Functional problems associated with colonic dysfunction: the irritable bowel syndrome.
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For the last few years the disorders of the motor function of the gastrointestinal tract are subjects of interest for investigators and physicians. The article presents an analysis of different abnormalities of the motor function of the stomach and duodenum made by gastroduodenoscintigraphy in patients with the biliary tract disorders. The most frequent types of motor gastric and duodenal dysfunctions are discussed in patients with gall bladder dysfunction, chronic cholescystitis, and patients after cholecystectomy.
A 26-year-old man presented with signs and symptoms of marked postganglionic cholinergic autonomic dysfunction manifested by non-reacting dilated pupils, paresis of accommodation, decreased salivation, dry skin, atony of the bladder, erectile impotence and complete gastrointestinal paresis. Standard neurophysiological tests for myelinated sensory and motor fibre function and quantitative methods to examine unmyelinated parasympathetic, sympathetic and afferent fibres were performed: parasympathetic function was measured by heart rate variation tests. Sympathetic cutaneous vasoconstrictor responses induced by deep inspiration were examined with laser Doppler flowmetry. Cutaneous nociceptive C-fibre function was assessed by measurement of axon reflex vasodilatation and flare size induced by histamine iontophoresis. The findings confirmed that the abnormalities were restricted exclusively to the cholinergic postganglionic autonomic systems. All other functions were completely preserved. Modern neurophysiological methods of testing sympathetic and afferent small fibre function might help in the diagnosis of cholinergic postganglionic dysautonomia in the early stages. The specificity of the dysfunction argues in favour of an immunological pathogenesis. However, antibody screening including acetylcholine receptor antibodies and voltage-gated calcium channel antibodies gave negative results. Whatever autoimmunological mechanism might be involved, the postulated antibodies act highly specifically on unknown structures of the cholinergic postganglionic autonomic neurons.
BACKGROUND: There is increasing evidence that autonomic neuropathies may adversely affect gastrointestinal motility by involving the extrinsic nerves of the gut. The authors' hypothesize that functional abdominal pain in children is associated with generalized autonomic dysfunction. METHODS: The authors performed detailed autonomic testing in eight patients with functional abdominal pain, including deep breathing, Valsalva, tilting (to assess parasympathetic and sympathetic adrenergic function), and axon-reflex function and thermoregulatory sweat testing to assess sympathetic cholinergic function. Patients also completed a questionnaire regarding other autonomic symptoms. RESULTS: Results of autonomic testing were abnormal in seven patients. Parasympathetic function was normal in all, and the abnormalities were restricted to sympathetic cardiac, vasomotor, and sudomotor function. Abnormal results of axon-reflex testing in six were consistent with peripheral nervous system dysfunction. Five had decreased sweating over the abdomen, determined by thermoregulatory sweat testing. Five eight had nongastrointestinal autonomic symptoms, primarily palpitations and flushing. CONCLUSIONS: Functional abdominal pain in the current patients is associated with generalized dysfunction of the autonomic nervous system. This dysfunction can be peripheral or central in different individuals but seems to be restricted to the sympathetic branch. The known function of the sympathetic nervous system as the motility "brake" suggests that pain could be a manifestation of unmodulated peristalsis, resulting in abdominal cramps.
We report three cases of drug-induced hemolytic uremic syndrome (HUS). Three patients with advanced gastrointestinal cancer underwent a curative operation and adjuvant chemotherapy with Mitomycin C (MMC), 5FU and Ara-C. Later, progressive anemia, thrombocytopenia, renal dysfunction and elevation of serum LDH were recognized. A diagnosis of HUS was made. As they had no symptoms of infectious diseases or relapse of cancer, the cause of HUS was thought to be MMC. Treatment with antiplatelet drugs and fresh frozen plasma was effective for two patients. However, one patient died of pulmonary edema.
