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Biomedical subjects

R W Goodgame

Publications and source records attributed to R W Goodgame.

At least 19 recordsLinked to original sources

Viral causes of diarrhea.

Viruses are important causes of diarrhea. In healthy adults, the main clinical manifestation is acute, self-limited gastroenteritis. Advances in molecular diagnostics have shown that epidemics of acute gastroenteritis most frequently are due to caliciviruses spread through contaminated food or through person-to-person contact. Application of similar technology is needed to make a definitive statement about the role of such candidate viruses as rotavirus, astrovirus, and adenovirus as the cause of nonepidemic acute gastroenteritis in adults. Rarely a previously healthy adult gets acute CMV colitis. CMV and EBV mainly cause diarrhea in immunocompromised patients, however. Advances in prophylaxis and treatment have reduced the frequency and severity of these diseases. Acute infantile gastroenteritis is caused by rotavirus, calcivirus, astrovirus, and adenovirus. These viral diseases of the gut are seen by the physician as routine and rare clinical problems.

Adult↗

Randomized controlled trial of clarithromycin and ethambutol in the treatment of Crohn's disease.

BACKGROUND: A mycobacterial infection may be the cause of Crohn's disease in some patients. Measurement of intestinal permeability may identify Crohn's disease patients with a high likelihood of relapse and may quantify the severity of intestinal injury. AIM: To assess the effect of 3 months of clarithromycin and ethambutol on the disease activity and intestinal permeability in patients with Crohn's disease at high risk of relapse. METHODS: Patients with Crohn's disease, with a lactulose-mannitol permeability test above 0.03, were randomly assigned to receive either clarithromycin, 500 mg twice daily, and ethambutol, 15 mg/kg daily, or identically appearing placebo for 3 months in addition to their regular therapy. The Harvey-Bradshaw index and the lactulose-mannitol test were assessed in a blind fashion every 3 months for 12 months. RESULTS: Thirty-one patients were randomized to receive either drugs (n=15) or placebo (n=16). The groups were similar in age, sex, duration of disease, location of disease, past complications and disease severity. Specifically, there was no difference between the drug or placebo groups in the mean Harvey-Bradshaw index (4.8 vs. 4.4), number with active disease (33% vs. 44%) and mean lactulose-mannitol test (0.06 vs. 0.10). During the 12-month follow-up period, there were no consistent, statistically significant differences in the mean Harvey-Bradshaw index or lactulose-mannitol test between treatment and placebo groups. Individual patients showed either improvement or worsening of these indices, but these were not related to study medication. Specifically, no 'cures' were noted with anti-mycobacterial treatment. CONCLUSIONS: Three months of treatment with clarithromycin and ethambutol does not benefit Crohn's disease patients who are receiving standard medical therapy.

Adult↗

Viral infections of the gastrointestinal tract.

Acute gastroenteritis is common in adults. It can occur in institutional epidemics or epidemics of food-borne illness; in these cases, caliciviruses are the major cause of the condition. When acute gastroenteritis occurs in nonepidemic form, its causes are less clear. It may be due to caliciviruses or to the less common serotypes of childhood gastroenteritis viruses, such as rotavirus, astrovirus, and adenovirus. The pathogenesis of acute viral gastroenteritis is not completely understood. Old evidence suggests that mild villus damage is responsible, but new evidence indicates that active secretion and motility disturbance may be involved in the production of symptoms. Five common viruses can remain latent in gastrointestinal tissues and produce disease many years after initial infection. Two major herpesviruses, cytomegalovirus and herpes simplex virus, cause ulcerative disease of the gastrointestinal tract. This disease occurs in healthy persons but is more common and more severe in immunocompromised patients. Three other viruses--Epstein-Barr virus, human papilloma virus, and human herpesvirus-8--are implicated in benign and malignant proliferative diseases of the gastrointestinal tract. Epstein-Barr virus has been associated with immunoproliferative disease after transplantation and may also cause small-bowel and colonic lymphoma in healthy adults. It causes most AIDS-related lymphomas. Human papillomaviruses cause anorectal condyloma and anal cancer. Human herpesvirus-8 causes gastrointestinal Kaposi sarcoma.

