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PubMed2006

Nitrergic modulation of gastrointestinal function during early endotoxemia.

After bacterial infection, the host reacts by signalling to the central nervous system where a cascade of physiologic, neuroendocrine and behavioural processes is orchestrated, collectively termed the acute phase response. Endotoxemia following Gram-negative bacterial infection induces a wide array of effects, including fever, loss of appetite and changes in gastrointestinal function that attempt to eliminate the challenge and restore homeostasis. Systemic administration of low doses of endotoxin (5-40 microg/kg) to rats is associated with changes in gastrointestinal motor function, inhibition of gastric acid secretion and increase in the gastric mucosal resistance to damage. These changes are rapid in onset (observed within one hour), not related to vascular dysfunction, and appear to be mediated by mechanisms that involve the peripheral and the central nervous system. Nitric oxide (NO) plays a central role in the physiology of the gastrointestinal tract and its response to illness. Accumulated evidence supports an increase of NO synthesis in the brainstem, as well as in the gastric myenteric plexus thirty minutes after endotoxin administration. Such a synthesis is due to constitutive nitric oxide synthase (NOS) and occurs before the induction of NOS takes place. In this review we provide experimental evidence supporting the hypothesis that activation of a physiologic mechanism, mediated by the autonomic and the central nervous systems as well as constitutive NOS isoforms, is involved in acute changes of gastrointestinal function during early endotoxemia.

Animals↗

PubMed1993

Verapamil intoxication: a literature review of overdoses and discussion of therapeutic options.

Calcium channel antagonists can be quite toxic. In the management of poisoning, early recognition is critical. Calcium channel antagonists are frequently prescribed, and the potential for serious morbidity and mortality with overdosage is significant. Ingestion of these agents should be suspected in any patient who presents in an overdose situation with unexplained hypotension and conduction abnormalities. The potential for toxicity should be noted in patients with underlying hepatic or renal dysfunction who are receiving therapeutic doses. Because there is no specific antidote, decontamination of the gastrointestinal tract is crucial. Intravenous calcium should be administered to symptomatic patients because it is relatively innocuous and may be beneficial. Volume expansion should be the initial approach to hypotension unrelated to bradycardia. Patients who have had a verapamil overdose should be observed in intensive care units where Swan-Ganz catheterization and ventricular pacing are routinely available. The choice of sympathomimetic agents for treatment remains controversial. According to the published literature, isoproterenol, epinephrine, and norepinephrine may be more effective in improving bradycardia and the resultant hypotension than dopamine. However, none of these agents is universally effective. A more logical approach may be to improve cardiac output with agents like amrinone. Bay K 8644 and 4-aminopyridine show promise as potential antidotes but at present are still experimental.

Adult↗

PubMed1994

Bacterial translocation in mesenteric ischemia-reperfusion injury: is dysfunctional motility the link?

The authors previously reported that mesenteric ischemia and reperfusion (I/R) in a chronic newborn piglet model creates dysfunctional intestinal motility. Whether this leads to inadequate bacterial clearance and translocation (BT) through the gastrointestinal tract remains unclear. To test this hypothesis the authors used their chronic piglet model (weight, 3.5 +/- 0.3 kg; age, 18 +/- 4 days; on formula feeding); nonocclusive mesenteric ischemia was induced via reversible pericardial tamponade. Mesenteric flow (SMA Doppler measurement via the retroperitoneal approach) was decreased to 25% +/- 5% of baseline for 300 minutes in the ischemia group (n = 7) and followed by 14 hours of reperfusion in the I/R group (n = 6). Control subjects had a sham operation (n = 7). Mesenteric lymph nodes (MLN), liver (L), spleen (S), ileum, peritoneum, and blood were harvested for blind quantitative microbial analysis. Subjects in the control group had no cultures positive for growth. Eighty-five percent of animals in the ischemia group had positive MLN cultures only (P < .05 v control). All piglets in the I/R group had positive MLN cultures (P < .05 v control), and one third of them manifested bacteremia. Histological examination did not show mucosal disruption in any group. The validity of this model is confirmed by the negative cultures in the control group and by the presence of normal ileal flora in all animals. In the ischemia and I/R groups, MLN cultures were consistently positive with gram-negative bacilli (Escherichia coli and/or Klebsiella pneumoniae). When subjects of the I/R group had more than 1,000 colonies in the MLN, bacteremia with the translocating organisms was also identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2003

Ultrastructural changes in smooth muscle cells of the small intestine in suckling rabbits with experimental cholera.

