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Biomedical subjects

R L Nelson

Publications and source records attributed to R L Nelson.

At least 217 records · Page 12Linked to original sources
PubMedDate not supplied

Anal adenocarcinoma: a comprehensive review.

Adenocarcinoma of the anal canal is a rare form of a rare tumor. It remains less prevalent than both basaloid and keratinizing tumors of the anal canal. Within the category of anal adenocarcinomas, uniformity in histology, biology, or etiology is lacking. This makes subdivision of this rare entity by various parameters necessary. Several etiologic associations have been described, such as chronic fistula-in-ano, anal Crohn's disease, and anal sexual intercourse, raising the issue of cancer prevention and early detection. Various available therapeutic options are also discussed with emphasis on the seemingly promising results of preoperative chemo- and radiation therapy. Because of the rarity and apparent heterogeneity of this tumor, no comparative or analytic epidemiologic studies have been conducted that might resolve these issues. Whether histology differentiates anal adenocarcinoma from anal squamous or cloacogenic tumors in the determination of natural history and allocation to optimal therapy remains unclear. It may be that the gross anatomic location of the tumor alone determines the above and histology is superfluous.

Adenocarcinoma↗
PubMedDate not supplied

Iatrogenic perforation of the colon and rectum.

In eight years at Cook County Hospital, 42,000 barium enemas, 16,325 proctosigmoidoscopies, and 1207 colonoscopies were performed. All endoscopic procedures were done by the house staff. There were three perforations due to proctosigmoidoscopy, with one death; three perforations due to colonoscopy, with no deaths; and seven perforations due to barium enema, with no survivors. The adjuvant effect of barium sulfate is proposed as the most likely cause for this excessively high mortality in barium-enema perforation.

Aged↗
PubMedDate not supplied

Chromosomal aberrations and sister-chromatid exchanges in tool and die workers.

Because tool and die workers are exposed to a number of potentially genotoxic agents, including mutagenic metals, polyaromatic hydrocarbons, and nitrosamines, and may be at increased cancer risk, the present study was undertaken to test whether chromosomal damage in peripheral blood cells is associated with work in the tool and die industry. Lymphocyte cultures were established from 27 tool and die fabrication workers from one manufacturing plant who had worked in the trade for more than 15 years. 15 of these workers also had some form of malignancy at the time of the study, but had not been treated with radiation or chemotherapies that could themselves induce chromosomal damage. The frequencies of chromosomal aberrations and sister-chromatid exchanges (SCEs) were measured in workers and the data compared with those of a control group consisting of 7 non-fabrication workers from the same plant and 8 age-matched community controls. In addition, the relative rates of lymphocyte proliferation were estimated for each group by analyzing the percentages of first-, second- and third-division mitotic cells after 72 h of culture. The results of the chromosomal studies show that tool and die workers have significantly increased frequencies of aberrations whether engaged in fabrication work or not, compared to control subjects. The frequency of SCEs and the frequencies of 1st, 2nd and 3rd division figures are not different among the study groups. Among workers who are engaged in fabrication, including those who are cancer patients, the frequency of more complex aberrations (i.e., interstitial deletions and small acentric fragments) is increased. In a five-year follow-up of these workers, 2 of the 13 workers with these aberrations developed some form of colon cancer. Whether the presence of interstitial deletions and small acentric fragments is related to the occupation of these workers, or is tangentially related to the development of cancer, is presently under consideration.

Cell Division↗
PubMedDate not supplied

Isolated intrathoracic injury with air bag use.

The restrained (air bag and seatbelt) driver of a vehicle involved in a high-speed motor-vehicle accident sustained a tear of the thoracic aorta with no signs of external injury. Air bag deployment may mask significant internal injury, and a high index of suspicion is warranted in such situations.

Accidents, Traffic↗
PubMedDate not supplied

Model of intestinal continence using an implantable pulse generator and a myoprosthetic sphincter.

