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Biomedical subjects
M Hauer-Jensen
Publications and source records attributed to M Hauer-Jensen.
Tolerance of rat small intestine to localized single dose and fractionated irradiation.
The tolerance of rat small intestine to localized single-dose and fractionated irradiation was assessed. In 168 rats, bilateral orchiectomy was performed and a loop of small intestine was transposed to the left part of the scrotum. Beginning 3 weeks postoperatively, single dose (18-24 Gy) or fractionated (4.2 Gy or 5.6 Gy per fraction) x-irradiation was delivered to the transposed intestine. The animals were observed for complications, and groups of animals were killed 2 and 26 weeks after completion of irradiation for assessment of injury. Mortality (i.e. the occurrence of lethal intestinal complications) and a semiquantitative histopathologic scoring system were used as endpoints to assess the degree of radiation injury. The most frequent intestinal complications were enterocutaneous fistula formation and intestinal obstruction. Logistic regression analysis ov complications data was used to estimate LD50 values and the alpha/beta ratio. There was good correlation between histopathologic scores and the incidence of lethal complications. The estimated LD50 values were 22.1 +/- 0.5 Gy, 37.0 +/- 4.4 Gy and 51.0 +/- 5.3 Gy for the single dose regimen and the fractionated regimens of 5.6 Gy and 4.2 Gy respectively. The estimated alpha/beta ratio was 10.7 +/- 2.4 Gy. The goodness of fit of the linear-quadratic isoeffect model to our data was satisfactory. Our results indicate that acute mucosal damage may be pathogenetically involved in the development of intestinal complications.
Animals↗
Chemotherapy and radiation therapy for anal carcinoma. Survival and late morbidity.
This study was performed to evaluate the survival and late morbidity rates of a widely used combined chemotherapy and radiation therapy regimen given to patients with carcinoma of the anal canal. One hundred six patients received radiation therapy (5000 cGy given by two anteroposterior-posteroanterior [AP-PA] opposed fields) and chemotherapy (mitomycin C plus 5-fluorouracil [5-FU]) from 1983 to 1989. Patients with primary tumors (n = 86) had a complete response rate of 84% and a 5-year survival rate of 72%. There was no significant difference in survival rate according to tumor stage. Patients with local recurrence (n = 20) after primary surgery had a complete response rate of 50% and a 5-year survival rate of 40%. Fifteen percent of the patients experienced late treatment-related symptoms including anal incontinence, intestinal obstruction, and chronic pelvic pain. The current treatment regimen is effective but carries a considerable risk of complications. As survival rate was independent of tumor stage, the locoregional treatment should probably be less extensive for small tumors than for advanced tumors. This strategy may reduce the late side effects for patients with small tumors without reducing the survival rate.
Adult↗
Statistical analysis in dBASE-compatible databases.
Database management in clinical and experimental research often requires statistical analysis of the data in addition to the usual functions for storing, organizing, manipulating and reporting. With most database systems, transfer of data to a dedicated statistics package is a relatively simple task. However, many statistics programs lack the powerful features found in database management software. dBASE IV and compatible programs are currently among the most widely used database management programs. d4STAT is a utility program for dBASE, containing a collection of statistical functions and tests for data stored in the dBASE file format. By using d4STAT, statistical calculations may be performed directly on the data stored in the database without having to exit dBASE IV or export data. Record selection and variable transformations are performed in memory, thus obviating the need for creating new variables or data files. The current version of the program contains routines for descriptive statistics, paired and unpaired t-tests, correlation, linear regression, frequency tables, Mann-Whitney U-test, Wilcoxon signed rank test, a time-saving procedure for counting observations according to user specified selection criteria, survival analysis (product limit estimate analysis, log-rank test, and graphics), and normal t and chi-squared distribution functions.
Database Management Systems↗
Long-term results of treatment of Cushing's disease by adrenalectomy.
