Importance of surgical assembly technique on the engagement of 12/14 modular tapers.

Fretting-corrosion at the modular taper junction in total hip replacements (THR), leading to implant failure, has been identified as a clinical concern and has received increased interest in recent years. There are many parameters thought to affect the performance of the taper junction, with the assembly process being one of the few consistently identified to have a direct impact. Despite this, the assembly process used by surgeons during THR surgery differs from a suggested 'ideal' process. For example, taper junctions of cutting tools should be pushed together rather than impacted, while ensuring as much concentricity as possible between the male and female taper and loading axis. This study devised six simple assembly methodologies to investigate how surgical variations affect the success of the compressive fit achieved at the taper interface compared to a controlled assembly method, designed to represent a more 'ideal' scenario. Key findings from this study suggest that a more successful and repeatable engagement can be achieved by quasi-statically loading the male and female taper concentrically with the loading axis. This was shown by a greater disassembly to assembly force ratio of 0.626 ± 0.07 when assembled using the more 'ideal' process, compared to 0.480 ± 0.05 when using a method closer to that used by a surgeon intraoperatively. Findings from this study can be used to help inform new surgical instrumentation and an improved surgical assembly method.

Geometric Variations of Modular Head-Stem Taper Junctions of Total Hip Replacements.

Taper degradation in Total Hip Replacements (THR) has been identified as a clinical concern, and the degradation occurring at these interfaces has received increased interest in recent years. Wear and corrosion products produced at the taper junction are associated with adverse local tissue responses, leading to early failure and revision surgery. Retrieval and in-vitro studies have found that variations in taper design affect degradation. However, there is a lack of consistent understanding within the literature of what makes a good taper interface. Previous studies assessed different design variations using their global parameters assuming a perfect cone such as: taper length, cone angle and diameters. This study assessed geometrical variations of as-manufactured head and stem tapers and any local deviations from their geometry. The purpose of this study was to provide a greater insight into possible engagement, a key performance influencing parameter predicted by Morse taper connection theory. This was achieved by taking measurements of twelve different commercially available male tapers and six female tapers using a coordinate measurement machine (CMM). The results suggested that engagement is specific to a particular head-stem couple. This is subject to both their micro-scale deviations, superimposed on their macro-scale differences. Differences in cone angles between female and male tapers from the same manufacturer was found to create a predominately proximal contact. However, distally mismatched couples are present in some metal-on-metal head-stem couples. On a local scale, different deviation patterns were observed from the geometry which appeared to be linked to the manufacturing process. Future work will look at using this measurement methodology to fully characterise an optimal modular taper junction for a THR prosthesis.

Percutaneous treatment of biliary cast syndrome after orthotopic liver transplantation: comparison of mechanical versus hydraulic rheolytic cast extraction.

PURPOSE: Biliary cast syndrome (BCS) is the presence of casts within the intrahepatic or extrahepatic biliary system after orthotopic liver transplantation. Our work compares two percutaneous methods for BCS treatment: the mechanical cast-extraction technique (MCE) versus the hydraulic cast-extraction (HCE) technique using a rheolytic system. MATERIALS AND METHODS: A total of 24 patients were included in the study. Six patients were referred for HCE, and 18 patients were treated with MCE. A statistically significant larger number of sessions was required in the MCE group (21.0, range 11 to 72 sessions) (p = 0.033). RESULTS: Median therapy duration was shorter in the HCE group at 2.4 months (range 2 to 5) compared with 6.7 months (range 3 to 39) in the MCE group (p < 0.001). Both patient acceptance was better and costs for total therapy were 40% less in the HCE group. No significant differences where found concerning clinical and biochemical improvement or graft and patient survival. CONCLUSION: The use of the hydraulic rheolytic system decreased total therapy time, thereby decreasing the induced inflammation time of the biliary tree. A significant benefit of HCE has been observed in our patients when we compare our results with those of MCE.

Coeliac sprue: abnormalities of the hormone profile of gastroduodenal mucosa.