Adult↗

Assessment of intestinal permeability with a two-hour urine collection.

The differential urinary excretion of orally administered lactulose and mannitol is used to evaluate intestinal permeability. This test usually involves a 5- to 6-hr urine collection. We hypothesized that a shorter collection time would give an equivalent result. Forty-three patients with a variety of gastrointestinal symptoms and diagnoses (group 1) and 42 patients with Crohn's disease (group 2) had a standard lactulose/mannitol permeability test. The lactulose and mannitol urinary excretion was calculated using the first urine (group 1) or the 1-hr and 2-hr urine (group 2) and was compared to the values calculated from the routine 5- or 6-hr collection. Lactulose excretion kinetics, expressed as the percent of the total urinary excretion within a given time period, were as follows: 21% in first hour (group 2), 29% in second hour (group 2), and 46% in first 2.5 hr (group 1). Mannitol urinary excretion kinetics were 16%, 31%, and 44%, respectively. The lactulose/mannitol ratio based on a standard urine collection correlated well with the ratio based on just the first urine produced by the patient (R2 = 0.94; P < 0.001; group 1) and the 2-hr urine (R2 = 0.464; P < 0.001; group 2). Future use of the lactulose/mannitol ratio to assess intestinal permeability may be able to be simplified by shortening the urine collection time.

Administration, Oral↗

Decrease in gastric permeability to sucrose following cure of Helicobacter pylori infection.

BACKGROUND: Gastric sucrose permeability is a noninvasive marker that reliably increases in association with gastrointestinal injury due to use of nonsteroidal antiinflammatory drugs. Despite the effect of Helicobacter pylori infection on the gastric mucosa, in a previous study we were unable to demonstrate that H. pylori infection was associated with abnormal gastric sucrose permeability. Our goal in this study was to explore further whether H. pylori infection changed gastric permeability; therefore, we evaluated the effect of treatment of H. pylori infection on gastric permeability to sucrose and the relation of sucrose permeability to density of polymorphonuclear leukocytes. MATERIALS AND METHODS: Five hundred milliliters of a solution containing 100 gm of sucrose was ingested by the subject at bedtime. Overnight urine was collected and assayed for sucrose by high-performance liquid chromatography. Sucrose permeability was assessed both before and approximately 4 weeks after anti-H. pylori therapy. RESULTS: Seventeen asymptomatic H. pylori-infected volunteers participated; 8 were cured. Sucrose permeability was in the range commonly found in normal controls both before and after anti-H. pylori therapy (mean excretion, 76.3 mg; range, 13-171 mg). Gastric sucrose permeability correlated with the density of polymorphonulcear cell infiltration of the mucosa. Cure of the H. pylori infection was associated with a small but significant decrease in sucrose permeability (98.8 +/- 18 mg to 51.7 +/- 9.8 mg (p = .01). Sucrose permeability was greater in those with a high density of mucosal polymorphonuclear cells compared to those with lower scores (119.5 +/- 4 vs 71.4 +/- 13 for those with scores > or = 5 compared to scores < or = 4; p = .023). Failed therapy resulted in an increase in the mucosal density of polymorphonuclear infiltration and sucrose permeability (56.4 +/- 13 mg-99.7 +/- 19 mg pretreatment vs posttreatment, respectively; p = .031). CONCLUSION: H. pylori gastritis causes a small but measurable increase in gastric permeability to sucrose that may reflect epithelial transmigration of neutrophils.

Anti-Bacterial Agents↗

Understanding intestinal spore-forming protozoa: cryptosporidia, microsporidia, isospora, and cyclospora.

