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The small Indian mongoose ( Herpestes auropunctatus ) is a rabies reservoir in areas of the Caribbean including Puerto Rico, but no rabies vaccination program targeting this host exists. We used two derivatives of iophenoxic acid (IPA) to evaluate placebo oral rabies vaccine bait uptake by mongooses in southwestern Puerto Rico. We hand-distributed baits at an application rate of 200 baits/km 2 at three, 400 ha, sites during autumn 2016 and spring 2017. Each site contained 90-100 cage traps in a 100 ha central trapping area. We used ethyl-IPA as a biological marker during the autumn and methyl-IPA during the spring. We live captured mongooses for 10 consecutive days, beginning 1 wk following bait application. We obtained a serum sample from captured mongooses and analyzed the sera for ethyl- and methyl-IPA by liquid chromatography-mass spectrometry. During autumn 2016, 63% (55/87) mongooses sampled were positive for ethyl-IPA. In spring 2017, 69% (85/123) of mongooses were positive for methyl-IPA. Pooling seasons, accounting for recaptures between years, and disregarding marker type, 74% (133/179) unique mongooses were positive for IPA biomarker, indicating bait consumption during either the autumn, spring, or both trials. We conclude that distributing baits at an application rate of 200 baits/km 2 is sufficient to reach over 60% of the target mongoose population in dry forest habitats of Puerto Rico.

The oral vaccination of wild badgers (Meles meles) with live Bacillus Calmette-Guérin (BCG) is one of the tools being considered for the control of bovine tuberculosis (caused by Mycobacterium bovis) in the UK. The design of a product for oral vaccination requires that numerous, and often competing, conditions are met. These include the need for a highly palatable, but physically stable bait that will meet regulatory requirements, and one which is also compatible with the vaccine formulation; in this case live BCG. In collaboration with two commercial bait companies we have developed a highly attractive and palatable bait recipe designed specifically for European badgers (Meles meles) that meets these requirements. The palatability of different batches of bait was evaluated against a standardised palatable control bait using captive badgers. The physical properties of the bait are described e.g. firmness and colour. The microbial load in the bait was assessed against European and US Pharmacopoeias. The bait was combined with an edible vaccine carrier made of hydrogenated peanut oil in which BCG vaccine was stable during bait manufacture and cold storage, demonstrating <0.5 log 10 reduction in titre after 117weeks' storage at -20°C. BCG stability in bait was also evaluated at +4°C and under simulated environmental conditions (20°C, 98% Relative Humidity; RH). Finally, iophenoxic acid biomarkers were utilised as a surrogate for the BCG vaccine, to test variants of the vaccine-bait design for their ability to deliver biomarker to the gastrointestinal tract of individual animals. These data provide the first detailed description of a bait-vaccine delivery system developed specifically for the oral vaccination of badgers against Mycobacterium bovis using live BCG., (Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.)

Iophenoxic acid and its derivatives (methyl, ethyl, and propyl) are organic chemicals used as markers in baiting campaigns to deliver vaccines, pharmaceuticals, contraceptives or poisons to wildlife. In this study we develop a method of detection of IPA derivatives by LC/ESI-MS (using butyl-IPA as internal standard) obtaining a limit of detection and quantification in wild boar (Sus scrofa) serum of 0.037 microg/ml and 0.123 microg/ml, respectively. The average recovery of IPA derivatives was 88% at levels >0.2 microg/ml, with coefficients of variation <15%. Wild boars in captivity were orally treated with 5 mg/kg b.w. (three adults) or 15 mg/kg b.w (two piglets and three adults) of methyl-, ethyl- and propyl-IPA and the serum levels of these were monitored during 18 months after dosing. Ethyl- and propyl-IPA were detected up to 18 months after a single oral dose in wild boar, especially at 15 mg/kg. Methyl-IPA was detected until 9 months after dosing. Half-lives of methyl-, ethyl- and propyl-IPA were (mean+/-SD) 41+/-5, 183+/-85 and 165+/-45 days, respectively. One control piglet not exposed to IPA, but housed in the same facility than treated animals showed detectable IPA levels in serum. Piglets born from mothers exposed to marked baits also showed detectable IPA levels in serum. The high persistence of Et- and Pr-IPA must be considered in the field trials, because the presence of the product at low levels in one animal may not reflect a real ingestion of the marked bait., (2010 Elsevier B.V. All rights reserved.)