To further characterize coeliac sprue, the hormonal content of routine endoscopic biopsies of gastroduodenal mucosa was estimated in 5 coeliac sprue patients and in 8 volunteers without upper gastrointestinal disease. Levels of cholecystokinin-like immunoreactivity tended to be lower in duodenal mucosa of coeliac sprue patients, while the mucosal map of GIP and somatostatin exhibited no peculiar profile. Gastrin was markedly elevated in the antral mucosa of coeliac sprue patients (3013 +/- 760 versus 1048 +/- 392 pmol/g), while basal plasma gastrin was normal. The mucosal VIP content of the descending duodenum was significantly higher in coeliacs than in controls (409 +/- 161 versus 81 +/- 16 pmol/g) and tended to be increased also in the remaining upper small intestine. This rise may be a reaction to mucosal irritation and a reason for enhanced fluid secretion. Even in antral mucosa of coeliac sprue patients, VIP levels were elevated when compared to controls (82 +/- 14 versus 40 +/- 8 pmol/g) and may have some impact, e.g. on local mucosal blood flow or mucus secretion. The mucosal concentration of another putative neurotransmitter, substance P, also showed a tendency to be raised in the mucosa of upper small intestine of coeliac sprue patients.

Jejunal mucosal enzyme activities, regulatory peptides and organelle pathology of the enteropathy of common variable immunodeficiency.

Jejunal biopsies from six patients having the small bowel enteropathy associated with common variable immunodeficiency have been subjected to analytical subcellular fractionation and enzymic and regulatory peptide microassay to define the organelle pathology of this syndrome. Compared with normal subjects, the immunodeficient patients had decreased activities of the three brush border enzymes: alkaline phosphatase, gamma-glutamyl transferase and alpha-glucosidase. The other organelle marker enzyme activities and all the regulatory peptide concentrations did not differ from the controls. Density gradient experiments showed a complete loss of particulate beta-glucosidase (lactase) with activity entirely located in the cytosol. The integrity of other organelles was normal. These data indicate that the enteropathy of common variable immunodeficiency is associated with abnormalities in the jejunal brush border analogous to those present in tropical malabsorption syndrome.

Gastroduodenal mucosal hormone content in duodenal ulcer disease.

To further elucidate the pathophysiological role of peptide hormones in duodenal ulcer (DU) disease, several endocrine, paracrine and neurocrine peptides were determined radioimmunologically in biopsies of gastroduodenal mucosa obtained endoscopically in 8 subjects without upper gastrointestinal disease, and in 8 duodenal ulcer patients. The DU patients had a BAO of 6.6 +/- 1.9 and a PAO of 41.8 +/- 6.1 mEq/h. In DU patients, a lack of the acid and gastrin-release inhibiting agent somatostatin was found neither in antral nor in fundic mucosa (185 +/- 60 vs 83 +/- 19 pmol/g tissue wet weight in controls). Basal and peak acid outputs of DU patients were positively correlated with fundic somatostatin concentrations (p less than 0.01). While gastrin levels were not significantly elevated in the antrum of DU patients, the mucosal content of potentially releasable gastrin of the duodenal bulb and the descending duodenum was higher than in controls (p less than 0.01). In the whole duodenum, CCK-like immunoreactivity was also more abundant in DU patients than in controls, whereas GIP and motilin did not exhibit characteristic profiles. Presumably as a reactive phenomenon, the mucosal levels of the peptidergic neurotransmitters VIP and substance P were markedly increased in the proximal duodenum of DU patients.

Gastrointestinal regulatory peptide storage granule abnormalities in jejunal mucosal diseases.

The mucosal concentrations of seven regulatory peptides and the density properties and integrity of their storage granules have been studied in mucosal biopsies from the human jejunum in eight gastrointestinal disease states and compared with normal controls. In diseases with associated mucosal inflammation (coeliac disease, Crohn's disease with jejunal involvement, postinfective tropical malabsorption, and common variable immunodeficiency) there was a selective increase in fragility of the gastric inhibitory polypeptide (GIP) and somatostatin storage granules. The gastrin, motilin, enteroglucagon, secretin, and vasoactive intestinal polypeptide granules had normal properties in these conditions. In diseases in which diarrhoea occurred in the absence of changes in jejunal mucosal histology (irritable bowel syndrome, pancreatic insufficiency, jejuno-ileal bypass for morbid obesity, and purgative abuse) there were no abnormalities of the storage granules. Increased mucosal concentrations of all peptides except vasoactive intestinal polypeptide (VIP) were found in coeliac disease and selective increases of VIP found in Crohn's disease, motilin in the irritable bowel syndrome and gastrin and GIP in pancreatic insufficiency. It is suggested that the storage granule abnormalities in the diseases with abnormal mucosal histology are secondary to the inflammatory changes.

Abundance of VIP in duodenal mucosa of coeliacs and duodenal ulcer patients.

