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PubMed2000

Gene expression of the phosphodiesterases 3A and 5A in human corpus cavernosum penis.

OBJECTIVE: The following study was performed to evaluate the importance of phosphodiesterases 3A (PDE3A) and 5A (PDE5A) for the regulation of penile smooth muscle tone. Furthermore, indications of side effects of specific inhibitors in certain tissues as well as of a possible relation between the level of PDE3A and PDE5A gene expression and erectile dysfunction should have been deduced from the results obtained. METHODS: Total ribonucleic acid was isolated from different human tissues (urogenital tract, gastrointestinal tract, cardiovascular system and central nervous system) and subjected to RTPCR analysis and Northern blotting using primers and probes specific for PDE3A and PDE5A. RESULTS: As shown by RT-PCR and Northern blotting, PDE3A and PDE5A mRNAs exhibit a distinct distribution throughout the tissues examined but were 2-fold higher in cavernous tissue than in all other tissues investigated. However, there were no significant differences in the levels of gene expression between the two subgroups of patients. CONCLUSIONS: Very high expression levels of PDE3A and PDE5A in human cavernous tissue underscore the physiological importance of these enzymes for the regulation of penile erection, emphasizing their therapeutical and pharmacological relevance. The distribution pattern of the mRNA for the isoenzymes PDE3A and PDE5A may explain the pharmacological effects as well as the side effects of milrinone and sidenafil.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2001

Irritable bowel syndrome: an update on therapeutic modalities.

Irritable bowel syndrome (IBS) is the most common condition that a physician faces in the GI clinic. Of the general population, 10 - 25% suffer from symptoms judged to be IBS. The negative impact of this disease includes not only pain, suffering and direct medical expenses but also significant social and job-related consequences. IBS can be the result of dysfunction in any part of the brain-gut axis: alterations in the CNS caused by psychological or other factors, abnormal gastrointestinal motility, or heightened visceral sensations. Diagnosis is based on either the Manning or Rome-II criteria. Education, reassurance and emotional support are the cornerstones of successful treatment. The mainstays of the current therapeutic approach continue to be: stress management strategies, dietary modification entailing addition of dietary fibre and pharmacotherapy. Pharmacotherapy is still limited to treating symptoms. Newer drugs that modulate motility or drugs that modulate visceral sensation may be useful in selected cases. Psychopharmacological agents are useful in the treatment of IBS, especially in those with psychological co-morbidity. Alternative therapies such as homeopathy, acupuncture, special diets, herbal medication and several forms of psychological treatments and hypnotherapy are sought by many patients and are now being offered by physicians as treatment options, either alone or in conjunction with conventional forms of therapy in patients with refractory symptoms.

Acupuncture Therapy↗

PubMed2004

Safety issues regarding colonic cleansing for diagnostic and surgical procedures.

There are various methods available to cleanse the colon in preparation for diagnostic and surgical procedures. The popular options are diet and cathartic regimens, gut lavage and phosphate preparations. Each method has its own unique characteristics and safety profile. Diet and cathartic regimens are based on traditional methods of colonoscopy preparation and remain an acceptable and safe alternative for patients unwilling or unable to tolerate other bowel preparations. Gut lavage methods involve ingestion of 2-4L of osmotically balanced solutions containing polyethylene glycol, which have been shown to be safe and effective for colon cleansing, including for special patient populations with cardiac, renal or hepatic dysfunction. Phosphate preparations have also been shown to be safe and effective for colon cleansing and are generally better tolerated than counterpart gut lavage solutions. However, this method has safety concerns for some patients with cardiac, renal and hepatic dysfunctions.

Cathartics↗

PubMed1979

Radiography of glycogen storage diseases.

Sixty-three patients with glycogen storage disease were evaluated. Findings on plain film examinations, excretory urography, barium gastrointestinal studies, ultrasonography, and angiography were categorized by type of glycogen storage disease. In type I findings include hepatomegaly with hepatic dysfunction, renomegaly with an increased incidence of renal calculi, and osteopenia with various associated osseous abnormalities. These changes were less pronounced in types III, IV, and VI. Type II displayed either cardiac or skeletal muscle glycogen deposition. Correlation with postmortem examination in 14 individuals is given.

