointestinal transit in the guinea pig and the mouse but not the rat. Opioid antagonists naloxone and naltrexone are mu (mu) preferring, while the antagonist nalmefene has more kappa binding activity. When administered orally, the specific opioid antagonists naloxone, naltrexone, and nalmefene are able to reverse the gastrointestinal transit delay caused by orally administered mu and kappa opioid agonists (morphine and U-50, 488H) in a dose dependent fashion as measured by the leading edge of charcoal meal in the guinea pig. Oral naltrexone and nalmefene have significantly more central nervous system (CNS) bioavailability than oral naloxone. However, orally administered naloxone was as effective as either naltrexone or nalmefene in reversing mu opioid agonist induced orocecal transit delays (single agonist dose apparent ED50s = 12.3 +/- 4, 7.3 +/- 4, and 13.5 +/- 6 mg/kg respectively). Nalmefene was more active than either naltrexone or naloxone in its ability to reverse the kappa agonist U-50,488H (single agonist dose apparent ED50s = 18.3 +/- 12*, 37.5 +/- 5, and 61.9 +/- 5 mg/kg respectively; * = p < 0.05). These data confirm the enteric action of orally administered opioids and further supports our earlier findings of the presence of kappa opioid activity in the guinea pig enteric nervous system.

Using enteral nutrition formulas.

A review of enteral tube feeding formulations is presented. When choosing an enteral formula product for a patient one must first determine the calorie and protein needs of the patient. Then one must determine the level of gastrointestinal tract function. First ask, to what degree is the small bowel functioning: totally, partially, or not at all? Has the small bowel lost surface area because of atrophy, inflammation, or surgical removal? Is the gut edematous because of hypoalbuminemia or congestive heart failure? Is bowel motility impaired by opioids, anticholinergics, or mechanical ileus? Is digestion limited by pancreatic or bile acid insufficiency? Has absorption been decreased by intestinal ischemia or gastrointestinal bleeding? Decreased surface area, bowel edema, and diminished digestive juices are only partial losses of small bowel function. An elemental formula should be tried first in these situations. Any of the other problems alone or in combination probably preclude the use of the small bowel and the patient will need total parenteral nutrition. If gastrointestinal function is adequate, then other organ failures that result in specific nutrient intolerance must be ruled out. If gastrointestinal function is adequate and no other organ failures preclude the use of a polymeric formula, then one must decide if stress and hypermetabolism are present. Enteral feeding is the preferred method of providing specialized nutrition support. Bowel rest reduces the barrier functions of the gut and malnutrition reduces cell-mediated immunity. The indications and relative contraindications for enteral tube feeding are also reviewed. The rationale for the formula design and the evidence for formula efficacy are presented. Polymeric, elemental, organ-specific, and immune-modulating formulas are discussed. Guidelines for formula selection are suggested.

Treatment of opioid-induced constipation with oral naloxone: a pilot study.

Opioids cause constipation by binding to specific opioid receptors in the enteric and central nervous systems. First-pass glucuronidation limits systemic bioavailability of oral naloxone. This study was designed to determine if oral naloxone could reverse opioid-induced constipation without precipitating abstinence or recrudescence of pain in opioid-dependent individuals. Concentrations of unmetabolized and total naloxone, including naloxone glucuronide, were measured by radioimmunoassay. A dose-related increase in symptoms of laxation resulted in all three opioid-dependent patients studied that paralleled the increase in active and total naloxone plasma levels. Withdrawal symptoms occurred with plasma naloxone area under the plasma concentration-time curves above 550 ng.min/ml and with dosing intervals less than 3 hours. Peak plasma levels did not predict withdrawal. Oral naloxone ameliorates opioid-induced constipation in opioid-dependent persons. Titration of dose to a maximum of 12 mg at least 6 hours apart may be needed to avoid adverse reactions.

beta-Endorphin and cortisol abnormalities in spinal cord-injured individuals.

Plasma beta-endorphin-like immunoreactivity (BEP-ir) and cortisol levels were measured by radioimmunoassay (RIA) in nine patients who were at least 12 months status post spinal cord injury (SCI). Plasma levels were obtained at 8:00 am and 4:00 pm to determine circadian rhythm, and on the day following administration of 1 mg dexamethasone, levels were again obtained at 8:00 am and 4:00 pm. The mean morning levels of plasma BEP-ir were significantly lower than control values for this laboratory (6.2 +/- 1.2 v 12.0 +/- 2.3 pg/mL). The morning BEP-ir values were lowest in patients who were closer to the time of injury (described by a second-order polynomial regression, R = .89; P less than .01). Mean morning cortisol levels were not significantly different from controls, but showed greater variability (mean, 15.1; range, 0.7 to 22.7 micrograms/dL v control, 15.5; range, 7 to 35). Dexamethasone suppressed cortisol secretion in all patients and BEP-ir levels in six of nine patients. Failure to detect BEP-ir suppression occurred in patients whose BEP-ir levels were less than 4.5 pg/mL and close to the minimum detection limit of the assay. Depression was present in five of nine patients as measured by the Beck Depression Inventory (BDI) and in three of nine patients as measured by the Hamilton Depression Scale (HSRD). However, the depression indices did not correlate with the neuroendocrine measures.

Neuroendocrine changes during functional electrical stimulation.

