Divergence of mucosal and motor effects of insulin-like growth factor (IGF)-I and LR3IGF-I on rat isolated ileum following abdominal irradiation.

BACKGROUND AND AIMS: In addition to its beneficial effects on small intestinal mucosal development and repair, insulin-like growth factor (IGF)-I has also been reported to improve neural function in toxic neuropathies. It has recently been recognized that enteric neural abnormalities contribute to the small intestinal dysmotility observed during and after abdominal radiotherapy for gynecological and pelvic malignancy. The aim of the present study was to evaluate the effects of IGF-I (5 mg/kg per day) and the more potent analog LR3IGF-I (5 mg/kg per day) on neurally mediated ileal dysmotility following irradiation. METHODS: Intestinal motor activity was recorded from 6-8 cm segments of explanted rat ileum using a miniaturized manometric technique during arterial perfusion with oxygenated fluorocarbon solution. Studies were performed 4 days after treatment with 10 Gy abdominal irradiation. At the time of irradiation, all rats underwent implantation of an osmotic mini-pump that contained 100 mmol/L acetic acid vehicle (n = 8), IGF-I (n = 8) or LR3IGF-I (n = 7). For each experiment, the total number of pressure waves, high-amplitude long-duration (defined as > 20 mmHg, > 6 s; HALD) pressure waves and long bursts (> 20) of pressure waves were determined. Ileal segments from 12 non-irradiated rats were used as controls for manometric studies. In radiotherapy treated animals, the degree of mucosal damage was determined using a standardized histologic scoring system. RESULTS: The HALD pressure waves were infrequent in non-irradiated rats but occurred in all irradiated animals. Insulin-like growth factor-I and LR3IGF-I had no effect on the frequency, amplitude or migration characteristics of HALD pressure waves compared with vehicle. Histologic damage was reduced in animals that received IGF-I and LR3IGF-I compared with vehicle-treated animals. CONCLUSIONS: In radiation enteritis, IGF-I has no effect on neurally mediated small intestinal dysmotility while improving mucosal histology. The disparity between these results suggests that parallel but separate pathologic processes underlie mucosal and motor abnormalities in radiation enteritis.

Oesophagitis-induced changes in capsaicin-sensitive tachykininergic pathways in the ferret lower oesophageal sphincter.

Prolonged oesophageal acidification may impair lower oesophageal sphincter (LOS) function in reflux disease. The aim of this study was to investigate aspects of altered LOS innervation in a model of oesophagitis. Oesophagitis was induced by acid (HCl, 0.15 M) and pepsin (0.1% w/v) infusions in anaesthetized ferrets. LOS muscle strip responses to the following stimuli were measured in vitro from control and acid/pepsin-treated ferrets: electrical field stimulation (EFS; 1-50 Hz), potassium chloride KCl; 20 mM), substance P, [beta-Ala8]-neurokinin A 4-10, [Sar9, Met (O2)11]-substance P (all 10(-10) to 10(-6) M) and capsaicin (10(-8) to 10(-6) M). LOS relaxation occurred in response to all stimuli except [beta-Ala8]-neurokinin A 4-10, which evoked contraction. In muscle strips from acid/pepsin-treated animals there were no differences in amplitude or sensitivity of relaxation following EFS, KCl or substance P vs controls. However, the inhibitory response to capsaicin was increased four-fold (10(-8) M; P < 0.05) and an increased sensitivity of the inhibitory response to [Sar9, Met (O2)11]-substance P occurred (pD2 = 8.64 +/- 0.12 acid/pepsin-treated vs 7.94 +/- 0.24 control, P < 0.05). We conclude that in acute oesophagitis, increased sensitivity of capsaicin-activated inhibitory pathways occurs in which activation of NK-1 receptors plays an integral role in the ferret LOS.

Effects of fractionated abdominal irradiation on small intestinal motility--studies in a novel in vitro animal model.

Disordered small intestinal motility occurs frequently during acute radiation enteritis. However, the characteristics and time course of the motor dysfunction are poorly defined. These parameters were assessed in a novel animal model of radiation enteritis. Ileal pressures were recorded in vitro with perfused micromanometric catheter using an arterially perfused ileal loop in 22 ferrets following fractionated abdominal irradiation (9 doses 2.50 Gy thrice weekly for 3 weeks). Tissue damage was graded histologically. Studies were performed 3 to 29 days after irradiation. Tissue from 7 control animals was also studied. All treated animals developed diarrhoea. Histology showed changes consistent with mild to moderate radiation enteritis. Following irradiation, there was an initial increase in frequency followed by a non-significant reduction in the frequency, but not the amplitude of ileal pressure waves. The frequency of pressure waves showed an inverse relationship with time after radiation (r = -0.634, p < 0.002). There was no relationship between motility and histology. We conclude that abdominal irradiation is associated with a time-dependent reduction in ileal motility which does not correlate with light microscopic changes.

