Postpartum haemorrhoids--evaluation of a cooling device (Anurex) for relief of symptoms.

Postpartum haemorrhoids are a common problem, for which the recently marketed cooling device, Anurex (Roussel Uclaf Australia, Pennant Hills, NSW), was evaluated in 129 women randomly allocated to treatment and control groups. There was no difference in the rate of resolution of pain between the groups. The test group estimated a greater duration of pain relief, but this was not statistically significant. Anal bleeding and itching were not significantly reduced in the test group. There was no difference between discomfort scores related to application of the device in the groups, but a significant number in the test group encountered difficulty in insertion of the device. It is concluded that the introduction of the Anurex device as a standard method of treatment of postpartum haemorrhoids is not justified.

Manipulation of gut hormone response to food by soluble fiber and alpha-glucosidase inhibition.

Preliminary data indicated that viscous fiber (guar) and alpha-glycosidase inhibition (acarbose) used in combination to slow carbohydrate absorption have an apparently additive effect in reducing the postprandial glycemic response. The full endocrine data reported here also demonstrate that reductions in insulin and gastric inhibitory polypeptide are most significant when guar and acarbose are used in combination. The results are divergent for enteroglucagon when guar and acarbose were given singly. Raised enterglucagon levels seen after acarbose are in keeping with inhibition of proximal absorption resulting in more distal absorption of carbohydrate. However, with viscous fiber, the enteroglucagon response was reduced, and this reduction was maintained even after addition of acarbose. The results demonstrate that the gut endocrine response can be manipulated by pharmacological interventions which alter the pattern of carbohydrate absorption.

Effect of modifying the rate of digestion of a food on the blood glucose, amino acid, and endocrine responses in patients with cirrhosis.

To see whether foods with slower rates of digestion may benefit the metabolic abnormalities seen in cirrhosis, the same food, processed in two different ways, was fed to seven patients with cirrhosis. The breakfast of lentils processed by prolonged heating, to produce more rapid in vitro digestion, resulted in a significantly higher incremental rise in large neutral amino acid levels at 60 min (p less than 0.02) and a tendency for a more rapid rise in total amino acid concentrations by comparison with conventionally cooked lentils with slower in vitro digestion rates. After more rapidly digested lentils, incremental levels of branched-chain amino acids were also higher at 60 min (67 +/- 9, p less than 0.001) despite a greater overall insulin response. Comparable incremental amino acid areas after both meals suggested that the total amount of amino acids absorbed was not influenced by processing. Greater blood glucose, insulin, and gastric inhibitory polypeptide responses were seen after the more processed meal with no significant differences in pancreatic glucagon, entroglucagon, or neurotensin levels. Processing a food to alter the rate of digestion may therefore be used to manipulate amino acid, glucose, and endocrine responses in cirrhosis.

Somatostatin-14 modulates postprandial glucose levels and release of gastrointestinal and pancreatic hormones.

Ingestion of a 4,500-kcal mixed meal by healthy volunteers resulted in a significant rise of plasma somatostatin-14-like immunoreactivity (9 +/- 1 pmol l-1. Whether this peptide has a role as a humoral agent or not is still controversial and, until recently, most studies investigating its effects by exogenous administration have produced vastly supraphysiological circulating plasma levels. In order to reproduce the rise obtained following the large meal, synthetic somatostatin-14 was infused at a dose of 0.8 pmol kg-1 min-1 before and during a 530-kcal test breakfast. This resulted in a rise of 8 + 2 pmol l-1 in the peripheral circulation. This infusion produced a significant reduction in the postprandial release of insulin, gastric inhibitory polypeptide, pancreatic polypeptide and in the preprandial motilin levels. In contrast, blood glucose levels following the breakfast were elevated when compared to the control saline infusion. This suggests that somatostatin possesses true endocrine functions and is capable of profoundly altering the postprandial glucose and hormone response.