Ultrastructural study of the small intestine in suckling rabbits with experimental cholera revealed involvement of the inner and outer smooth muscle layers into the pathological process. Smooth muscle cells were characterized by vacuolar and fatty degeneration and focal colliquative necrosis. Apoptosis played little role in gastrointestinal motility disturbances. The presence of considerable amounts of fluid in intestinal loops reflects peristaltic dysfunction due to generalized damage to smooth muscle cells.

Animals↗

PubMed1997

A case-control study to examine any association between idiopathic detrusor instability and gastrointestinal tract disorder, and between irritable bowel syndrome and urinary tract disorder.

OBJECTIVE: To assess whether there are common malfunctions (e.g. of the autonomic nervous system and smooth muscle) that underlie disorders of the urinary and gastrointestinal tracts by determining whether there is an increased prevalence (i) of urinary symptoms in patients with irritable bowel syndrome (IBS) and (ii) of gastrointestinal symptoms in patients with idiopathic detrusor instability (IDI). PATIENTS AND METHODS: Questionnaires were sent to patients with a diagnosis of IBS or IDI who were seen in the Departments of Gynaecology, Gastroenterology and Urology at the John Radcliffe and Churchill Hospitals, Oxford, during the 3 year period 1993-1995. The questionnaires were also distributed to control patients who were recruited from the day-surgery unit of the Churchill Hospital. Of 236 questionnaires sent out, 168 replies were analysed; 64 from patients with IBS, 49 from patients with detrusor instability and 55 from controls. The questionnaire included questions about micturition and defecatory behaviour (frequency, regularity, urgency, continence, pain, and ease in passing urine and stools). RESULTS: Patients with IBS were more likely to experience certain urinary symptoms than controls (nocturia, urgency and some forms of urinary urge incontinence) and patients with IDI were as likely as patients with IBS to experience gastrointestinal symptoms more frequently than controls. Control patients showed an unexpectedly high probability of experiencing many of the gastrointestinal and urinary symptoms. CONCLUSIONS: The frequent occurrence of symptoms in control patients makes the significance of the results less clear, but the association between certain symptoms of urinary tract disorder and patients with IBS, and of symptoms of gastrointestinal tract disorder with patients with IDI, suggests that they may share some common underlying dysfunction.

Adult↗

PubMed1980

The neurotoxicity of the rat poison vacor. A clinical study of 12 cases.

Oral ingestion of a new rat poison that antagonizes nicotinamide metabolism, N-3-pyridylmethyl-N'-p-nitrophenyl urea (PNU, Vacor), is known to cause diabetes mellitus. I describe neurologic complications of PNU ingestion in 12 patients 19 to 50 years of age who swallowed between 0.39 and 7.02 g of PNU. One died within a day, and five died of chronic complications 40 to 182 days after taking the poison. Apart from the acute hyperglycemic ketoacidosis, the clinical presentation was variable, but orthostatic hypotension, gastrointestinal hypomotility, peripheral neuropathy, and encephalopathy were typical. The peripheral, autonomic, and central-nervous dysfunction could develop either acutely or other several days. It is possible that nicotinamide, given parenterally within minutes, prevents toxicity, but the cases discussed in this paper indicate that the neurologic deficits may progress despite later nicotinamide administration. Neurologic improvement took many months. Full recovery was uncommon, and the orthostatic, hypotension tended to persist.

Adult↗

PubMed2002

Multicenter non-randomized phase II study of raltitrexed (Tomudex) and oxaliplatin in non-pretreated metastatic colorectal cancer patients.

