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At least 1,135 records · Page 63Linked to original sources
PubMed1986

Treatment of acute leukaemia with m-AMSA in combination with cytosine arabinoside.

A series of 46 patients with acute leukaemia were treated with amsacrine (m-AMSA) and cytosine arabinoside (ara-C). Complete remission (CR) was achieved in 15 of 38 (40%) patients with acute myelogenous leukaemia (AML) and 4 of 8 (50%) patients with acute lymphoblastic leukaemia (ALL). The CR rate was significantly higher (P less than 0.05) for the younger, previously treated patients with AML (9/16) than for the older previously untreated ones (6/22), because of higher treatment mortality in the latter group. Myelosuppression was prolonged and profound. Major nonhaematological toxicity affected the gastrointestinal tract (nausea, vomiting, mucositis, bleeding and ileus associated with severe diarrhoea). Many patients also developed reversible hepatic dysfunction and two elderly patients died of cardiac arrhythmia. Further trials of this combination are justified in patients with relapsed or resistant leukaemia, but for older patients dose reduction is recommended.

Aged↗
PubMed2004

A patient with a VEGF and endostatin producing gastrointestinal autonomic nerve tumour.

Tumour associated neovascularisation has been characterised as chaotic and insufficient. This report details the results of the analysis of angiogenic factors in tumour cyst fluid, pleural fluid, and blood from a patient with a gastrointestinal autonomic nerve tumour. The tumour produced vascular endothelial growth factor and endostatin in large quantities, which may explain the dysfunctional angiogenesis and tendency to bleeding seen in this tumour type.

Adult↗
PubMed2001

Comparative effects of mibefradil and nifedipine gastrointestinal transport system on autonomic function in patients with mild to moderate essential hypertension.

BACKGROUND: L-type dihydropyridine calcium channel blockers (CCBs) have been implicated in increased cardiovascular events in patients with hypertension, perhaps due to adverse effects on autonomic nervous system (ANS) function. Blockade of T-type calcium channels may limit ANS dysfunction by inhibition of T channel-mediated neuroendocrine effects. OBJECTIVE AND DESIGN: This double-blind, parallel group study compared the effect of nifedipine gastrointestinal transport system (GITS) (L-type CCB) versus mibefradil (T-type CCB) on ANS function in patients with mild-moderate essential hypertension. METHODS: Sixteen patients (10 male, 6 female; age 57.2 +/- 2.3 years), diastolic blood pressure (DBP) < 95 mmHg were randomized to nifedipine 30 mg daily or mibefradil 50 mg daily (2 weeks), then nifedipine 60 mg daily or mibefradil 100 mg daily (4 weeks). Sympathetic nervous system activity (SNSA) was assessed using norepinephrine kinetics. Parasympathetic nervous system activity (PSNA) was assessed from 24 h Holter recordings of heart rate variability (HRV). Non-invasive baroreflex sensitivity (BRS) provided integrated assessment of ANS. RESULTS: Patient groups were well matched at baseline. Achieved DBP was lower in patients treated with mibefradil compared with nifedipine, (83.4 +/- 1.7 versus 95.25 +/- 3.3 mmHg). There were no significant differences in SNSA and BRS between groups, however the root mean square of successive differences and high frequency power (HFP) were increased in mibefradil compared with nifedipine-treated patients [(+ 1.07 +/- 1.6 versus -3.36 +/- 1.2 ms, P < 0.05) and (+ 0.28 +/- 0.1 versus -0.23 +/- 0.1 ms2, P < 0.01), respectively]. Furthermore, Ln HFP/Ln total power was increased from week 0 to week 6 in the mibefradil-treated group, (0.71 +/- 0.02 versus 0.74 +/- 0.03, P = 0.046). CONCLUSION: No differences existed between effect of L- and T-type CCBs on SNSA and BRS. However, T-type CCBs increased PSNA, independent of achieved changes in heart rate.

Autonomic Nervous System↗
PubMed2000

Lack of correlation between failure of gut barrier function and septic complications after major upper gastrointestinal surgery.