The effects of ileal transposition and jejunoileal bypass on food intake and GI hormone levels in rats.

Male Wistar rats received three different types of small intestinal surgery. Two groups of rats had either 10 or 20 cm of lower ileum transposed to mid-duodenum. A third comparison group of rats had 85% jejunoileal bypass. All three experimental groups showed a sustained post-operative reduction in food intake and a change in body weight gain. Measurements made 36 days after surgery showed that all experimental groups had a large increase in basal and meal-stimulated enteroglucagon. The total-integrated plasma levels of gastrin, GIP, insulin and blood glucose were significantly reduced. At sacrifice, there were large increases in the wet weight of the small intestine and pancreas. These changes were probably due to the chronic stimulation of the lower ileum with nutrient-rich chyme and may be due to the release of ileal hormones.

Slowly digested carbohydrate food improves impaired carbohydrate tolerance in patients with cirrhosis.

To test whether impaired carbohydrate tolerance in cirrhosis could be modified by dietary means ten cirrhotic patients, five of them taking insulin, took as breakfast either lentils or wholemeal bread and cottage cheese containing the same amount of carbohydrate and protein. Lentils resulted in significantly diminished blood glucose, insulin (in those not on insulin) and gastric inhibitory peptide responses. Enteroglucagon and neutrotensin levels were high with lentils, suggesting that absorption of lentil carbohydrate continued into the ileum with perhaps some malabsorption, so confirming the results of earlier studies in vitro. However, breath hydrogen studies on a separate group of eight healthy volunteers indicated that the difference in carbohydrate malabsorption between lentil, and wholemeal bread was insignificant. It is suggested that slowly digested carbohydrate foods, such as leguminous seeds, may minimize carbohydrate intolerance in patients with cirrhosis.

Categories of family-mediated abuse and neglect of elderly persons.

The records of 22 cases of family-mediated abuse and neglect of elderly persons were retrospectively reviewed by the physician and nurse responsible for their care using a modification of the OARS Multidimensional Functional Assessment form. Cases were divided into three categories: Category I cases (n = 4) involved extremely impaired elders who received extensive care from the individuals responsible for the abuse or neglect. Category II cases (n = 9) involved impaired elders who received inadequate or intermittent care. Category III cases (n = 9) involved independent elders whose only care needs resulted from threats or violence from relatives. Among the statistically significant differences found between these categories were the age of the abuser, the manifestations of abuse or neglect, the interventions offered, the durations of abuse, and the outcomes of the cases. The results suggest that these three categories represent different subgroups of abused and neglected elderly persons, all with different implications for identification, intervention, and outcome.

Glucose-dependent insulinotropic polypeptide augmentation of insulin. Physiology or pharmacology?

Glucose-dependent insulinotropic polypeptide (GIP) is said to be a major physiologic factor in the augmentation of the insulin response to oral glucose. Whether GIP promotes insulin release at physiologic concentrations of glucose or GIP, however, is questionable. To investigate this further, volunteers were infused with 10, 20, or 40 g intravenous (i.v.) glucose, with or without simultaneous GIP infusion, to produce plasma levels of GIP or glucose similar to those seen after oral glucose. The effect of 40 g i.v. glucose with three times the original dose of GIP was also investigated. No significant enhancement of glucose-stimulated insulin secretion was seen when GIP was infused with 10 or 20 g i.v. glucose; however, with 40 g a doubling of the insulin response occurred. The higher dose of GIP caused a further increase in insulin response (30-min increment, 972 +/- 191 pmol/L; compared with glucose alone, 356 +/- 100 pmol/L, P less than 0.01; and compared with low GIP, 602 +/- 247 pmol/L, P less than 0.02). The glucose increment after the 40-g i.v. dose was +9.2 mmol/L. The concentration of GIP and glucose required to produce significant potentiation of the insulin response appears to be in the pharmacologic, rather than physiologic, range.