Past attempts at artificial continence using a wide range of surgical procedures and devices have met with only limited success because of excessive rates of infection, rejection, incomplete continence, and technical difficulty. Presented here is a model of artificial continence using a lumen-occluding Teflon loop powered by the rectus abdominus muscle and activated by an implantable pulse generator. Eight female mongrel dogs underwent laparotomy with creation of a Brooke ileostomy and insertion of a hand-tooled Teflon band around the ileum. The free ends of the loop were sutured, under tension, to the posterior rectus sheath creating extrinsic compression of the bowel by the tightened loop. After denervation of the rectus, stimulating electrodes were implanted and connected to a transcutaneously activated pulse generator (Medtronic SE-4). Stimulation caused contraction of the muscle segment. As the free ends of the prosthetic sling approach each other, the occlusive band loosens, resulting in free drainage of intestinal contents and reduction in intraluminal pressure of the proximal ileum. Withdrawal of current allows for relaxation and return of the muscle to its resting length; this reoccludes the bowel. At 2 weeks, all dogs were continent to solid matter and all but two were continent to liquids. Two dogs developed wound infections requiring drainage. Signal attenuation across the skin resulted in total uncontrollable continence in two dogs because of an inability to transfer sufficient current to the muscle. Direct probe stimulation by an external pulse generator resulted in drainage in these dogs. Necropsy showed no evidence of bowel ischemia in any of the specimens examined at 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗
PubMedDate not supplied

Characteristics of glycemic stability.

Glucose homeostasis in healthy subjects is characterized by postmeal glucose increases of about 40 mg/dl, peaks at about 45 min, decreases close to antecibal levels 1 h after the peak, and no spontaneous oscillations until the next meal. Diabetes is characterized by progressive loss of glucose homeostasis from stable to unstable, which is directly proportional to loss of insulin secretory reserve. Degree of instability of diabetes in ambulatory subjects within a 24-h period can be expressed as mean amplitude of glycemic excursion of M-value and between two successive 24-h periods as mean of daily differences of blood glucose. Stable diabetic persons have lower values, which are closest to those of nondiabetic persons, and unstable diabetic persons have higher values. The mean diurnal blood glucose level is a measure of glycemic control. The failure to restore glycemic patterns of diabetic to those of nondiabetic persons is largely due to the failure of subcutaneously administered insulin to mimic the pattern of insulinemia of healthy subjects.

Blood Glucose↗
PubMedDate not supplied

Considerations for the programming of an open-loop insulin infusion device from the biostator glucose controller.

To assess the feasibility of preprogramming an open-loop device with insulin flow rates generated by the Biostator Glucose Controller, comparisons were made in 10 juvenile-onset diabetic patients between meals of equal size and composition taken in the morning, at noon, and in the evening and a bedtime snack during a 24-h period of Biostator glucose control. Four additional diabetic patients had Biostator glucose control for 72 h. Similar amounts of insulin were infused for the meals taken at differing times of the day and, except for the morning meal, for the same meal on two successive days. The meal-related glycemic patterns expressed as mean indices of meal excursions (MIME) were similar for meals of identical size and composition during a single day and for the same meal taken on two consecutive days. Preliminary results using an open-loop device preprogrammed by the Biostator system, although encouraging, underscore the deficiency of the subcutaneous route viz. the delayed entry of insulin into the circulation in achieving normal glucose levels and patterns.

Adult↗
PubMedDate not supplied

Factors influencing the absorption, serum insulin concentration, and blood glucose responses after injections of regular insulin and various insulin mixtures.

Normal fasting subjects received regular insulin and mixtures of regular with NPH or lente to assess the effects of the combinations on serum insulin concentrations (SIC) and blood glucose responses (BGR). In addition, the influence of concentration, depth, and method and site of administration was investigated. In studies of mixtures of regular with NPH and with lente, it was observed that the regular: lente ratio needed to achieve peak SIC was higher than with the regular: NPH combination. Increased SIC, including either the peak and/or the time interval required to achieve the peak, were related to the depth and site (deltoid and abdominal greater than anterior thigh or buttocks). Assuming linear kinetics of absorption, significant quantities of insulin fail to reach the serum. Marked intra- and intersubject variations in SIC and BGR to regular, NPH, and lente insulins were observed.