Adolescent↗

PubMedDate not supplied

Stress ulcer prophylaxis: the case for a selective approach.

Although stress-related mucosal damage is common (and potentially serious) in critically ill patients, the risk of clinically significant gastrointestinal bleeding appears to be confined to patients with certain factors: mechanical ventilation, coagulopathy, multiple trauma, increased intracranial pressure, and multiorgan dysfunction. Because prophylactic therapy also poses risks, we advocate reserving it for patients in these high-risk groups.

Anti-Ulcer Agents↗

PubMed1992

The irritable bowel syndrome: mechanisms and a practical approach to management.

OBJECTIVE: To develop a practical strategy that facilitates the management of patients with the irritable bowel syndrome (IBS). STUDY SELECTION AND DATA EXTRACTION: Review of the pertinent literature published in major English-language journals for the last 25 years, describing the pathophysiology and treatment of subgroups of patients with IBS. RESULTS: A stepwise approach for practical management of patients with suspected IBS is identified. The first step includes a combination of positive diagnosis of symptoms with limited investigations to exclude underlying structural or biochemical disorders. In the second step, therapeutic trials focus on alleviating the predominant symptoms. For patients with intractable symptoms, the third step combines novel tests to assess altered function and therapeutic trials to correct the dysfunction identified in the individual patient. CONCLUSIONS: A practical approach has been developed for management of IBS. It is based on advances in our understanding of the mechanisms resulting in IBS and on targeting therapy to correct the dysfunctions in these patients.

Colonic Diseases, Functional↗

PubMed1996

Unexplained chest pain: the hypersensitive, hyperreactive, and poorly compliant esophagus.

OBJECTIVE: To determine whether neuromuscular dysfunction of the esophagus causes chest pain in patients in whom no disease is found on cardiac work-up, upper gastrointestinal endoscopy, esophageal manometry, and 24-hour pH studies. DESIGN: Prospective study. SETTING: Tertiary referral center. PATIENTS: 24 consecutive patients and 12 healthy controls. MEASUREMENTS: A new technique, impedance planimetry, was used to measure the sensory, motor, and biomechanical properties of the human esophagus. The impendance planimeter, which consists of a probe with four ring electrodes, three pressure sensors, and a balloon, simultaneously measures intraluminal pressure and cross-sectional areas. This allows calculation of the biomechanical variables of the esophageal wall. RESULTS: Stepwise balloon distentions from 5 to 50 cm H2O induced a first sensation at a mean pressure (+/- SD) of 15 +/- 9 cm H2O in patients and 30 +/- 11 cm H2O in controls (P < 0.001). Moderate discomfort and pain were reported by 20 of 24 patients (83%) at 26 +/- 9 cm H2O and at 36 +/- 9 cm H2O, respectively, but by none of the controls (P < 0.001). Typical chest pain was reproduced in 20 of 24 patients (83%). In patients, the reactivity of the esophagus to balloon distention was greater (P = 0.01), the pressure elastic modulus was higher (P = 0.02), and the tension-strain association showed that the esophageal wall was less distensible (P = 0.02). Distention excited tertiary contractions and secondary peristalsis at a lower threshold of pressure (P = 0.05) and with a higher motility index in patients than in controls (P = 0.04). CONCLUSION: In patients with chest pain and normal cardiac and esophageal evaluations, impedance planimetry of the esophagus reproduces pain and is associated with a 50% lower sensory threshold for pain, a 50% lower threshold for reactive contractions, and reduced esophageal compliance.

Adult↗

PubMed1990

Radiation induced changes in the blood capillaries of rat duodenal villi: a corrosion cast, light and transmission electron microscopical study.

