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Biomedical subjects

N D Nigro

Publications and source records attributed to N D Nigro.

At least 19 recordsLinked to original sources
PubMed1992

Clinical impact of magnetic resonance imaging in foot osteomyelitis.

The impact of magnetic resonance imaging (MRI) on the clinical management of patients with foot inflammation and suspected osteomyelitis was evaluated in 44 patients with 47 foot MRI exams. Twenty-nine patients were diabetic. Bone biopsy or bone culture was obtained in 34 patients, and routine radiographs and bone scan studies were available in most patients for comparison. Magnetic resonance imaging showed reliable identification of bone infection with a sensitivity of 100% and specificity of 95%. Plain radiographs were inaccurate and, as expected, bone scans were highly sensitive (90%) but not specific (33%). The high accuracy of MRI allowed for better identification of patients with osteomyelitis and, therefore, improved targeting of potential operative candidates.

Adult↗
PubMed1989

Dynamic management of squamous cell cancer of the anal canal.

For many years the accepted treatment for squamous cell cancer of the anal canal has been abdominoperineal resection of the rectum. Recently, high dose radiation therapy has been advocated by some, and we initiated a study using a combination of radiation, chemotherapy and surgery. This review includes 44 patients treated by us from December 1971 to July 1983. We discontinued routine operation after 1975 because chemoradiation therapy eliminated the primary lesion in most patients. In fact, the gross lesion disappeared in 40 patients, 13 of whom had radical operations done on routine basis. Four operations were done for residual disease after chemoradiation treatment and one for local recurrence. The corrected, projected five year survival rate was 79% with a follow-up of at least four years in all patients. Most failures occurred in patients with large primary tumors, all of whom had radical operations after the preoperative therapy. This experience suggests that patients with primary lesions over 5 cm in maximum diameter should have an additional course of chemoradiation and/or abdominoperineal resection on a routine basis.

Adult↗
PubMed1989

The essential fatty acid requirement for azoxymethane-induced intestinal carcinogenesis in rats.

The essential fatty acid requirement for the development of intestinal carcinogenesis was determined and compared to the overall essential fatty acid status of the animals as measured by the triene/tetraene ratio in the plasma, liver and colon. To induce tumors, male Sprague-Dawley rats were given two weekly injections (20 mg/kg body wt) of azoxymethane. Two weeks after the last injection, the rats were divided into groups of 25 and given one of six diets containing various levels of essential fatty acids (as linoleate). The diets contained 5% total fat and were prepared by mixing safflower oil (high essential fatty acids, beef fat (low essential fatty acids), and medium chain triglyceride oil (no essential fatty acids). One group of rats was fed a 20% beef fat diet. The range of essential fatty acids was from less than 0.03% to 1.28% (w/w). Twenty-six weeks after the first azoxymethane injection, the animals were killed and intestinal tumor incidence and multiplicity were determined. Samples of plasma, liver and colon were also taken for measurement of the triene/tetraene ratio by gas chromatography. Large bowel tumor incidence showed a dependence on the essential fatty acid content of the diet. The results were as follows: (percent essential fatty acids: percent tumor incidence) Group A (1.28: 72.4), Group B (0.60: 73.3), Group C (0.11: 55.2), Group D (0.08: 39.3), Group E (less than 0.03: 37.9) and Group F, which was fed 20% beef fat, (0.34: 88.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Structural requirements for stimulation of colonic cell proliferation by oxidized fatty acids.

The primary autoxidation products of polyunsaturated fatty acids are known to stimulate DNA synthesis and induce ornithine decarboxylase activity in colonic mucosa. In the present study we have determined the structural features of the oxidized fatty acids necessary for the stimulation of these two components of mitogenesis. Compounds were instilled intrarectally in either aqueous or mineral oil vehicles and 3 h later (ornithine decarboxylase activity) or 12 h later (tritiated thymidine incorporation), the animals were killed and the colonic mucosa harvested for measurement of the two parameters of cell proliferation. Hydroperoxy and hydroxy fatty acids derived from oleate and stearate were studied. Ricinoleic acid and the alpha,beta-unsaturated ketone derived from oleic acid were also investigated. The minimal requirement for stimulation of cell proliferation is the presence of an oxidized functionally adjacent to a carbon-carbon double bond. All active compounds studied were roughly equipotent, which suggests a common mediator may be involved. These results imply that, in addition to biliary steroids, the autoxidation products of unsaturated fatty acids may play a role in the enhancement of tumorigenesis by high levels of dietary fat. Furthermore, the data suggest a possible mechanism of action for the active compounds.