BACKGROUND: This multicenter, phase II, open-label study evaluated the antitumor efficacy and safety of oxaliplatin and raltitrexed (Tomudex) in non-pretreated advanced colorectal cancer patients. PATIENTS AND METHODS: Seventy-one patients received oxaliplatin 130 mg/m(2) and raltitrexed 3 mg/m(2) intravenously on an outpatient basis every 3 weeks. All patients had histologically proven metastatic colorectal adenocarcinoma, performance status <or=2 and good baseline organ function. Most (56%) had only one disease site. All patients were assessed for safety, and 66 of 69 eligible patients were assessed for response. RESULTS: A total of 404 cycles were administered, with a median of six cycles per patient (range 1-12 cycles). Relative dose intensities were 0.98 and 0.98 for oxaliplatin and raltitrexed, respectively. The most common grade 3-4 toxicities (National Cancer Institute Common Toxicity Criteria) among treated patients were as follows: neutropenia (21 patients, 30%), asthenia (eight, 11%), diarrhea (12, 17%), liver function test abnormalities (24, 34%), nausea (nine, 13%) and vomiting (nine, 13%). Two treatment-related deaths occurred (hematotoxicity in one patient and gastrointestinal toxicity in the other) and two further deaths were possibly related to treatment (hepatic dysfunction in one patient and neuropathy in the other). Thirty-seven objective responses (one complete) were obtained [objective response rate 54%; 95% confidence interval (CI) 42% to 65%] in eligible patients. The median response duration was 8.5 months (95% CI 6.7-12.2 months), while median progression-free and overall survival among eligible patients were 6.2 (95% CI 5.1-6.9 months) and 14.6 months (95% CI 11.0-18.9 months), respectively. CONCLUSIONS: The present study confirms the feasibility of the raltitrexed plus oxaliplatin combination and its activity in non-pretreated advanced colorectal cancer patients.

Adenocarcinoma↗

PubMed2003

Effects of nitric oxide synthase inhibitor to esophagus in a feline esophagitis model.

The present study explores the effects of nitric oxide synthase inhibitor on esophageal motility in a feline model with esophagitis. Perfusion of the esophagus with acid produced inflammatory changes of esophageal mucosa. The esophageal motility was measured before and after the perfusion. One group of cats was given nitric oxide inhibitor orally at the same time as the perfusion of acid. The control group was given water instead. Esophagitis impairs the motility of the esophagus. However, the esophageal motility of the cats that were given nitric oxide synthase inhibitor decreased less than that of the control group. The results suggested that during esophagitis there is an alteration of the nitric oxide synthase/nitric oxide pathway in the esophagus, which may be one of the important mechanisms of esophageal motility dysfunction.

Animals↗

PubMed1990

Hormonal changes in hemodialysis.

When chronic renal failure becomes advanced, the serum or tissue levels and/or the functions of most hormones are altered because of several interplaying mechanisms involving synthesis, transport, accumulation of inhibitors, abnormality of target organ responsiveness, and impaired renal clearance. As regular dialysis treatment is performed, most of these uremic hormone abnormalities are not reversed, and some of them may even get worse. The main endocrine derangements can be grouped as sexual hormone dysfunction, thyroid abnormalities, growth retardation, hormone-related disorders of metabolism, derangements of pressor substances, gastrointestinal peptide abnormalities, renal osteodystrophy, and anemia. The endocrine abnormalities play a major role as for the clinical and metabolic rehabilitation of dialysis patients.

Endocrine System Diseases↗

PubMedDate not supplied

Ileo-anal pouch function and dysfunction.

Ileal pouch-anal anastomosis (IPAA) has become well established as the ideal surgical option for the majority of patients with chronic ulcerative colitis. Improvements and simplifications in operative technique over recent years mean that such patients need no longer live with the fear of a permanent ileostomy with its associated physical, sexual and sometimes psychological problems. Most patients who have undergone IPAA achieve a good quality of life. There are, however, a number of questions with regard to the ileal pouch that remain unanswered. The purpose of this review is to summarize the advantages and disadvantages of the various designs of pouch which have been described, to discuss the function of the normal pouch and manifestations of dysfunctional pouches.

Colitis, Ulcerative↗

PubMed1990

Dietary fiber: a brief review and potential application to enteral nutrition.