Gastrointestinal symptoms are commonly seen in anticholinesterase insecticide intoxication. A few studies in adults have demonstrated some evidence for pancreatic damage in this poisoning. To see whether this association exists also in children, we conducted a prospective study in 17 consecutive children with typical organophosphate and carbamate poisoning. On admission and following recovery, serum amylase, immunoreactive trypsin, glucose, calcium, urea, creatinine, and arterial blood gas values were determined and compared with those of age-matched control subjects. Acute pancreatitis was diagnosed in 5 subjects. They demonstrated significantly elevated (greater than mean + 2 SD) serum levels of both immunoreactive trypsin (914.0 +/- 317.4 ng/mL, 159.9 +/- 36.4 ng/mL, and 169.7 +/- 41.2 ng/mL, respectively; P less than .01) and amylase (448.0 +/- 264.4 U/L, 152.8 +/- 90.9 U/L, and 56.8 +/- 26.3 U/L, respectively; P less than .001; n = 4), compared with other patients and control subjects. Gastrointestinal symptoms were noted in all 5 subjects, with severe abdominal pain in 2. Such symptoms were evident in only 41% of the other 12 patients. Serum glucose levels were significantly elevated in these subjects compared with others (389.0 +/- 66.2 mg/100 mL vs 180.4 +/- 72.3 mg/100 mL; P less than .01). None had hypocalcemia, renal dysfunction, or acidosis. All had complete recovery. It is concluded that acute pancreatitis is probably not rare in children with anticholinesterase insecticide poisoning. This may contribute to the development of gastrointestinal symptoms and hyperglycemia often observed in these patients.
BACKGROUND: Cyclosporine (CsA)-induced renal dysfunction is common after liver transplantation. We evaluated the efficacy of tapering CsA to a very low dose and introducing mycophenolate mofetil (MMF) in long-term liver-transplant recipients with renal dysfunction. In addition, we assessed the impact of this strategy on calcineurin inhibition and on transforming growth factor (TGF)-beta levels. METHODS: We prospectively enrolled 19 adult, long-term (>1 year) liver-transplant recipients with a decreased creatinine clearance greater than 25% compared with the first month posttransplant. MMF was introduced, and CsA was tapered to 25 mg twice daily. Calcineurin inhibition and TGF-beta were measured at baseline and 3 months thereafter. RESULTS: The CsA dose was tapered over 13+/-3 weeks. At 1-year follow-up, serum creatinine decreased from 141+/-24 to 105+/-22 micromol/L (P=0.002), creatinine clearance increased from 53+/-9 to 71+/-19 ml/min (P=0.02), and glomerular filtration rate increased from 40+/-13 to 64+/-18 mL/min (P=0.002). The incidence of acute rejection was 29%. Antihypertensive medications were discontinued in 71% of the patients. Although CsA levels decreased significantly, serum TGF-beta did not differ from normal controls, and calcineurin inhibition remained stable. The incidence of gastrointestinal side-effects and leukopenia was 18% and 24%, respectively. CONCLUSION: In long-term liver-transplant recipients with renal dysfunction, the introduction of MMF followed by tapering of CsA to a very low dose resulted in a significant improvement in renal function. However, this strategy maybe associated with a risk of acute rejection. The clinical pertinence of measuring serum TGF-beta levels and calcineurin inhibition remains to be determined.
Hydration and volume expansion regimens are widely thought to offer symptomatic benefit in many human ailments. Many varied theories for the phenomenon exists such as decreased blood viscocity in cardiac disease, dilution of toxins in cancer, and cleansing effect on airways in asthma. While it is plausible that disparate mechanisms are involved in different conditions, we propose an alternative, unifying hypothesis that many of the clinical benefits of hydration and volume expansion are partly related to reduced sympatho-vagal ratio. Hypovolemia triggers baroreceptor-mediated sympathetic response and neurohormonal activation to promote fluid retention. Emerging evidence suggests that many diseases including cardiovascular, neurologic, gastrointestinal, metabolic, inflammatory, thrombotic, viral, and oncologic conditions are manifestations of abnormal sympathetic bias and associated T helper 2 bias. Hypovolemia-induced sympathetic activation, especially if baroreceptor dysfunction is involved, can worsen these conditions. Hydration and volume expansion may lower sympatho-vagal ratio, thereby tempering a wide variety of clinical conditions linked directly or indirectly to adrenergia including, but not limited to, acute coronary syndromes, asthma, cancer, and stroke. Interestingly, isotonic or hypertonic hydration, rather than a low-salt diet, may be a counterintuitive potential strategy to treat some cases of hypertension associated with dehydration and autonomic dysfunction. In contrast to the putative causal relationship between them, perhaps hypertension and end-organ damage represent independent consequences of dysfunctional sympathetic and neurohormonal activation. Venipuncture enables faster volume expansion but may also be a source of sympathetic hyperactivity. Oral hydration may additionally promote vagal tone by triggering gastric distension, a benefit not offered by intravenous fluids. The empiric benefits of hydration and volume expansion portend novel methods to treat a wide range of clinical conditions through pharmacologic or electrical modulation of cardiovascular or gastrointestinal baroreceptors.
