Steen Lindkær Jensen

Lateral subcutaneous sphincterotomy versus anal dilatation in the treatment of fissure in ano in outpatients: a prospective randomised study.

Fifty eight patients with idiopathic chronic anal fissure were included in a randomised prospective trial of lateral subcutaneous sphincterotomy versus simple anal dilatation carried out as outpatient procedures. Operations were performed under local anaesthesia and the patients reviewed 10-30 months later (median follow up time 18 months). Altogether 30 patients were treated by lateral subcutaneous sphincterotomy and 28 by anal dilatation. No serious complications were observed in either group. One recurrence was observed in the group treated by sphincterotomy, whereas eight occurred in the other group (p less than 0.05). Functional results with respect to impaired control of flatus and soiling of underwear were significantly better after sphincterotomy (p less than 0.002). It is concluded that lateral subcutaneous sphincterotomy is the treatment of choice for idiopathic chronic anal fissure resistant to conservative measures.

Comparison of podophyllin application with simple surgical excision in clearance and recurrence of perianal condylomata acuminata

60 patients with first-episode perianal condylomata acuminata were randomly assigned to podophyllin application or surgical excision. 58% of the male patients were homosexual and 33% of the female patients regularly had anal intercourse. Podophyllin completely cleared warts from 23 of 30 (76.6%) patients compared with 28 of 30 (93.3%) for surgical excision. After wart clearance the cumulative recurrence rates were 18% for surgical excision and 43% for podophyllin at 3 months (p less than 0.05), 22% and 56% at 6 months (p less than 0.01), 26% and 56% at 9 months (p less than 0.01), and 29% and 65% at 12 months (p less than 0.01). All patients were treated as outpatients and all surgical procedures were carried out under local anaesthesia. Both regimens were well tolerated.

Vasoactive intestinal polypeptide (VIP) in the pig pancreas: role of VIPergic nerves in control of fluid and bicarbonate secretion

Vasoactive intestinal polypeptide (VIP) in the pig pancreas is localized to nerves, many of which travel along the pancreatic ducts. VIP stimulates pancreatic fluid and bicarbonate secretion like secretin. Electrical vagal stimulation in the pig causes an atropine-resistant profuse secretion of bicarbonate-rich pancreatic juice. In an isolated perfused preparation of the pig pancreas with intact vagal nerve supply, electrical vagal stimulation caused an atropine-resistant release of VIP, which accurately parallelled the exocrine secretion of juice and bicarbonate. Perfusion of the pancreas with a potent VIP-antiserum inhibited the effect of vagal stimulation on the exocrine secretion. It is concluded, that VIP is responsible for (at least part of) the neurally controlled fluid and bicarbonate secretion from the pig pancreas.

Gastrin-Releasing Peptide in the Porcine Pancreas

The presence of gastrin-releasing peptide (GRP) was studied in extracts of porcine pancreata. Gel filtration and high-pressure liquid chromatographic profiles of these extracts as monitored with both C-terminally and N-terminally directed radioimmunoassays against GRP showed pancreatic GRP to consist of one main form, namely the 27-amino acid peptide originally extracted from porcine stomach, and small amounts of a C-terminal fragment identical with the C-terminal 10-amino acid peptide. Gastrin-releasing peptide-like immunoreactivity released from the isolated perfused porcine pancreas during electrical vagal stimulation was shown by gel filtration to consist of the same two forms. By use of immunocytochemical techniques employing an antiserum directed against its N terminus, GRP was localized to varicose nerve fibers in close association with the exocrine tissue of the porcine pancreas in particular. Some fibers were found penetrating into pancreatic islets also. Immunoreactive nerve cell bodies as well as fibers were found within intrapancreatic ganglia. The potency of GRP in stimulating exocrine as well as endocrine secretion from the porcine pancreas, its presence in close contact with both acini and islets, and its release during vagal stimulation indicate that GRP may have a role in the parasympathetic regulation of endocrine and exocrine secretion from the pig pancreas.

Regulatory peptides in the lower esophageal sphincter of man.

Smooth muscle specimens were taken from the lower esophageal sphincter of patients suffering from achalasia or hiatus hernia with gastro-esophageal reflux. The specimens were analysed for neurohormonal peptides using immunochemistry and immunocytochemistry. Control specimens were obtained from patients subjected to esophageal resection because of esophageal cancer. The concentration of vasoactive intestinal polypeptide (VIP) was higher and the VIP nerve supply greater in patients with hiatus hernia than in control patients. The VIP nerve supply and the content of this peptide was lower in patients with achalasia than in controls. The same tendency was observed for substance P and enkephalin although the changes in their concentrations were not statistically significant. Enkephalin fibers were few, both in specimens from control patients and from patients with hiatus hernia; they could not be detected in specimens from patients with achalasia. Never fibers containing somatostatin or gastrin/cholecystokinin could not be detected in any of the groups and somatostatin and gastrin/cholecystokinin could not be measured in extracts of the lower esophageal sphincter. We propose that changes in the concentration of neuropeptides may at least contribute to manifestations of achalasia and of decreased lower esophageal sphincter pressure and gastro-esophageal reflux.