Adult cystic fibrosis: postprandial response of gut regulatory peptides.

Responses of 11 gastrointestinal regulatory peptides to a standard test meal were assessed in 10 adult patients with cystic fibrosis. The basal plasma neurotensin was significantly elevated in patients with cystic fibrosis, being 31.5 +/- 6.1 pmol/L compared with a control value of 10.3 +/- 1.5 pmol/L (p less than 0.005). Plasma neurotensin remained elevated throughout the test period. Basal plasma enteroglucagon was similarly elevated, the patients with fibrocystic disease having levels of 51.3 +/- 4.6 pmol/L compared to controls with levels of 33.2 +/- 6.7 pmol/L (p less than 0.02). There was, however, no significant difference in postprandial levels of plasma enteroglucagon. Postprandial motilin was significantly elevated in the patients with cystic fibrosis; this elevation is in contrast with previous findings in children. Release of gastric inhibitory polypeptide was impaired, while release of cholecystokinin showed no significant difference in control values, although there was a tendency for delay. There was no significant postprandial rise of pancreatic polypeptide in the patients, whose levels were grossly lower than controls. Insulin showed a delayed response. No significant differences were observed between patients and controls in levels of gastrin, pancreatic glucagon, somatostatin, or vasoactive intestinal peptide. The elevation of plasma neurotensin and enteroglucagon in the basal state may reflect an adaptive response and may be part of the improved digestive function in adults compared with children with fibrocystic disease.

Disparity between glucose-dependent insulinotropic polypeptide and insulin responses in obese man.

Studies were carried out in 32 obese patients and 30 normal-weight control subjects to ascertain the response of glucose-dependent insulinotropic polypeptide (GIP) and insulin to (1) oral and intravenous glucose (10 obese and 10 control subjects), (2) oral fat and intravenous glucose (eight obese and six control subjects) and (3) mixed test meal (14 obese and 14 control subjects). Basal mean insulin was higher in the obese (99 pmol/l) than in the control group (40 pmol/l), but fasting blood glucose and GIP were not significantly different from normal. The total integrated response of insulin in obese subjects after oral glucose was 54.1 versus 33.3 nmol . l-1 . h-1 in control subjects; glucose and GIP responses were similar in both groups. After intravenous glucose the integrated insulin response was 8.8 in the obese versus 5.0 nmol . l-1 . h-1 in control subjects; GIP was unaffected by intravenous glucose and glucose levels were similar. Following oral fat and intravenous glucose, insulin secretion was again abnormal in the obese, 24.5 versus 7.3 nmol . l-1 . h-1 in controls, but GIP responses were normal. However, the control subjects became hypoglycaemic after this test: blood glucose 2.8 mmol/l at 150 min compared with 4.6 mmol/l in the obese group. The insulin response to a mixed meal was also abnormal in obesity.

Gut hormones in inflammatory bowel disease.

We have studied fasting levels and the response to a standard test breakfast of blood glucose and several gut hormones in 24 patients with ulcerative colitis, in 14 patients with Crohn's disease, and in 14 healthy control subjects. Patients with ulcerative colitis had significantly elevated fasting human pancreatic polypeptide (HPP) concentrations, and both basal and postprandial levels of gastrin, gastric inhibitory polypeptide (GIP), and motilin were greater than normal. In contrast, patients with Crohn's disease had normal gastrin levels but had increased fasting and postprandial levels of GIP and motilin and, in addition, of enteroglucagon, compared with controls. These patients also had greater than normal HPP concentrations 30 min after the breakfast. Normal levels of insulin, pancreatic glucagon, neurotensin, and vasoactive intestinal polypeptide were found in both groups of patients. Much remains to be known about the pathophysiology of these two debilitating diseases, and the abnormal release of gut hormones may be of importance.

Gut hormones in acute diarrhoea.