OBJECTIVES: To summarize recent information about the "new" gastrointestinal protozoal pathogens (cryptosporidia, microsporidia, isospora, and cyclospora) and to help practicing clinicians integrate this information into their clinical databases by emphasizing the similarities among these organisms. DATA SOURCES: Relevant English-language articles published between 1988 and 1995 were identified through a MEDLINE search done using the names of the intestinal spore-forming protozoa. Articles cited in the bibliographies of these and other articles were searched manually. STUDY SELECTION: Studies that contained information on the history, taxonomy, life cycle, epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of the pathogens were reviewed. DATA EXTRACTION: Cryptosporidium parvum, Isospora belli, Cyclospora cayetanensis, Enterocytozoon bieneusi, and Septata intestinalis are intestinal spore-forming protozoa that cause intracellular infections, predominantly in the epithelial cells of the intestine. They are transmitted either by stool from person to person or through contaminated water or food by an infectious particle called a spore or oocyst. Asymptomatic infections occur; the most common symptom of infection is diarrhea. Infections have been associated with intestinal inflammation, disordered architecture (such as villus blunting), and abnormal function (for example, malabsorption). Mild to moderate, self-limited diarrhea is common in healthy persons, but patients with immune dysfunction can have severe intestinal injury and prolonged diarrhea. Diagnosis is made by a microscopic examination of the stool and the use of appropriate staining techniques. Effective antibiotic treatment for prolonged infection in immunocompromised patients is available for most of these infections. CONCLUSIONS: The intestinal spore-forming protozoa are four frequently identified gastrointestinal pathogens that have important similarities in epidemiology, disease pathogenesis, clinical manifestations, diagnosis, and treatment.

Animals↗

Intestinal function and injury in acquired immunodeficiency syndrome-related cryptosporidiosis.

BACKGROUND/AIMS: The pathogenesis of the diarrhea in acquired immunodeficiency syndrome (AIDS)-related cryptosporidiosis is not known. The hypothesis of this study was that the intestinal dysfunction and injury are related to the number of organisms infecting the intestinal mucosa. The aim of this study was to study the influence of intensity of infection on intestinal function and injury in AIDS-related cryptosporidiosis. METHODS: In 16 patients with AIDS with intestinal Cryptosporidium infection, the intensity of infection was quantified by counting the total number of fecal oocysts excreted in 24 hours and by determining the percent of duodenal epithelium covered by organisms. Intestinal function was assessed by vitamin B12 absorption and serum D-xylose test. Intestinal injury was assessed by morphology of duodenal mucosa, differential urinary excretion of lactulose and mannitol, and fecal alpha 1-antitrypsin clearance. Measurements were repeated after treatment with paromomycin. RESULTS: Vitamin B12 and D-xylose absorption negatively correlated with intensity of infection. Villus atrophy occurred only in patients with oocyst excretion of > 10(8) oocyst/24 hours. Lactulose/mannitol urinary excretion ratio showed a positive correlation with intensity of infection. Intestinal function and injury improved in patients whose oocyst counts were reduced by treatment with paromomycin. CONCLUSIONS: Cryptosporidium infection in patients with AIDS causes malabsorption and intestinal injury in proportion to the number of organisms infecting the intestine.

AIDS-Related Opportunistic Infections↗

Paromomycin for cryptosporidiosis in AIDS: a prospective, double-blind trial.

To test the effects of paromomycin, 10 patients with AIDS and cryptosporidiosis were randomized to paromomycin or placebo in a double-blind trial. After 14 days, patients were switched to the other treatment for 14 additional days. Measures included the number and character of each stool and weekly 24-h stool specimens for weight and oocyst excretion. During the paromomycin treatment phase, oocyst excretion decreased from 314 x 10(6) to 109 x 10(6)24 h (P < .02). Oocyst excretion increased for the 4 patients initially on placebo compared to a median decrease of 128 x 10(6)/24 h for the 6 initially treated with drug (P < .02). Stool frequency also decreased more in those treated with drug (3.6 fewer vs. 1.25 fewer/24 h, P < .05). Trends favored drug over placebo for stool weight, stool character, and Karnofsky score. Paromomycin treatment resulted in improvement in both clinical and parasitologic parameters in cryptosporidiosis in AIDS.

AIDS-Related Opportunistic Infections↗

Infectious esophagitis.

This article presents the epidemiology, pathogenesis and pathology, clinical manifestations, and diagnosis and treatment of Candida, herpes simplex virus, cytomegalovirus, Mycobacterium tuberculosis, Aspergillus, histoplasmosis, blastomycosis, and HIV. Uncommon AIDS-related esophageal infections are also discussed.

Acquired Immunodeficiency Syndrome↗

Gastrointestinal cytomegalovirus disease.