Biological Availability↗
PubMedDate not supplied

An analysis of diabetic pregnancies at Mayo Clinic, 1950-79.

We reviewed the records of pregnant diabetic women attended at Mayo Clinic during the years 1950-79 and matched each nonaborted diabetic pregnancy with two control pregnancies. Abortions occurred in 49 of 277 diabetic pregnancies (17.7%). The relative risk of other adverse outcomes of pregnancy (+/- 95% confidence interval) in comparison with controls was as follows: perinatal mortality, 7.0 (3.6-13.8); major congenital birth defects, 6.3 (2.8-14.2); and respiratory distress, 9.0 (4.5-17.9). Diabetic ketoacidosis resulted in fetal death in 5 of 18 cases. Patients with mean fasting blood glucose levels of less than or equal to 140 mg/dl had a perinatal mortality of 81 per 1000 births and an incidence of respiratory distress and congenital birth defects of 18.9% and 9.9%, respectively. Patients with mean blood glucose levels greater than 140 mg/dl had corresponding rates of 306 per 1000, 20.4%, and 11.2%, respectively. Hydramnios occurred almost exclusively in diabetic women, and its presence was associated with a twofold increase in the frequency of perinatal death. Analysis of diabetic pregnancy outcome by decade showed no appreciable decrease in the occurrence of perinatal mortality, congenital birth defects, or respiratory distress over the 30-yr period.

Abnormalities, Multiple↗
PubMedDate not supplied

Is hereditary hemochromatosis a balanced polymorphism: an analysis of family size among hemochromatosis heterozygotes.

BACKGROUND/AIMS: Hereditary hemochromatosis (HH) has a homozygote frequency of 0.5% and a heterozygote frequency of 13%, which suggests that hemochromatosis might be a balanced polymorphism. Evidence for this was sought by assessing reproductive success among hemochromatosis heterozygotes through determining their family size and incidence of miscarriage when compared to nongene carriers. METHODOLOGY: A cohort was defined in which the exposure variable was heterozygosity for hereditary hemochromatosis. Heterozygotes were identified by mailing individuals homozygous for hereditary hemochromatosis questionnaires concerning the number of siblings born alive and the number of miscarriages suffered by their mothers (predominantly heterozygotes, or HHH). Spouses of the hereditary hemochromatosis homozygotes were asked to complete accompanying questionnaires concerning their mothers (CONT). RESULTS: Five hundred and ninety-six responses were received from hereditary hemochromatosis homozygotes and 532 responses from spouses of the hereditary hemochromatosis homozygote respondents. The mothers of the hereditary hemochromatosis homozygote respondents had a mean family size of 3.699. The mothers of the unexposed spouse controls a mean family size of 3.639 (P = 0.66 by ANOVA). One hundred and twenty-three of the HHH mothers suffered a total of 201 miscarriages, whereas 94 of the CONT mothers suffered 147 miscarriages (P = 0.38 by ANOVA). CONCLUSIONS: In this cohort, no evidence among hemochromatosis heterozygotes of reproductive advantage and therefore heterozygous advantage by this mechanism was seen.

Abortion, Spontaneous↗
PubMedDate not supplied

Chromosome rearrangements in fumigant appliers: possible relationship to non-Hodgkin's lymphoma risk.

Appliers of pesticides (n = 18) who are exposed to the fumigant phosphine or who have a mixed exposure to other pesticides and phosphine demonstrate a significant increase in chromosome rearrangements in G-banded chromosomes from peripheral blood compared to control subjects (n = 26). Appliers who had discontinued using phosphine for at least 8 months prior to specimen collection (n = 5) do not demonstrate significant increases in chromosome rearrangements compared to controls. Breakpoint analysis of 6,138 metaphases from all subjects demonstrates 196 breaks per 3605 metaphases in exposed subjects and 102 breaks per 2,533 metaphases in control subjects. Bands with significantly more breaks than expected based on band length in all study subjects were 1q32, 3p14, 7p15, and 14q11. Three of these four bands had significantly more breaks than expected in the exposed group, and all four bands had a significant excess of breaks in the control group. There are four bands with a significant excess of breaks in the exposed group and no breaks in the control group; each of these occurs in a known protooncogene region. These are 1p13 (NRAS), 2p23 (NMYC), 14q32 (ELK2), and 21q12 (ETS-2). Most breaks at bands 1p13, 14q32, and 21q22 are associated with chromosome rearrangements and occurred in appliers who have a mixed exposure to phosphine and other pesticides. Cytogenetic abnormalities, i.e., rearrangements and/or deletions involving bands 1p13, 2p23, and 14q32, are associated with non-Hodgkin's lymphoma. We speculate that these findings could relate to the risk of evolution of a neoplastic clone in these workers. Epidemiological studies of similarly exposed workers indicate an excess of non-Hodgkin's lymphoma.

