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Biomedical subjects

J A Leighton

Publications and source records attributed to J A Leighton.

17 recordsLinked to original sources
PubMed2006

The yield of capsule endoscopy in patients with abdominal pain or diarrhea.

BACKGROUND AND STUDY AIMS: Capsule endoscopy, proven effective for evaluation of obscure gastrointestinal bleeding and suspected Crohn's disease, is increasingly used to investigate other small-intestine disorders, but its yield for other indications is not well known. We sought to evaluate its yield and findings for abdominal pain or diarrhea. PATIENTS AND METHODS: Medical records of patients with abdominal pain or diarrhea (> 6 weeks' duration) who underwent capsule endoscopy between August 2001 and June 2004 were retrospectively reviewed for demographic data, indications, findings, diagnoses, complications, and radiologic studies. All patients had previous endoscopic or radiologic examinations (colonoscopy, enteroscopy, upper endoscopy, small-bowel series, computed tomography enterography, or computed tomography) demonstrating no abnormalities sufficient for diagnosis. RESULTS: 64 patients (26 men; 38 women; mean age, 43 years; age range, 19 - 83 years) who met study criteria had 68 capsule endoscopy studies. Indications were abdominal pain (35 patients), diarrhea (14), or both (15). Complete small-bowel visualization with identification of the cecum was achieved in 81 %; yield of positive findings was 9 % (6 patients). By indications, the yield was 6 % for abdominal pain, 14 % for diarrhea, and 13 % for both. Diagnoses included Crohn's disease (3), enteropathy induced by nonsteroidal anti-inflammatory drugs (2), and submucosal tumor (1). Capsule retention occurred in two patients, requiring surgical removal. CONCLUSIONS: Capsule endoscopy had a low yield for evaluation of abdominal pain or diarrhea and cannot be recommended as a first-line test without further study. Nonetheless, it facilitated diagnosis in 9 % of patients with negative endoscopic and radiologic examinations.

Abdominal Pain↗
PubMed2001

Gastrointestinal basidiobolomycosis in Arizona: clinical and epidemiological characteristics and review of the literature.

Gastrointestinal basidiobolomycosis (GIB) is an unusual fungal infection that is rarely reported in the medical literature. From April 1994 through May 1999, 7 cases of GIB occurred in Arizona, 4 from December 1998 through May 1999. We reviewed the clinical characteristics of the patients and conducted a case-control study to generate hypotheses about potential risk factors. All patients had histopathologic signs characteristic of basidiobolomycosis. Five patients were male (median age, 52 years; range, 37--59 years) and had a history of diabetes mellitus (in 3 patients), peptic ulcer disease (in 2), or pica (in 1). All patients underwent partial or complete surgical resection of the infected portions of their gastrointestinal tracts, and all received itraconazole postoperatively for a median of 10 months (range, 3--19 months). Potential risk factors included prior ranitidine use and longer residence in Arizona. GIB is a newly emerging infection that causes substantial morbidity and diagnostic confusion. Further studies are needed to better define its risk factors and treatment.

Adult↗
PubMed2000

Endoscopic perforation of the colon: lessons from a 10-year study.

OBJECTIVES: To assess the incidence, clinical features, and management of endoscopic colon perforations in a large number of patients at a major medical teaching center. METHODS: A retrospective review of medical records of all patients with colon perforations from endoscopy over a 10-yr period. RESULTS: A total of 10,486 colonoscopies were performed over a 10-yr period. There were 20 (0.19%) perforations and two (0.019%) deaths related to colonoscopy and two perforations with no deaths in 49,501 sigmoidoscopies (0.004%). The majority of perforations (65%) occurred in the sigmoid colon. The mean age of the patients was 72 yr (range, 48-87 yr). Multivariate analysis using gender and age showed that female gender was an independent predictor of a higher risk of perforation (p < 0.05). Electrocautery injury (36%) and mechanical injury (32%) from the tip and shaft of the endoscope were the major causes for perforation. Most patients (91%) presented within 48 h of endoscopy. Nine patients (47%) required a surgical resection with primary anastomosis; seven (37%) required a simple closure. The average hospital length of stay was 7.7 +/- 2.8 days. Although trainee endoscopists were involved in only 20% of the colonoscopies performed, eight (40%) perforations occurred while the training fellow was involved in the case. However, this increased risk of perforation with a training fellow was not statistically significant (p = 0.625). CONCLUSIONS: Colonoscopy can result in significant morbidity and carries a small risk of death. Sigmoidoscopy has lower risk. The following situations may represent increased risk to colonoscopy patients: unusual difficulty in traversing the sigmoid colon; difficult examinations in female patients, and difficult examinations performed by trainee physicians.