The gut hormone response to a breakfast meal was studied in 12 subjects hospitalised for an episode of acute diarrhoea (presumed infective) who were otherwise well and in 13 healthy control subjects. Fasting blood glucose concentrations were low but basal insulin concentrations were raised. Basal concentrations of pancreatic polypeptide and both basal and postprandial responses of motilin, enteroglucagon, and vasoactive intestinal polypeptide (VIP) were also significantly greater than controls. No abnormalities in plasma concentrations of gastrin, gastric inhibitory polypeptide (GIP) or pancreatic glucagon were found. The suggested physiological actions of the raised hormones may be relevant to the pathophysiology of diarrhoea.

Autoantibodies to gut hormone secreting cells as markers of peptide deficiency.

Autoantibodies reacting with endocrine cells in the gastrointestinal mucosa were found by indirect immunofluorescence in 22 out of 268 sera (8.2%) obtained from patients with coeliac disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome, and from subjects without bowel disease. A double immunofluorescence technique showed that the autoantibodies reacted with cells secreting gastric inhibitory polypeptide (glucose dependent insulinotropic polypeptide, GIP), secretin, somatostatin or enteroglucagon. Most sera contained antibodies against more than one cell type. Neither the presence of a particular antibody nor the pattern of antibody combinations appeared to be specific for any diagnostic category. The mean plasma GIP concentrations, however, both fasting and two hours after a test meal, were significantly lower in subjects with GIP cell autoantibodies. Thus gut hormone cell autoantibodies may be markers of impaired hormone secretion.

Enteroglucagon and GIP after oral glucose in patients with prolactinoma and acromegaly.

We have performed oral glucose tolerance tests (OGTT) in nine patients with prolactinomas, eight patients with active acromegaly, five patients with acromegaly in remission and nine normal controls, and measured blood glucose, plasma insulin, pancreatic glucagon, enteroglucagon, gastric inhibitory polypeptide (GIP) and GH during the test. Patients with prolactinomas and with active acromegaly were hyperinsulinaemic and five of the nine patients with prolactinomas had impaired glucose tolerance, with blood glucose levels that were significantly higher than the normal controls. Prolactinoma patients had higher GIP levels than those with active acromegaly and both showed a failure of suppression of pancreatic glucagon. Of particular interest was the finding that enteroglucagon, a putative gut growth factor, was low in active acromegaly when compared with acromegaly in remission, but similar to normal in the rest of the patients.

Familial chylomicronemia due to a circulating inhibitor of lipoprotein lipase activity.

A mother and her son who have lipoprotein phenotype I are described. They differed from subjects with lipoprotein lipase deficiency in that lipoprotein lipase was present in adipose tissue respectively at 30- and 2-fold the levels seen in normal subjects, and from subjects with apoprotein C-II deficiency in that apoprotein C-II was present in their plasma. They appeared to have an inhibitor to lipoprotein lipase activity in their whole plasma that inhibited that activity eluted from adipose tissue with heparin and that activity present in postheparin plasma of normals. The inhibitor was non-dialyzable, heat-stable, sensitive to repeated freezing and thawing, and appeared to be present in the non-lipoprotein fraction of plasma. The presence of chylomicronemia and the plasma inhibitor in the mother and her son, and possibly in her father and grandson, argues against this being inherited as an autosomal recessive abnormality, as are lipoprotein lipase deficiency and apoprotein C-II deficiency.

Effect of partial ileal bypass on the gut hormone responses to food in man.

The integrated response of the regulatory peptides of the gastrointestinal tract to a test meal was studied in six hypercholesterolaemic patients who had undergone partial ileal bypass (PIB) and compared with responses in ten age- and sex-matched controls. Plasma motilin was found to rise significantly whereas plasma pancreatic polypeptide release was impaired after PIB. Plasma cholecystokinin rose promptly in both controls and the partial ileal bypass patients, and the latter group showed marked further rises, at 60 and 120 minutes after the meal, which were significantly higher than controls. Basal and postprandial plasma gastrin, gastric inhibitory peptide, neurotensin, enteroglucagon, insulin and pancreatic glucagon were similar in the two groups.