Chronic pancreatitis is marked by recurrent bouts of pain, complications of pancreatitis, and progressive exocrine and endocrine dysfunction. Objective complications are generally well managed, although they do not alter the natural or progressive course of the disease. Treatment of palpable pseudocysts is varied, and the multiple surgical alternatives are equally effective, since most pancreas function until the pseudocyst decompresses. For patients with recurrent and/or persisting pain, selection of candidates is as important as selection of operations. The goal of preserving as much parenchyma as possible and doing decompressive procedures is attractive for this reason alone. Success, as measured by relief of pain and ability to return to work, is dependent upon cessation of abuse of alcohol and other drugs and perhaps progressive dysfunction of the pancreas.
Esophageal motor function was tested in 12 patients with a clinical diagnosis of diabetic gastroenteropathy by radionuclide transit (RT) studies. Other insulin-dependent diabetics with and without symptoms of peripheral neuropathy but with no symptoms of gastrointestinal disease were similarly studied. Eleven of the 12 patients with gastroenteropathy were found to have abnormal esophageal function, even though only five had esophageal symptoms. Half the diabetics with peripheral neuropathy symptoms, and a quarter of those with no symptoms had abnormal esophageal transit studies. No abnormalities were found in a group of asymptomatic volunteers studied in a similar manner. We conclude that esophageal dysfunction, often subclinical, is present in nearly all patients with suspected diabetic gastroenteropathy. Esophageal dysfunction correlates less well with peripheral neuropathy. This study implies that if a diabetic, presenting with diarrhea or nausea and vomiting, has normal esophageal transit, then a cause for these symptoms, other than diabetic gastroenteropathy, may exist.
Liposome-entrapped cis-bis-neodecanoate-trans-R,R-1,2-diaminocylohexane platinum(II) (L-NDDP) is a new lipophilic cisplatin derivative formulated in a liposomal carrier currently in phase I clinical trials. The preclinical toxicity and pharmacology of L-NDDP were studied in mice and dogs. At the LD50 dose (i.v. bolus) in mice (60.5 mg/kg or 181.5 mg/m2), a tenfold decrease in the granulocyte and platelet counts was observed in the absence of renal toxic effects. In dogs, the maximum tolerated dose (MTD) of L-NDDP given i.v. over a period of 45-60 min was 150 mg/m2. This dose produced significant vomiting (6-18 episodes), minimal renal dysfunction, a maximal decrease in granulocyte and platelet counts of from 30% to 70%, and acute and transient elevation of liver enzymes. Higher doses (225 and 300 mg/m2) resulted in severe gastrointestinal (GI) toxicity in one animal and the death of two others within 48 h. Autopsy results showed multifocal hemorrhages in the lungs, GI tract, kidney, and liver. Three dogs were treated monthly with the MTD up to a cumulative dose of 637.5-712.5 mg/m2 with excellent tolerance. No cumulative myelosuppression or liver dysfunction was observed, whereas a slight increase in the creatinine baseline level was detected in all three animals. Autopsy results at the end of the study showed mild changes limited to the liver, kidney, and GI tract. Pharmacologic studies showed that the drug was cleared, fitting a two-compartment model with a mean t1/2 alpha of 7.1 min and a t1/2 beta of 87.8 h. These studies show that L-NDDP can safely be given at therapeutic doses to animals and that the dose-limiting toxic effects consists of myelosuppression in mice and a multiorgan hemorrhagic syndrome related to vascular injury in dogs.