Patients treated by adrenalectomy for suspected Cushing's syndrome were reviewed for the incidence to early and late complications, side effects, survival, and quality of life. Of a total of 141 patients, 109 had Cushing's disease, and were treated with subtotal (n = 15) or total (n = 94) adrenalectomy. All hospital charts were reviewed, and surviving patients were asked to fill in a questionnaire. Ten patients died in hospital. Morbidity was 13% (n = 18). Five patients required reoperation because of recurrent adrenal hyperplasia after subtotal adrenalectomy (n = 3) or incomplete adrenalectomy (n = 2). All patients received conventional corticosteroid supplementation. Ten patients developed Nelson's syndrome 3-20 years after adrenalectomy. Of the 109 patients with Cushing's disease 80 were alive 1-34 years after operation. Only four late deaths were related to Cushing's disease: 3 postoperative deaths followed reoperation and 1 was the result of an Addisonian crisis. About two thirds of the patients interviewed had satisfactory quality of life and were able to work. Total bilateral adrenalectomy has a five to seven fold higher perioperative mortality than transphenoidal operations. The prognosis of patients who survive the early postoperative period, however, is comparable to that of the general population.
Adolescent↗
The prevalence and severity of late effects in normal rat duodenum following intraoperative irradiation.
In humans, a portion of the duodenum is often at risk for radiation-induced complications following intraoperative radiation therapy for pancreatic carcinoma. To determine experimentally the prevalence and severity of late effects in the normal mammalian duodenum, 190 rats received single doses of 0, 15, 20, 25, 30, or 40 Gy orthovoltage X rays to temporarily exteriorized 3 cm circumferential segments of duodenum. The animals were killed 2, 6, 8, or 10 months later. Actuarial survival, change in body weight, and a radiation injury score based on eight histopathologic alterations were used as endpoints. Epithelial atypia, intestinal wall fibrosis, serosal thickening, and vascular sclerosis were the dominant histopathologic alterations at all dose levels throughout the 10-month observation period. The prevalence and severity of histologic radiation injury showed sigmoidal dose-response relationships with the plateaus starting at 20 Gy. Doses of 20 Gy or greater also resulted in a substantial loss of body weight and a high level of early deaths (20-80 days). All endpoints indicate that intraoperative doses of 20 Gy or greater are associated with unacceptable risks of late and irreversible complications.
Animals↗
Late radiation injury of the small intestine. Clinical, pathophysiologic and radiobiologic aspects. A review.
Transient symptoms due to injury of the intestinal mucosa occur in the majority of patients receiving radiation therapy for pelvic or intra-abdominal neoplasms. Late (chronic) radiation enteropathy, although less common, is a more serious condition, associated with high morbidity and mortality. The manifestations of late radiation enteropathy are primarily due to changes in compartments other than the mucosa, such as intestinal wall fibrosis and obliterating vascular sclerosis. As a result of recent clinical and experimental studies, considerable knowledge about the pathogenesis, dose-response relationship, and time-course of development of late radiation enteropathy has been obtained. Also, the advent of new animal models has facilitated studies of time-dose-fractionation relationships in the intestine. The present paper summarizes clinical, pathophysiologic, and radiobiologic aspects pertinent to the development of chronic intestinal radiation injury.
Humans↗
Intestinal complications following accelerated fractionated x-irradiation. An experimental study in the rat.
Due to paucity of suitable animal models, it has been difficult to study the development of long-term intestinal complications following fractionated irradiation. We recently developed a model which allows multiple radiation exposures of a short segment of rat ileum without the need for repeated surgery. In the present series, this model was used to study the influence of shortening the total treatment time (accelerated fractionation) on development of radiation enteropathy. Male rats were orchiectomized and a short segment of distal ileum was transposed to the scrotum. Starting 3 weeks after surgery, the scrotum containing the intestinal segment was x-irradiated with 20 fractions of 2.8 Gy (total dose 56 Gy). Two fractionation schedules were compared: One fraction per day (total treatment time 26 days) and 3 fractions per day (total treatment time 7 days). Actuarial survival curves were obtained, and the degree of radiation injury was assessed 2, 8, and 26 weeks after the last radiation exposure using a semiquantitative histopathologic scoring system. There was no mortality from acute radiation injury in either treatment group. All animals of the 1-fraction/day group survived the observation period (26 weeks). In the 3-fraction/day group, there was significant mortality due to intestinal obstruction, and cumulative mortality at 26 weeks was 100%. Radiation injury, as assessed by the histopathologic scoring system, was also more pronounced in this group than in the 1-fraction/day group. We conclude that shortening the total treatment time significantly increases the severity of late intestinal complications. Our data are suggestive of an association between acute mucosal damage and chronic radiation injury of the small intestine.