Advances in enteral nutrition include the provision of organ-specific fuels to improve gut structure and function. Examples of these fuels include soluble fiber as a fuel precursor, and the SCFAs acetate, propionate, and butyrate. Butyrate appears to exert its trophic effect primarily in the colon, whereas the combined SCFAs affect the whole gastrointestinal tract. The provision of these fuels may be indicated for selected patients with intestinal dysfunction.

Dietary Fiber↗

PubMed2004

Passive transfer of autoimmune autonomic neuropathy to mice.

Autoimmune autonomic neuropathy (AAN) is an acquired, often severe, form of dysautonomia. Many patients with AAN have serum antibodies specific for the neuronal ganglionic nicotinic acetylcholine receptor (AChR). Rabbits immunized with a fusion protein corresponding to the N-terminal extracellular domain of the ganglionic AChR alpha3 subunit produce ganglionic AChR antibodies and develop signs of experimental AAN (EAAN) that recapitulate the cardinal autonomic features of AAN in man. We now demonstrate that EAAN is an antibody-mediated disorder by documenting sympathetic, parasympathetic, and enteric autonomic dysfunction in mice injected with rabbit IgG containing ganglionic AChR antibodies. Recipient mice develop transient gastrointestinal dysmotility, urinary retention, dilated pupils, reduced heart rate variability, and impaired catecholamine response to stress. The autonomic signs are associated with a reversible failure of nicotinic cholinergic synaptic transmission in superior mesenteric ganglia. Mice injected with IgG from two patients with AAN (of three tested) demonstrated a milder phenotype with evidence of urinary retention and gastrointestinal dysmotility. The demonstration that ganglionic AChR-specific IgG causes impaired autonomic synaptic transmission and autonomic failure in mice implicates an antibody-mediated pathogenesis for AAN. The antibody effect is potentially reversible, justifying early use of immunomodulatory therapy directed at lowering IgG levels and abrogating IgG production in patients with AAN.

Animals↗

PubMed1992

[Experimental studies of urinary incontinence. Effect of tiropramide on the urinary stage and evacuation].

Tiropramide, a tyrosine derivative, has an antispasmodic effect on the gastrointestinal smooth muscles and it is suggested that the effect is mediated by cAMP. Therefore, we studied the effects of tiropramide on the lower urinary tract smooth muscle functions. In animal experiments, the effects of tiropramide on vesicourethral smooth muscle contraction were investigated and cAMP and cGMP levels following tiropramide administration were measured in the vesicourethral and gastrointestinal smooth muscles. In clinical trials, five healthy volunteers and five patients with neurogenic bladder dysfunction were treated orally with tiropramide 300 mg a day for two weeks and examined for urodynamic parameters before and after tiropramide treatment. Tiropramide significantly inhibited contraction of the vesicourethral smooth muscle and the inhibitory effect upon the bladder was remarkable particularly at the lower concentrations. Tiropramide remarkably increased cAMP level but it had no effect on cGMP level in the bladder at the lower concentrations. Tiropramide at the lower concentrations did not affect cAMP and cGMP levels in the smooth muscles of the urethra, stomach and intestines. In the patients with neurogenic bladder dysfunction treated with tiropramide orally, the urine volume at first desire to void and maximum bladder capacity increased significantly, but the volume of residual urine did not significantly increase. In the healthy volunteers, there were no significant changes in urodynamic parameters. These findings indicate that tiropramide relaxes the urinary bladder smooth muscle via cAMP to increase the urinary bladder capacity.

Adult↗

PubMedDate not supplied

Selective serotonin-reuptake inhibitors: an update.

Selective serotonin-reuptake inhibitors (SSRIs), including fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram, represent an important advance in the pharmacotherapy of mood and other disorders. They are chemically unrelated to tricyclic, heterocyclic, and other first-generation antidepressants. SSRIs are the treatment of choice for many indications, including major depression, dysthymia, panic disorder, obsessive-compulsive disorder, eating disorders, and premenstrual dysphoric disorder, because of their efficacy, good side-effect profile, tolerability, and safety in overdose, as well as patient compliance. A review of the literature was conducted using Medline and the terms "SSRIs," "fluoxetine," "sertraline," "paroxetine," "fluvoxamine," and "citalopram." Articles were limited to those published in English within the last 15 years. The search revealed that indications for antidepressants include unipolar depression, dysthymia, bipolar depression, treatment-resistant depression, depression in the medically ill, panic disorder, obsessive-compulsive disorder, eating disorders, social phobia, and premenstrual dysphoric disorder. One SSRI, fluoxetine, has demonstrated safety in pregnancy. Side effects of SSRIs include gastrointestinal disturbances, headache, sedation, insomnia, activation, weight gain, impaired memory, excessive perspiration, paresthesia, and sexual dysfunction.