VIP levels were determined in gastroduodenal mucosal biopsies of 8 duodenal ulcer patients, of 5 coeliac sprue patients, and of 8 volunteers without upper gastrointestinal disease. In duodenal ulcer patients, mucosal VIP concentrations were significantly elevated in the proximal duodenum (e.g., in the duodenal bulb 225 +/- 48 versus 95 +/- 17 pmol/g in controls), while in coeliac sprue VIP levels tended to be increased in the whole duodenum and upper jejunum (e.g., descending duodenum 409 +/- 161 versus 81 +/- 16, p less than 0.05). In both disease entities, the rise in mucosal VIP may be a reaction of the peptidergic nervous system to chronic mucosal irritation and a reason for enhanced fluid and electrolyte secretion in the affected areas.

Molecular forms of human enteroglucagon in tissue and plasma: plasma responses to nutrient stimuli in health and in disorders of the upper gastrointestinal tract.

A means of estimating human enteroglucagon (glucagon-like immunoreactivity of intestinal origin) in tissues and plasma is described, based on the subtraction of RIA values obtained with the C-terminal-directed glucagon antiserum RCS5 from the total glucagon-like immunoreactivity determined with the N-terminal- to midmolecule-directed glucagon antiserum R59. Gel filtration on Sephadex G-50 of human plasma and extracts of normal human intestine separated the R59 immunoreactivity into three peaks: a small peak of void volume material, a major peak coeluting with porcine glicentin, and a smaller peak coeluting with pancreatic glucagon. No RCS5 immunoreactivity was detected in the human gut, except for a small amount constituting less than 2% of the total glucagon-like immunoreactivity in the ileum and rectum only. In extracts of human pancreas, the chromatographic profiles obtained with RCS5 and R59 assays differed from the intestinal patterns, but were identical to each other, giving no evidence of a significant amount of pancreatic R59 immunoreactivity that was not also reactive with RCS5. Chromatography of plasmas from healthy subjects and patients with dumping syndrome, active coeliac disease, and tropical sprue showed that only the second major peak of R59 immunoreactivity reflected the basal or postnutrient increases in the plasma enteroglucagon concentration. In patients with exaggerated enteroglucagon release, the rise was again found to be entirely due to an increase in this peak of immunoreactivity. This major molecular form of human enteroglucagon, similar in size to porcine glicentin, is, thus, the form most likely to be of physiological and pathophysiological significance.

Molecular forms of glucagon-like immunoreactivity in porcine intestine and pancreas.

Glucagon-related polypeptides in porcine pancreas and intestine were analysed by gel-permeation chromatography and RIA. Three assays were employed: a nonspecific glucagon assay (R59) of 94% cross-reactivity with glicentin; a pancreatic glucagon assay (RCS5) directed against the C-terminal region of glucagon and of less than 0.01% cross-reactivity with glicentin; and a glicentin assay (R64) of less than 0.01% cross-reactivity with glucagon. For extracts of porcine pancreas all three assays gave similar molar concentrations of immunoreactivity. In porcine intestinal extracts immunoreactivity was detected in significant amounts only by the nonspecific glucagon (R59) and the glicentin (R64) assays, again in similar molar concentrations. The immunoreactivities present in pancreas and intestine were chromatographically and immunologically separable into six main peaks, peaks I, II, III, V, and VI being present in the pancreas, and peaks I, II, and IV in the intestine. The different immunoreactivities of the peaks allowed probable identities to be assigned to their main components. Apart from peak I, which consists of void-volume material that may interfere nonspecifically with the assays, the main components of the peaks can be interpreted as glicentin (in peak II) or fragments derived from glicentin. Peak III contains the N-terminal portion of glicentin (glicentin-related pancreatic peptide), peak IV probably contains glucagon with its 8 amino-acid C-terminal extension, peak V is pancreatic glucagon and peak VI contains smaller N-terminal glicentin fragments. These findings fit with the proposition that glicentin fulfills the role of proglucagon in the pancreas, and is the major component of enteroglucagon in the intestine.

Measurement of gut hormonal peptides in biopsies from human stomach and proximal small intestine.

Using sensitive and specific radioimmunoassays, concentrations of hormonal peptides have been measured in small biopsies taken from the human stomach, duodenum, and proximal jejunum. Comparison is made of these hormone concentrations and the number of respective endocrine cells present determined by quantitative immunocytochemistry. Immunoreactive somatostatin, VIP, motilin, and gastrin were detected in all regions examined, whereas secretin and GIP were undetectable in antral extracts. Enteroglucagon-like immunoreactivity was present only at and beyond the ligament of Treitz, although a few enteroglucagon-producing cells were shown by immunocytochemistry in the duodenum. The variation of hormone concentration was found to be small in these biopsies of normal tissue within each region of the gut examined, indicating that representative hormone concentrations may be reliably obtained from small biopsy tissues. An attempt has been made to establish reference values for gut hormone concentrations in such biopsies; this may allow future study of any changes in concentration that may occur in pathological conditions.