Animals↗
Surgical treatment of left ventricular aneurysm. Analysis of risk factors, morbidity and mortality in 205 cases.
Left ventricular aneurysm was surgically treated in 205 patients during the decade 1975-1984. The patients had had one to five myocardial infarctions, the latest days to years (mean 32 months) preoperatively and 92% were in NYHA functional class III or IV. The main indications for surgery were angina (47%), congestive heart failure (38%) and arrhythmia (15%). The 176 anterior, 23 posterior and six combined aneurysms were treated with resection (130 cases) or plication (75). The early mortality was 5%. Univariate analysis identified arrhythmia, concomitant valve replacement and need for intra-aortic balloon pumping (IABP) as significant risk factors, and multivariate analysis revealed the indication for surgery and need for IABP as the only independent predictors of total mortality. The survival rates 5 and 10 years postoperatively were respectively, 74% and 60%. At follow-up after 1/2-10 years, almost 90% of the surviving patients had improved functional status. Left ventricular aneurysm thus can be surgically treated with low mortality rate and good functional result.
Adult↗
Intraoperative irradiation in a rat model: histopathological changes in irradiated segments of duodenum.
During intraoperative radiation therapy for carcinoma of the head of the pancreas in humans, a portion of duodenum is often at risk for radiation-induced complications because of its fixed anatomical position within the treatment field. This study was undertaken to determine the feasibility of using the rat as a model to determine the radiotolerance of normal mammalian duodenum. The procedures used to exteriorize and irradiate a selected segment of duodenum are described. Histopathologic changes in 5-cm segments of midduodenum were studied 14 and 28 days after 0, 30, 40, or 50 Gy X-radiation. Complete denudation of the epithelium and thickening of the muscularis and serosal layers occurred in all irradiated segments by day 14. By day 28, even though crypt and villus architectures were atypical, large areas of epithelial regeneration were seen in rats receiving 30 Gy. In contrast, complete denudation of the epithelium were still evident along most of the length of the irradiated segments in rats receiving 40 or 50 Gy. Serosal fibrosis was prominent in all irradiated animals, regardless of dose. These results indicate that radiation doses above 30 Gy carry high risks of complications. The rat is considered a suitable animal model.
Animals↗
Effects of accelerated fractionation on radiation injury of the small intestine: a new rat model.
The present study assessed the influence of shortening the overall treatment time (accelerated fractionation) on radiation injury of the small intestine. A rat model which allowed repeated irradiation of a localized segment of small intestine was developed. Young adult male Sprague-Dawley rats were orchiectomized, and a loop of the distal ileum was transposed to the left part of the scrotum. The intestinal segment was irradiated with a total dose of 56 Gy, given in 20 fractions, the total treatment time being either 26, 12, or 7 days (i.e. 1, 2, or 3 fractions per day). Radiation injury was assessed by histopathologic examination at 6 hr and at 2 weeks after the last irradiation. The surgical procedure was without complications. Shortening the overall treatment time by giving more than one radiation dose per day resulted in markedly increased injury both at 6 hr and at 2 weeks. It is concluded that accelerated fractionation results in increased radiation injury of the intestine when compared with standard fractionation. Because there may be a relationship between early and late effects in the intestine, our results also indicate that increased late radiation enteropathy may result from accelerated fractionation.
Animals↗
Intestinal disaccharidase activity following pancreatic duct occlusion in the rat.
The influence of pancreatic secretions on growth and brush-border enzyme activity, throughout the entire small intestine, was examined in the rat. Pancreatic secretions were excluded from the gut lumen by stapling the pancreatic ducts, without interruption of bile flow. The entire small intestine was studied as four segments; the duodenum and three distal segments of equal length. Weight of intestine and mucosa, and mucosal sucrase, isomaltase, lactase, and alkaline phosphatase activity were measured 10-15 days following pancreatic duct occlusion, or sham-operation. The duodenum of pancreatic duct-occluded animals exhibited significant hypertrophy. In general, specific and total disaccharidase activities were greater in duct-occluded animals than in controls throughout the intestine. The increase was more pronounced in distal than in proximal segments. The sucrase/isomaltase ratio was significantly greater in pancreatic duct-occluded animals than in controls in the two distal segments. Alkaline phosphatase activity was not affected by pancreatic duct occlusion. The greater relative increase of disaccharidase activities and sucrase/isomaltase activity ratios in the distal segments of duct-occluded animals, indicates a more important regulatory role of pancreatic enzymes in the distal small intestine. It is concluded that regulation of intestinal brush-border enzyme activity by pancreatic secretion is selective for enzyme and site as follows: disaccharidases, but not alkaline phosphatase, are regulated; the sucrase subunit of the sucrase/isomaltase complex is most sensitive to regulation, while lactase is least sensitive; and the regulatory effect on disaccharidases is greater in distal than in proximal intestine.