Animals↗
PubMed1987

Prospects for the prevention of colorectal cancer.

Cancer research has been productive in developing new knowledge on the role of diet in cancer. It is clear from epidemiologic observations that diet is the principal factor in the cause of colorectal cancer in most people. Therefore, a significant reduction in incidence is possible in countries where the disease is common. The ingestion of excessive amounts of fat appears to be the major factor that promotes cancer development. Animal studies confirm this and have recently shown that the sources of fat vary in the degree of their promotional effect. Fiber is generally considered to inhibit cancer but it is now clear that only some types of fiber are effective. These include whole grain cereals, and fruit and vegetables containing large amounts of uronic acid. In addition to fiber, a number of micronutrients, chemicals, and drugs have been found to be effective inhibitors. It is clear that the basic information concerning dietary changes that can reduce colorectal cancer incidence in this country has been uncovered. Additional information is needed about specific details of dietary guidelines. These include identification of the best mixture of sources of fat and how to incorporate such a mixture in the diet. Substances in foods need to be identified that, when included in the diet, help to lower cancer risk. People at high risk may require an additional supplement of inhibitors. New epidemiologic studies and human intervention trials should provide the necessary information to design dietary guidelines that are more specific than current ones.

Colonic Neoplasms↗
PubMed1987

The impact of dietary fat and fiber on intestinal carcinogenesis.

The effect of dietary fiber on intestinal carcinogenesis in animals is controversial. Some find that the addition of wheat bran or cellulose inhibits intestinal cancer in rats, while others report no effect. Such mixed results often are due to differences in the design of experiments. One important aspect in this regard is the amount of fat in the diet. Some fiber supplements inhibit cancer formation when the fat content is normal but not when it is high. However, a recent epidemiological study in Scandinavia showed a lower cancer incidence in a rural population compared with an urban area, in spite of the fact that the dietary fat content was high in both regions. There was a modest difference in the amount of fiber, and this may not have accounted completely for the variation in cancer incidence. Other dietary factors might have added inhibitory response to help overcome the promotional effect of an excessive amount of fat. The interaction among dietary components must be considered when designing animal experiments to assess the effect of fiber on cancer development.

Animals↗
PubMed1987

Importance of the duration of inhibition on intestinal carcinogenesis by difluoromethylornithine in rats.

The effect of the duration and sequence of inhibition of intestinal tumor formation in rats was studied to determine whether part time inhibition has any value. Four groups of male Sprague-Dawley rats were given 8 weekly s.c. injections of azoxymethane (AOM) 8 mg/rat. Three groups were given the inhibitor, difluoromethylornithine (DFMO) in the drinking water; one for the entire 26 weeks of the study, one for the first 13 weeks only, and one for the last 13 weeks. A control group was not given the inhibitor. While the continuous treatment group developed the least number of tumors per rat (1.5 vs. 5 for controls), still both groups given the inhibitor for just 13 weeks also developed fewer tumors than controls 5 vs. 3.2 (early treatment) and 5 vs. 2.8 (late treatment). These results show that part time inhibition, including its late application, does reduce intestinal tumor formation in rats.

Animals↗
PubMed1986

Inhibition of intestinal carcinogenesis in rats: effect of difluoromethylornithine with piroxicam or fish oil.