Objectives: To develop an encapsulation method for delivery of vaccines to feral pigs, and quantify the effect of iophenoxic acid on captive feral pig blood iodine concentrations to assist in investigation of factors affecting vaccine uptake., Design and Methods: Feral pigs were administered iophenoxic acid by oral gavage, and consumption was assessed for different encapsulation methods in baits. Blood iodine concentrations were monitored for eight days after consumption. The relationship between dose rate, time since dosing and blood iodine concentration was assessed for gavaged and baited captive feral pigs. Wild feral pigs were baited with PIGOUT baits containing 20 mg of encapsulated iophenoxic acid to simulate a vaccination program. Using knowledge from the pen studies, bait uptake and factors affecting bait uptake were investigated., Results: Bait-delivered iophenoxic acid led to variable and inconsistent changes in blood iodine concentrations, in contrast to pigs receiving iophenoxic acid by gavage. This precluded accurate assessment of the quantity consumed, but still allowed a conservative determination of bait uptake. Iophenoxic acid in smaller capsules was consumed readily. Increasing baiting intensity appeared to increase bait uptake by wild feral pigs, and pigs of varying sexes, ages and weights appeared equally likely to consume baits., Conclusions: Encapsulated liquids can be delivered to feral pigs within baits, should the need to vaccinate feral pigs for fertility or disease management arise. High baiting intensities may be required.

Background and Aims: Amiodarone-induced thyrotoxicosis is a life-threatening condition. A prompt control of thyrotoxicosis is obtained by thyroidectomy. Preparation with iopanoic acid proved to be very effective in reducing cardiovascular complications. Nevertheless, general anesthesia and extensive surgery may affect negatively patients also after adequate preparation. Safety and efficacy of minimally invasive video-assisted thyroidectomy performed under regional anesthesia (bilateral modified deep cervical block) in patients with amiodarone-induced thyrotoxicosis was evaluated., Patients and Methods: Eight patients with amiodarone-induced thyrotoxicosis (three with type I and five with type II), mean age 66.2 years, were prepared with iopanoic acid. There were five men and three women. Three patients had dilatative cardiomyopathy, three had heart failure secondary to severe myocardial infarction, and two had refractory unstable rhythm disorders., Results: Minimally invasive video-assisted thyroidectomy was performed under regional anesthesia. Mean operative time was 55.5 min. During surgery, lung and heart function remained well and no surgical complications occurred. After surgery, all patients remained on amiodarone therapy and two patients were subsequently removed from the checklist for heart transplantation., Conclusion: Minimally invasive video-assisted thyroidectomy under regional anesthesia can be proposed as resolution of amiodarone-induced thyrotoxicosis in high risk patients with severe cardiac disorders, after preparation with iopanoic acid.

This study was carried out to assess whether Rhodamine B, ethyl-iophenoxic acid (EtIPA), and propyl-iophenoxic acid (PrIPA) can be used as long-lasting systemic bait markers for free-living badgers (Meles meles). Between June and November 2003, these chemicals were incorporated into bait distributed around badger setts. Serum, hair, and whiskers from individually marked badgers were collected in the following 4 to 24 wk. Rhodamine B was detectable as fluorescent bands up to 24 wk after ingestion of the bait. Individual badgers were found positive for EtIPA and PrIPA up to 20 wk and 18 wk after exposure, respectively. This study indicates that Rhodamine B, PrIPA, and EtIPA could be used as long-lasting markers for badgers.

Fasting is characterized by disrupted thyroid feedback, with suppressed levels of thyroid hormones and paraventricular thyrotropin releasing hormone (TRH). We found that third ventricle administration of the deiodinase inhibitor, iopanoic acid, dose-dependently reduced deiodinase type II (DII) activity selectively in the hypothalamus. This suppression of DII by iopanoic acid during fasting prevented elevated DII activity and blunted the decline in hypothalamic TRH mRNA levels. Because fasting-induced elevation in hypothalamic DII activity is paralleled by increased hypothalamic T3 concentration, our study suggests that T3 formation by DII in the hypothalamus is the cause of disrupted thyroid feedback during fasting.

