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PubMed1993

[The efficacy of intra-arterial infusion chemotherapy in patients with non-resectable liver metastasis from colorectal cancer--a randomized study comparing FAM versus FEM].

The efficacy of FAM (5-FU, ADM, MMC) chemotherapy was compared with that of FEM (5-FU, EPIR, MMC) chemotherapy, in which the EPIR dose was about 1.3 times the ADM dose, by hepatic arterial infusion. Twenty-one patients with unresectable hepatic metastasis from colorectal cancer were the subjects of this multi-institutional randomized study. The response rate in evaluable 15 patients was 0% (0/6) in FAM group and 22% (2/9) in FEM group, with a 50% survival time of 15.3 months in FAM group and 15.1 months in FEM group. The major toxicities were gastrointestinal, together with hepatic dysfunction, both of which were not serious. Total incidence of > or = grade 2 toxicities was 50% (3/6) in FAM group and 80% (8/10) in FEM group. There was no statistical difference between the two groups in response rate, 50% survival time and toxicities. The clinical results of FAM and FEM were therefore considered equal, and an expected improvement in efficacy by increasing the EPIR dose was not confirmed. However, two patients in FEM group showed an objective response not observed in FAM group; one of them showed CR and survived about 3 years. These findings seem to suggest the efficacy of FEM hepatic arterial infusion chemotherapy for treatment of unresectable hepatic metastasis from colorectal cancer.

Adult↗
PubMed2006

Oral dimethyl sulfoxide for systemic amyloid A amyloidosis complication in chronic inflammatory disease: a retrospective patient chart review.

BACKGROUND: Amyloid A amyloidosis is an obstinate disease complication in chronic inflammatory disease, and there are few effective therapies. The objective of this study was to investigate the effect of oral dimethyl sulfoxide (DMSO) on amyloid A amyloidosis. METHODS: Fifteen secondary amyloid A amyloidosis patients (4 men, 11 women; age, 23-70 years) were treated with DMSO between 1995 and 2003. DMSO was administered orally in all patients at a dose of 3-20 g/day. The clinical symptoms together with the renal and gastrointestinal functions were evaluated before and after treatment. RESULTS: Among the 15 patients, amyloid A amyloidosis was a complication of rheumatoid arthritis (RA) in 10, of Crohn's disease in 4, and of Adult Still's disease in 1. Nine cases mainly involved the kidney, with renal dysfunction and proteinuria, five mainly involved the gastrointestinal tract, with protein-losing gastroenteropathy and intractable diarrhea, and one involved both gastrointestinal and renal amyloidosis. DMSO treatment was successful in 10 (66.7%) of the 15 patients (RA, 6/10; Crohn's disease, 4/4; Adult Still's disease, 0/1). Eight weeks of DMSO administration improved the renal function and proteinuria in five out of ten renal amyloidosis patients, but had no effect on those patients with severe and/or advanced renal dysfunction. With regard to gastrointestinal amyloidosis, gastrointestinal symptoms, including diarrhea and protein-losing gastroenteropathy, were improved in six patients. No serious side effects were encountered with the DMSO treatment. CONCLUSIONS: Oral administration of DMSO is an effective treatment for amyloid A amyloidosis, especially for gastrointestinal involvement and the early stage of renal dysfunction.

Administration, Oral↗
PubMed2002

Autonomic nerve dysfunction in pathologically obese patients.

BACKGROUND: Obese patients frequently present clinical symptoms related to gastrointestinal motility alterations and autonomic nervous system dysfunction. AIM: To evaluate the possible correlation between cardiovascular autonomic nervous dysfunction and oesophageal motility in pathologically obese patients. PATIENTS AND METHODS: Enrolled in the study were 22 patients with a body mass index of 45.72 +/- 7.48 and 10 control subjects, all within 20% of their ideal weight. Oesophageal motility was measured by stationary manometry and scintigraphic transit. Tests for the evaluation of autonomic nervous system were: Valsalva ratio, deep breathing, sustained handgrip, sudormotor axon reflex test and spectral analysis of the variability of R-R interval. RESULTS: The mean pressure of oesophageal peristaltic waves in patients and controls was 39.36 +/- 14 mmHg and 73 +/- 12 mmHg, respectively The scintigraphic mean transit time was 22.96 +/- 16.26 seconds in patients and 10.23 +/- 16.26 seconds in controls (p < 0.001). Spectral analysis of the variability of the R-R interval showed an increase in the parasympathetic component both in the lying and standing position compared to controls. The other autonomic nervous system function tests showed no significant difference between obese patients and controls. CONCLUSIONS: These results suggest that obese patients present a reduction of oesophageal transit and autonomic nervous system dysfunction albeit no direct correlation was found between these phenomena.