OBJECTIVE: To determine the influence of abnormal gut barrier function on the risk of septic complications in patients undergoing major resectional surgery for upper gastrointestinal cancer. SUMMARY BACKGROUND DATA: A failure of the gut mucosal barrier to exclude bacteria and endotoxin from the portal and systemic circulation is incriminated in the development of sepsis and multiple organ failure. Although the experimental data is compelling, corroborative evidence from studies in humans is sparse. This study attempted to correlate both preoperative gut barrier dysfunction and the pattern of change after surgery with septic outcome. METHODS: Sixty-eight patients undergoing curative resectional surgery for upper gastrointestinal cancer were monitored for 30-day septic morbidity (intraabdominal abscesses/empyema and pneumonia). Intestinal permeability, serum IgM and IgG anti-endotoxin antibodies (EndoCAb), and serum C-reactive protein were measured before surgery and on postoperative days 1 and 7. RESULTS: Increased intestinal permeability before surgery did not predict septic outcome. Major surgery was associated with increased intestinal permeability and evidence of endotoxin exposure. Comparing sepsis and nonsepsis groups, however, there was no significant difference in intestinal permeability, endotoxin exposure, and the acute phase response after surgery. CONCLUSIONS: This study demonstrates that gut barrier dysfunction occurs after surgery, but the magnitude of change does not differentiate patients in whom sepsis develops and those in whom it does not. Preoperative increased intestinal permeability had no predictive value for sepsis. This study failed to support the thesis that gut barrier dysfunction is directly linked to sepsis.

Acute-Phase Reaction↗
PubMed1995

Nitric oxide and active oxygen species in severe sepsis and surgically stressed patients.

To clarify how the kinetics of nitric oxide (NO) and active oxygen species are correlated with the occurrence of organ dysfunction in sepsis, the levels of monocyte-associated NO2, NO3, and active oxygen species were examined in severely septic patients with multiple organ dysfunction syndrome (group M; n = 5), and the results compared with those of postoperative patients who had undergone gastrointestinal surgery (group S; n = 5) and healthy volunteers (group C; n = 10). The production of NO2 and NO3 by monocytes was significantly higher in group M than in the other two groups, while the production of active oxygen species by monocytes was significantly higher in groups M and S, than in group C. A significant correlation between the production of NO2 and that of active oxygen species by monocytes was noted only in group M. These findings indicate that the simultaneous activation of NO and active oxygen species production by monocytes is a prerequisite for the onset of multiple organ dysfunction in severe sepsis.

Aged↗
PubMed1998

Review article: colonic sensorimotor physiology in health, and its alteration in constipation and diarrhoeal disorders.

AIM: To review the physiology of colonic motility and sensation in healthy humans and the pathophysiological changes associated with constipation and diarrhoea. SOURCE: Medline Search from 1965 using the index terms: human, colonic motility, sensation, pharmacology, neurohormonal control, gastrointestinal transit, constipation, diarrhoea and combinations of these. RESULTS: In health, the ascending and transverse regions of colon function as reservoirs to accommodate ileal chyme and the descending colon acts as a conduit; the neuromuscular functions and transmitters control colonic motility and sensation and play pivotal roles in disorders associated with constipation and/or diarrhoea. Disorders of proximal colonic transit contribute to symptoms in idiopathic constipation, diarrhoea-predominant irritable bowel syndrome and carcinoid diarrhoea. Colonic function in patients presenting with constipation is best assessed clinically by colonic transit time using radiopaque markers ingested orally. Measurements of colonic contractility are less useful clinically but they can help identify motor abnormalities including colonic inertia; in some patients with irritable bowel syndrome, abdominal pain, urgency and diarrhoea are temporally associated with high amplitude contractions, which originate in the proximal colon and traverse the distal conduit at very high propagation velocities. Visceral hypersensitivity contributes to the urgency and tenesmus in irritable bowel syndrome and inflammatory bowel disease. Colonic motility and sensation can be reduced by anticholinergic agents, somatostatin analogues and 5HT3 antagonists. CONCLUSION: Physiological and pharmacological studies of the human colon have provided new insights into the pathophysiology of colonic disorders, and offer possibilities of novel therapeutic approaches for constipation or diarrhoea associated with colonic motor or sensory dysfunction.

Colon↗
PubMed1980

Bacteremic infection and malnutrition in patients with solid tumors: investigation of host defense mechanisms.