An inhibitor of ornithine decarboxylase, difluoromethylornithine (DFMO), and two inhibitors of prostaglandin biosynthesis, piroxicam and menhaden fish oil, were examined for their effect on intestinal tumorigenesis in male Sprague-Dawley rats fed a 5% fat semisynthetic diet. Each agent was given individually in one of two doses as follows: DFMO, 0.05% and 0.1% in the drinking water; piroxicam, 65 mg/kg diet and 130 mg/kg diet; and menhaden fish oil, 1.25% and 2.50% of the diet. Additional animal groups were given combinations of the lower dose of DFMO and the lower dose of either piroxicam or fish oil. Intestinal tumors were induced by sc injections of azoxymethane (AOM; CAS: 25843-45-2) at 8 mg/kg (body wt) weekly for 8 weeks. Test diets were started 1 week prior to the first dose of AOM, and the rats were sacrificed 26 weeks later. Rats that received either dose of DFMO or the high dose of piroxicam developed significantly fewer intestinal tumors compared to controls. The low dose of piroxicam and the fish oil given at either dose level had no effect. The combination of the low dose of DFMO and the low dose of piroxicam reduced tumor formation more than either dose of DFMO alone, whereas the low dose of DFMO and fish oil together was no more effective than either dose of DFMO alone. These results show that a combination of a small amount of DFMO and piroxicam, each acting through a different mechanism, exerts an additive inhibitory effect on intestinal tumor formation in rats.

Animals↗
PubMed1985

Animal model for colorectal cancer.

The development of a satisfactory rodent model for cancer of the large intestine began with the discovery by Laqueur and associates in 1962 that the plant product, cycasin (methylazoxymethanol glycoside), is a potent carcinogen for rodents. Soon after that, DMH, AOM, and MAM were found to be even more efficient intestinal carcinogens in rats. These three compounds, plus two direct acting carcinogens (MNNG, MNU) are used almost exclusively in current animal investigations. Although all these chemicals have some degree of activity in all rodents, they are most effective in rats. Various rat strains differ somewhat in susceptibility, Sprague-Dawley being the most sensitive to these carcinogens. Cancers of the large intestine in the animal model resemble adenocarcinomas in humans, and they spread in a similar manner except that metastases to the liver and lung are very uncommon in animals. Animal studies support epidemiological and human experimental observations of dietary factors involved in colorectal cancer formation. Most physicians believe that the majority of colorectal cancers develop from preexisting adenomas. Morson has shown that large adenomas and villous adenomas have a greater risk of developing cancer than small adenomas. Hill has theorized that there are different factors responsible for the formation of small adenomas from normal mucosa, for the growth of small to large adenomas, and for the development of cancer from large adenomas. Animal studies provide some support for this concept. Weak intestinal carcinogens tend to induce more benign adenomas than carcinomas. Very small doses of strong carcinogens also induce some adenomas and a few early polypoid intestinal cancers after a long latent period. Moderate to large amounts of DHM, for example, induce only malignant lesions even when these lesions are as small as 1 mm. These observations suggest a relationship between adenomas and carcinomas. There is also biochemical evidence to support the staged progression of carcinogenesis. An example is the graded increases in ODC activity that occur in tissues undergoing tumorigenesis.

Adenoma↗
PubMed1984

An evaluation of combined therapy for squamous cell cancer of the anal canal.

Carcinoma of the anal canal develops in the area of the dentate line and is referred to as cloacogenic, transitional, basaloid, epidermoid, and squamous cell cancer. For years, the accepted treatment for these lesions has been abdominoperineal resection. The use of preoperative radiation and chemotherapy was begun by our group in 1972. By 1975, it became apparent that radiation and chemotherapy alone appeared effective enough so that radical operation was not done routinely. An evaluation of the results in 104 patients, 44 of whom were treated by us (the rest of the data was collected by questionnaire), suggests that radiation and chemotherapy alone are at least as effective as radical surgery in most patients with this disease.

Adult↗
PubMed1984

Ornithine decarboxylase activity in the rat and human colon.