Adult↗
PubMed1998

Effects of therapy with nifedipine GITS or atenolol on mental stress-induced ischemic left ventricular dysfunction.

OBJECTIVES: We sought to determine the effect of nifedipine gastrointestinal therapeutic system (GITS) or atenolol on ischemic left ventricular dysfunction induced by mental stress. BACKGROUND: The efficacy of conventional antianginal therapy in preventing myocardial ischemia induced by mental stress is unknown. METHODS: Nifedipine GITS, atenolol and placebo were administered to 15 subjects with stable angina in a double-blind crossover trial. Subjects underwent a series of mental stressors at the end of each treatment. Radionuclide ventriculography was performed at baseline and at peak mental stress. Other measured variables included time to ischemia on exercise treadmill testing, ischemia on 48-h ambulatory electrocardiogram (ECG) monitoring, and resting and mental stress-induced levels of plasma catecholamines, tissue plasminogen activator antigen, plasminogen activator inhibitor-1 and platelet aggregability. RESULTS: Mental stress resulted in a significant increase in plasma epinephrine and norepinephrine levels during each treatment phase. Atenolol therapy was associated with lower baseline and postmental stress rate-pressure product compared with nifedipine or placebo. Therapy with either nifedipine GITS or atenolol prevented the development of wall-motion abnormalities and the decline in regional ejection fraction (EF) in the segment with the largest deterioration in wall motion during placebo therapy. Both medications prevented the decrease in global EF in subjects who demonstrated at least a 5% fall in global EF on placebo therapy. No therapy exerted a statistically significant benefit on exercise performance or frequency of ischemia during ambulatory ECG monitoring. CONCLUSIONS: Both nifedipine GITS and atenolol are effective at preventing mental stress-induced wall-motion abnormalities, although the mechanisms may be different.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Gastrointestinal consequences of left ventricular assist device placement.

Left ventricular assist devices effectively improve hemodynamic function and reverse renal and hepatic dysfunction; however, their effects upon the gastrointestinal (Gl) system have not been addressed. We evaluated Gl function in 27 left ventricular assist device recipients using interviews, Gl contrast studies, endoscopy, and 99mTc sulfur colloid studies of esophageal transit and gastric emptying. While on left ventricular assist device support (mean duration of 84 days), 19 patients reported early satiety and/or nausea, and 1 was unable to tolerate oral intake. Esophageal transit time (normal, < 10 sec) was borderline slow at 14 +/- 4 (mean +/- standard error of the mean) and gastric emptying (normal < 90 min) was prolonged (range of 106-506 min, mean = 283 +/- 69 min). In a 1-38 month follow-up, gastric function subjectively improved in all. Six patients had intraperitoneal device placement. One died of aspiration pneumonia secondary to small bowel obstruction, and one had prolonged inability to tolerate oral intake, which required feeding jejunostomy tube placement. The 21 patients with pre peritoneal placement of the device did not require Gl operative interventions and had no catastrophic Gl events; they had mild to no Gl complaints. Pre peritoneal placement may mitigate early satiety and obviate serious Gl complications.

Digestive System Physiological Phenomena↗
PubMed1981

Myoelectric control of gastrointestinal and biliary motility: a review.