OBJECTIVE: To describe the pathogenesis of gastrointestinal cytomegalovirus (CMV) disease, the types and locations of gastrointestinal lesions, the clinical settings in which they occur, and the specific methods available to diagnose and treat the disease. DATA SOURCES: Relevant English-language articles were identified through a MEDLINE search from 1985 to 1992. Articles referenced in the bibliographies of these articles and others were searched by hand. STUDY SELECTION: All articles that documented the occurrence of gastrointestinal CMV infection in humans, based on the finding of typical cytomegalic cells in histologic specimens, were selected for review. DATA EXTRACTION: Studies were grouped by content pertaining to pathogenesis, clinical setting, gastrointestinal location, diagnosis, or treatment. DATA SYNTHESIS: Gastrointestinal CMV disease is an erosive or ulcerative process that can occur at any location in the gastrointestinal tract, from mouth to rectum. Cytomegalovirus infection of columnar epithelial cells, endothelial cells, myocytes, and fibroblasts causes tissue destruction and ulceration. Serious CMV disease most frequently occurs with immune deficiency, such as the acquired immunodeficiency syndrome, after organ transplantation, after cancer chemotherapy, and after steroid therapy. Symptoms and signs depend on which part of the gastrointestinal tract is involved. Diagnosis depends on a positive mucosal biopsy that shows the presence of CMV by histopathologic or other techniques. In patients with persistent immune deficiency, progressive intestinal disease and death are frequent. Treatment with ganciclovir or foscarnet often heals intestinal lesions. CONCLUSIONS: Internists should be aware of the various clinical settings and locations in the gastrointestinal tract in which CMV disease occurs. Patients with immune deficiency and gastrointestinal signs and symptoms should have imaging tests and mucosal biopsies to investigate the possibility of CMV intestinal disease. Treatment with antiviral chemotherapy improves outcome in many patients.

Cytomegalovirus Infections↗

Duodenal morphology and intensity of infection in AIDS-related intestinal cryptosporidiosis.

BACKGROUND: The pathogenesis of intestinal cryptosporidiosis is not known. Previous studies have shown that the intensity of infection varies between patients. The hypothesis of this study is that intestinal injury is related to the intensity of infection. METHODS: The histological abnormalities associated with Cryptosporidium infection were evaluated in duodenal biopsy specimens from 18 patients with acquired immunodeficiency syndrome-associated cryptosporidiosis. The intensity of Cryptosporidium infection was assessed histologically in all patients as the percentage of mucosa covered by organisms and by quantitation of oocyst excretion in the stools of 14 patients. RESULTS: Duodenal biopsy specimens from 13 patients (72%) showed normal villous architecture. In these patients, the inflammatory component of the lamina propria was either normal or moderately increased. This increase consisted mostly of lymphocytes and plasma cells. Five of 18 patients (28%) had flattening of the mucosa associated with a prominent neutrophilic infiltrate. The intensity of infection in patients with villous flattening as measured from biopsy specimens and stool was significantly higher than in those without flattening (92% vs. 12% mucosa occupied with organisms; 738 x 10(3) vs. 199 x 10(3) oocyst/mL stool) (P < 0.004 in both cases). CONCLUSIONS: Most patients with intestinal Cryptosporidium infection had normal duodenal villous architecture. Severe duodenal morphological abnormalities, including flattening of the villi, were associated with high-intensity infections.

AIDS-Related Opportunistic Infections↗

Intensity of infection in AIDS-associated cryptosporidiosis.

A fluorescent monoclonal anti-Cryptosporidium antibody was used to count the oocysts in stools of 12 AIDS patients with chronic cryptosporidiosis. Oocyst excretion was present throughout the day in all 12 patients. Stool-to-stool variation in oocyst concentration was within one order of magnitude. Small variations were also found in daily mean oocyst concentration and total daily oocyst excretion in 3 patients who had multiple 24-h stool collections. However, there was a large patient-to-patient variation in mean oocyst concentration (from < 5.0 x 10(3) to 9.2 x 10(5) oocysts/mL) and 24-h total oocyst excretion (from < 6.0 x 10(6) to 1.2 x 10(9) oocysts/day). There was a significant correlation between oocyst excretion and numbers of Cryptosporidium organisms seen on small bowel biopsy. Oocyst excretion was reduced in 4 patients treated with paromomycin, but diarrhea improved only in the 2 patients with high initial oocyst excretion.