BACKGROUND/AIMS: The perimenopausal and postmenopausal states are frequently accompanied by a variety of symptoms of hormonal imbalance. Although vasomotor, vaginal and genitourinary symptoms prevail, gastrointestinal complaints such as abdominal bloating may occur. In this study, we investigated the nature and prevalence of gastrointestinal and irritable bowel syndrome (IBS)-type complaints in women going through their climacteric and postmenopausal periods. PATIENTS/METHODS: 228 women (170 postmenopausal and 58 premenopausal) who presented for evaluation at a primary care practice limited to women's health were evaluated prospectively by a previously validated gastrointestinal symptoms questionnaire designed to evaluate symptoms suggestive of IBS. At the time of their participation in the study, none of these women was presenting for evaluation of abdominal or genitourinary symptoms. RESULTS: Thirty-eight percent of postmenopausal women reported altered bowel function, in contrast to 14% of premenopausal ones (p < 0.001). Despite this, the two groups did not differ in regards to the occurrence of abdominal pain, diarrhea or constipation, suggestive of IBS. The prevalence of IBS-type complaints peaked to 36% during the climacteric period (40-49 years). Laxative usage (9.4% prevalence), gaseousness/excessive flatulence (48% prevalence) and heart-burn/acid regurgitation (34% prevalence) were also more common among postmenopausal women. Estrogen use did not affect gastrointestinal symptoms in any of the two groups. CONCLUSIONS: Although the possible role of aging on symptom perception-regardless of hormonal status-cannot be ruled out, these results suggest that peri- and postmenopausal women have a high prevalence of altered bowel function and IBS-like gastrointestinal complaints that should be carefully assessed. If the diagnosis of IBS is confirmed, appropriate treatment may improve patients' symptoms, although this approach requires further study.
BACKGROUND: There is a well-documented relationship, with unknown aetiology, between aortic valve stenosis and occult gastrointestinal bleeding in elderly patients. Despite several studies attempting to determine the prevalence and to discuss the aetiology, there are still many unanswered questions. METHODS: A total of 288 consecutive patients with valvular aortic stenosis--mean age 73 +/- 9 years aortic stenosis group (ASG)--were compared with 129 pacemaker-treated patients, mean age 73 +/- 9 years control group (CG). Screening for occult blood in stools was performed in both groups. Those with a positive Hemocult test or a history of gastrointestinal bleeding were scheduled for further examination including upper endoscopy and colonoscopy. Template bleeding time was performed on patients in both groups and in patients with a prolonged bleeding time with an extended coagulation evaluation was carried out. Patients referred to aortic valve replacement and with a preoperatively prolonged bleeding time were re-examined after surgery. RESULTS: There was a significant difference in the number of subjects with prolonged bleeding time between groups (ASG 19; CG 2; P = 0.028). Re-examination of the bleeding time after aortic valve surgery revealed normalized values in nine of 12 (P = 0.0003). The number of patients with positive Hemocult test did not differ between groups (ASG 29; CG 12; NS). Comparison of the pressure gradient over the aortic valve demonstrated a significantly higher maximal gradient amongst patients with a preoperatively prolonged bleeding time (113 mm HG vs. 90 mmHG; P = 0.005). CONCLUSION: Prolonged bleeding time is related to valvular aortic stenosis and seems to be caused by acquired platelet dysfunction. The normalization of the bleeding time after valve surgery supports the hypothesis that the calcified cusps may interact with the platelet function.
UNLABELLED: Patients with glycogen storage disease type 1b (GSD1b) not only show hepatomegaly, hypoglycaemia and lactic acidosis, but also neutropenia and neutrophil dysfunction. Here, we report improvement of neutropenia and neutrophil function in a 22-year-old male GSD1b patient who had undergone living-related partial liver transplantation (LT) at 18 years of age. After LT, the patient's infectious episodes decreased, gastrointestinal symptoms ameliorated, neutrophil counts increased, and neutrophil function tests normalised. CONCLUSION: Although it is not known whether this improvement was causally related to liver transplantation, this may be the first recorded case of restoration of neutrophil dysfunction in a glycogen storage disease type 1b patient.