The movement of ingested food and secretions through the gastrointestinal and its appendages depends on a highly integrated and coordinated response of the smooth muscle contained within the wall of the gut. This review will consider, in detail, the various myogenic factors that contribute to the usual aboral propulsion of the gastrointestinal contents. The role of myoelectrical complexes as represented by slow waves and spike potentials are emphasized, for they appear to play a central role in the initiation of sphincter function and gastrointestinal peristalsis. The myoelectric control of the sphincter of Oddi is discussed in relationship to gastroduodenal motility, since disturbances in this finely modulated sphincter may lead to biliary-pancreatic dysfunction and symptoms of upper gastrointestinal disease.

Animals↗
PubMed1998

Sexual dysfunction in patients with irritable bowel syndrome and non-ulcer dyspepsia.

The prevalence and type of sexual dysfunction in patients with functional gastrointestinal (GI) disorders involving the upper (functional dyspepsia) or lower GI tract (irritable bowel syndrome) were studied in 683 patients seen at a tertiary referral center and a comparison group of 247 community volunteers. Associations between sexual dysfunction and type and severity of GI symptoms, and psychological symptoms were examined. All subjects were evaluated with a validated bowel syndrome questionnaire, which included questions about sexual function. Psychological symptom severity was assessed by SCL-90R. The prevalence of self-reported sexual dysfunction in patients with functional GI disorders was 43.3% and did not differ by gender, age stratification or disease subtype: irritable bowel syndrome (IBS); non-ulcer dyspepsia (NUD), and IBS + NUD. In the comparison subjects without IBS symptoms and those with IBS symptoms but not seeking health care (IBS non-patients), the reported sexual dysfunction prevalence was significantly lower (16.1 and 24.4%, respectively, p < 0.005). Decreased sexual drive was the symptom most commonly reported by both male (36.2%) and female (28.4%) patients. Dyspareunia was reported by 16.4% of females and 4% of males with IBS, but was rarely observed in patients with NUD. Report of sexual dysfunction was positively associated with perceived GI symptom severity, but not with psychological symptom severity. Sexual dysfunction should be incorporated into the quality-of-life assessment of patients with functional GI disorders and addressed in future outcome studies.

Adult↗
PubMed2004

Molecular basis of functional gastrointestinal disorders.

There are a number of abnormalities of gastrointestinal function, including sensory and motor dysfunction, which are believed to play a role in the manifestation of symptoms in patients with functional gastrointestinal disorders (FGID). In addition, there is a remarkable psychiatric comorbidity. Family and twin studies have provided strong evidence for a clustering of FGID in families and an increased concordance in monozygotic compared to dizygotic twins. This points towards the role of one or more hereditary (genetic) factors. Considering these disorders of function and the psychiatric comorbidity, polymorphisms of adrenergic, opioidergic or serotonergic receptors as well as G-protein beta3 (GNB3) subunit gene polymorphisms (C825T) and polymorphisms of 5-HT transporter genes are suitable causes. In addition, mediators or regulators of mucosal inflammation may trigger events that ultimately result in the manifestation of FGID. Thus, relevant polymorphisms of genes with immunmodulating and/or neuromodulating features (OPRM1, IL-4, IL-4R, TNFalpha) may also play a role in the manifestation of FGIDs.

Animals↗
PubMed1990

The role of intestinal barrier failure and bacterial translocation in the development of systemic infection and multiple organ failure.

Traditionally, evaluation of intestinal function has been limited largely to monitoring gastric pH and intestinal motility. This clinical approach has led clinicians to equate normal intestinal motility with normal intestinal function and to assume that if stress-induced gastric bleeding can be prevented, all will be well. However, it is becoming increasingly clear that the gastrointestinal tract is not a passive organ and that intestinal dysfunction is not limited to ileus and upper gastrointestinal bleeding. Instead, the gastrointestinal tract is recognized as having important endocrine, metabolic, immunologic, and barrier functions, as well as its traditional role in nutrient absorption. Over the last 5 years, there has been a resurgence of interest in the role of intestinal barrier failure in the development of systemic infection and multiple organ failure in the critically ill or injured patient.

Bacteria↗
PubMed1990

Colostomy as treatment for complications of spinal cord injury.

