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Biomedical subjects

R L Nelson

Publications and source records attributed to R L Nelson.

At least 55 records · Page 3Linked to original sources

Serum selenium and colonic neoplastic risk.

BACKGROUND: Selenium deficiency has been associated with cancer risk in several organs. This association was investigated in neoplasia of the colorectum. DESIGN: A case-control study is reported with two patient series, colorectal cancer and colorectal adenomatous polyps, and a control group found to be free of colorectal neoplasia. Diagnosis was determined by colonoscopy and histologic review of suspected neoplasms. Serum drawn at the time of colonoscopy was subsequently assayed for selenium content, and quartiles based on selenium were defined. Crude and adjusted odds ratios with 95 percent confidence intervals for adenoma related to selenium were calculated, controlling for known or suspected risk factors including gender, age, race, body mass index, family history, tobacco use, alcohol consumption, serum beta carotene, serum alpha tocopherol, and serum ferritin. RESULTS: There were 138 controls who had no neoplastic disease, 139 adenoma patients, and 25 cancer patients. For adenoma, comparing higher quartiles of selenium to the first (lowest selenium), the adjusted odds ratio for the second quartile was 1.7 (95 percent confidence interval, 0.8-3.7), the third quartile was 1.4 (0.7-3.2), and the fourth (highest selenium) quartile was 1.8 (0.9-4). The odds ratios for cancer patients were 0.8 for the second quartile, 1 for the third quartile, and 1.7 for the fourth quartile. CONCLUSION: No trend could be detected toward a protective effect of higher levels of serum selenium for colonic benign or malignant tumors.

Adenoma↗

Prevalence of benign anorectal disease in a randomly selected population.

BACKGROUND: The prevalence of benign anorectal diseases (BAD) in the general population has been difficult to establish, either because the individual diseases themselves were difficult to characterize in surveys or because of bias in the selection of the survey population. Reported herein is a prevalence survey of BAD symptoms and treatment history of a sample of the general population, selected by random digit dialing. METHOD: A survey instrument that inquired into symptoms of BAD, BAD treatment history, and health-seeking behaviors was administered by telephone interview with 102 individuals, between the ages of 21 and 65 of both genders and all races, chosen by random digit dialing in the Joliet, Illinois area. For selected variables (gender, education level, obesity, previous BAD treatment, fiber supplementation, time for defecation and reading during defecation all related to BAD symptoms) odds ratios and 95 percent confidence intervals were calculated. RESULTS: Of the 102 individuals, 9 had been previously treated for hemorrhoids, 4 by surgery, and 5 medically. Twenty individuals currently have BAD symptoms, six of these have multiple symptoms frequently, implying established BAD, and four of these have been previously treated for hemorrhoids. Seven of eight individuals with rectal bleeding in the past year have not sought medical evaluation. Of the associations tested, statistical significance was found only between female gender and BAD symptoms (odds ratio = 4.6; 95 percent confidence interval = 1.3-20.4). CONCLUSIONS: History of hemorrhoidal treatment and current BAD symptomatology are highly prevalent in a randomly selected population, and 80 percent of the subjects with symptoms of BAD have not consulted a physician regarding BAD. Some previously held correlates of hemorrhoidal symptoms, such as obesity and extended time for defecation, showed no apparent association with hemorrhoid treatment history or current BAD symptoms. The best predictors of current BAD symptoms were female gender (odds ratio = 4.6; 95 percent confidence interval = 1.3-20.4) and previous hemorrhoid treatment (odds ratio = 3.9; 95 percent confidence interval = 0.7-20).

Adult↗

Pull-through procedures performed months to years after permanent proctectomy.

PURPOSE: Patients who have undergone proctectomy without concomitant rectal reconstruction or coloanal anastomosis were not normally considered candidates for re-establishment of anal continuity until a case report published in 1985. With the addition of nine patients, reported herein is a series of ten patients who have undergone delayed pull-through procedures months to years after permanent proctectomy. PATIENTS: Ten patients (including the single case reported in 1985) have undergone delayed pull-through procedures up to 24 years after permanent proctectomy and ostomy formation. Delayed ileal pouch-anal anastomoses were performed in nine patients, and delayed coloanal anastomosis was performed in one patient. There were four males and six females, each of whom had evidence of external sphincter contraction on physical examination. Average age was 33 (range, 24-51) years at the time of reconstruction. Average duration of follow-up is 32 (range, 1-96) months. RESULTS: One patient is awaiting ileostomy closure. Five of nine patients use constipating agents. Two patients are constipated and use enemas to aid in evacuation. None are wearing protective undergarments. One patient had his ileostomy reconstructed eight years after delayed pull-through for uncontrollable diarrhea associated with chemotherapy for multiple myeloma and recently died. Postoperative complications included wound infection (3), enterocutaneous anastomotic stricture requiring anoplasty (2), small bowel obstruction (1), pneumonia (1), presacral abscess (1), and pouchitis (1). CONCLUSIONS: Delayed pull-through procedures performed months to years after permanent proctectomy can be performed in selected patients, with results comparable to rectal reconstruction done at the time of proctectomy.