Chromatids↗
PubMedDate not supplied

Chlorophyllin, an antimutagen, acts as a tumor promoter in the rat-dimethylhydrazine colon carcinogenesis model.

Chlorophyllin (CHL), the water soluble sodium/copper salt of chlorophyll, was investigated for its effect on colorectal cancer risk in the rat-dimethyldrazine colon carcinogenesis model. Ninety weanling Fisher 344 male rats were treated with five weekly injections of 1,2 dimethylhydrazine (DMH), 20 mg base/kg body weight. Rats had been previously divided into three groups, consuming either rat chow and water (Group I), rat chow and CHL 1.5 mM in water throughout the experiment (Group II), or water and rat chow during DMH injection, adding CHL 1.5 mM to the drinking water after completion of the DMH treatments. At sarcifice, the incidence and yield of colorectal tumors were as follows: Group I 10% and 0.1; Group II, 23% and 0.27; and Group III, 47% and 0.53 (p less than 0.005 for incidence and = 0.003 for yield). These data demonstrate that, though it is well established that CHL is an antimutagen, CHL in this colorectal carcinogenesis model acted as a tumor promoter.

1,2-Dimethylhydrazine↗
PubMedDate not supplied

Disposition in humans of racemic picenadol, an opioid analgesic.

Racemic picenadol is being tested clinically as an analgesic. The (+)-enantiomer of picenadol is an opioid agonist and the (-)-enantiomer is a weak agonist/antagonist. The disposition of racemic [14C] picenadol was studied in healthy men after a single dose was administered im (N = 3) and orally (N = 5). After the dose, virtually none of the radioactivity that appeared in blood was associated with the red cells. In plasma, approximately 4% of the radioactivity was attributable to the parent drug, the remainder being picenadol glucuronide (approximately 35%) and other metabolites. The t1/2 for total radioactivity was 6 hr, that for the unchanged drug was 3.5 hr. Picenadol was present in plasma almost exclusively as the (+)-enantiomer. However, after incubation with glucuronidase and sulfatase, plasma contained 2 to 4 times more (-)- than (+)-picenadol, indicating that more conjugated (-)-picenadol than conjugated (+)-picenadol was in the plasma. After im and oral administration of [14C]picenadol, plasma levels of radioactivity were generally 10 and 70 times higher than those in saliva, respectively. More than 90% of the administered radioactivity was excreted in the urine, mostly as picendol glucuronide, and lesser amounts of picenadol sulfate and N-desmethylpicenadol sulfate. Only about 1% of the administered dose of picenadol appeared unchanged in urine. The disposition of racemic picenadol in humans was stereoselective, the (-)-picenadol apparently being metabolized preferentially over the (+)-enantiomer. This finding was of particular interest in view of the dissimilar pharmacologic activities of the enantiomers.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMedDate not supplied

The effect of iron on experimental colorectal carcinogenesis.

The effect of parenteral and oral iron was examined in the rat 1,2 dimethylhydrazine (DMH) colorectal carcinogenesis model in a series of experiments. Parenteral supplementation of iron was found to augment tumor yield (p = 0.012) and oral iron was found to augment tumor incidence (p = 0.03, when control groups were combined). In addition, phytic acid, a significant component of dietary fiber was found to reverse the augmenting effect of oral iron on tumor yield and incidence (p = 0.09 for both). Furthermore, in a short term DMH nuclear toxicity assay, analysis of the karyorrhectic index (KI), there was no difference in the KI between oral iron and phytate dietary groups (p = 0.53 for the left colon and p = 0.2 for the right colon), implying that iron's effect on colorectal tumor induction takes place during the promotional phase of carcinogenesis and not during initiation. These experiments support the epidemiologic observation that dietary iron may augment colorectal cancer risk and that the mechanism by which dietary fiber diminishes colorectal cancer risk may be the chelation of dietary iron by the phytic acid component of dietary fiber.