Eighty-five patients with solid tumors without neutropenia were studied in order to determine host characteristics associated with bacteremic infection. Twenty patients without neoplastic disease who had bacteremia served as controls. Bacteremia frequently occurred in patients with tumors of the gastrointestinal and urinary tract, who were over 51 years of age, and had evidence of malnutrition. Peripheral blood lymphocyte dysfunction in vitro was commonly noted in infected patients with cancer. Polymorphonuclear leukocyte (PMNL) dysfunction was common in older bacteremic patients with and without cancer. The PMNL abnormality appeared to be cellular, it was not corrected with use of pooled normal serum, and was manifested by poor uptake of the assay organisms.

Adult↗
PubMed1996

[Clinical evaluation of TPA-assay kit using monoclonal antibodies].

The clinical utility of a newly-developed radioimmunometric assay kit for tissue polypeptide antigen (TPA) was evaluated focusing on the serum diagnosis of gastrointestinal cancers. Serum TPA concentrations of normal subjects, patients with various benign and gastrointestinal malignant diseases were measured using this kit. From the TPA concentrations of normal subjects, the cut-off value was determined to be 70 U/l, which was 40 U lower than the previous kit. It showed a fairly high false positive rate in patients with liver dysfunction, so care should be taken in evaluating patients with liver disorders. It showed high positive rates in patients with wide range of gastrointestinal cancers, confirming the wide-range usefulness of this assay. Cancer patients with advanced stages and recurrences showed a higher positive rate and also higher serum TPA concentrations than in the early stages, indicating that this TPA assay is especially useful in the evaluation of therapeutic effects and in the detection of recurrent diseases.

Antibodies, Monoclonal↗
PubMed1978

Misleading noninvasive signs of Bjork--Shiley mitral valve dysfunction.

Three months after receiving a Bjork--Shiley mitral valve prosthesis, a patient experienced acute gastronintestinal bleeding associated with heavy alcohol intake and poor compliance with oral anticoagulation therapy. As a result of the gastrointestinal bleeding, treatment with warfarin was discontinued. Ten months later, the patient presented with symptoms of transient cerebral ischemia. Despite demonstrated loss by phonocardiography of the previously well-recorded opening click and echocardiographic suggestion of a thrombosed prosthetic mitral valve, no thrombosis or dysfunction of the prosthetic mitral valve was revealed at reoperation.

Diagnosis, Differential↗
PubMed2003

Opioid-induced bowel dysfunction: pathophysiology and potential new therapies.

Opioid treatment for postoperative or chronic pain is frequently associated with adverse effects, the most common being dose-limiting and debilitating bowel dysfunction. Postoperative ileus, although attributable to surgical procedures, is often exacerbated by opioid use during and following surgery. Postoperative ileus is marked by increased inhibitory neural input, heightened inflammatory responses, decreased propulsive movements and increased fluid absorption in the gastrointestinal tract. The use of opioids for chronic pain is characterised by a constellation of symptoms including hard dry stools, straining, incomplete evacuation, bloating, abdominal distension and increased gastroesophageal reflux. The current management of opioid-induced bowel dysfunction among patients receiving opioid analgesics consists primarily of nonspecific ameliorative measures. Intensive investigations into the mode of action of opioids have characterised three opioid receptor classes -mu, delta and kappa- that mediate the myriad of peripheral and central actions of opioids. Activation of mu-opioid receptors in the gastrointestinal tract is responsible for inhibition of gut motility, whereas receptors in the central nervous system mediate the analgesic actions of opioids. Blocking peripheral opioid receptors in the gut is therefore a logical therapeutic target for managing opioid-induced bowel dysfunction. Available opioid antagonists such as naloxone are of limited use because they are readily absorbed, cross the blood-brain barrier, and act at central opioid receptors to reverse analgesia and elicit opioid withdrawal. Methylnaltrexone and alvimopan are recently developed opioid antagonists with activity that is restricted to peripheral receptors. Both have recently shown the ability to reverse opioid-induced bowel dysfunction without reversing analgesia or precipitating central nervous system withdrawal signs in non-surgical patients receiving opioids for chronic pain. In addition, recent clinical studies with alvimopan suggest that it may normalise bowel function without blocking opioid analgesia in abdominal laparotomy patients with opioid-related postoperative ileus.

Constipation↗
PubMed1993

Experience with 1509 patients undergoing thoracoabdominal aortic operations.