Adult↗

Aortic dissection: rupture into right ventricle and right pulmonary artery.

Rupture of an acute ascending aortic dissection into a surrounding cardiac chamber or pulmonary artery is an uncommon occurrence, and is often only diagnoses post mortem. Although fistulization (aortopulmonary and aorta-right atrial) after acute aortic dissection has been well documented in the literature, acute aortic dissection fistulizing into both the right ventricle and pulmonary artery has not. We report on a 75-year-old woman who presented with an acute ascending aortic dissection with both aortopulmonary and aorta-right ventricular fistulas who underwent repair and had long-term survival.

Aged↗

Body iron stores and risk of colonic neoplasia.

BACKGROUND: Body iron stores and dietary iron intake have both been shown to be positively associated with subsequent risk of colon cancer. This finding comes from a cohort study involving 14,000 men, but the positive association occurred in only 12 cases. PURPOSE: We performed a case-control study of 264 men and 98 women to test for an association between serum ferritin levels and the presence of adenoma of the colon that would be independent of other known risk factors. METHODS: Serum ferritin levels were determined in this study from sera, frozen at -80 degrees C for 5-8 years, that had been originally obtained between 1984-1987 at the Walter Reed Army Medical Center from adult male and postmenopausal female patients undergoing routine colonoscopic examination and previously enrolled in a case-control study that assessed the potential dietary and environmental risk factors for colonic neoplasia. The presence of fecal occult blood in the stool or the suggestion of colonic polyps seen on barium enema defined eligibility for the study. Patients with known preexisting colonic disease were excluded. Eligible patients had their blood drawn and serum prepared. Following colonoscopy and histologic review, the patients were classified into three groups: normal (without neoplastic disease), 159 subjects; adenoma, 145 subjects; and colon cancer, 29 subjects. Body iron stores were determined by measuring serum ferritin levels by a competitive-binding radiometric immunoassay. Ferritin levels categorized into quintiles for adenoma were defined. Crude and adjusted odds ratios (ORadj) with 95% confidence intervals (CIs) for cancer and adenoma related to ferritin were calculated, controlling for known or suspected risk factors including sex, age, race, body mass index, family history, tobacco use, and alcohol consumption. RESULTS: Statistically significant associations of adenoma risk were seen in the third ([ORadj] = 3.8; 95% CI = 1.5-9.5) and fourth (ORadj = 5.1; 95% CI = 2.0-12.7) quintiles of ferritin relative to the first quintile, for smoking history (ORadj = 2.4; 95% CI = 1.3-4.3), for male sex (ORadj = 1.9; 95% CI = 1.0-3.7), and for family history of polyps or cancer (ORadj = 1.8; 95% CI = 1.0-3.4). From a second set of analyses that excluded 36 patients with serum ferritin of greater than or equal to 399 ng/mL, the greatest effect of ferritin on adenoma risk by anatomic subsite was seen in the right colon. CONCLUSION: The apparent dose-response for serum ferritin level and adenoma risk suggest that exposure to iron may be related to adenoma formation.

Adenoma↗

Colorectal.

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Colorectal Neoplasms↗

Phase I study of (6R)-5,10-dideazatetrahydrofolate: a folate antimetabolite inhibitory to de novo purine synthesis.