Gastric acid regulates the release of plasma secretin in man.

Fasting plasma secretin determined in nine healthy subjects, twelve patients with active duodenal ulcer and four with Zollinger-Ellison syndrome were 3.2 +/- 0.4, 5.1 +/- 1.2 and 20.3 +/- 1.3 pmol/l respectively (mean +/- SEM). Cimetidine significantly (P less than 0.05) reduced levels in those with duodenal ulcer, as did gastric aspiration in the Zollinger-Ellison group. A significant correlation (P less than 0.001) was found between basal acid output and mean fasting plasma secretin. After a solid meal and subsequent liquid soft drink, no sustained mean rise in plasma secretin was observed; changes in secretin appeared to coincide in time with rapid falls in duodenal pH, though little relationship could be established between the absolute level of pH and changes in plasma secretin. The mean peak post-prandial rise in plasma secretin observed after solids was significantly (P less than 0.05) greater in duodenal ulcer patients than controls (9.1 +/- 1.1 versus 6.7 +/- 0.5 pmol/l) as was the mean integrated post-prandial release (1002 +/- 110 versus 710 +/- 67 pmol min-1 1(-1)). Cimetidine reduced both rises (P less than 0.05) and was associated with significantly less duodenal pH readings below 4 (P less than 0.001). These results suggest that gastric acid is a major release mechanism for plasma secretin both fasting and after meals but it is likely the acid load rather than absolute pH in the duodenum which determines circulating levels.

Development of intestinal regulatory peptides in the human fetus.

The time of first appearance and subsequent development of eight regulatory peptides in the small and large intestine of human fetuses has been investigated. Gastrin, secretin, motilin, gastric inhibitory peptide, vasoactive intestinal peptide, enteroglucagon, and somatostatin were first detected as early as 8 wk of age, while neurotensin was only demonstrated at 12 wk. Adult patterns of distribution were established by 20 wk of age. Of the peptides examined only vasoactive intestinal peptide was localized to nerve fibers and these were seen clearly in the myenteric plexus at the 12-wk fetal stage and in the later fetuses in both the enteric plexuses. The concentrations of regulatory peptides increased steadily until term when they were close to adult levels. Secretin and vasoactive intestinal peptide showed only a single molecular size species by gel permeation chromatography but the other peptides showed multiple peaks, the ratios tending to change through the gestational period in favor of the smaller molecular sized moieties. Thus the regulatory peptide system of the gut is present in th early fetus and its role in the process of maturation requires investigation.

Pancreatic glucagon in human foetal stomach.

A combination of immunocytochemistry at light and electron microscopic levels, direct radioimmunoassay and measurement after gel chromatography have been used to identify and characterise a glucagon-like peptide detected in human foetal stomach. Immunocytochemistry, with region specific antisera, demonstrated that the glucagon-containing cells were indistinguishable from pancreatic A cells. Radioimmunoassay of tissue extracts confirmed the presence of significant quantities of glucagon, mean 21 pmol/g wet weight (range 14-29) in 16-26 week old foetuses, increasing to 41 pmol/g wet weight (range 31-52) in 33-30 week old foetuses and after gel chromatography the peptide was found to elute at the same position as standard porcine glucagon. It is apparent, therefore, that the human foetal fundus contains significant quantities of true pancreatic-type glucagon.

Mucosal enzyme activities, peptide hormone concentrations and hormone secretory granule properties in functioning proximal jejunum after shunt operation for obesity.

Crosby capsule biopsies were obtained from functioning jejunum in 6 patients between 7 and 15 months after jejuno-ileal for morbid obesity and compared with 6 normal control biopsies. Brush border and other mucosal enzyme activities and seven regulatory peptide concentrations were measured in each biopsy. Analytical subcellular fractionation by sucrose density gradient centrifugation was used to investigate brush border and peptide secretory granule properties. Specific activities of all the brush border enzymes assayed in the bypass patients were similar to the normal controls and subcellular fractionation studies showed no change in brush border properties. Similarly, properties of other mucosal organelles and their associated enzyme activities were unchanged in the bypass patients. The mucosal regulatory peptide concentrations in the bypass patients showed no significant difference from the normal controls and no changes were detected in peptide storage granule properties. These studies therefore support the concept that the adaptive changes occurring after jejuno-ileal bypass are due to changes in cell numbers or other parameters of function rather than changes in the specific activities of the brush border enzymes themselves. They also show that the marked abnormalities of plasma hormone release after bypass surgery are not in themselves due to alterations in mucosal hormone concentrations, or of the secretory granule properties.

