Complications and survival of conversion to total hip arthroplasty after failed primary osteosynthesis compared to primary total hip arthroplasty in femoral neck fractures.

INTRODUCTION: Surgical treatment options for patients with an intracapsular fracture of the femoral neck (FFN) are primary osteosynthesis as a femoral head-spearing technique or primary (hemi)arthroplasty. The most common complications after primary osteosynthesis, such as avascular necrosis (AVN) or non-union, can result in conversion to Total Hip Arthroplasty (cTHA). Data concerning complications and survival rates of cTHA in comparison to primary Total Hip Arthroplasty (pTHA) after FFN are limited due to the absence of well-designed studies. METHODS: A multicentre retrospective cohort study was conducted in three Dutch hospitals comparing the rate of postoperative dislocations, periprosthetic fractures, prosthetic joint infections, blood loss during surgery (>1000 mL), postoperative cardiac- and pulmonary complications after pTHA and cTHA in the first year after surgery. As a secondary outcome implant survival of pTHA and cTHA in terms of revision rates was evaluated. RESULTS: In total 548 patients were included (pTHA n = 264 and cTHA n = 284) with a mean follow-up of 5 years (±3.5 SD). No significant differences were found in postoperative complications rates. The revision rate in the pTHA group was 7.2% in comparison to 7.7% in the cTHA group (p = 0.81). No difference in the short-term implant survival was found between both groups (p = 0.81). CONCLUSION: This study showed no significant differences in terms of postoperative complication rates in the first year after pTHA and cTHA in patients with FFN. Also, no significant difference in short-term implant survival of primary and conversion total hip arthroplasty was found.

Risk assessment of exotic disease incursion and spread.

This Technical Report describes the activities developed in the scope of the EU-FORA Fellowship, within the work programme of risk assessment (RA) of exotic disease incursion and spread, developed at Wageningen Bioveterinary Research (WBVR). The programme focused on the work carried out in the Generic risk assessment for introduction of animal diseases (G-RAID) project, which brings together a number of different generic RA tools from multiple European partners. The aim of the fellowship was to gain understanding of veterinary import risk assessment by using different RA tools and to learn how different algorithms can be used to calculate disease incursion risks. G-RAID's tools cover a wide range of RA methodologies; from purely qualitative, to semi-quantitative and fully stochastic quantitative methods, which allowed the fellow to understand a variety of algorithms used to produce the final risk estimate. The fellowship programme provided the fellow with the chance to learn in detail about how generic RAs are performed across Europe, understanding how to deal with the uncertainty and variability involved in RAs and the potential problems of data availability and reliability. The fellow made an inventory of publicly available databases on disease occurrence and international trade that could be used for import RA and assessed their quality and usefulness for the different generic RA tools. The programme also provided the fellow the opportunity to perform several import risk assessments using the RA tools of G-RAID. She completed a RA on African swine fever using the MINTRISK model developed by WBVR. Furthermore, she assessed the risk of foot and mouth disease introduction using the Rapid Risk Assessment Tool (RRAT) model developed by WBVR and the COMPARE model developed by the Animal and Plant Health Agency (APHA). To this end, the fellow completed a short-term visit to APHA, enabling her to have additional training in quantitative RA and to expand her professional network in this area.

A spatiotemporal model to assess the introduction risk of African horse sickness by import of animals and vectors in France.

BACKGROUND: African horse sickness (AHS) is a major, Culicoides-borne viral disease in equines whose introduction into Europe could have dramatic consequences. The disease is considered to be endemic in sub-Saharan Africa. Recent introductions of other Culicoides-borne viruses (bluetongue and Schmallenberg) into northern Europe have highlighted the risk that AHS may arrive in Europe as well. The aim of our study was to provide a spatiotemporal quantitative risk model of AHS introduction into France. The study focused on two pathways of introduction: the arrival of an infectious host (PW-host) and the arrival of an infectious Culicoides midge via the livestock trade (PW-vector). The risk of introduction was calculated by determining the probability of an infectious animal or vector entering the country and the probability of the virus then becoming established: i.e., the virus's arrival in France resulting in at least one local equine host being infected by one local vector. This risk was assessed using data from three consecutive years (2010 to 2012) for 22 regions in France. RESULTS: The results of the model indicate that the annual risk of AHS being introduced to France is very low but that major spatiotemporal differences exist. For both introduction pathways, risk is higher from July to October and peaks in July. In general, regions with warmer climates are more at risk, as are colder regions with larger equine populations; however, regional variation in animal importation patterns (number and species) also play a major role in determining risk. Despite the low probability that AHSV is present in the EU, intra-EU trade of equines contributes most to the risk of AHSV introduction to France because it involves a large number of horse movements. CONCLUSION: It is important to address spatiotemporal differences when assessing the risk of ASH introduction and thus also when implementing efficient surveillance efforts. The methods and results of this study may help develop surveillance techniques and other risk reduction measures that will prevent the introduction of AHS or minimize AHS' potential impact once introduced, both in France and the rest of Europe.