The purpose of this study was to report our initial experience with a swine model for biliary interventions by using a percutaneous transcholecystic access after suture anchor of the gallbladder. Telepaque tablets were given to five pigs to opacify the gallbladder. Under fluoroscopy, the opacified gallbladder was punctured percutaneously and three suture anchors were used to fix the anterior wall of the gallbladder to the abdominal wall. Two weeks later, the gallbladder was punctured and access into the distal common bile was obtained through the cystic duct. Balloon expandable stents were deployed into the distal common bile duct. Follow-up cholangiograms were obtained at 1 and 2 weeks. Necropsy was performed after 2 weeks to evaluate the relationship between the gallbladder and abdominal wall. Suture anchor placement was successful in all five pigs. One pig with a deep and highly positioned gallbladder developed fever, anorexia, and vomiting secondary to excessive stretch of the gallbladder. Placement of the guidewire through the extremely tortuous and small cystic ducts proved to be the most challenging step of the procedure. Metallic stents were successfully deployed in all four pigs in which it was attempted. Four animals tolerated the procedures without changes in their clinical conditions and no symptoms. Successful follow-up cholangiograms were performed at 1 and 2 weeks post-stent deployment without complications. All stents remained patent during the follow-up period. Necropsy demonstrated close attachment and adherence of the gallbladders to the antero-lateral abdominal wall in all four animals. Suture anchoring of the gallbladder is feasible in most pigs with superficially located gallbladders. This technique allows a safe and repeat access into the biliary system using a transcholecystic approach.

Objective: Traditionally, neonatal thyrotoxicosis has been managed with antithyroid drugs and/or iodine as well as sedatives, propranol and digitalis when necessary. The purpose of this study was to evaluate the management of neonatal thyrotoxicosis using the radio-contrast agent iopanoic acid., Methods: We managed five cases of neonatal thyrotoxicosis. All infants were treated initially with propranolol (1.7 mg/kg/day) and iopanoic acid 250 to 500 mg every third or fourth day., Results: In all cases, clinical signs improved and T(3) and T(4) levels decreased dramatically within 24 to 72 hours. No toxic side effects were noted., Conclusion: Neonatal thyrotoxicosis can be managed successfully using iopanoic acid. Iopanoic acid is essentially free of side effects and need only be administered every 3 to 4 days. When administered until (transplacental) maternal TSI has been metabolized by the neonate, iopanoic acid maintains euthyroid status with no risk of hypothyroidism. With conventional therapy, propylthiouracil (PTU) must be administered three times a day. PTU also carries a significant risk of toxic side effects and a week or more of therapy is required to correct the hyperthyroid state and may induce hypothyroidism.

Objective: To describe our experience of CT (Computed tomographic) Cholangiography examination for detection of choledocholithiasis at the Aga Khan University Hospital (AKUH) Karachi Pakistan., Methods: Seven patients underwent helical CT cholangiography for suspected choledocholithiasis. Iopanoic acid (6 grams) was administered orally 8-12 hours before acquisition of a helical CT cholangiogram. Three-dimensional reconstructions and curved multiplanar reformations were generated from a set of axial source images., Results: Our patients had no adverse reactions to iopanoic acid. The degree of biliary opacification was sufficient to perform three-dimensional and curved planar reformations in 5 patients. In two patients, the biliary tree was not opacified. Both of these studies were considered failures. Findings on CT cholangiography in the remaining 5 patients were the following: cholelithiasis with normal bile duct (n=2), choledocholithiasis (n=1), stone in gallbladder remnant with long cystic duct (n=1) and infiltrating adenocarcinoma of the gallbladder (n=1)., Conclusion: Spiral CT cholangiography is a safe, non-invasive, and cost effective alternative test and, in a carefully selected patient population can play a role in the diagnostic work-up of patients with suspected choledocholithiasis.