Depressive Disorder↗

PubMed2002

[A case of idiopathic hypereosinophilic syndrome with hepatic involvement in a 5-year-old boy].

Idiopathic hypereosinophilic syndrome is defined as the presence of prolonged eosinophilia without an identifiable underlying cause and with evidence of end-organ dysfunction. The organs involved are the heart, bone marrow, nervous system, lungs, liver, skin, and gastrointestinal tract. Hepatic involvement is found in about 30% of patients of idiopathic hypereosinophilic syndrome. It occurs rarely in infants and children. In this report, we experienced one case of idiopathic hypereosinophilic syndrome with hepatic involvement in a 5-year-old boy who complained of intermittent fever and right upper quadrant abdominal pain. An abdominal ultrasound examination revealed an ill-defined low-echoic lesion in the liver. Pathologic findings of a biopsy specimen clearly showed the infiltration of eosinophils in the liver. Laboratory data disclosed absolute eosinophilia. There was no evidence of allergic disease or parasitic infestation.

Child, Preschool↗

PubMed1990

Management of uremic bleeding.

The pathogenesis, clinical manifestations, and management of uremic bleeding are discussed, and the role of pharmacologic intervention in the treatment of this disorder is emphasized. Care of the patient with uremia is frequently complicated by spontaneous, life-threatening bleeding episodes. Although not completely elucidated, this bleeding tendency may be associated with ineffective binding of the von Willebrand Factor (a component of factor VIII) to platelet membranes, acquired storage-pool deficiency, and anemia. Uremic patients may develop a number of clinical manifestations, including epistaxis, purpura, and bleeding from the gastrointestinal tract. Dialysis, while frequently effective for the short term, does not completely correct platelet dysfunction. Red-blood-cell transfusions may partially reduce bleeding time; however, their use places the patient at risk for viral infection. Cryoprecipitate is often used in acute situations because of its short onset of action. Desmopressin is likewise effective when an immediate effect is desired. Conjugated-estrogen therapy appears beneficial for patients in whom a long-lasting effect is desired. Management of uremic bleeding may include dialysis, red-blood-cell transfusions, cryoprecipitate, desmopressin, and conjugated estrogens. Adverse effects, particularly the risk of viral infection, as well as duration of action, must be considered in therapy selection.

Blood Transfusion↗

PubMed1982

[FT-207 maintenance therapy of malignant gynecologic cancer].

Maintenance treatment with FT-207 was applied to 92 patients with uterine cancers after initial treatments were performed. Daily dosage of FT-207 was either 600 or 800 mg and the drug was administered orally. The duration of 6 months and the total dosage of 100 g were proposed as administration schedule and 34 patients (37%) received this regimen. Side effects during the treatment were observed in 35 cases (38%). Gastrointestinal disturbance was most frequently observed and other side effects included myelosuppression, general fatigue, hepatic dysfunction and skin toxicities. There were no serious side effects, the treatment was continued in most patients and was interrupted only in 7 cases (8%). In the cases of recurrence or advanced cancer, however, the side effect was the predominant cause for interruption of administration. As for the antitumor effect of the treatment, a survival rate of the patients with cervical cancer of early stages was evaluated. Three-year survival rate in the treatment group was higher comparing to the one reported hitherto.

Antineoplastic Agents↗

PubMed1996

Nonulcer dyspepsia: pathophysiology update.

The condition remains poorly defined-it may represent several disorders that share symptoms. The search for a cause is shifting from infection, inflammation, and acid/peptic mucosal damage to dysmotility and CNS dysfunction.

Anorexia Nervosa↗