PURPOSE: The purpose of this study was to retrospectively identify variables associated with early death and postoperative complications in patients undergoing thoracoabdominal aortic operations. METHODS: The data on 1509 patients who underwent 1679 thoracoabdominal aortic repairs between 1960 and 1991 were retrospectively reviewed. The median age was 66 years (range 1.5 years to 86 years), and aortic dissection was present in 276 (18%) patients. The extent of the first repair performed included 378 (25%) type I (proximal descending to upper abdominal aorta), 442 (29%) type II (proximal descending aorta to below the renal arteries), 343 (23%) type III (distal descending and abdominal aorta), and 346 (23%) type IV (most of the abdominal aorta). The median total aortic clamp time was 43 minutes. RESULTS: The 30-day survival rate was 92% (1386/1509) for the 30-year period. On multivariate analysis the preoperative and operative variables associated with death included (p < 0.05) increasing age, preoperative creatinine level, concurrent proximal aortic aneurysms, coronary artery disease, chronic lung disease, and total aortic clamp time. When the postoperative variables were also included in the stepwise logistic regression model, then in addition, cardiac complications, stroke, kidney failure, and gastrointestinal hemorrhage became significant (p < 0.05). The overall incidence of paraplegia or paraparesis was 16% (234/1509). By use of stepwise logistic regression analysis, the significant predictors (p < 0.05) of paraplegia or paraparesis developing were total aortic clamp time, extent of aorta repaired, aortic rupture, patient age, proximal aortic aneurysm, and history of renal dysfunction. Kidney failure (postoperative creatinine level > 3 mg/dl or dialysis) occurred in 18% (269/1509) of patients; dialysis was required in 9% (136/1509). Gastrointestinal complications manifested in 7% (101/1509) of patients. CONCLUSION: Although the survival rate has improved, paraplegia/paraparesis and kidney failure continue to be vexing problems that require further research.

Adolescent↗
PubMed1999

Gastrointestinal manifestations in children with cerebral palsy.

We describe the prevalence and nature of gastrointestinal (GI) symptoms in 58 children affected by cerebral palsy (range: from 6 months to 12 years of age) referred to a pediatric neurology outpatient clinic. In each patient we assessed (GI) symptoms and defined the associated GI functional or structural abnormalities. Furthermore, we tried to correlate the type of GI dysfunction with findings on computed tomography (CT) or magnetic resonance imaging (MRI) of the brain. Our results showed that 92% of children with cerebral palsy had clinically significant gastrointestinal symptoms. Swallowing disorders were present in 60% of patients, regurgitation and/or vomiting in 32%, abdominal pain in 32%, episodes of chronic pulmonary aspiration in 41% and chronic constipation in 74%. Dysfunction of the oral and/or pharyngeal phase of swallowing was found in 28 of 30 (93%) patients with swallowing disorders. Of the 45 patients with symptoms suggesting gastroesophageal reflux, 41 (91%) had an abnormal pH-monitoring and/or esophagitis. Furthermore, a significant delay in the scintigraphic gastric emptying of liquids was found in 12 of 18 patients (67%) and an abnormal esophageal motility in 11 of the 18 (61%) investigated patients. In 25 patients with chronic constipation evaluation of colonic transit showed a delay at level of the proximal segments of the colon in 13 (52%), at level of the left colon and rectum in 9 (36%) and in 3 (12%) at level of the rectum only. Computed tomography and/or magnetic resonance imaging were normal in 5 (9%) and abnormal in 53 (91%) of the 58 children with cerebral palsy. No GI symptom was significantly associated with any kind of abnormal neuroimaging. In conclusion, children with cerebral palsy exhibited diffuse GI clinical manifestations, mostly due to disorders of GI motility. The GI symptoms seemed not to be related to any specific finding on CT or MRI of the brain.

Adult↗
PubMed1975

Minimising the risks of treating acute allograft rejection.

The risks of treating allograft rejection are primarily related to high-dose steroid therapy. To determine when the possible benefit of anti-rejection therapy might not justify the risks, we analysed 20 severe rejection (SAR) episodes for indices of reversibility. Prior renal function was similar in all patients. Ccr fell to 10 ml/min or less, but degree of renal dysfunction was not predictive of reversibility, nor were time since transplant, oliguro/anuria, proteinuria, or hypertension. The only consistent finding was that function began to improve in reversible rejection 3.8 +/- 1 days after beginning therapy. Our rejection treatment, based on this finding, is to use gram doses of IV prednisolone, up to three times in five to seven days. Among 41 patients with 45 grafts so treated, there was no fatality or gastrointestinal haemorrhage. Other complications (fistulae and/or infections) were related to total dose and frequency, to intensive therapy during severe renal dysfunction or to urinary leaks. Limitation of the period of high-dose steroid therapy was associated with reduced morbidity and mortality in renal allograft recipients.