Disturbances of gastrointestinal function are an important limiting factor in radiotherapy of the abdominal and pelvic regions. The pathogenesis of radiation induced intestinal dysfunction is not completely understood, although the intestinal mucosa has been shown to respond to irradiation by a progressive reduction in villous size. Since blood vessels in other organs have been implicated in the initiation of post-irradiation changes, the present study examines the response of villous blood vessels to an X-ray dose of 10 Gy after 3 days. Vascular corrosion casts and light and transmission electron microscopy (TEM) were used to study the post-irradiation vascular response. In control and sham-irradiated animals, the villous plexus was fountain-like: an arteriole entered the villous base and divided apically into two terminal branches. Villous capillaries apparently derived from the terminal branches, and united to form venules. In capillary loops the vertical inter-capillary distance was greater than the horizontal inter-capillary distance. After irradiation, the vessels became tortuous and the plexus was compressed apico-basally, shown by a decrease in the vertical inter-capillary distance. The capillary luminal diameter, as measured on resin semi-thin sections, was significantly increased. TEM showed that the endothelium was irregular and there was evidence of plasma leakage. These results suggest that villous damage seen after irradiation can include changes in the villous vasculature.

Animals↗

PubMed1978

Paraquat poisoning: a review.

The pathophysiology, symptoms and treatment of paraquat intoxication, primarily from oral ingestion, and the pharmacology and pharmacokinetics of paraquat are reviewed. Toxicity has occurred after topical application, oral ingestion or inhalation of paraquat. Systemic toxicity has not been reported from smoking of paraquat-contaminated marijuana but heavy abusers of contaminated marijuana may experience coughing, hemoptysis and mouth irritation. Following ingestion of 30 mg/kg or 50 ml of a 21% (w/w) solution of paraquat (as the base), hepatic, cardiac or renal failure or death may occur. Smaller doses (greater than or equal to 4 mg/kg of paraquat base) may cause respiratory distress, renal dysfunction or, occasionally, jaundice or adrenal cortical necrosis. When paraquat ingestion is suspected, the drug should be removed immediately from the gastrointestinal tract by gastric lavage or by whole-gut irrigation. Adsorbents such as Fuller's earth, bentonite or activated charcoal may be used during gastric lavage. Combined use of forced diuresis (with furosemide, mannitol and i.v. dextrose in water or normal saline), hemodialysis or hemoperfusion is recommended until the compound cannot be detected in body fluids or the dialysate. Immediate and effective treatment is necessary to prevent systemic toxicity or death from paraquat intoxication.

Cannabis↗

PubMed1979

Clinical study of aclacinomycin A.

A phase I study of a new anthracycline antibiotic, aclacinomycin A, was performed in a total of 15 patients with advanced malignancy to determine the maximum-tolerated dose. The gastrointestinal toxicity which occurred was not dose-related and was not severe. Epilation and stomatitis were extremely minimal. Both hepatic dysfunction and hematologic toxicity were dose-limiting. A recommended dose for phase II study was determined to be 2.5--3.0 mg/kg (approximately 100--120 mg/m2) given in 3-week intervals. Objective response was observed in two patients with malignant lymphomas.

Aclarubicin↗

PubMed1995

Managing the triage of GI hemorrhage as a function of stability.

The authors present a refined triage tool to assist in the identification of patients with GI hemorrhage. Criteria include orthostasis; current, active GI hemorrhage; hemoglobin under 10 g/dl or a 3 g/dl drop from a known baseline; and history of underlying organ system dysfunction.

Adult↗

PubMed1994

The use of an unbaited radial maze in neurotoxicology: II. Sensory inputs, general malaise and locomotor activity.