Aim: In this study, we describe our experience in treating subacute thyroiditis patients with 2 OCAs (sodium ipodate and sodium iopanoate)., Methods: We studied 10 consecutive patients with subacute thyroiditis treated with 1 of the 2 oral cholecystography agents (OCAs)., Results: Hyperthyroidism was controlled and symptoms improved markedly in each case without any evidence of subsequent relapse of thyroiditis after withdrawal of OCAs. Three of the 10 patients had been treated previously with corticosteroids and had demonstrated relapse of thyroiditis and hyperthyroidism after tapering or withdrawal of steroids. We observed no side effects of treatment with OCAs., Conclusion: Our data suggest that OCAs are effective and safe agents for management of hyperthyroidism in patients with subacute thyroiditis, even when they have relapsed after treatment with corticosteroids.

Background: Amiodarone-induced thyrotoxicosis (AIT) may develop either in apparently normal glands (type II AIT) or in the presence of thyroid abnormalities (type I AIT). Sometimes AIT is resistant to conventional treatment. Thyroidectomy was used in patients with AIT, but in patients who are thyrotoxic it may be hazardous. METHODS; Seven patients with AIT (6 type I and 1 type II, 5 men, 2 women, mean age 70 years [range, 60-82 years]) were prepared for total thyroidectomy with a short course of iopanoic acid (1 g/day orally for a mean of 13 days), an oral iodinated cholecystographic agent inhibiting 5'-deiodinase and causing a reduction in the peripheral conversion of thyroxine to triiodothyronine. Mean thyroid volume was 64 mL (range, 10-145 mL)., Results: Mean serum-free triiodothyronine levels decreased from 20 +/- 16.7 pmol/L to 6 +/- 2 pmol/L (P =.0004), whereas serum-free thyroxine values remained unchanged. Euthyroidism was rapidly (7-20 days) restored, allowing an uncomplicated total thyroidectomy in all patients and the ability to continue amiodarone therapy in 6 patients. None had increased surgical bleeding, recurrent nerve palsy, or hypoparathyroidism. No cardiovascular complications occurred., Conclusions: Iopanoic acid is an effective drug allowing rapid control of hyperthyroidism in AIT.

As there is a possibility that Se influences the growth of animals via thyroid hormone metabolism, the following three experiments were undertaken in order to determine the effects of dietary Se on growth, skeletal muscle protein turnover and thyroid hormone status in broiler chickens. Broiler chickens were raised on a Se-deficient diet until 12 d of age and then used for the experiments. In Experiment 1, twenty-eight birds were randomly assigned to four groups and fed purified diets with the following amounts of Se supplementation: 0.0, 0.1, 0.3 and 0.5 mg Se/kg diet. Dietary Se supplementation significantly increased plasma 3,5,3'-triiodothyronine (T3) concentration and improved growth, while plasma thyroxine (T4) concentration was decreased. In Experiment 2, twenty-eight birds were assigned to four groups and fed either a Se-deficient diet or a Se-supplemented diet (0.3 mg Se/kg diet) with or without the supplementation of iopanoic acid, a specific inhibitor of 5'-deiodinase (5 mg/kg diet). The growth was promoted and feed efficiency was improved by dietary Se supplementation as was also observed in Experiment 1. However, this effect of Se was halted by iopanoic acid supplementation. Hepatic 5'-deiodinase activity was elevated by Se and inhibited by iopanoic acid. In Experiment 3, birds were fed on the following diets to show that Se influences growth of birds via thyroid hormone metabolism: Se-deficient diet, Se-supplemented diets (0.1 and 0.3 mg/kg) and T3 supplemented diets (0.1 and 0.3 mg/kg diet). Lower dietary T3 supplementation (0.1 mg/kg diet) resulted in growth promotion similar to Se supplementation, while higher level of T3 caused growth depression. Furthermore, it was observed that the rate of skeletal muscle protein breakdown tended to be increased by Se similarly to the effect of T3. In conclusion, it was shown in the present study that Se deficiency depresses growth of broilers by inhibiting hepatic 5'-deiodinase activity which causes lower plasma T3 concentration.