Aged↗
PubMed1999

A randomized dose-response and pharmacokinetic study of methotrexate for refractory inflammatory Crohn's disease and ulcerative colitis.

BACKGROUND AND AIMS: The optimum initial dose of methotrexate for steroid-requiring inflammatory bowel disease is not known. AIM: To compare directly the efficacy and toxicity of methotrexate 15 and 25 mg/week, and to explore the value of methotrexate blood levels as predictors of outcome. METHODS: A 16-week randomized single-blind comparison of subcutaneous methotrexate 15 or 25 mg/week was performed in 32 patients with steroid-requiring Crohn's disease or ulcerative colitis. Patients who did not respond to methotrexate 15 mg/week were further studied for an additional 16 weeks on methotrexate 25 mg/week. Blood was drawn every 2 weeks for methotrexate levels. RESULTS: After 16 weeks, 17% of patients in each group achieved remission; 39% of patients randomized to 15 mg/week and 33% of patients randomized to 25 mg/week improved (P=N.S. ). Clinical status improved in four out of 11 patients after methotrexate dose escalation from 15 to 25 mg/week. Toxicity was not different between the treatment groups. Methotrexate blood levels did not predict efficacy or toxicity. CONCLUSIONS: For induction of remission in steroid-requiring inflammatory bowel disease, subcutaneous methotrexate at initial doses of 15 and 25 mg/week are equally efficacious. At these doses, response is not associated with blood methotrexate concentrations.

Adult↗
PubMed1999

Evaluation of 5-aminosalicylic acid (5-ASA) for cancer chemoprevention: lack of efficacy against nascent adenomatous polyps in the Apc(Min) mouse.

Recent experimental and epidemiological evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in the prevention of colorectal cancer. However, the toxicity associated with the long-term use of most classical NSAIDs has limited their usefulness for the purpose of cancer chemoprevention. Inflammatory bowel disease (IBD) patients, in particular, are sensitive to the adverse side effects of NSAIDs, and these patients also have an increased risk for the development of intestinal cancer. 5-Aminosalicylic acid (5-ASA) is an anti-inflammatory drug commonly used in the treatment of IBD and may provide protection against the development of colorectal cancer in these patients. To directly evaluate the ability of 5-ASA to suppress intestinal tumors, we studied several formulations of 5-ASA (free acid, sulfasalazine, and Pentasa) at multiple oral dosage levels [500, 2400, 4800, and 9600 parts/million (ppm)] in the adenomatous polyposis coli (Apc) mouse model of multiple intestinal neoplasia (Min). Although the ApcMin mouse is not a model of colitis-associated neoplasia, it is, nonetheless, a useful model for assessing the ability of anti-inflammatory agents to prevent tumor formation in a genetically preinitiated population of cells. We used a study design in which drug was provided ad libitum through the diet beginning at the time of weaning (28 days of age) until 100 days of age. We included 200 ppm of piroxicam and 160 ppm of sulindac as positive controls, and the negative control was AIN-93G diet alone. Treatment with either piroxicam or sulindac produced statistically significant reductions in intestinal tumor multiplicity (95% and 83% reductions in tumor number, respectively; P < 0.001 versus controls). By contrast, none of the 5-ASA drug formulations or dosage levels produced consistent dose-progressive changes in polyp number, distribution, or size, despite high luminal and serum concentrations of 5-ASA and its primary metabolite N-acetyl-5-ASA. Thus, 5-ASA does not seem to possess direct chemosuppressive activity against the development of nascent intestinal adenomas in the ApcMin mouse. However, because intestinal tumor development in the ApcMin mouse is driven by a germline mutation in the Apc gene rather than by chronic inflammation, we caution that these findings do not definitively exclude the possibility that 5-ASA may exert a chemopreventive effect in human IBD patients.

Adenomatous Polyps↗
PubMed1997

Basidiobolomycosis: an unusual fungal infection mimicking inflammatory bowel disease.