Autonomic nervous control of the endocrine secretion from the isolated, perfused pig pancreas

The effect of electrical stimulation of the splanchnic and the vagus nerve supply to isolated, perfused pig pancreas on the secretion of insulin, glucagon and pancreatic polypeptide (PP) was investigated. Functional integrity of the autonomic nerve supply was assessed by the effect of nerve stimulation on vascular resistance and exocrine secretion. Splanchnic nerve stimulation increased glucagon and PP output (2 to 3-fold) and inhibited insulin output (by 42%). Propranolol abolished the effect on PP and glucagon secretion, but did not affect the inhibition of insulin secretion. Phenoxybenzamine abolished the inhibition of insulin secretion, reduced the effect on glucagon secretion and enhanced the effect on pancreatic polypeptide secretion. Combined alpha- and beta-adrenergic blockade abolished all effects of splanchnic nerve stimulation. Vagus nerve stimulation increased the secretion of all 3 hormones (PP: up to 30-fold, insulin and glucagon: 3 to 5-fold). The effect on insulin and PP-secretion was mimicked by acetylcholine at 10(-7)-10(-6) M, whereas glucagon secretion was inhibited. The effect of vagus nerve stimulation on insulin and PP secretion was augmented by physostigmine, and inhibited (but not abolished) by atropine at 10(-7)-10(-6) M. The effect on glucagon secretion was inhibited by physostigmine and unaffected by atropine. It is concluded that all of the effects of splanchnic nerve stimulation on insulin and PP secretion can be explained by interactions of norepinephrine with excitatory beta-receptors on PP-cells and inhibitory receptors on the insulin cells. Both cell types are also stimulated via muscarinic cholinoceptors, but the partial atropine resistance suggests that other transmitters participate in vagal activation. The nervous regulation of glucagon secretion is complex and may involve the peptidergic innervation of the pancreatic islets.

Regulatory peptides in lower esophageal sphincter of pig and man

Smooth muscle specimens from the lower esophageal sphincter (LES) region of pig and man were analyzed for vasoactive intestinal peptides (VIP), substance P (SP), enkephalin, neuropeptide Y (NPY), gastrin/cholecystokinin (CCK), neurotensin, and somatostatin using immunocytochemistry and radioimmunoassay. VIP-, SP-, enkephalin-, and NPY-immunoreactive nerve fibers were observed in the LES of both species, whereas nerve The peptide-containing nerve fibers occurred in the intramural ganglia and in the smooth muscle layers. There was a rich supply of VIP-and NPY-immunoreactive fibers, whereas the supply of SP-and enkephalin-immunoreactive nerve fibers were moderate in number in both species examined. The concentration of VIP, SP, enkephalin and NPY was comparable in the two species. The present study shows that the pattern of peptidergic innervation of the LES is similar in pig and man. It is proposed that neuronal VIP, SP, enkephalin, and NPY may serve to modulate the motor activity of the LES and that the pig is a suitable experimental animal for the study of regulatory peptides and LES functions.

Diet and other risk factors for fissure-in-ano. Prospective case control study

The findings of a partly prospective case control study of chronic fissue-in-ano conducted in two Danish outpatient clinics are reported. One hundred seventy-four patients with chronic fissure-in-ano were matched by age and sex to outpatients from the same community suffering from benign skin tumors. All subjects were interviewed regarding diet, beverage consumption, occupational exposures, and medical and surgical history. Significantly decreased risks were associated with frequent consumption of raw fruits, vegetables, and whole-grain bread, and significantly increased risks were associated with frequent consumption of white bread, sauces thickened with roux, and bacon or sausages. Risk ratios for consumption of coffee, tea, and alcohol were not significantly different. No statistical associations were found with particular occupational exposures. However, a history of previous anal surgery was reported significantly more often for cases than for controls. Current evidence indicates that anal fissure is likely to result at least partly from an inappropriate diet and that dietary manipulations might reduce the incidence of fissure-in-ano.

The effect of gastrin-releasing peptide on the endocrine pancreas.

The 27-amino acid peptide gastrin releasing peptide (GRP-(1-27] was infused at 4 dose levels (0.01, 0.1, 1.0, and 10 nM) into the arterial line of the isolated perfused porcine pancreas. Infusions were performed at 3 different perfusate glucose levels (3.5, 5.0, and 8.0 mM) and at two levels of amino acids (5 and 15 mM). GRP-(1-27) stimulated insulin and pancreatic polypeptide secretion and inhibited somatostatin secretion in a dose-dependent manner. Glucagon secretion was unaffected by infusion of GRP under all circumstances. The effect of GRP-(1-27) on insulin secretion was enhanced with increasing perfusate glucose levels, whereas the effects upon somatostatin and pancreatic polypeptide secretion were independent of perfusate glucose levels. The responses to GRP were unaffected by elevation of the concentration of amino acids in the perfusate. The effects of GRP were unaffected by atropine at 10(-6) M. The localization of GRP within the porcine pancreas, its release during electrical stimulation of the vagus nerve, and its potent effects upon pancreatic endocrine secretion make it conceivable that the peptide participates in parasympathetic regulation of pancreatic endocrine secretion.

The natural history of symptomatic haemorrhoids

In order to calculate the prognosis for a person who has developed a first episode of second degree haemorrhoids, 186 patients were randomly assigned to either no active treatment (expectant management) (n=91) or rubber band ligation (n=98) and reviewed every 6 months. The median follow-up period was 48 months in both groups with a range from 6–48 months in the banding group and from 18–48 months in the expectant management group. Rubber band ligation was performed at most three times with three weekly intervals. There were 6 treatment failures in the banding group in contrast to 31 in the expectant management groupp<0.01). The calculated recurrence rate by actuarial analysis among patients initially cured by rubber band ligation was 33% (95% confidence limits: 23–45) at four years and 61% (95% confidence limits: 48–74) in the expectant management group (p<0.05). It is concluded that rubber band ligation of symptomatic second degree haemorrhoids in up to three single treatments at three weekly intervals at the time of diagnosis significantly altered the prognosis without causing significant morbidity. However, 25% of the patients treated by expectant management never developed another episode during the four years observation time.