Purpose: To investigate the capabilities of Helical CT in imaging the biliary tract after administration of an oral cholecystographic contrast agent., Material and Methods: Forty-five adult patients and one 8-year-old child were examined with Helical CT 12 hours after the oral administration of hyopanoic acid (3 g). All the examinations were performed with the following parameters: thickness 5 mm, pitch factor 1.5, standard reconstruction algorithm, acquisition time 20-30 s, image index 2.5 mm, 130 kV, 125 mA. In 37 cases CT was performed in patients candidate to laparoscopic cholecystectomy, in 8 cases to assess the positioning of surgical clips in patients with postcholecystectomy syndrome and in 1 case (the 8-year-old child) to confirm the US diagnosis of choledochal cystic dilatation. Helical CT images were reconstructed with a Volume Rendering (VR) software., Results: The extrahepatic biliary tract was visualized in all the cases with CT and VR. II grade biliary ducts were visualized in 87% (CT) and 91% (VR), III grade ducts in 76% (CT) and 78% (VR), IV grade ducts in 28% and 35%, respectively. No statistically significant difference was found between CT and VR in the visualization of the biliary structures (p > 0.05), while three-dimensional VR reconstructions improved the evaluation of the anatomical relations in the biliary tract in comparison with CT both in normal cases and in patients with congenital abnormalities of the biliary tract. Also, three-dimensional VR reconstructions were superior in assessing the correct positioning of surgical clips in patients with postcholecystectomy syndrome (p < 0.05)., Discussion and Conclusions: Cholecysto-cholangio-CT with VR reconstructions is a reliable imaging technique for the biliary tract in patients candidate to laparoscopic cholecystectomy, to diagnose choledochal cystic dilatation and to assess the positioning of surgical clips.

Twenty asymptomatic volunteers underwent helical computed tomographic (CT) cholangiography 10-12 hours after ingesting iopanoic acid. Three observers assessed the images for the extent of bile duct visualization and image quality. The common bile duct and common hepatic duct were adequately visualized in 19 (95%) subjects. Helical CT cholangiography with oral cholecystographic contrast material is feasible and deserves further clinical studies.

Objective: We evaluated the feasibility and image quality of a new noninvasive biliary imaging technique: helical CT cholangiography with three-dimensional volume rendering using an oral biliary contrast agent., Subjects and Methods: Nineteen subjects including five healthy volunteers and 14 patients underwent helical CT cholangiography. Subjects ingested 6.0 g of iopanoic acid 6-10 hr before undergoing imaging. Axial data were used to construct three-dimensional volume-rendered cholangiograms. Two radiologists, an endoscopist, and a laparoscopic surgeon reviewed the images and evaluated overall image quality. In the 14 patients, findings from CT cholangiography were compared with those from ERCP, surgery, and intraoperative cholangiography., Results: All segments of the biliary tree were opacified in all volunteers except one, in whom the intrahepatic ducts were not opacified. Image quality was good to excellent in all volunteers. Anomalous cystic duct insertions were seen in two volunteers. Opacification of the biliary tree was rated as acceptable to excellent in nine patients and suboptimal in five. In five patients with good or excellent opacification, the biliary anatomy correlated with findings on intraoperative cholangiography or ERCP. CT cholangiography revealed additional conditions (gallbladder varices and acute pancreatitis) and variant anatomy in three patients., Conclusion: Results of this pilot project suggest that obtaining CT cholangiograms using an oral biliary contrast agent is a feasible, noninvasive method for revealing biliary anatomy. However, visualization of the biliary tree was suboptimal in 36% of the patients, which represents a limitation of this technique.