Basidiobolus ranarum is a fungus belonging to the Entomophthoraceae family and is mainly associated with subcutaneous soft tissue infection. The disease is usually characterized by an insidious onset of massive induration of the subcutaneous tissue involving the limbs, trunk, or buttocks. Most cases of basidiobolomycosis have been reported from Africa, South America, and tropical Asia. Visceral involvement is extremely rare. Only 4 cases with involvement of the gastrointestinal tract, including 1 fatal case originating in the United States, have been well documented in the English-language literature. This case report describes the first successfully treated patient residing in the United States who had B. ranarum infection involving the gastrointestinal tract.

Colonic Diseases↗
PubMed1997

Nicotine tartrate liquid enemas for mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy: a pilot study.

BACKGROUND: Ulcerative colitis is predominantly a disease of non-smokers, and transdermal nicotine is therapeutic but often results in side-effects. Administration of nicotine as a liquid rectal enema results in less systemic nicotine absorption. AIM: To determine the safety and clinical response of nicotine tartrate liquid enemas for active left-side ulcerative colitis in a pilot study. METHODS: Ten non-smoking patients with mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy were treated in an open protocol with nightly nicotine tartrate liquid enemas at a dose of 3 mg nicotine base for 1 week then 6 mg for 3 weeks. Clinical assessments were determined at baseline and 4 weeks by endoscopy, physician assessment and a patient diary of daily symptoms. Peak and trough serum nicotine and trough plasma cotinine were determined by gas chromatography/mass spectrometry and high performance liquid chromatography, respectively. RESULTS: After 4 weeks of treatment, 5/7 patients (71%) showed clinical and sigmoidoscopic improvement (per protocol analysis). The other three patients discontinued therapy within 7 days because of inability to retain the liquid enemas. No patients showed histologic improvement. Six of the patients who completed the 4-week study had peak and trough serum nicotine concentration determined, only 1 of 6 patients had a detectable peak nicotine concentration (value 2.3 ng/mL), and all six patients had undetectable trough nicotine concentrations. The mean trough plasma cotinine concentration was 13 +/- 10 ng/mL. Transient and mild adverse events occurred in 4/10 patients (nausea, lightheadedness, tremor, sleep disturbance). Given the low or undetectable serum nicotine concentrations, these adverse events are not likely to be related to the nicotine enemas. CONCLUSIONS: Nicotine tartrate liquid enemas administrated at a dose of 3 mg nicotine base/day for 1 week and then 6 mg/day for 3 weeks are safe and appear to result in clinical improvement in some patients with mildly to moderately active, left-sided ulcerative colitis unresponsive to first-line therapy. Placebo-controlled trials are warranted to confirm these preliminary findings.

Adult↗
PubMed1997

Rectal bleeding from a mucous fistula secondary to a Dieulafoy's lesion.

Dieulafoy's lesion is a submucosal artery associated with a minute mucosal defect, and it is an extremely rare cause of profuse but intermittent gastrointestinal bleeding. Most cases have occurred in the proximal stomach within 6 cm of the gastroesophageal junction. Less commonly, cases are encountered in the antrum, duodenum, jejunum, colon, and rarely the rectum. Only three cases of rectal Dieulfoy's lesion have been reported in the English medical literature: one in a child and two in otherwise healthy young men. We report a case of a rectal Dieulafoy's lesion in an elderly man with a mucous fistula. Successful treatment was administered with a combination of injection therapy and heater-probe coagulation followed by elective surgical oversewing. Rectal Dieulafoy's lesions should be included in the differential diagnosis of unexplained rectal bleeding in the elderly.

Aged↗
PubMed1996

Radical resection of malignant thymoma with reconstruction of the mediastinal venous confluence.

Thymic tumors are classified as epithelial neoplasm, thymic carcinoids, and thymic carcinoma. Differentiation between benignity and malignancy of thymic epithelial tumors is determined on the basis of local tissue invasion. Surgery is the treatment of choice for locally invasive disease without signs of metastasis. We present a patient who underwent en bloc tumor excision with reconstruction of the mediastinal venous confluence using pericardium.

Animals↗
PubMed1993

Anorectal dysfunction and rectal prolapse in progressive systemic sclerosis.