We reviewed our experience with colostomy performed in 20 spinal cord injury (SCI) patients to determine the effectiveness and safety of colostomy when it is performed for a late complication of SCI. Objective evaluation of gastrointestinal function, ie, colonic transit time and anorectal manometry, was performed in six patients with chronic gastrointestinal complaints to identify the site and severity of bowel dysfunction. Twelve patients had colostomy performed for chronic gastrointestinal problems, seven as an adjunct in the treatment of perineal pressure ulcers, and one for rectal cancer. When patients with difficult bowel evacuation or incontinence were considered, colostomy reliably simplified bowel care, relieved abdominal distention, and prevented fecal incontinence. The amount of time spent on bowel care decreased from an average of 98.6 min/day to 17.8 min/day (p less than .05) after colostomy. When performed as an adjunct in the treatment of pressure ulcers, colostomy provided a dry, clean environment, and seven of seven ulcers healed. Colostomy was well accepted by all patients; all patients with chronic gastrointestinal complaints reported that colostomy improved the quality of their lives. Objective testing differentiated between failure of the colon to adequately transport material to the rectum and inability to adequately evacuate the rectum. Testing was useful in choosing the level at which a colostomy was created, and, in one instance, it identified a specific syndrome (ischemic proctitis) which required colostomy.

Colostomy↗
PubMed1987

Chronic severe constipation. Prospective motility studies in 25 consecutive patients.

The purpose of this study was to determine the patterns of gastrointestinal and anal sphincter motility in 25 consecutive patients with severe constipation. Three patterns of abnormal motility were observed in 68% of the patients: (a) isolated anal sphincter dysfunction (20%), (b) a generalized disorder of gastrointestinal motility (24%), and (c) rectosigmoid dysfunction (24%). The remaining patients had either a previously unrecognized primary disorder leading to constipation or the irritable bowel syndrome. Duration of symptoms, laxative usage, or other historical features failed to distinguish each of the groups. Anal sphincter dysfunction was diagnosed by demonstrating impaired sphincter relaxation during rectal distention. Generalized motor disorders were diagnosed by demonstrating impaired colonic and esophageal function together with an abnormality in gastric emptying. Rectosigmoid dysfunction was manifest by an impaired rectosigmoid motor response to feeding without evidence of other organ dysfunction. These studies indicate that a high percentage of patients with more severe degrees of constipation have a serious but sometimes treatable disorder of bowel function, rather than the irritable bowel syndrome.

Adult↗
PubMedDate not supplied

Indomethacin disposition and indomethacin-induced platelet dysfunction in premature infants.

Indomethacin failed to produce permanent ductal closure in any of four premature infants with patent ductus arteriosus to whom the drug was given. Indomethacin half-lives measured in two premature infants were 21 and 24 hours, respectively, much longer than in full-term newborns or adults. Platelet function, as measured by platelet aggregation, was grossly abnormal for two to four days after indomethacin administration, normal values returning only by the ninth and tenth days. Gastrointestinal bleeding and transient renal dysfunction occurred in one infant. Measurement of plasma indomethacin concentrations in sick, low-birthweight infants could help guide indomethacin dose and dosage interval, prevent drug accumulation, and reduce toxicity. Further studies of potential toxicity seem to be indicated before instituting widespread indomethacin administration for ductal closure in premature infants.

Blood Platelet Disorders↗
PubMed1990

Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression.

A double-blind, placebo- and amitriptyline-controlled comparison study was performed to evaluate the antidepressant efficacy of sertraline, a specific serotonin uptake inhibitor. Patients with DSM-III-defined major depression randomly received either sertraline (N = 149), amitriptyline (N = 149), or placebo (N = 150) once daily for the 8-week study period. The mean final daily medication dose for the all-patients group was 145 mg and 104 mg for the sertraline- and amitriptyline-treatment groups, respectively. As measured by the Hamilton Rating Scale for Depression and the Clinical Global Impressions Scale, both the sertraline and amitriptyline treatment groups showed a significantly greater improvement from baseline (p less than or equal to .001) than the placebo group. The sertraline group had a higher proportion of gastrointestinal complaints and male sexual dysfunction than either the amitriptyline or the placebo group. The amitriptyline group showed a higher proportion of anticholinergic and sedative side effects and dizziness compared with patients who received either sertraline or placebo.