Abnormalities of the colonic regulatory peptides in Hirschsprung's disease.

We describe here a depletion of peptide containing nerves and cells in Hirschsprung's disease, in comparison with specimens of bowel taken from age-matched neonates with no evidence of chronic constipation. VIP content in the diseased specimens was reduced by almost 80%, from 110/+-10.6 (mean +/- SEM) pmol VIP/g wet weight of tissue in controls to 23.8 +/- 3.5 pmol/g in the mid-portion of the diseased specimens. In addition, the numbers of enteroglucagon and somatostatin cells in the mucosa were significantly reduced in the aganglionic portions. Enteroglucagon cells were reduced from 55 +/- 7 in controls to 27 +/- 2 in proximal portions rising to 44 +/- 3 and 49 +/- 4 cells/mm2 in middle and distal areas. Somatostatin cell numbers also fell, from 5.5 +/- 1.9 to 1.8 +/- 0.8, 2.5 +/- 0.7 and 3.8 +/- 0.9 cells/mm2 in similar areas. Further investigation of the abnormalities of the diffuse neuroendocrine system in Hirschsprung's disease may help in understanding the nature of this condition and provide additional information on the role of these peptides in the control of gut function.

Characterisation of gut hormone storage granules from normal human jejunum using metrizamide density gradients.

Analytical subcellular fractionation techniques using metrizamide density gradients have been used to investigate the properties of the gut hormone storage granules and the principal organelles from homogenates of normal human jejunal mucosa obtained by peroral mucosal biopsy. The individual hormones, detected by radioimmunoassay, each showed single discrete peaks in the density gradient experiments indicating localisation to single granules each with characteristic modal densities. Thus motilin showed a modal density of 1.15, gastrin 1.16, gastric inhibitory polypeptide (GIP) 1.17, enteroglucagon 1.18 and somatostatin and vasoactive intestinal peptide (VIP) 1.10 g/ml. The following organelles, characterised by their marker enzymes were located in the density gradients; plasma membrane (5'-nucleotidase) brush border (alpha-glucosidase, pH 6.0) mitochondria (particulate malate dehydrogenase), peroxisomes (catalase), lysosomes (N-acetyl-beta-glucosaminidase), endoplasmic reticulum (alpha-glucosidase, pH 8.0), cytosol (lactate dehydrogenase). These studies provide biochemical evidence of the distinct nature of the individual gut hormone storage granules and provide a basis for studying dynamic changes in the granules in response to physiological stimuli and pathological processes.

Mixed pancreatic apudoma with symptoms of excess vasoactive intestinal polypeptide and insulin: improvement of diarrhoea with metoclopramide.

A female patient is described with a single pancreatic tumour producing vasoactive intestinal polypeptide (VIP), insulin, and pancreatic polypeptide. The initial presentation was with diarrhoea and hypokalaemia and a raised plasma VIP was demonstrated. Her symptoms improved with metoclopramide administration and absolute concentrations of 28 aminoacid (peak IV) VIP were found to have fallen. She then developed hypoglycaemia with hyperinsulinism. All symptoms resolved after surgical excision. This case emphasises the potential of these tumours to contain more than one endocrine cell type synthesising different biologically active peptides.

Clinicopathological study of pancreatic and ganglioneuroblastoma tumours secreting vasoactive intestinal polypeptide (vipomas).

During a six-year period (1973-9) 52 patients with pancreatic tumours and 10 with ganglioneuroblastomas were found to have raised plasma vasoactive intestinal polypeptide (VIP) concentrations. All the patients had severe secretory diarrhoea, weight loss, dehydration, hypokalaemic acidosis, and a raised plasma urea concentration. Reduced gastric acid secretion was seen in 72% of patients. Plasma VIP concentrations were not raised in patients with diarrhoea due to other types of tumour or disease or in hormone-secreting tumours not associated with diarrhoea. Plasma VIP measurement may therefore give clinical guidance in a patient with persistent watery diarrhoea and hypokalaemic acidosis. Surgical excision was clearly the treatment of choice, but metastatic pancreatic tumours usually responded to streptozotocin.