Epidemic threats to the European Union: expert views on six virus groups.

In recent years, several animal disease epidemics have occurred within the European Union (EU). At the 4th Annual Meeting of the EPIZONE network (7-10 June 2010, St. Malo, France), an interactive session was run to elicit the opinions of delegates on a pre-defined list of epidemic threats to the EU. Responses from over 190 delegates, to questions relating to impact and likelihood, were used to rank six virus groups with respect to their perceived threat now (2010) and in 2020. The combined opinions of all delegates suggested that, from the pre-selected list of virus groups, foot-and-mouth disease and influenza are currently of most concern. Delegates thought that influenza would be less of a threat and zoonotic arboviruses would be more of a threat in 2020. Although the virus group rankings should not be taken as definitive, the results could be used in conjunction with experimental and field data, by scientists, policy-makers and stakeholders when assessing and managing risks associated with these virus groups.

Risk of introducing African horse sickness virus into the Netherlands by international equine movements.

African horse sickness (AHS) is a vector-borne viral disease of equines that is transmitted by Culicoides spp. and can have severe consequences for the horse industry in affected territories. A study was performed to assess the risk of introducing AHS virus (AHSV) into the Netherlands (P_AHS) by international equine movements. The goal of this study was to provide more insight into (a) the regions and equine species that contribute most to this risk, (b) the seasonal variation in this risk, and (c) the effectiveness of measures to prevent introduction of AHSV. Countries worldwide were grouped into three risk regions: (1) high risk, i.e., those countries in which the virus is presumed to circulate, (2) low risk, i.e., those countries that have experienced outbreaks of AHS in the past and/or where the main vector of AHS, Culicoides imicola, is present, and (3) very low risk, i.e., all other countries. A risk model was constructed estimating P_AHS taking into account the probability of release of AHSV in the Netherlands and the probability that local vectors will subsequently transmit the virus to local hosts. Model calculations indicated that P_AHS is very low with a median value of 5.1×10(-4)/year. The risk is highest in July and August, while equine movements in the period October till March pose a negligible risk. High and low risk regions contribute most to P_AHS with 31% and 53%, respectively. Importations of donkeys and zebras constitute the highest risk of AHSV release from high risk regions, while international movements of competition horses constitute the highest risk of AHSV release from low and very low risk regions. Preventive measures currently applied reduce P_AHS by 46% if compared to a situation in which no preventive measures are applied. A prolonged and more effective quarantine period in high risk regions and more stringent import regulations for low risk regions could further reduce P_AHS. Large uncertainty was involved in estimating model input parameters. Sensitivity analysis indicated that uncertainty about the probability of non-notified presence of AHS in low and very low risk regions, the protective effect of quarantine and the vector-host ratio had most impact on the estimated risk. Furthermore, temperature values at the time of release of AHSV largely influenced the probability of onward spread of the virus by local vectors to local hosts.

Impact of climate change on risk of incursion of Crimean-Congo haemorrhagic fever virus in livestock in Europe through migratory birds.