Xylene: its toxicity, measurement of exposure levels, absorption, metabolism and clearance.

Xylene is an aromatic hydrocarbon widely used in industry and medical technology as a solvent. Health and safety authorities in most countries, including Australia, recommend a threshold limit value (TLV) of 100 ppm in the working environment. Recently, the amount of the major metabolite of xylene, methylhippuric acid (MHA), in urine has been recommended as a better indicator of exposure. The American Conference of Governmental Industrial Hygienists has recommended an upper limit for this indicator, called a biological exposure index (BEI), of 2.0 g MHA/L urine (SG 1.016). Xylene vapour is absorbed rapidly from the lungs, and xylene liquid and vapour are absorbed slowly through the skin. Of the xylene absorbed, about 95% is metabolised in the liver to MHA and 70 to 80% of metabolites are excreted in the urine within 24 hours. However, the many variables which affect the absorption, metabolism and clearance of xylene include exercise, alcohol intake, cigarette smoking, co-exposure to other solvents, gender, and gastrointestinal, hepatic and renal pathology. Xylene in high concentrations acts as a narcotic, inducing neuropsychological and neurophysiological dysfunction. Respiratory tract symptoms are also frequent. More chronic, occupational exposure has been associated with anemia, thrombocytopenia, leukopenia, chest pain with ECG abnormalities, dyspnea and cyanosis, in addition to CNS symptoms. Concomitant exposure to xylene and other solvents, including toluene, affected hematological parameters, liver size, liver enzymes, auditory memory, visual abstraction, and vibration threshold in the toes. Normal metabolic pathways were altered and significant increases in some serum bile acids may reflect early liver damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Density of lymphoid follicles in the rectum and at the anorectal junction.

To determine the density of mucosal lymphoid follicles in 10 histologically normal rectums, including the anorectal junction, we counted the follicles macroscopically after the specimens were fixed in 10% acetic acid. The mean density in the rectum was 25.6/cm2. The mean density at the anorectal junction was slightly but not significantly higher, at 29.2/cm2. We found no significant change in follicle density with increasing age in specimens from people between the ages of 17 and 90 years.

Activity of duodenal disaccharidases in relation to normal and abnormal mucosal morphology.

Endoscopic duodenal biopsy specimens from 100 predominantly adult Caucasian patients under investigation for gastrointestinal symptoms were used to establish reference ranges for lactase, sucrase, and maltase in the duodenum. Duodenal and jejunal disaccharidase values were compared and the association between disaccharidase activity and morphology in the duodenum was examined. Mean lactase activities were about 40% lower in the duodenum compared with the jejunum; maltase was reduced to a lesser extent; and sucrase activities were much the same in the two sites. Lactase deficiency was found in 24 patients of whom 14 (58%) had duodenal disease. The presence of moderate to severe duodenal lesions was associated with a significant decrease in all disaccharidase activities, while only lactase was reduced in mild lesions. Twelve patients had normal lactase activity, despite the presence of duodenal disease. It is concluded that specific reference ranges for duodenal mucosal disaccharidase activity are required as this is less than that of jejunum. Reduced duodenal disaccharidase activity is usually but not invariably associated with morphological abnormality.

Endometriosis of the large bowel: a report of 11 cases.

The clinical and pathological features of 11 cases of large bowel endometriosis are reported, one of which also had lesions in the small intestine. All of the cases had rectal or rectosigmoid involvement. Altered bowel habit and pain were common symptoms but were rarely associated with the menstrual cycle. Sigmoidoscopy was generally unhelpful. Rectal or vaginal examination and barium enema often revealed a mass which was usually diagnosed preoperatively as a malignancy. A correct diagnosis was made preoperatively in only two cases; carcinoma was suspected in four and carcinoid in one case. Histological evidence of recent hemorrhage was confined to those cases where endometriosis seemed to be the major cause of intestinal symptoms. The colonic mucosa overlying the endometriotic deposits was commonly histologically abnormal. It showed a range of changes resembling colitis, solitary ulcer, prolapse or even neoplasm. An appreciation of these mucosal alterations is important to those reporting colonic and rectal biopsies; when observed to be focal in a female patient they should arouse a suspicion of endometriosis.

Early gastric cancer: 52 cases of combined experience of two south Australian teaching hospitals.