Objective: The objective of this investigation was to assess the performance of helical CT cholangiography after administration of an oral biliary contrast agent for the diagnosis of choledocholithiasis., Subjects and Methods: Helical CT cholangiography was performed on 31 patients referred for endoscopic retrograde cholangiography of suspected choledocholithiasis. Iopanoic acid (6 g) was administered orally 8-12 hr before acquisition of helical CT cholangiograms. Three-dimensional and two-dimensional reformations were generated from a set of axial source images. Two radiologists independently interpreted the helical CT cholangiograms. Sensitivity and specificity were calculated using findings on retrograde cholangiography as the standard of reference. In addition, interobserver agreement was determined using kappa statistics., Results: Our patients had no adverse reactions to iopanoic acid. The degree of biliary opacification was sufficient to perform three-dimensional and two-dimensional reconstructions in 29 patients (93.5%). Two patients were excluded from statistical analysis because cannulation of the common bile duct during retrograde cholangiography failed. Findings on endoscopic retrograde cholangiography in the remaining 29 patients were the following: choledocholithiasis (n = 14), common bile duct dilatation with no stones (n = 11), and normal bile ducts (n = 4). Sensitivity and specificity of oral-contrast-enhanced CT cholangiography for detection of choledocholithiasis were 92.9% (95% confidence interval [CI], 66.1-99.8%) and 100% (95% CI, 78.2-100%), respectively, for observer 1 and 85.7% (95% CI, 57.2-98.2%) and 100% (95% CI, 78.2-100%), respectively, for observer 2. Interobserver agreement was .92 (excellent)., Conclusion: Helical CT cholangiography performed after oral administration of iopanoic acid appears promising for diagnosis of choledocholithiasis.

Background: To demonstrate the radiologic-pathologic correlation of adenomyomatosis of gallbladder (GBA) and emphasize the role of high-resolution real-time ultrasound (RTUS) in the diagnosis of GBA., Methods: Ten (four male and six female, mean age = 49 years) patients with proven GBA (three diffuse, three segmental, and four fundal) diagnosed by histopathology or confirmed by oral cholecystography (OCG) were reviewed. Radiologic studies included OCG (n = 8), RTUS (n = 8), and computed tomography (CT; n = 4). Six patients subsequently underwent cholecystectomy., Results: Histopathologic correlation between pathologic specimens and OCG, RTUS, and CT was possible in six patients. The diagnostic criteria with ultrasound included numerous tiny intramural cysts containing echogenic foci with reverberation artifacts and associated segmental or diffuse gallbladder wall thickening. OCG with fatty meal demonstrated intramural diverticula. Localized fundal GBA was better visualized on RTUS and CT scan than on OCG., Conclusion: Accurate diagnosis of GBA may be made by either OCG or high-resolution RTUS preoperatively. CT scan may used as an alternative method to help make the diagnosis in equivocal cases.

Poly(benzyl L-glutamate) (PBLG) microcapsules, prepared by a solvent evaporation technique for intravenous injection, are evaluated for their potential use in diagnostic computed tomographic enhancement of liver images. The smaller microcapsules, < 3 microns, loaded with a radiopaque contrast material, ethyl iopanoate (IOPAE), produced prolonged opacification of the liver when delivered intravenously. In vivo tissue distribution studies of PBLG-131I-IOPAE (5 microCi/rat, iv) showed that liver had the highest uptake (percent of injected dose/g of tissue) among other organs 24 h postinjection. An in vitro estrogen receptor assay in pig uteri indicated that PBLG conjugated with estrone did not interfere with estrogen receptor affinity, suggesting the estrogen therapy potential of PBLG-estrone.

We investigated whether the inhibition of placental T4 5-deiodinase (5-D) activity would decrease the amniotic fluid (AF) concentration of rT3. Iopanoic acid (IOP) was used to inhibit placental T4 5-D activity. From gestation days 14 to 17, a group of rats received IOP (10 mg/100 g bw/day, sc) once daily in experiment (exp) 1, and received it (40 mg/100 g bw/day) four times daily in exp 2. In exp 2, control dams received propylthiouracil (PTU; 2 mg/100 g bw/day) instead of IOP. Methimazole and T4 were also given to all dams in exp 1 and 2. On day 17 of gestation, we collected the liver, placenta, blood, and AF of each animal. In the IOP-treated group in both experiments, the serum T4 concentration was significantly increased. Hepatic T4 5'-deiodinase activity was significantly decreased by either PTU or IOP administration. In both experiments placental T4 5-D activity was significantly decreased in the IOP-treated group. The concentration of rT3 in AF was significantly decreased in the IOP-treated group in exp 2 (1.71 vs. 0.75 nmol/l, P < 0.01) despite a higher serum T4 concentration. There was a significant positive correlation between placental T4 5-D activity and the concentration of rT3 in AF in exp 2 (r = 0.62, P < 0.05). These observations indicate that the inhibition of placental T4 5-D activity decreases the concentration of rT3 in rat AF, and that placental T4 5-D and the T4 concentration in maternal serum plays important roles in maintaining the concentration of rT3 in rat AF.