AIMS: To predict the risk of incursion of Crimean-Congo haemorrhagic fever virus (CCHFV) in livestock in Europe introduced through immature Hyalomma marginatum ticks on migratory birds under current conditions and in the decade 2075-2084 under a climate-change scenario. METHODS AND RESULTS: A spatial risk map of Europe comprising 14 282 grid cells (25 × 25 km) was constructed using three data sources: (i) ranges and abundances of four species of bird which migrate from sub-Saharan Africa to Europe each spring, namely Willow warbler (Phylloscopus trochilus), Northern wheatear (Oenanthe oenanthe), Tree pipit (Anthus trivialis) and Common quail (Coturnix coturnix); (ii) UK Met Office HadRM3 spring temperatures for prediction of moulting success of immature H. marginatum ticks and (iii) livestock densities. On average, the number of grid cells in Europe predicted to have at least one CCHFV incursion in livestock in spring was 1·04 per year for the decade 2005-2014 and 1·03 per year for the decade 2075-2084. In general with the assumed climate-change scenario, the risk increased in northern Europe but decreased in central and southern Europe, although there is considerable local variation in the trends. CONCLUSIONS: The absolute risk of incursion of CCHFV in livestock through ticks introduced by four abundant species of migratory bird (totalling 120 million individual birds) is very low. Climate change has opposing effects, increasing the success of the moult of the nymphal ticks into adults but decreasing the projected abundance of birds by 34% in this model. SIGNIFICANCE AND IMPACT OF THE STUDY: For Europe, climate change is not predicted to increase the overall risk of incursion of CCHFV in livestock through infected ticks introduced by these four migratory bird species.

Arthroereisis of the subtalar joint: an uncommon complication and literature review.

Arthroereisis is an operation to prevent abnormal pronation in the subtalar joint in children and adults with symptomatic flexible flatfeet. In the present report, we describe an uncommon late complication of a former variation of this procedure, namely the case of an adult male who experienced migration of a xenogeneic bone graft that had been implanted 55 years earlier. A thorough review of the existing data was also undertaken to better understand the complications of this procedure.

Simulation evaluation of Salmonella monitoring in finishing pigs in Lower Saxony, Germany.

Results of serological monitoring for Salmonella in finishing pigs are used to classify herds and target control measures at herds with high prevalence. The outcome of monitoring is determined by three factors: (a) the cut-off value for the optical density percentage (OD%) to declare a sample positive, (b) the classification scheme to allocate farms to different Salmonella prevalence classes, and (c) the annual number of samples per herd to calculate its Salmonella prevalence. Our goal was to analyse the impact of these three factors on (i) the accuracy of Salmonella monitoring in finishing pigs and (ii) the total number of tests required. We constructed a stochastic simulation model in Excel and @Risk to evaluate 12 monitoring scenarios based on: (a) four cut-off values for the OD% (10, 20, 30, and 40) and (b) three herd classification schemes. Furthermore, eight different sampling schemes were evaluated. The main outputs of the model are (a) the accuracy of monitoring which is reflected by the percentage of herds that retain classification when re-sampled at the same moment in time and (b) the total number of tests. To illustrate the model, we used input data from Salmonella monitoring in Lower Saxony, Germany. Model calculations demonstrated that - with the tests in use - monitoring scenarios based on cut-off OD% 10 are most accurate with 80-90% of herds retaining classification. Monitoring scenarios based on cut-off OD% 20 or 30 are, however, comparable to those based on cut-off OD% 40 with 50-70% of herds retaining classification. Besides, we predicted that herd classifications based on three classes (low-, moderate-, and high-prevalence) give more accurate results than when a zero-prevalence class is included. The total number of tests depends heavily on the sampling scheme and - if sampling is based on Salmonella prevalence class - the distribution of herds over the different classes. We predicted that the current German sampling scheme that is based on herd size requires more tests than those sampling schemes based on herd classification. Of these, the sampling scheme in which most samples are taken from high-prevalence herds is most accurate and might be a good incentive to reduce Salmonella prevalence at herd level if farmers had to pay for the tests themselves.

Cost-effectiveness of measures to prevent classical swine fever introduction into The Netherlands.

Recent history has demonstrated that classical swine fever (CSF) epidemics can incur high economic losses, especially for exporting countries that have densely populated pig areas and apply a strategy of non-vaccination, such as The Netherlands. Introduction of CSF virus (CSFV) remains a continuing threat to the pig production sector in The Netherlands. Reducing the annual probability of CSFV introduction (P(CSFV)) by preventive measures is therefore of utmost importance. The choice of preventive measures depends not only on the achieved reduction of the annual P(CSFV), but also on the expenditures required for implementing these measures. The objective of this study was to explore the cost-effectiveness of tactical measures aimed at the prevention of CSFV introduction into The Netherlands. For this purpose for each measure (i) model calculations were performed with a scenario tree model for CSFV introduction and (ii) its annual cost was estimated. The cost-effectiveness was then determined as the reduction of the annual P(CSFV) achieved by each preventive measure (DeltaP) divided by the annual cost of implementing that measure (DeltaC). The measures analysed reduce the P(CSFV) caused by import or export of pigs. Results showed that separation of national and international transport of pigs is the most cost-effective measure, especially when risk aversion is assumed. Although testing piglets and breeding pigs by a quick and reliable PCR also had a high cost-effectiveness ratio, this measure is not attractive due to the high cost per pig imported. Besides, implementing such a measure is not allowed under current EU law, as it is trade restrictive.