We have investigated the effect of age, a high-fat diet, sodium deoxycholate, and the ornithine analogue alpha-difluoromethylornithine on ornithine decarboxylase (ODC) activity in the rat colon. The relative levels of ODC activity were also determined in normal mucosa and tumor tissue from rat and human colon. The colonic ODC activity induced by intrarectal instillation of sodium deoxycholate in male Sprague-Dawley rats was highest in young animals, and it decreased with increasing age. A high level of dietary fat caused both an increased in basal colonic ODC activity and enhanced ODC induction by deoxycholate. alpha-Difluoromethylornithine given in drinking water inhibited, in a dose-dependent fashion, deoxycholate-induced ODC activity. The frequency of azoxymethane-induced intestinal tumors was also significantly reduced by alpha-difluoromethylornithine. Since colonic ODC activity is increased in carcinogenesis by known promoting agents and decreased by tumor inhibitors, this short-term assay may provide a useful system for identifying colon tumor promoters and inhibitors. The ODC activity in colon tumors of Sprague-Dawley rats was found to be significantly higher than in normal-appearing mucosa in the same animals. Similarly, ODC activity in human colon cancer was found to be higher than that of the normal-appearing mucosa in the same specimen. These results strengthen the utilization of the rat model for studies, the results of which may apply to the human situation.

Animals↗
PubMed1984

In vivo stimulation of DNA synthesis and induction of ornithine decarboxylase in rat colon by fatty acid hydroperoxides, autoxidation products of unsaturated fatty acids.

The effect of intrarectal instillation of hydroperoxy and hydroxy fatty acids on colonic DNA synthesis and ornithine decarboxylase activity in male Sprague-Dawley rats was examined. A mixture of hydroperoxy-arachidonic acid isomers was prepared by methylene blue-sensitized photooxygenation. Pure 13-hydroperoxy-9,11-octadecadienoic acid was prepared by the action of soybean lipoxygenase on linoleic acid. Sodium borohydride reduction yielded the respective hydroxy fatty acids. Twelve hr after instillation of solutions of either hydroperoxy or hydroxy fatty acids, at concentrations up to 10 mM, DNA synthesis was increased in a dose-dependent fashion up to 240% above control values. The induction of ornithine decarboxylase occurred over a similar concentration range 3 hr after instillation of oxidized linoleic acid. In this case, the hydroxy acids (49-fold increase at 10 mM), were more stimulatory than the hydroperoxy derivatives (23-fold at 10 mM). Highly purified linoleic and arachidonic acids did not stimulate either activity at concentrations up to 50 mM. These data indicate that autoxidation products of unsaturated fatty acids, likely components of high-fat diets, can evoke proliferative responses in colonic mucosa. These responses may be relevant to the promotional effect of high dietary fat on colon carcinogenesis.

Animals↗
PubMed1983

Combined preoperative radiation and chemotherapy for squamous cell carcinoma of the anal canal.

Twenty-eight patients with squamous cell carcinoma of the anal canal were treated by preoperative radiation therapy and chemotherapy. The radiation therapy was given for 3000 rad (30 Gy) at 200 rad per day, 5 days a week, to the primary tumor with margin and to the pelvic and inguinal lymph nodes. Chemotherapy was given in the form of 5-fluorouracil infusion 1000 mg/m2 on days 1-4 of the radiation therapy and repeated on days 29-32 of the treatment regimen. Mitomycin C was given in the form of intravenous bolus for 15 mg/m2 on day 1. Surgery was done 4-6 weeks following the last day of radiation treatment. Twelve patients underwent anteroposterior resection, and seven of the 12 had no residual tumor in the surgical specimen, while one patient had microscopic tumor only. An additional 14 patients had complete clinical disappearance of their tumor, and, on excision of the scar, it was found free of microscopic cancer. Two other patients are clinically free of tumor but had no biopsy after therapy. While transient proctitis leukopenia and thrombocytopenia were moderate to severe, no serious complications were observed in these patients. Twenty-two patients are free of tumor and alive one to eight years after treatment. One patient died a cardiac death without tumor four years after surgery. Four patients, all with residual tumor in the specimen, have died of cancer. Their primary lesions were more than 7 cm in maximum diameter at initial examination. One patient died of disseminated disease with no local recurrence after abdominal perineal resection.

Adult↗