Cell death of gastrointestinal epithelial cells occurs by a process referred to as apoptosis. In this review, we succinctly define apoptosis and summarize the role of apoptosis in the physiology and pathophysiology of epithelial cells in the liver, pancreas, and small and large intestine. The physiological mediators regulating apoptosis in gastrointestinal epithelial cells, when known, are discussed. Selected pathophysiological consequences of excessive apoptosis and inhibition of apoptosis are used to illustrate the significance of apoptosis in disease processes. These examples demonstrate that excessive apoptosis may result in epithelial cell atrophy, injury, and dysfunction, whereas inhibition of apoptosis results in hyperplasia and promotes malignant transformation. The specific cellular mechanisms responsible for dysregulation of epithelial cell apoptosis during pathophysiological disturbances are emphasized. Potential future areas of physiological research regarding apoptosis in gastrointestinal epithelia are highlighted when appropriate.
This review will focus on the pacemaker mechanisms underlying gastrointestinal autonomic rhythmicity in an attempt to elucidate the differences and similarities between the pacemaker mechanisms in the heart and gut. Interstitial cells of Cajal (ICC) form networks that are widely distributed within the submucosal (ICC-SM), intra-muscular (ICC-IM, ICC-DMP) and inter-muscular layers (ICC-MY) of the gastrointestinal tract from the esophagus to the internal anal sphincter. The ICC generate spontaneously active pacemaker currents that may be recorded as plateau and slow potentials. These pacemaker currents drive the spontaneous electrical and mechanical activities of smooth muscle cells. The enteric nervous system, composed of both the myenteric (inter-muscular) plexus and the submucosal plexus, is also distributed in the gastrointestinal tract from the esophagus to the internal anal sphincter. The role of the ICC and the enteric nervous system in the integrative control of gastrointestinal function and especially of spontaneous rhythmic activity, is still unknown. Nevertheless, at least from the results presented in this review of studies of the jejunum, ileum and proximal colon of the mouse, it is convincing that the ICC drive spontaneous rhythmic motility, although a role for the enteric nervous system in the regulation of spontaneous rhythmic motility cannot be overlooked. Furthermore, intracellular Ca2+ handling has a critical role in the generation of pacemaker activity in the gut and heart, although respective players such as the Ca2+-ATPase of the sarcoplasmic reticulum (endoplasmic reticulum), IP3 receptors, ryanodine receptors and plasma membrane ion channels may have divergent roles in the Ca2+-release refilling cycles. In conclusion, intracellular Ca2+ handling plays a key role in the gut pacemaker responsible for spontaneous rhythmicity, as well as in the cardiac pacemaker responsible for spontaneous beating. Pharmacotherapeutic targeting of intracellular Ca2+ handling mechanisms may be a promising approach to the treatment and cure of gut motility dysfunction.
Mycophenolate sodium (EC-MPS) has been shown to be as effective and as safe as mycophenolate mofetil (MMF) in renal transplant patients. Nevertheless, compared to MMF its use in liver transplant patients has been limited. The purpose of this study was to analyze the efficacy of EC-MPS as a primary immunosuppressant or as a replacement for MMF in liver transplant patients. Ninety among 470 liver transplant recipients were receiving or had added an antimetabolite to their immunosuppressant therapy. The most common reason for this change was renal dysfunction (47.8%) or diabetes (32.2%). EC-MPS was started at a median of 30 months after liver transplantation. The mean administered daily dose was 720 mg/d. At least one gastrointestinal symptom was reported by 25 patients. Abdominal pain (16.6%) and diarrhea (14.5%) were the most frequent. EC-MPS had to be discontinued in two patients, while six others required dose reduction to resolve the symptoms. Hematological adverse events were infrequent: three patients had leukopenia and one, anemia, all of which responded to dosage reduction. There was a creatinine reduction within 6 months of drug commencement and maintenance of the lower creatinine levels at 1 year among patients who began EC-MPS for renal dysfunction. Serum low-density lipoprotein cholesterol and triglyceride levels were significantly lower among patients on EC-MPS than on MMF. In conclusion, EC-MPS appears to have a similar efficacy and safety profile as MMF in liver transplant patients. Hematological and gastrointestinal adverse events were infrequent; seldom had the drug to be discontinued.