The risk of the introduction of classical swine fever virus at regional level in the European Union: a conceptual framework.

Recent classical swine fever (CSF) epidemics in the European Union (EU) have clearly shown that preventing the introduction of CSF virus (CSFV) deserves high priority. Insight into all the factors contributing to the risk of CSFV introduction is a prerequisite for deciding which preventive actions are cost-effective. The relations between virus introduction and spread, prevention and control, and economic losses have been described using the conceptual framework presented in this paper. A pathway diagram provides insight into all the pathways contributing to the likelihood of CSFV introduction (LVI_CSF) into regions of the EU. A qualitative assessment based on this pathway diagram shows that regions with high pig densities generally have a higher LVI_CSF, although this cannot be attributed to pig density only. The pathway diagram was also used to qualitatively assess the reduction in LVI_CSF achieved by restructuring the pig production sector. Especially integrated chains of industrialised pig farming reduce the LVI_CSF considerably, but are also difficult and costly to implement. Quantitative assessment of the LVI_CSF on the basis of the pathway diagram is needed to support the results of the qualitative assessments described.

The economic evaluation of control and eradication of epidemic livestock diseases.

Many countries have implemented strategies to control and eradicate epidemic diseases. These strategies are usually based on either stamping-out or routine vaccination, sometimes complemented by emergency vaccination. The authors describe these strategies, using examples to illustrate each one. The economic evaluation of control and eradication of epidemic diseases is a complex matter. The authors provide further insight into this area by describing the various elements involved in both the 'non-outbreak periods' and the 'outbreak periods'. In addition, a system of categorisation of the direct costs and consequential losses is suggested for the calculation of costs and losses incurred by outbreaks. The economic impact of epidemic diseases on farmers and the livestock sector as a whole differs; these differences may be influenced by the control and eradication strategies applied. An attempt is made to provide a basic framework for economic evaluation on various economic levels.

Neurochemical studies with the potential antipsychotic compound trans-5-Chloro-2-methyl-2,3,3a,12b-tetrahydro-1H- dibenz[2,3:6,7]oxepino[4,5-c]pyrrolidine maleate.

trans-5-Chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz [2,3:6,7]oxepino[4,5-c]pyrrolidine maleate (Org 5222) has dopamine D2 antagonistic and negligible anticholinergic properties of the classical neuroleptic haloperidol. In addition it combines the strong antiserotonergic and antihistaminergic properties of chlorpromazine and clozapine with the potent dopamine D-1 antagonistic properties of Sch 23390 (R-(+)-delta-chloro-2,3,4,5-tetrahydro-3-methyl-5- phenyl-1H-3-benazepin-7-ol(Z)-2-buteneoate). This in conjunction to its behavioural properties, warrants clinical testing in psychotic patients.

Scintigraphic distribution of 123 I labelled proinsulin, split conversion intermediates and insulin in rats.

Insulin, biosynthetic human proinsulin and 2 human proinsulin conversion intermediates, des (64, 65) human proinsulin and des (31, 32) human proinsulin, were labelled with 123 I and the derivatives monosubstituted on Tyr A14 were purified by reverse phase high performance liquid chromatography. The four tracers were injected into anaesthetized rats via a jugular or a portal vein and time activity curves were generated for the liver and kidneys using a gamma camera and an online computer. Liver extraction coefficients varied in the order insulin (38%), des (64, 65) human proinsulin (11.7%), des (31, 32) human proinsulin (3.2%), human proinsulin (1.6%); whereas half-life of hepatic activity varied in the reverse order, from 6 min for insulin, to 45 min for human proinsulin. As expected for a non-receptor mediated process, kidney extraction varied conversely to liver extraction, being highest for human proinsulin and lowest for insulin. It is concluded that the kinetics of human proinsulin conversion intermediates depends upon the site of cleavage and deletion and is intermediate between those of insulin and intact human proinsulin.

Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, Org 3770 and its enantiomers.