BACKGROUND: Cancer chemotherapy with folate antimetabolites has been traditionally targeted at the enzyme dihydrofolate reductase and is based on the requirement of dividing tumor cells for a supply of thymidylate and purines. However, a new compound, 5,10-dideazatetrahydrofolate (DDATHF, whose 6R diastereomer is also known as Lometrexol), has become available that prevents tumor cell growth by inhibiting the first of the folate-dependent enzymes involved in de novo purine synthesis, glycinamide ribonucleotide formyltransferase. PURPOSE: We investigated the toxicity and therapeutic activity of DDATHF in a phase I clinical trial. METHODS: DDATHF was given at one of the following dose levels to 33 patients (16 females and 17 males) with malignant solid tumors: 3.0 mg/m2 per week (level A) to 10 patients, 4.5 mg/m2 per week (level B) to 13 patients, or 6.0 mg/m2 per week (level C) to 10 patients. Each drug cycle consisted of three weekly injections of DDATHF followed by a 2-week rest prior to redosing in the next cycle. RESULTS: Of 33 patients, 27 received at least one full cycle of DDATHF. Thrombocytopenia was the major dose-limiting toxicity, and it was severe in one of 10 patients during the first cycle and in two of four patients during the second cycle. Because of cumulative toxicity at 6.0 mg/m2, second or later cycles were abbreviated to two weekly doses. Stomatitis was generally mild, but it was dose-limiting in one patient. Neutropenia was infrequent and mild, and normocytic anemia requiring blood transfusion was common with repeat dosing. Leucovorin was given for grade 2 or greater thrombocytopenia and resulted in hematologic recovery within 1 week in all eight patients so treated. Without leucovorin, the thrombocytopenia lasted from 7 to 49 days in three patients. A partial response was noted in one patient with non-small-cell lung cancer and a minor response in one patient with breast cancer. Three patients with colorectal cancer achieved stable disease for greater than 3 months with improvement in carcinoembryonic antigen levels in one patient. CONCLUSIONS: DDATHF has an unusual pattern of toxicity with repetitive dosing, and humans with advanced cancer are considerably more sensitive than would be predicted from previous animal studies. Although doses of 6.0 mg/m2 per week on our schedule have been determined to be safe, repeated cycles require careful monitoring because of cumulative toxic effects. IMPLICATIONS: Additional phase I studies of DDATHF that relate toxicity to folate intake and tissue folate pools appear warranted.

Adult↗

The decision to treat patients with recurrent colorectal cancer.

Although universally performed, postoperative diagnostic screening in patients with colorectal cancer has not been demonstrated to diminish overall mortality. Such screening often leads to second-look surgery, with many anecdotal successes but again no evidence that overall mortality is reduced. The cost of such interventions is at least $1 billion dollars per year in the United States and may be twice that amount. The research that is needed to support postoperative screening and surgery is feasible and economically easily justified. The endpoints must be shifted from that of previous studies, which have focused on sensitivity of screening techniques, to mortality. Such a study is ongoing in Denmark, and early results of that study should be reported soon.

Colonic Neoplasms↗

Radiometric assay of red cell and plasma cholinesterase in pesticide appliers from Minnesota.

In this study we demonstrate the uses of radiometric assay to detect anticholinesterases in a human population (N = 80) exposed to a broad spectrum of pesticides. The assay is nondilutional. Therefore, anticholinesterase (AChE) agents with low binding affinity can be detected. Our initial results show statistically significant exposure-related decreases in either red cell (AChE) or plasma cholinesterase activity ((butyrl)cholinesterase; BuChE) occurred not only among pesticide appliers who use organophosphates, but also among appliers of the fumigant phosphine. These data extend earlier observations made in laboratory animals exposed to this fumigant. Significant exposure-related decreases in AChE activity were seen in herbicide appliers and appear to be associated with exposure to the herbicide 2-methoxy-3,6-dichlorobenzoic acid. There was no evidence of exposure-related decreases in BuChE activity in herbicide appliers. Our in vivo data, coupled with preliminary in vitro studies of phosphine (50% AChE inhibition, 10 ppm) and 2-methoxy-3,6-chlorobenzoic acid (50% AChE and BuChE inhibition, 70 ppm), suggest that the radiometric assay may be used to detect a broader spectrum of biologically active anticholinesterase agents.

Acetylcholinesterase↗

Role of the seton in the management of anorectal fistulas.

PURPOSE: To identify the incidence of major fecal incontinence and recurrence after staged fistulotomy using a seton. METHODS: A five-year retrospective chart review of 116 patients (70 males and 46 females) ranging in age from 18 to 81 years (mean, 42 years), in whom setons were placed as part of a surgical procedure for anorectal fistulas, was carried out. Follow-up ranged from 2 to 61 months (mean, 23 months). RESULTS: Setons were employed to identify and promote fibrosis around a complex anorectal fistula as part of a staged fistulotomy in 65 patients (56 percent). Other indications for seton placement included 24 women with anteriorly situated high transsphincteric fistulas (21 percent) and three patients with massive anorectal sepsis (floating, freestanding anus) (2.5 percent). In addition, setons were used to preclude premature skin closure and promote controlled long-term fistula drainage in 21 patients with severe anorectal Crohn's disease (18 percent) and in three patients with AIDS (2.5 percent). Major fecal incontinence (requiring the use of a perineal pad) occurred in five patients (5 percent), and recurrent fistulas were noted in three (3 percent). CONCLUSIONS: Staged fistulotomy using a seton is a safe and effective method of treating high or complicated anorectal fistulas.