1,2-Dimethylhydrazine↗
PubMedDate not supplied

Sulfasalazine alters the character of dimethylhydrazine-induced colorectal carcinoma in rats.

The etiologic variables involved in the increased incidence of colorectal carcinoma in patients with chronic ulcerative colitis have not been defined. Sulfasalazine is the most commonly used medication in the treatment of ulcerative colitis. It is not known whether the pharmacologic treatment of ulcerative colitis alters the incidence of cancer in man, but a drug related to sulfasalazine has been shown to reduce the incidence of colorectal carcinoma in rats. In this study we examined the effect of sulfasalazine on the development of 1,2-dimethylhydrazine-induced (DMH) colorectal carcinogenesis in rats. Daily oral ingestion of sulfasalazine in doses equivalent to human daily doses resulted in serum salicylate levels in those animals that were comparable to human therapeutic serum salicylate levels. Sulfasalazine administration did not significantly effect the incidence of DMH-induced colorectal tumors. However, sulfasalazine treated animals were found to have significantly smaller tumors and to show a trend towards multiple, flat, sessile, frequently microinvasive tumors compared to the fewer, larger, exophytic tumors observed in animals treated only with DMH. These results demonstrate that in the doses given, sulfasalazine treatment alters the character of DMH-induced colorectal tumors without significantly effecting tumor incidence.

1,2-Dimethylhydrazine↗
PubMedDate not supplied

Inhibition of 1,2-dimethylhydrazine-induced nuclear damage in rat colonic epithelium by chlorophyllin.

Chlorophyllin (CHL) was tested for its effect on 1,2-dimethylhydrazine (DMH)-induced nuclear aberrations in rat colonic epithelium. Rats were given water containing CHL (1.5 mM) and food ad libitum. After 5 wks on this dietary regimen, the rats were given a single intraperitoneal injection of DMH (20 mg DMH base/kg body weight). The rats were sacrificed 18 hours later and their colons were removed. Ten consecutive crypts from the proximal and distal portion of each specimen were scored for nuclear aberrations and the karyorrhectic index (KI) was determined. Rats receiving CHL + DMH had significantly fewer nuclear aberrations (lower KI) in the colonic epithelium than rats given DMH alone. This implies that CHL, a known antimutagen, may have anticarcinogenic properties as well.

1,2-Dimethylhydrazine↗
PubMedDate not supplied

Intraaortic balloon rupture.

To identify patients at risk and assess management strategies, nine Datascope intraaortic balloon (IAB) ruptures in 8 patients were reviewed. This is a 2.4% incidence for this complication (382 insertions over 75 months). Time to initial rupture was 4.7 days, range 1.1 to 6.8 days. This was 1.3 days after the average intact device was removed. Women were three times more likely to sustain rupture than men (4 vs. 1.3%, P less than 0.05). Rupturing IABs were characterized by a greater magnitude of diastolic augmentation than intact IABs, 69.4 +/- 24.9 vs. 25.5 +/- 12.6 Torr (P = 0.01). A hypertensive treatment history was more prevalent in patients rupturing (83 vs. 41%) (P less than 0.05). Rupture was diagnosed by finding blood in the safety chamber in all patients. There was no gas embolization nor did any patient become infected. Ruptured devices showed abrasion wear in the most distal portion of the IAB, where the aorta is smallest. In vitro testing with CO2 showed no driving gas loss but withdrawal of the surrounding fluid into the IAB system. Ruptured IAB replacement in four patients was associated with three survivors. In four patients the device was not replaced and two patients survived. There were no complications as a consequence of IAB rupture (all values +/- SD).

Aged↗