AIDS-Related Opportunistic Infections↗

Frequency of positive tests for cytomegalovirus in AIDS patients: endoscopic lesions compared with normal mucosa.

Ten patients with the acquired immunodeficiency syndrome and an endoscopic erosive/ulcerative lesion in esophagus (4), stomach (3), or colon (3) were prospectively studied with multiple biopsies (244 biopsies from 33 sites) to determine: 1) the frequency of positive tests for cytomegalovirus (CMV) in the lesions versus normal mucosa, 2) the influence of number of biopsies on the rate of positivity. As seen on histology, five out of 10 lesions had cytomegalic cells, but only six of 45 (13%) of the biopsies taken from lesions that were positive showed the diagnostic changes. Immunoperoxidase was positive in two of the lesions with cytomegalic cells, but the positive staining occurred in only three of 35 (9%) biopsies from the histologically positive lesions. Culture was positive in one of 10 lesions, and the rate of positivity did not depend on number of cultures sent or number of biopsies per culture. Polymerase chain reaction was positive in six of 10 lesions, including all lesions positive by either histology (5), immunoperoxidase stain (2), or culture (1). The frequency of a biopsy being positive for CMV in normal mucosa was found to be 4%, 0%, 17%, and 28% by histology, immunoperoxidase stain, culture, and polymerase chain reaction, respectively. In AIDS patients at high risk for CMV, histologic evidence of CMV infection is uncommon in normal mucosa but is frequent in suspicious lesions. However, the frequency of diagnostic histology is highly dependent on the number of biopsies taken and the diligence of the pathologist. Polymerase chain reaction has the potential to become a rapid test to rule out CMV infection in gastrointestinal tissue.

AIDS-Related Opportunistic Infections↗

Severe cholestatic jaundice associated with piroxicam.

A 62-year-old man with rheumatoid arthritis developed jaundice while taking piroxicam. A full evaluation including ultrasound, computerized tomography, endoscopic cholangiography, and liver biopsy confirmed the diagnosis of intrahepatic cholestasis. The patient's jaundice and all other liver function abnormalities normalized 4 months after he discontinued taking piroxicam. This is the first case report in the United States of severe liver toxicity associated with piroxicam. The six cases in the English-language literature are reviewed, featuring the presentation, patterns of liver injury, and outcome in each. Piroxicam should be considered as a potential cause of cholestatic jaundice when other more common etiologies have been excluded.

Biopsy↗

Esophageal stricture after cytomegalovirus ulcer treated with ganciclovir.

A 49-year-old man with the acquired immune deficiency syndrome (AIDS) developed epigastric pain, nausea, vomiting, and gastrointestinal bleeding secondary to a cytomegalovirus (CMV)-induced ulceration in the distal esophagus and proximal stomach. All symptoms improved on treatment with ganciclovir. However, 1 month later severe dysphagia led to discovery of a fibrous stricture in the area of the healed ulcer. The dysphagia was controlled by esophageal dilation. Ulcerative lesions caused by CMV can heal with ganciclovir treatment but, as with other esophageal ulcers, healing may be associated with fibrosis and stricture.

Acquired Immunodeficiency Syndrome↗

Whipple's disease can mimic chronic AIDS enteropathy.

Previous case reports have demonstrated that the intestinal pathology of Mycobacterium avium-intracellulare (MAI) infection in the acquired immune deficiency syndrome (AIDS) has a light microscopic appearance similar to Whipple's disease. This case report describes a 52-yr-old male patient with a clinical picture suggestive of AIDS, including diarrhea, weight loss, oral thrush, and intestinal cryptosporidiosis. The intestinal biopsy showed light microscopic features compatible with either MAI or Whipple's disease, but electron microscopy confirmed the presence of the Whipple bacillus. Markers of human immunodeficiency virus (HIV) infection were absent. Although immune abnormalities have been reported in Whipple's disease, this is the first report of opportunistic infections complicating this condition. A useful clinical pearl emerges from this and other cases: AIDS can mimic Whipple's disease; Whipple's disease can mimic AIDS.

Acquired Immunodeficiency Syndrome↗