An unbaited 6-arm radial tunnel maze (6-arm RTM) is used in our laboratory to screen for working- and reference memory deficits in rats in the course of neurotoxicological studies. In the 6-arm RTM animals are minimally stressed, and do not need food reward as a reinforcer. Maze behavior is assessed using mean error score of arm repetitions as a measure of 'working memory', left-right discrimination within each arm (expressed as percent "blind-alley" visits) as a measure of 'reference memory' and trial time (time to complete 12 arm entries) as a measure of locomotor activity. As shown for other mazes sensory deficits may affect spatial orientation. Sensory dysfunction are likely to be induced by neurotoxic compounds, while at toxic doses reduced locomotor activity is a common finding. When using the 6-arm RTM in the course of neurotoxicity studies to assess cognitive functions such potentially confounding effects have to be excluded to allow the conclusion of a cognitive impairment. The aim of the following experiments was to assess if visual, vibrissal or olfactory dysfunction, or hypoactivity may affect memory parameters in the 6-arm RTM. Loss of visual, olfactory or vibrissal input alone did not affect any of the maze parameters. Combined loss of visual and vibrissal or olfactory inputs increased mean error score. Loss of olfaction prolonged trial time under both lighting conditions. Acrylamide- and vitamin B6-induced sensorymotor dysfunctions and hypoactivity did not affect mean error score or percent blind-alley visits in the 6-arm RTM. Similarly, gastrointestinal distress and hypoactivity induced by lithium chloride injections did not affect parameters of working or reference memory. Results indicate that in the 6-arm RTM (1) olfactory, visual and, to a minor extent, vibrissal input contribute to the sensory information necessary for spatial orientation and (2) reduced locomotor activity secondary to impaired sensorymotor abilities or drug-induced illness do not influence working or reference memory parameter.

Analysis of Variance↗

PubMedDate not supplied

[Multiple organ failure syndrome in critically ill patients].

A new approach to defining the notion of multiple organ failure is proposed. It is based on division of the organ humoral injuries at the stages of dysfunction, insufficiency, and failure. Criteria of these stages are defined for the central nervous and cardiovascular systems, lungs, liver, kidneys, and gastrointestinal tract.

APACHE↗

PubMed1998

[Abdominal pain and ascites as manifestations of hereditary angioneurotic edema].

Hereditary angioneurotic edema (HAE) is an infrequent autosomal dominant disorder characterized by a decrease in the levels or a dysfunction of the complement C1 inhibitor factor (C1 inh). The clinical presentation varies widely and involves any area of the organism. Gastrointestinal involvement is usually as abdominal pain and may be accompanied by ascites. De novo diagnosis of HAE with abdominal pain and ascites as a form of presentation is difficult with differential diagnosis with abdominal pain of unknown origin. The appearance of ascites is rare with few cases reported in the literature. Both abdominal pain and ascites disappear a few days after initiation of medical treatment. Occasionally exploratory laparotomy has been required. A new case of abdominal pain and ascites as manifestations of HAE is herein reported.

Abdominal Pain↗

PubMed1997

Inflammatory Bowel Disease--A Complicating Factor in Gynecologic Disorders?

Gynecologic disorders occur commonly in women with Crohn's disease and ulcerative colitis. Frequently, these women also suffer menstrual disorders with gastrointestinal symptoms that overlap with those related to inflammatory bowel disease (IBD). Knowledge of the range of gynecologic problems--for example, dysfunctional uterine bleeding, fistula or abscess of the perineum or vagina, dyspareunia, subfertility possibly due to tubal blockage, and ovarian dysfunction related to bowel disease--that have been associated with IBD will assist practitioners in treating these women. Prostaglandins, released by the endometrium at menstruation, cause contraction of uterine smooth muscle, resulting in the cramping pain of dysmenorrhea. Prostaglandins also are an important component of the inflammatory process in active IBD; by increasing contractility of GI smooth muscle, they are associated with diarrhea and abdominal pain. Menstrual pain and menses-related GI symptoms may be difficult to distinguish from symptoms related to IBD. Endometriosis may present with symptoms similar to an acute episode of IBD. Mucosal changes in the bowel can occur in association with endometriosis, and can be confused with the histologic features of IBD. The distinction is important. For example, while nonsteroidal anti-inflammatory drugs may relieve symptoms of dysmenorrhea, they often are contraindicated in IBD. To provide optimal evaluation and treatment, all health care professionals who treat women with IBD should be aware of the spectrum of gynecologic conditions that may be encountered.

