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Biomedical subjects

D Pelot

Publications and source records attributed to D Pelot.

11 recordsLinked to original sources
PubMed1998

Effect of alpha-difluoromethylornithine on rectal mucosal levels of polyamines in a randomized, double-blinded trial for colon cancer prevention.

BACKGROUND: Polyamines (e.g., putrescine, spermidine, and spermine) are required for optimal cell growth. Inhibition of polyamine synthesis suppresses carcinogen-induced epithelial cancers, including colon cancer, in animal models. In a short-term phase IIa trial, we determined that low doses of alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (an enzyme involved in polyamine synthesis), reduced the polyamine content of normal-appearing rectal mucosa of subjects with a prior history of resected colon polyps. In a follow-up study, we have attempted to determine the lowest dose of DFMO that can suppress the polyamine content of rectal mucosa over a course of 1 year with no or minimal side effects. METHODS: Participants were randomly assigned to daily oral treatment with a placebo or one of three doses (0.075, 0.20, or 0.40 g/m2) of DFMO. Baseline and serial determinations of polyamine levels in rectal mucosa and extensive symptom monitoring (including audiometric measurements, since DFMO causes some reversible hearing loss at higher doses) were performed over a 15-month period. RESULTS: DFMO treatment reduced putrescine levels in a dose-dependent manner. Following 6 months of treatment, doses of 0.20 and 0.40 g/m2 per day reduced putrescine levels to approximately 34% and 10%, respectively, of those observed in the placebo group. Smaller decreases were seen in spermidine levels and spermidine:spermine ratios. Polyamine levels increased toward baseline values after discontinuation of DFMO. Although there were no statistically significant differences among the dose groups with respect to clinically important shifts in audiometric thresholds and nonaudiologic side effects, statistically significant higher dropout and discontinuation rates were observed in the highest dose group. CONCLUSIONS: Polyamine levels in rectal mucosa can be continuously suppressed by daily oral doses of DFMO that produce few or no side effects. A dose of 0.20 g/m2 can be used safely in combination phase IIb or single-agent phase III chemoprevention trials.

Adult↗
PubMed1998

Effects of experimental hemosiderosis on pancreatic tissue iron content and structure.

The effects of iron overload on pancreatic iron content and morphology were investigated. Sprague-Dawley rats were randomized into an iron-overloaded group, which received a single subcutaneous injection of 1.2 g/kg elemental iron as iron-dextran complex, and placebo-treated pair-fed controls. Animals were studied after a 10-month observation period. Tissue nonheme iron content was measured, and histologic examination was carried out. Chronic iron-overloaded animals showed significant increases in tissue iron content. There was a statistically significant increase in stainable iron in perivascular, parenchymal, and lymphoid tissue in the iron-overloaded group. Although pancreatic fibrosis was present in the iron-overload group, it was not statistically significant. The iron-overloaded animals showed some islet cell destruction. In contrast, no significant islet cell destruction was seen in the control group. However, the difference was not statistically significant. Moreover, the serum glucose levels were the same in both groups, suggesting that there was no significant impairment of pancreatic endocrine function. Thus, chronic experimental iron overload in rats leads to significant increases in tissue iron content, but no significant morphologic alterations of the pancreas with the dose and route of iron administered in this animal model.

Animals↗
PubMed1994

Dose de-escalation chemoprevention trial of alpha-difluoromethylornithine in patients with colon polyps.

BACKGROUND: alpha-Difluoromethylornithine (DFMO) is a potent inhibitor of carcinogenesis in experimental animal models. In these animal models, DFMO has been especially active in preventing carcinogen-induced epithelial cancers, including those of the skin, colon, breast, and urinary bladder. Although DFMO is known to exert its diverse biological effects by suppressing intracellular pools of the polyamines putrescine and spermidine, the precise mechanism by which polyamine depletion, induced by DFMO, suppresses carcinogenesis is unknown. PURPOSE: The specific aim of our study was to determine the lowest dose of DFMO that would deplete target tissue (colorectal mucosa) levels of these polyamines in humans who had undergone prior removal of colon polyps while producing minimal toxic effects. METHODS: A dose de-escalation chemoprevention trial of DFMO was conducted in 111 patients (36 female and 75 male) who were in generally good health, aged 39-79, and who had undergone colonoscopy for surgical removal of an adenomatous colon polyp greater than 3 mm within 5 years prior to entering the study. Groups of patients (12-20 patients per group) were orally treated with single, daily doses of DFMO ranging from 3.0 to 0.1 g/m2 for 4 weeks (28 days). Prior to initiation of DFMO treatment and at the end of treatment, six colorectal biopsy specimens were collected from each patient, along with serum samples. All biopsies were performed between 9 AM and noon to avoid possible effects of diurnal variations in laboratory end points. Samples for analysis of plasma DFMO levels were also collected during this time period on the day after the last day of drug administration. RESULTS: DFMO caused a decrease in both putrescine content and the ratio of spermidine to spermine for all dose groups down to 0.25 g/m2. Both putrescine content and the ratio of spermidine to spermine and changes in these parameters as a function of DFMO treatment decreased as a function of donor age. None of the 30 patients receiving either 0.25 or 0.5 g/m2 experienced any clinical ototoxicity in this trial. CONCLUSIONS: DFMO is both safe and effective in reducing colorectal mucosal polyamine contents when it is administered orally to patients at doses as low as 0.25 g/m2 for 28 days. No ototoxicity was observed at doses up to twice this amount. IMPLICATIONS: If DFMO is also found to be effective in suppressing polyamine contents in other target tissues, it may be useful in preventing a wide range of human epithelial cancers, including those of the prostate and breast.