This study examined the effects of a computerized functional electrical stimulation exercise program on plasma beta-endorphin-like immunoreactivity (BEP-ir), cortisol levels and depression parameters in spinal cord-injured individuals. Nine subjects from 1.2 to 33.5 yr postinjury with both motor and sensory complete lesions between C5 and T12 participated. It was determined that patients who sustained spinal cord-injuries less than 5 yr before this study had lower than normal baseline levels of BEP-ir and flattened circadian rhythms. Patients who sustained their injury greater than 5 yr before this study had higher baseline levels of BEP-ir with some return to normal circadian rhythmicity. Baseline cortisol levels, regardless of time since injury, appeared to be dysregulated. Regular exercise with computerized functional electrical stimulation caused significantly (P less than 0.05) sustained increases in BEP-ir in all patients and improved the regulation of cortisol. Furthermore, the more strenuous the exercise training, greater increases in BEP-ir levels were seen. Last, depression scores improved, which suggests a possible association between subjective mood and BEP-ir levels.

Effect of home total parenteral nutrition on body composition in patients with acquired immunodeficiency syndrome.

Malnutrition occurs commonly in patients with acquired immunodeficiency syndrome (AIDS). The efficacy of nutritional support is unknown. A prospective, longitudinal study was conducted to determine the effect of prolonged total parenteral nutrition on body composition in 12 AIDS patients. Five patients were malnourished because of problems with food intake or absorption, while seven had systemic infections, with or without a malabsorption syndrome. The AIDS patients gained body weight and body fat content in response to total parenteral nutrition, while mean body cell mass, estimated as total body potassium content, was unchanged. However, all five patients with altered intake or absorption had significant repletion of body cell mass which was significantly different from the patients with systemic infections. Calorie and nitrogen intake did not differ between the two groups. It is concluded that body mass repletion is possible in AIDS patients in whom malabsorption is the major pathogenetic factor in producing malnutrition and is less successful in patients with serious ongoing systemic diseases. Thus, the response to nutritional support is dependent on the particular clinical circumstances.

Intestinal dysmotility syndromes in the elderly: measurement of orocecal transit time.

Altered bowel habits are common symptoms in the elderly, yet the pathophysiology of age-related gastrointestinal dysmotility syndromes is poorly understood. The present study was designed to correlate changes in orocecal transit time (TT) in healthy elderly subjects with or without gastrointestinal dysmotility complaints. Twenty-two geriatric facility resident volunteers, mean age 82 yr (range 65-94 yr) participated, of whom 16 had gastrointestinal dysmotility symptoms. Orocecal TT in the elderly subjects did not differ from that in younger adult controls (100 +/- 11 min vs 93 +/- 20 min). However, orocecal TT was longer in geriatric females (112 +/- 14 min) than in males (70 +/- 6 min, p less than 0.01). We conclude that age alone does not prolong orocecal TT, except when dysmotility symptoms have been present for a prolonged period.

Evaluation of diagnostic criteria for mucosal cytomegalic inclusion disease in the acquired immune deficiency syndrome.

Mucosal cytomegalic inclusion disease (CID) is a serious complication in acquired immune deficiency syndrome (AIDS) that usually is associated with disseminated cytomegalovirus (CMV) infection, and leads progressively to death in many patients. Early diagnosis may improve the chances of responding to specific antiviral therapy. We analyzed retrospectively the diagnostic evaluations of 26 AIDS patients with histopathologically confirmed CID infections and 19 AIDS or AIDS-related complex patients without CMV infections. The groups were similar demographically and clinically. Characteristic CMV inclusion bodies were found on antemortem biopsy in 92% of patients, including 80% for rectal biopsy alone. The specificity of the viral inclusions for CMV was established using an immunohistological technique. Rectal culture for virus isolation was much less sensitive (30%) than biopsy. Urine cultures were positive more frequently (39%) than were rectal cultures, but were less specific. Furthermore, the presence of immunoglobulin G anti-CMV was nonspecific and the presence of immunoglobulin anti-CMV was both insensitive and nonspecific. We conclude that mucosal biopsy is a rapid and reliable means of detecting cytomegalovirus infections, and is an indispensible part of the evaluation for this disease.

Treatment of disseminated cytomegalovirus infection with 9-(1,3 dihydroxy-2-propoxymethyl)guanine: evidence of prolonged survival in patients with the acquired immunodeficiency syndrome.

Disseminated cytomegalovirus (CMV) infection is a common complication of the acquired immunodeficiency syndrome (AIDS) and contributes significantly to its morbidity and mortality. Dihydroxypropoxymethyl guanine, DHPG, is an antiviral agent that has been shown to inhibit CMV replication and to provide clinical benefit in patients with CMV infections, especially retinitis. In this study, the clinical characteristics, results of diagnostic evaluations, and survival were compared in 11 AIDS patients with disseminated CMV infections who were seen between August 1981 and October 1984 and were not treated with DHPG, and in 18 AIDS patients seen since that time who were treated with DHPG. The study groups were similar though the untreated group was somewhat more tissue depleted. Survival from diagnosis was significantly prolonged with DHPG therapy based upon life table analysis (p = 0.001). Therapy improved the quality of life, as 12 of 18 treated patients and only 2 of 11 untreated patients could be discharged from the hospital. Progression of CMV infection did not appear to play a role in the mortality of patients who died during DHPG therapy. We conclude that DHPG prolongs survival in patients with AIDS who have disseminated CMV infections.