Fifty-two patients with early gastric cancer are described. At presentation, the average age was 60 years and the male:female ratio was 3:2. The patients had presenting symptoms indistinguishable from those due to benign peptic ulcer disease. Endoscopic examination with multiple biopsies was the most accurate means of diagnosis, with an overall 93% detection rate. The tumours were located predominantly along the lesser curve (75%) and in the antrum (64%), with ulcerated or depressed lesions most common and flat lesions least common. Approximately 58% of lesions were of intestinal type, submucosal invasion was seen in 45% and lymph node metastases had occurred in 7% of cases. Lesser curve and antral lesions were more likely to be ulcerated. Ulcerated lesions were on average, the same size as non-ulcerated lesions. Body lesions were larger than antral lesions and lesions which had spread to the submucosa were larger than mucosal lesions. Diffuse-type lesions were more likely to be ulcerated than intestinal-type lesions and dysplasia was more commonly associated with intestinal-type lesions than with diffuse or mixed-type lesions. The crude 5-year survival rate was 80%, but only one death was associated with a recurrence of gastric cancer.

The number and distribution of lymphoid follicles in the human large intestine.

The density of mucosal lymphoid follicles has been determined in the large intestines of five sudden death victims. The specimens were fixed in acetic acid which made the follicles visible macroscopically. The estimated total number of follicles in the large intestine ranged from 12761 to 18432. The average density of follicles was 18.4 per cm2 in the caecum, 15.0 per cm2 in the colon and 25.4 per cm2 in the rectum. These results indicate that the density of lymphoid follicles has been grossly underestimated in the past where three to five follicles per cm2 have been accepted as normal. The cause for this major discrepancy is discussed as is its bearing on the diagnosis of lymphoid hyperplasia.

Lymphoid aggregates in the guinea pig large bowel: development of quantitation techniques for number, volume and distribution.

A technique for assessing the number, distribution and volume of the lymphoid aggregates (LA) in the guinea pig large bowel is described. Aggregates could be visualised macroscopically after immersion of the bowel in 10% acetic acid and their number and distribution recorded by tracing on plastic sheets. Serial sections through a sample of 13 LA showed that they were ellipsoidal and this was confirmed by mathematical comparison with hypothetical ellipsoids. In practice, only the length and width of each LA could be measured but, using the sample of 13 LA, it was established that regression analysis enabled the volumes of all except the smallest LA to be predicted accurately from the knowledge of length and width alone.

Carrageenan colitis in the guinea pig: pathological changes and the importance of ascorbic acid deficiency in disease induction.

In guinea pigs deprived of ascorbic acid, the oral administration of degraded E. spinosum carrageenan induced mild to moderate colitis, while E. cottonii consistently induced severe colitis. A variable degree of colitis was observed in scorbutic animals not receiving carrageenan. By contrast, in animals given large daily supplements of ascorbic acid, neither type of carrageenan consistently induced colitis and severe disease was rarely observed. The severe colitis induced by E. cottonii in scorbutic animals markedly affected the mid and distal colon and showed histological changes similar to human ulcerative colitis.

[Place of aspiration lipolysis in the surgical treatment of Launois-Bensaude syndrome]. / Place de la lipolyse-aspiration dans le traitement chirurgical du syndrome de Launois-Bensaude.

Modifying the mass contour with liposuction by developing numerous subcutaneous "tunnels" with subsequent homogeneous contractions of the overlying skin will add a new dimension to the treatment of the Launois-Bensaude syndrome. Successful correction of these deformities can be obtained without a large amount of surgical undermining and skin resection and with minimal scar formation.

The influence of excess vitamin A on neural tube closure in the mouse embryo.

The effect of excess vitamin A on the closure of the neural tube in mouse embryos was examined with light microscopy, transmission and scanning electronmicroscopy. The embryos were treated with the vitamin just before closure of the brain vesicles and examined during the following 24 h, a period during which under normal conditions the brain completely closes. At 18--24 h after treatment the external features of the treated specimens began to differ from those of the controls. In the treated embryos the neural walls folded laterally and became widely separated, whereas those of the controls folded dorsomedially and fused in the midline. Histologically, the first difference between treated and control embryos was noted at two hours after treatment, when large intercellular spaces appeared between the neuroepithelial cells of the treated embryos. These spaces were mainly present between the apical ends of the wedge-shaped neuroepithelial cells. This accumulation of intercellular spaces interfered with the normal morphogenetic movement of the neural walls which remained convex instead of becoming concave. This convex bending resulted in non-closure of the neural tube. In addition to the appearance of large intercellular spaces some neuroepithelial cells as well as some mesenchymal, endothelial, and surface ectoderm cells showed swelling and degeneration as a result of the vitamin A treatment. This cell degeneration probably contributes to failure of the neural tube to close due to loss of cohesion at the luminal surface and the lack of mesenchymal support needed for the elevation of the neural walls. However, the increase of intercellular spaces at the apical side of the neuroepithelium is in all probability the major cause for the failure of the neural tube to close.