Acute Disease↗
PubMed1986

Depression and functional bowel disorders in gastrointestinal outpatients.

Although depression has been linked with both the irritable bowel syndrome and non-organic abdominal pain, which are common in gastrointestinal outpatients, the prevalence of depression in most surveys of outpatient practice has been low. Use of the Beck Depression Inventory to screen new referrals to a general medical and gastrointestinal clinic and to a minor surgical clinic showed that 50 of 100 medical patients were rated as having some degree of depression, compared with 14 of 75 (19%) of the surgical patients in whom abdominal pain and bowel dysfunction were rare (X2 = 9.6, p less than 0.01). In the medical clinic no organic disorder was detected in 64% of the depressed patients, the majority of whom presented with abdominal pain or irritable bowel syndrome. Depression was significantly commoner in this group of patients than in those with other conditions, (X2 = 6.63, p = 0.01). That depression is common in gastrointestinal outpatients is not always appreciated and its symptoms should be sought in all patients with bowel dysfunction and chronic abdominal pain.

Adolescent↗
PubMed1999

[Headache syndrome in children with autonomic dysfunction].

Morbidity analysis of 350 children from somatic hospital has revealed clinical manifestations of autonomic dystonia syndrome (ADS) in 36% of the cases in the form of gastrointestinal, cardiovascular disorders, headache syndrome, etc. It was found that in the patients with a prevalence of vagotonia clinical manifestations of ADS rose at earlier age and differed by more variety than in combined and sympathotonic types of autonomic homeostasis. Headache syndrome was rather frequent in ADS and was observed in 35% of the patients. In children with vagotonic type of ADS, a headache syndrome presented most frequently (43%) in the forms of migraine and headache of tension (HAT). Clinical manifestations of autonomic dystonia were more pronounced in children with HAT. Meanwhile, autonomic dysfunction had hereditary origin and was milder in periods between the attacks in cases of migraine.

Adolescent↗
PubMed2000

COX-2-Specific inhibitors--the emergence of a new class of analgesic and anti-inflammatory drugs.

The prostaglandin series of bioactive compounds is formed by the interaction of two distinct but related enzymes, cyclo-oxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). COX-1 is a constitutive form which is present mainly in the gastric mucosa, kidney and platelets. COX-2 is mainly an inducible form, although also to some extent present constitutively in the CNS, the juxtaglomerular apparatus of the kidney and in the placenta during late gestation. Both isoforms contribute to the inflammatory process, but COX-2 is of considerable therapeutic interest as it is induced, resulting in an enhanced formation of prostaglandins, during acute as well as chronic inflammation. Conventional NSAIDs inhibit both isoforms to a similar extent and in an approximately equal dose and concentration range. The two recently developed and clinically available selective COX-2 inhibitors, celecoxib and rofecoxib, are about 100-1000 times more selective on the COX-2 than on the COX-1 isoform. In Europe rofecoxib is today indicated for the symptoms and signs of osteoarthritis, whereas celecoxib is indicated for both osteoarthritis and rheumatoid arthritis. The major clinical interest of these drugs has been related to the lower incidence of gastrointestinal bleeding which, with the conventional COX-1/COX-2 agents has been a source of hospitalisation, disablement and death, especially in the elderly. Clinical trials have convincingly demonstrated that celecoxib and rofecoxib in clinical use induce very few gastrointestinal complications compared to conventional and non-selective NSAIDs. However, the well known contraindications for NSAIDs, such as late pregnancy, aspirin-induced asthma, congestive heart failure and renal dysfunction, will so far apply also to the COX-2 inhibitors. Compared to the traditional and non-selective NSAIDs, COX-2 inhibitors may provide an insight into additional therapeutic areas, such as gastrointestinal cancer and dementia, where the potential relevance to COX-2 mechanisms are currently being explored and clinical trials being performed. With the rapid clinical acceptance of celecoxib and rofecoxib, knowledge about their clinical usefulness in various inflammatory disease states and pain disorders is increasing. For the many patients suffering from such conditions, the selective COX-2 inhibitors are likely to become a significant addition to the therapeutic arsenal of analgesic and anti-inflammatory drugs.

Analgesics↗