Animals↗
Pancreatic duct occlusion in the rat: report and assessment of a new technique.
Temporary reduction of the exocrine pancreatic secretion may be desirable in various experimental models. In the rat this can be achieved by obstructing the connection between the pancreas and the duodenum. A new, simple technique of pancreatic duct occlusion using metal hemostatic clips is described. The reduction of secretion produced by the procedure was assessed by measuring duodenal protein, amylase, and trypsin during stimulation with cholecystokinin. Stimulated duodenal amylase activity 1 and 4 weeks following duct occlusion was reduced by approximately 80% compared with sham-operated controls, whereas proteolytic activity was reduced by 96 and 60%, respectively. The magnitude and duration of pancreatic insufficiency achieved by this technique is equivalent to that achieved with more complicated methods.
Amylases↗
Effects of exocrine pancreatic secretions on hyperthermic injury of rat small intestine.
The influence of the exocrine pancreatic secretions on development of small intestinal injury following localized hyperthermia was studied. In male Holtzman rats the excretory pancreatic ducts were occluded with metal hemostatic clips. An intraperitoneal injection of [3H]thymidine was given 3 weeks later. Three or 48 h after the injection a 10 cm segment of small intestine was exteriorized through a midline abdominal incision and heated at 38.0 degrees C, 42.5 degrees C, or 43.5 degrees C for 45 min. Intestinal damage was assessed 24 h after hyperthermia. The following four endpoints were used: histopathological injury score, the number of villi per intestinal circumference, the number of labelled epithelial cells in fixed areas of autoradiographic specimens, and incorporation of [3H]thymidine as determined by liquid scintillation counting. The correlation of results among the four methods of assessment was highly significant. The autoradiography data showed better correlation with both morphological parameters than the results of liquid scintillation counting. There was significantly less damage in heated segments from pancreatic duct-occluded animals than in segments from sham-operated controls. When hyperthermic injury was assessed morphologically the protection conferred by pancreatic duct occlusion was equivalent to lowering the temperature of heating by 1 degree C. It is concluded that morphological criteria may be superior to endpoints based on [3H]thymidine incorporation for assessment of hyperthermic injury in rat small intestine. Reducing the intraluminal pancreatic secretions appears to confer significant protection from small bowel injury after localized hyperthermia.
Animals↗
Morphological and functional recovery of rat small intestine following localized hyperthermia.
Structural and functional changes in the rat small intestine following localized hyperthermia were examined. In anaesthetized male Sprague-Dawley rats a 10 cm segment of mid-small intestine was temporarily exteriorized, suspended in a cup containing Krebs-Ringer solution, and either heated at 43.5 degrees C or sham-heated at 38 degrees C for 45 min. The intestinal segments were studied 1, 4, 7, 21 and 42 days later by histopathological examination, determination of wet weight, dry weight and gross segment area, and by measuring absorption of 15 mM D(+)-glucose containing 14C-labelled D(+)-glucose as a tracer. Intestinal glucose transport was assessed by two different techniques: the everted sac method (in vitro) and luminal perfusion-recirculation (in vivo). After 1 day, heated intestinal segments exhibited marked mucosal damage, consisting of loss of epithelial cells and destruction of villi. Re-epithelialization had occurred by day 4, but mucosal architecture remained abnormal throughout the observation period. Hyperthermia caused significant thickening of the intestinal wall: at 4 days the thickening was due to oedema, whereas at 42 days tissue mass per cm2 in heated segments had increased by approximately 53 per cent compared with sham-heated control segments. At 1 day, net glucose transport in vitro in heated segments was reduced to 20 per cent and the serosal/mucosal concentration ratio to 57 per cent of that of control segments. In vivo, glucose transport in heated intestine at 4 days was 45 per cent of that of controls. From 4 days on, glucose transport improved gradually, and at 42 days there was no significant difference between heated and sham-heated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