The neurochemical and autonomic pharmacological profile of 1,2,3,4,10, 14b-hexahydro-2-methyl-pyrazino[2,1-a]pyrido[2,3-c]pyrido[2, 3-c] [2] benzazepine [+/-)Org 3770) and the related antidepressant drug, mianserin, have been compared. The uptake of [3H]noradrenaline ([3H]NA) in vitro was weakly affected by (+/-)Org 3770 (pKi = 5.6) in contrast to mianserin (pKi = 7.4). Both (+/-)Org 3770 and mianserin facilitated the release of [3H]NA in slices of cortex. The effects of NA mediated by alpha 2-adrenoceptors on the release of both [3H]NA or [3H]serotonin ([3H]5-HT) were antagonized by (+)Org 3770 with pKi values of 8.4 and 8.1, respectively. However, (-)Org 3770 only antagonized the effect of NA on the release of [3H]5-HT (pA2 = 7.7). The binding of [3H]rauwolscine to alpha 2-adrenoceptors was inhibited by (+/-)Org 3770 and mianserin with identical affinity (pKi = 7.0), whereas the binding of [3H]prazosin to alpha 1-adrenoceptors was less potently affected by (+/-)Org 3770 (pKi = 6.4) than by mianserin (pKi = 7.1). A similar difference was found for alpha 1- and alpha 2-adrenoceptors in vas deferens of the rat. The binding of [3H]mianserin to 5-HT2 receptors was less potently blocked by (+/-)Org 3770 (pKi = 8.1) than by mianserin (pKi = 9.4) while the binding of [3H]mepyramine to histamine-1 receptors was more potently affected by (+/-)Org 3770 (pKi = 9.3) than by mianserin (pKi = 8.75). The binding of [3H]quinuclidinylbenzilate to muscarinic cholinergic receptors was blocked equally by (+/-)Org 3770 (pKi = 6.1) and mianserin (pKi = 6.3). Similar data on tryptamine-D, histamine-1 and muscarinic cholinergic receptors in isolated organs were obtained. A prominent role for the blockade of alpha 2-adrenoceptors in the therapeutic effects of mianserin and (+/-)Org 3770 in depression is suggested, probably excluding a role of inhibition of the uptake of NA.

The pharmacological profile of Org 6906, a potential non-sedative antidepressant that combines monoamine uptake inhibition with alpha 2-adrenolytic activity.

(dl)-(5 alpha,8 alpha,9 alpha)-5,8,9,10-Tetrahydro-5,9- methanobenzocycloocten-8-amine hydrochloride (Org 6906) is a potential new antidepressant agent, with a neurochemical profile quite different from that of the classical tricyclic antidepressant drugs. The compound was found active in behavioural tests which are considered to be predictive for antidepressant activity, such as the muricidal test in the rat and the acquired immobility model. Neurochemical studies showed that Org 6906 was an inhibitor of the reuptake of monoamines both in vitro and ex-vivo without having appreciable anticholinergic, antihistaminergic or alpha 1-adrenolytic activity. The facilitatory effect on monoaminergic neurotransmission was confirmed by the reversal of hypothermia induced by reserpine. The drug Org 6906 appeared to have selective alpha 2-adrenolytic properties. It facilitated potassium-stimulated release of noradrenaline from slices of cortex, displaced [3H]rauwolscine and [3H]dihydroergocryptine from their binding sites but only weakly blocked alpha 1-adrenoceptors. The alpha 2-adrenolytic properties were also apparent in behavioural interaction models. The compound antagonized the sleep-inducing effects of clonidine in chicks and mice and it antagonized the mydriasis induced by clonidine in the rat. Finally, it was shown that the two enantiomers of Org 6906 contributed almost equally to the relevant neurochemical and behavioural properties.

Scintigraphic distribution of complexes of antiinsulin antibodies and 123I-insulin. In vivo studies in rats.

Clearance of immune complexes made of antiinsulin antibodies and 123I-insulin was studied with scintillation scanning in anesthetized rats. Complexes made with purified guinea pig antiinsulin IgG2 (cytophilic isotype) were rapidly cleared by the liver whereas those made with IgG1 remained in the plasma, as did 123I-labeled IgG1 or IgG2 of control animals. Hepatic clearance of insulin-antiinsulin IgG complexes was not inhibited by either an excess of insulin or decomplementation, thereby ruling out interaction with insulin and C3b receptors. Insulin and guinea pig antiinsulin serum or its purified IgG isotypes formed large aggregates exceeding 5 IgG. Antiinsulin antibodies of diabetics, mostly IgG1 and IgG3 (cytophilic isotypes), formed complexes that either remained in plasma (small aggregates) or were cleared by the liver (large aggregates). In conclusion, clearance of insulin-antiinsulin IgG complexes is probably mediated by Fc gamma receptors on macrophages and requires cytophilic subclass composition and formation of large IgG aggregates.