The pharmacokinetics of porcine glucose-dependent insulinotropic polypeptide (GIP) in man.

The pharmacokinetics of porcine glucose-dependent insulinotropic polypeptide were investigated in six healthy volunteers. At the maximum infusion dose (0 . 5 pmol kg-1 min-1) a plateau concentration of 115 +/- 5 . 0 pmol/l plasma was obtained. On discontinuation of the infusion, the half-time of disappearance was calculated to be 20 . 3 +/- 1 . 2 min. The metabolic clearance rate was 2 . 6 +/- 0 . 1 ml kg-1 min-1 and the apparent space of distribution was 75 . 8 +/- 5 . 7 ml kg-1. Blood glucose, pancreatic and gastrointestinal hormones remained at basal concentrations throughout. No side effects were noted by any of the subjects studied.

Gut hormone release after intestinal resection.

To investigate the possible role of gut and pancreatic hormones in the adaptive responses to gut resection, plasma concentrations of the circulating hormones were measured, in response to a test breakfast, in patients with either small or large intestinal resection and in healthy control subjects. In 18 patients with partial ileal resection a significant threefold rise was found in basal and postprandial levels of pancreatic polypeptide, a fourfold increase in motilin, and more than a twofold increase in gastrin and enteroglucagon levels compared with healthy controls. In contrast, nine patients with colonic resection had a threefold rise in levels of pancreatic polypeptide only. One or more of these peptides may have a role in stimulating the adaptive changes found after gut resection.

Slow release dietary carbohydrate improves second meal tolerance.

Breakfasts of lentils or wholemeal bread of identical carbohydrate content were taken by seven healthy volunteers. The lentils produced a significant 71% (p less than 0.001) reduction in the blood glucose area and flattened the plasma insulin and gastric inhibitory polypeptide responses by comparison with the bread. In addition, the lentil breakfast was followed by a significantly flatter blood glucose response to the standard bread lunch which followed 4 h later (by 38%, p less than 0.01). The blood glucose pattern was mimicked by feeding the bread breakfast slowly over the 4 h before lunch. Giving a bread breakfast containing a quarter of the carbohydrate reduced the breakfast glucose profile but resulted in a significantly impaired blood glucose response to lunch (168% of control, p less than 0.01). These results, together with breath hydrogen studies, performed on a separate group of four volunteers, indicate that the flattened response to lentils is not due to carbohydrate malabsorption. Slow release or "lente" carbohydrate foods such as lentils may form a useful part of the diets of those with impaired carbohydrate tolerance.

Bombesin: action on gut hormones and calcium in man.

Bombesin, a peptide with widespread biological actions, has been demonstrated in human tissues by immunological methods. To investigate its effect in man, synthetic bombesin was infused at low doses in six male volunteers. Bombesin at 2.4 pmol kg-1 min-1 produced significant rises in plasma insulin, glucagon, pancreatic polypeptide, gastrin, cholecystokinin, motilin, glucose-dependent insulinotropic polypeptide, neurotensin, enteroglucagon, vasoactive intestinal polypeptide, and serum calcium. In contrast, bombesin caused a profound fall in parathyroid hormone levels and reduced plasma glucose concentrations. A late rise in plasma calcitonin was also observed. Bombesin had no significant effect on the pituitary hormones, TSH, GH, PRL, or cortisol. No hormonal changes or alterations in calcium were noted during saline infusions. Bombesin has a marked stimulatory effect on gastrointestinal hormones, which is unique and opposite to the effect of somatostatin, a potent inhibitor of gut hormone release. Bombesin also influences calcium-regulating hormones, either directly or through its action on gut hormones. The bombesin concentrations achieved with the dosages used were low enough to indicate a possible physiological role for the endogenous peptide.