Our aim was to characterize the clinical spectrum of anorectal dysfunction among eight patients with progressive systemic sclerosis (PSS) who presented with altered bowel movements with or without fecal incontinence. The anorectum was assessed by physical examination, proctosigmoidoscopy, and anorectal manometry. There was concomitant involvement of the other regions of the digestive tract in all patients as determined by barium studies, endoscopy, or manometry: eight esophageal, three gastric, four small bowel, and two colonic. Seven patients had fecal incontinence, and four also had second-degree complete rectal prolapse. Abnormal anorectal function, particularly abnormal anal sphincter resting pressures, were detected in all patients; anal sphincter pressures were lower in those with rectal prolapse. Rectal capacity and wall compliance were impaired in seven of seven patients. Successful surgical correction of prolapse in three patients resulted in restoration of incontinence for six months and seven years in two of the three patients. We conclude that rectal dysfunction and weakness of the anal sphincters are important factors contributing, respectively, to altered bowel movements and fecal incontinence in patients with gastrointestinal involvement by PSS. Rectal prolapse worsens anal sphincter dysfunction and should be sought routinely as it is a treatable factor aggravating fecal incontinence in patients with PSS.

Aged↗
PubMed1991

Colchicine clearance is impaired in alcoholic cirrhosis.

Colchicine may have benefit in primary biliary cirrhosis and alcoholic liver disease. It is currently used in patients with impaired liver function, yet little is known about its elimination in such patients. Colchicine clearance in the rat is significantly impaired in various models of liver disease. To study this in human beings, colchicine pharmacokinetics were compared in normal subjects and patients with alcoholic cirrhosis. Colchicine clearance was impaired in the cirrhotic patients. Normal subjects had a mean clearance of 10.65 +/- 1.82 ml/min.kg, whereas cirrhotic patients had a mean clearance of 4.22 +/- 0.45 ml/min.kg (p less than 0.01). The half-life was 57.4 +/- 14.2 min in control subjects vs. 114.4 +/- 19.7 min in cirrhotic patients (p = 0.054). Volume of distribution was not different in the two groups (0.718 +/- 0.1 L/kg in control subjects; 0.716 +/- 0.158 L/kg in cirrhotic patients, p greater than 0.99). No correlation was seen between colchicine clearance and bilirubin, albumin, prothrombin time or Child-Pugh classification, but this may be the result of the small number of patients studied. Based on the values measured, it is estimated that colchicine steady state would change from an average 1.12 ng/ml in normal individuals to 2.82 ng/ml in the cirrhotic patients if 0.6 mg were taken every 12 hr. It is unknown whether this change would be clinically significant. These data show that cirrhosis impairs colchicine clearance and demonstrates that the liver is a major route of colchicine elimination.

Adult↗
PubMed1990

The effect of liver dysfunction on colchicine pharmacokinetics in the rat.

Recent work has shown that colchicine may benefit patients with primary biliary or alcoholic cirrhosis. However, very little is known about its pharmacokinetics in the presence of impaired liver function. To study this we examined the effects of three models of experimental liver dysfunction and one of cytochrome P-450 inhibition on colchicine elimination in the rat. The models of experimental liver dysfunction included bile duct ligation (with sham-operated controls), alpha-naphthylisothiocyanate-induced intrahepatic cholestasis and galactosamine-induced diffuse hepatocellular necrosis. The control group had a colchicine clearance of 77.33 ml/min.kg +/- 8.27 ml/min.kg, a half-life of 16.68 min +/- 0.97 min and a volume of distribution of 1.84 L/kg +/- 0.15 L/kg. Cimetidine administration, 120 mg/kg intraperitoneally 15 min before colchicine administration, caused clearance to decrease by 32% (p less than 0.05) and half-life to increase by 38% (p less than 0.05). Volume of distribution did not change. At 48 hr after bile duct ligation, colchicine clearance decreased by 84% (p less than 0.05), terminal half-life increased to 513.7 min +/- 106.6 min (p less than 0.05) and volume of distribution increased by 175% (p less than 0.05). Colchicine pharmacokinetics in sham-operated rats were not statistically different from the above mentioned controls.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Naphthylisothiocyanate↗
PubMed1989

Toxic delirium in a patient taking amantadine and trimethoprim-sulfamethoxazole.

Acute mental confusion occurred in a patient on a stable dose of amantadine after he was started on trimethoprim-sulfamethoxazole. Discontinuation of the drugs led to rapid improvement. Studies in a rat model of organic cation secretion demonstrate that both amantadine and trimethoprim, but not sulfamethoxazole, inhibit the renal secretion of the organic cation procainamide. This case may represent an amantadine-trimethoprim interaction.

Aged↗