Visualization of viral clearance in the living animal.

The early events in viral dissemination via the bloodstream were identified by monitoring the fate of 123I-radiolabeled reovirus after it was injected intravenously in rats. Continuous scintillation camera imaging showed that reovirus serotypes 1 and 3 were cleared from the circulation in less than 10 minutes by specific and distinct target organs. Reovirus serotype 1 accumulated predominantly in the lungs and the liver, whereas serotype 3 accumulated in the liver and the spleen with very little virus uptake by the lungs. Incubation of reovirus serotype 1 with a monoclonal antibody directed against the viral hemagglutinin before injection totally inhibited the clearance of the virus by the lungs. Similar results were obtained when viruses biolabeled with 35S were used. These results demonstrate that viruses can be rapidly transported through the bloodstream to specific target organs and that the localization of the viruses depends on the interaction between specific viral surface components and the target organ.

Differing effects of antiinsulin serum and antiinsulin receptor serum on 123I-insulin metabolism in rats.

Anesthetized rats were treated with saline, antiinsulin receptor serum, or antiinsulin serum, and the biodistribution of high pressure liquid chromatography-purified 123I-Tyr A14-insulin was studied by scintillation scanning. Time activity curves over organs of interest were calibrated by sacrificing the rats at the end of the experiment and directly determining the radioactivity in the blood, liver, and kidneys. Saline-treated rats exhibited normal insulin biodistribution. The highest concentration of 123I-insulin was found in the liver, and reached 30% of total injected dose between 3 and 5 min after injection. After this peak, activity rapidly decreased with a t1/2 of 6 min. Activity of 123I-insulin in kidney showed a more gradual rise and fall and was approximately 15% of injected dose at its maximum. In rats treated with antiinsulin antiserum, insulin biodistribution was markedly altered. Peak liver activity increased with increasing antibody concentration with up to 90% of injected dose appearing in the liver. In addition, there was no clearance of the liver 123I-insulin over 30 min. Autoradiographic studies demonstrated that in contrast to the normal rats in which radioactivity was associated with hepatocytes, in rats passively immunized with anti-insulin serum, 125I-insulin was associated primarily with the Kuppfer cells. In contrast, antibodies to the insulin receptor markedly inhibited 123I-insulin uptake by the liver. Kidney activity increased, reflecting the amount of free 123I-insulin that reached this organ. This is similar to the pattern observed when insulin receptors are saturated with a high concentration of unlabeled insulin. Thus, both insulin antibodies and anti-receptor antibodies alter the distribution of insulin, but with very different patterns. The use of 123I-insulin and scintillation scanning allows one to study specific alterations in insulin distribution in animal models of insulin-resistant states, and should also be useful in human disease states.

Insulin receptors in the gastrointestinal tract of the rat fetus: quantitative autoradiographic studies.

Purified carrier-free 125I-insulin was injected into the vitelline vein of rat fetuses in utero after 17, 19 or 21 days of a 22-day gestation. Three minutes later, the weight and radioactivity of various organs and the remaining carcass were measured. A radioactivity concentration index was calculated by dividing the specific activity of each organ by that of the whole feto-placental unit. In each of the three age groups studied, the gastrointestinal tract radioactivity concentration indices were 1.7, 2 and 1.9 respectively, indicating that the gastrointestinal tract concentrated the labelled hormone. Three, 9 and 15 min after 125I-insulin injection, the gastrointestinal tract was removed, homogenized and chromatographed on a G-50 fine Sephadex column. At 3 min, 91.4% of gastrointestinal tract radioactivity co-eluted with a standard of 125I-insulin. At the later time intervals studied, the percentage of 125I-insulin decreased while that of low molecular weight degradation products increased. Quantitative autoradiographic study of the fetal gastrointestinal tract indicated that epithelial cells bound 125I-insulin and that this binding was inhibited by co-injection of large amounts of unlabelled insulin. 125I-insulin binding was highest in the proximal small bowel and lowest in the colon. Insulin binding did not appear to depend upon degree of cell maturation or cell type. These results indicate that the epithelium of the gastrointestinal tract is characterized by the presence of numerous insulin receptors and is a potentially important insulin target.