1-Naphthylamine↗
PubMed2004

Subfertility and gastrointestinal disease: 'unexplained' is often undiagnosed.

Subfertility can be more reliably explained and effectively treated with an improved understanding of the contribution of chronic medical disease to reproductive dysfunction. This review addresses several common gastrointestinal disorders which are increasingly implicated in infertility and early pregnancy loss: celiac disease, inflammatory bowel disease (ulcerative colitis and Crohn's disease), and hemochromatosis. Appreciating the reproductive impact of these comorbidities and their treatments enables clinicians to accurately counsel patients and to modify medical and fertility treatments based on etiology. Because unexplained infertility can represent the initial presentation of undiagnosed medical disease, considering these often-subclinical gastrointestinal disorders in the differential diagnosis of subfertility provides an opportunity not only to increase the probability of conception and uncomplicated pregnancy, but also to improve overall maternal health.

Celiac Disease↗
PubMed2006

Autonomic involvement in tick-borne encephalitis (TBE): report of five cases.

BACKGROUND: Tick-borne encephalitis (TBE) is a viral infection of the CNS with significant acute and long-term morbidity. Dysfunction of the autonomic nervous system may be a potentially harmful complication of TBE. MATERIAL AND METHODS: In a retrospective case series, 5 patients with acute TBE were evaluated for clinical signs of autonomic dysfunction and subject to autonomic testing. Heart rate variability (HRV) with 6 per minute deep breathing was performed between day 9 to 31 after onset of meningitis. Follow-up data were available in three cases. RESULTS: All patients showed clinical signs of autonomic dysfunction, including upper and lower gastrointestinal tract symptoms, orthostatic hypotension, and urinary retention. A reduced HRV was observed in 4 patients, with sustained sinus tachycardia in 2 of them. The minimum of the HRV was reached 9 to 20 days after onset of meningitis. In one patient, normalization of the HRV occurred within 3 months. CONCLUSION: Acute TBE can be associated with autonomic dysfunction including reduced HRV and tachycardia. Prospective studies are needed to analyze the incidence of autonomic dysfunction in TBE, and to clarify which patients have the highest risk for autonomic failure.

Aged↗
PubMed2000

[Specific cyclooxygenase-2 inhibitors. Basis and options of a pharmacotherapeutic concept].

The therapeutic and unwanted side effects of non-steroidal antiinflammatory drugs (NSAIDs) are attributable to inhibition of the cyclooxygenase (COX) enzyme which catalyzes the first step of the synthesis of prostanoids. In the early 1990s, COX was demonstrated to exist as two distinct isoforms. COX-1 is constitutively expressed as a 'housekeeping' enzyme in most tissues. In contrast, COX-2 can be upregulated by various proinflammatory agents, including endotoxin, cytokines and growth factors. Whereas many of the side effects of NSAIDs (e.g. gastrointestinal ulceration and bleeding, platelet dysfunctions) are due to a suppression of COX-1 activity, inhibition of COX-2-derived prostanoids facilitates the anti-inflammatory, analgesic and antipyretic effects of NSAIDs. Thus, the hypothesis that specific inhibition of COX-2 might have therapeutic actions similar to those of NSAIDs, but without causing the unwanted side effects, was the rationale for the development of specific inhibitors of the COX-2 enzyme as a new class of anti-inflammatory and analgesic agents with improved gastrointestinal tolerability. However, the simple concept that COX-2 is an exclusively proinflammatory and inducible enzyme cannot be supported any longer. Recently, COX-2 was shown to be also expressed under basal conditions in organs such as the ovary, uterus, brain, spinal cord, kidney and bone, suggesting that this isoenzyme may play a more complex physiological role than was expected. The present review assesses concept and molecular mechanism underlying specific COX-2 inhibition as well as indications, pharmakokinetics and unwanted side effects of the recently approved specific COX-2 inhibitors celecoxib and rofecoxib. Moreover, recent advances in COX-2 research, with particular emphasis on new insights into physiological functions of this isoenzyme will be discussed.

Animals↗