Administration, Oral↗
PubMed1986

The role of antegrade barium studies in the evaluation of colitis.

The retrograde barium enema is considered to be contraindicated in patients with acute colitis because of the risk of precipitating toxicity. The purpose of this study was to investigate the antegrade evaluation of the colon in such patients. Thirteen patients were examined by antegrade barium study. The right and left colon to the level of the descending colon-sigmoid junction were well seen in all (100%), the sigmoid in 77% and the rectum in 54%. Excellent correlation between the extent of disease seen on antegrade study and retrograde enema, endoscopy, and surgery was achieved. The antegrade study was found to be a safe and effective study in patients with acute colitis.

Adult↗
PubMed1981

PIPIDA excretory scintigraphy in the diagnosis of hepatobiliary disorders.

The diagnostic accuracy of hepatobiliary radionuclide imaging using 99mTC-labeled para-isopropyl acetanilido-iminodiacetic acid (99mTc-PIPIDA) in patients with hepatobiliary disorders was assessed in 50 patients. Thirty of the study group were jaundiced; the remaining 20 had other clinical features suggestive of some hepatobiliary disorder. The findings using PIPIDA proved to be correct in 22 (73%) of the 30 jaundiced patients and in 18 (90%) of 20 patients without jaundice. There appears to be a close relationship between the diagnostic accuracy of the test and the level of serum bilirubin. Thus, the diagnosis indicated by the PIPIDA test was correct in 30 (88%) of 34 patients in whom the serum bilirubin was less than 5 mg./dl. but only in 10 (62%) of 16 patients whose serum bilirubin exceeded 5 mg./dl. It is concluded from these observations that: 1. PIPIDA is diagnostically useful in the evaluation of hepatobiliary disorders, especially when the serum bilirubin is less than 5 mg./dl. and 2. the accuracy of this test is not absolute and the findings are not always definitive.

Adult↗
PubMed1977

The diagnostic value of serum lysozyme activity in inflammatory bowel disease.

Serum lysozyme (muramidase) activity was determined by the Lyso-Plate diffusion technic in 419 subjects consisting of normal persons and patients with Crohn's disease, ulcerative colitis, nonspecific diarrhea and various other disorders. Lysozyme activity in the normal subjects did not exceed 37.8 microgram/ml. The values in the several groups of patients overlapped markedly with each other and with the normal range. Approximately two-thirds (62.1%) of the 37 patients with Crohn's disease had values that were within the normal range. In about half (51.8%) of the patients with this disease in whom the process was clinically active, serum lysozyme activity was increased. Of 10 patients with Crohn's disease who had undergone resection, heightened serum lysozyme activity was found only in the three patients in whom there was clinical evidence of recurrence of the disease. It is concluded that serum lysozyme activity is not a dependable means of distinguishing Crohn's disease from ulcerative colitis or nonspecific diarrheas. The determination would appear to be of value, however, in helping to identify activity, recurrence, or extension of the disease in patients with Crohn's disease.

Adolescent↗
PubMed1975

Constipation of prolonged duration.

A case is reported of a 19-year old man who went periods of four and a half and four months without a bowel movement and who experienced no distress throughout these periods except for late appearing abdominal cramps.

Adult↗
PubMed1974

The nature and significance of hyperamylasemia follwing operation.

Total serum amylase activity was found to be significantly elevated postoperatively in 11 (10%) of 110 patients undergoing various surgical procedures. Isoamylase analysis revealed that the rise was chiefly in the pancreatic-type isoamylase in seven of the 11 patients showing postoperative serum amylase elevations; in the other four patients, the elevation occurred principally in the salivary-type isoamylase. These data demonstrate that postoperative hyperamylasemia occurs surprisingly often and that serum amylase activity may rise even when the surgical procedure is extra-abdominal. Moreover, elevation of serum amylase activity after surgery is not necessarily an indication of pancreatitis and may reflect instead a rise in salivary-type isoamylase.

Abdomen↗