Adolescent↗

Determination of inflammatory bowel disease activity by breath pentane analysis.

PURPOSE: Quantitative determination of breath pentane, an alkane generated by peroxidation of cellular fatty acids, has been used as a noninvasive determinant of inflammation. Herein we report the first examination of the relationship between breath pentane and intestinal inflammation in humans. METHODS: Patients (N = 33), either with a known history of inflammatory bowel disease (IBD) with symptoms of relapse or with no known history of but having symptoms consistent with IBD, were evaluated with indium-111-labeled leukocyte imaging to assess the presence of active inflammation. At the time of the indium scan, the exhaled breath of the patients was obtained via a collecting tube. Gas chromatography was used to quantify the pentane content, and these values were compared with graded indium scans. RESULTS: The range of breath pentane found in our population (36 determinations in 33 patients) was from 0 to 38.4 nmol/l of exhaled air. For patients with negative scans, the mean pentane was 2.1 nmol/l, for intermediate scans 3.1, for positive scans 4.3, and for nonintestinal nuclide imaging 5.5 [P = 0.005 by analysis of variance (ANOVA)]. CONCLUSIONS: We have previously demonstrated the correlation of breath pentane with gross and histologic evidence of intestinal inflammation in a rodent colitis model. This current study also demonstrates that pentane analysis can be correlated with inflammatory bowel disease activity in humans.

Adult↗

Quantitative determination of pentane in exhaled air correlates with colonic inflammation in the rat colitis model.

Oxygen radicals play a key role in inflammation and inflammatory tissue damage. Quantitative determination of pentane, a hydrocarbon generated by membrane lipid peroxidation initiated by oxygen radicals, in expired air has been used as a noninvasive determinant or index of inflammation in various conditions. Herein we report the first examination of the relationship between exhaled pentane and colonic inflammation in a rodent model of colitis. Colitis was induced in rats (n = 33) using the trinitrobenzene-sulfonic acid (TNB) model of colitis. Exhaled air was collected in a closed chamber on randomly selected animals on days 1, 2, 4, 7, 11, 13, 15, 20, and 25 post-TNB treatment, and pentane was assayed by means of gas chromatography. Gross and microscopic evidence of inflammation was compared with exhaled pentane levels. Pentane levels varied from 0.0 to 14.6 nmol/l of air and were significantly increased in TNB-treated rats compared with control rats only on days 7 to 15 after treatment (P < 0.05). Gross inspection showed severe colonic inflammation through the first week (mean score = 4.7 out of a possible 5), persistent inflammation on days 7 to 15 (3.2), and healing and fibrosis from the end of week two until day 25 (1.9 to 0). Histologic evaluation confirmed a progression of inflammation from acute ulceration to chronic inflammation to fibrosis and scarring. We have demonstrated that pentane exhalation is increased after the induction of colonic inflammation, with a seven-day lag time, and returns rapidly to normal as acute inflammation resolves. This suggests that pentane exhalation can be used as a noninvasive measure of colonic inflammation in rodent models of colitis and perhaps clinically in humans.

Air↗

Diagnostic techniques in inflammatory bowel disease.

Additional diagnostic modalities exist in the clinical laboratory, as outlined in Tables 1 through 3. In general, the usefulness of each test in determining the optimal therapy for a patient with inflammatory bowel disease is inversely related to the cost of that test, with history and physical examination ranking first. Each additional test must be ordered only if the result can answer a specific question necessary for the care of the patient.

Endoscopy, Gastrointestinal↗

The effect of vagotomy and pyloroplasty on colorectal tumor induction in the rat.

Epidemiologic studies have suggested that vagotomy increases subsequent colorectal cancer risk. This hypothesis was investigated in the rat 1,2 dimethylhydrazine (DMH) colorectal carcinogenesis model. Eighty-five rats were divided into four groups having either truncal vagotomy and Heineke-Mickulicz pyloroplasty, pyloroplasty alone, laparotomy alone, and anesthesia alone. After recovery from the procedures, colon tumors were induced with five injections of DMH. Results of carcinogenesis show a trend towards increased incidence and yield of colorectal and duodenal tumors after vagotomy, though this was not statistically significant, perhaps because the high postoperative mortality from vagotomy diminished the power of the study.

1,2-Dimethylhydrazine↗