Journal Article↗

PubMed1995

Multiple organ involvement in perinatal asphyxia.

OBJECTIVES: (1) To evaluate the frequency and spectrum of severity of multisystem dysfunction after perinatal asphyxia and (2) to analyze the relationship between the clinical and biochemical markers of perinatal asphyxia and multiorgan involvement. STUDY DESIGN: Seventy-two consecutive term newborn infants with perinatal asphyxia were studied prospectively. Systematic neurologic, renal, pulmonary, cardiac, and gastrointestinal evaluations were performed. Involvement of each organ was classified as moderate or severe. RESULTS: Involvement of one or more organs occurred in 82% of the infants; the central nervous system (CNS) was most frequently involved (72%). Severe CNS injury (7 infants) always occurred with involvement of other organs, although moderate CNS involvement was isolated in 14 infants. Renal involvement occurred in 42%, pulmonary in 26%, cardiac in 29%, and gastrointestinal in 29% of the infants; 15% neonates had renal failure and 19% had respiratory failure. The Apgar scores at 1 and 5 minutes were the only perinatal factors related to the number of organs involved and the severity of involvement; the Apgar score at 5 minutes had the stronger independent association. No relationship or organ dysfunction was found with the umbilical cord arterial blood pH, meconium-stained amniotic fluid, umbilical cord abnormalities, presentation, or type of delivery. CONCLUSIONS: Our findings indicate that the Apgar score at 5 minutes, in infants who have other criteria for asphyxia, is the perinatal marker that may best identify infants at risk of organ dysfunction.

Apgar Score↗

PubMed2004

Two-stage total hepatectomy and liver transplantation for acute deterioration of chronic liver disease: a new bridge to transplantation.

Two-stage total hepatectomy and liver transplantation has been reported for acute liver disease such as fulminant hepatic failure, primary graft failure, severe hepatic trauma, and spontaneous hepatic rupture secondary to hemolysis, elevated liver function tests, low platelets syndrome, and preeclampsia. This is the first report of patients with cirrhosis to undergo a 2-stage total hepatectomy and liver transplantation. From 1984 to 2002, our institution performed 2008 orthotopic liver transplantations. We identified 4 patients with chronic liver disease who underwent a 2-stage hepatectomy and liver transplantation. This is a retrospective review of these 4 patients and a review of the literature on this procedure. All 4 patients were young men with an age range of 29-31 years and had underlying cirrhosis as well as a previous transjugular intrahepatic portosystemic shunt (TIPS)procedure. Acute decompensation fulfilling Ringes' criteria for toxic liver syndrome secondary to an upper gastrointestinal bleed occurred in all patients. The approximate average time between hepatectomy and liver transplantation was 20 hours (range: 8-42 hours). In all cases, the explanted liver showed histological changes of acute hepatic necrosis within the background of cirrhosis. After hepatectomy, vasopressor requirements were well documented in 2 patients. For 1 patient, there was a clear improvement in their hemodynamic status. The mean hospital stay of the 4 patients was 63 days. All patients were discharged from the hospital and are alive and well with adequate liver function at 6 to 37 months follow-up. Two-stage total hepatectomy and liver transplantation may be a life-saving procedure in highly selected cirrhotic patients with acute hepatic decompensation and multiorgan dysfunction.

Adult↗

PubMed1984

Depressed women with panic attacks.

Of a group of 288 depressed female inpatients, 43 (15%) had secondary panic attacks. Compared to other depressives, the subgroup with panic attacks had significantly higher frequencies of anorexia, weight loss, gastrointestinal disturbances, hypochondriasis, and psychomotor agitation, and significantly lower frequencies of melancholic symptoms, including loss of interest in usual activities, guilt feelings, delusional thinking, psychomotor retardation, and orientation or memory impairment. Patients with panic attacks were less likely to have a depressed parent and were more likely to be described as having been nervous, worrisome, sensitive, and sexually dysfunctional before the onset of depression. Phenomenologically, they resembled "anxious depressives" as described by other authors.

Adult↗