Background: The thiourea drugs take a few weeks to control the symptoms of hyperthyroidism whilst iodine containing radiographic contrast agents (iopanoic acid and sodium ipodate) have a more rapid effect. There is no report on the use of iopanoic acid administered in conjunction with carbimazole, so we evaluated the efficacy of this combination in the early medical management of patients with hyperthyroidism., Methods: Thirty hyperthyroid patients diagnosed by clinical and biochemical criteria were randomized into two treatment groups. Group A (n = 16) received iopanoic acid (500 mg orally twice a day for the first 3 weeks) and carbimazole (30 mg orally in three divided doses) while group B (n = 14) received carbimazole alone. Clinical examination and estimation of serum total T3, total T4 and TSH were done by radioimmunoassay at the start of therapy, weekly for 4 weeks and then at 6, 8 and 12 weeks., Results: In the initial 3 weeks, iopanoic acid induced a significantly greater fall in mean serum total T3 levels (Z = 2.298, p < 0.02) and a slower fall in mean serum total T4 (Z = 2.396, p < 0.05) in group A patients compared to those in group B. This was accompanied by earlier clinical improvement in group A patients. The mean serum total T3 and T4 values rose to higher levels in group A at 4 weeks, one week after discontinuation of iopanoic acid. At the end of 12 weeks, however, there was no significant difference in the mean serum total T3 and T4 levels between the two groups (p > 0.05). Biochemical euthyroidism (i.e. total T3 < 3 nmol/L and total T4 < 170 nmol/L) was achieved later in group A patients than in group B (10.4 +/- 5.0 weeks v. 3.6 +/- 1.2 weeks, p < 0.0001)., Conclusions: Iopanoic acid given together with carbimazole induces rapid clinical improvement in hyperthyroid patients than carbimazole alone. However, the delayed achievement of euthyroidism may preclude its routine use in the management of patients with hyperthyroidism except in those with thyrotoxic emergencies.

Objective: We have evaluated an alternative method of preparation of hyperthyroid patients for surgery, using betamethasone, iopanoic acid and propranolol., Design: Betamethasone (0.5 mg every 6 hours), iopanoic acid (500 mg every 6 hours) and propranolol (40 mg every 8 hours) were given orally for 5 days; thyroidectomy was performed on the 6th day. We analysed patient acceptability, clinical and hormonal effects, ease of surgery and final outcome., Patients: Thirteen females and 1 male, aged 16-59 years, ten with diffuse goitre and four with nodular goitre were submitted to subtotal thyroidectomy because antithyroid drugs had failed to control thyrotoxicosis or because hyperthyroidism coexisted with other conditions (pregnancy, hypertensive disease)., Measurements: Daily clinical assessments were made together with T3, T4 and rT3 serum concentrations before and while on drug treatment, during the surgical procedure and post-operatively., Results: Daily assessment showed progressive clinical improvement so that on day 5 the patients were considered clinically euthyroid. Serum levels of T3 (mean +/- SD) showed significant decrease (by 38.2 +/- 24.9%, P less than 0.01) as early as 24 hours after medication was started, reaching almost euthyroid levels on day 3; on the day of operation T3 had diminished by 64.5 +/- 16.6% (P less than 0.0001). Serum T4 concentration showed a slight but significant decrement only from day 4 on and never reached euthyroid levels. Serum rT3 values exhibited a brisk increment at 24 hours (+333 +/- 194%, P less than 0.0001) and remained elevated between 8 and 10 nmol/l until medication was stopped. Drug tolerance was considered as excellent since no serious side-effects were noted, even in pregnant patients. There were no anaesthetic incidents or postoperative complications and patients were discharged 48-72 hours after operation. The final outcome has been satisfactory and pregnant patients continued their pregnancies without incident, bearing normal children., Conclusions: Pharmacological combination of betamethasone, iopanoic acid and propranolol has proved to be safe and effective and is of low cost. Provided there is adequate supervision of the patients, it may be used in patients requiring urgent thyroidectomy or in those who for reasons of non-compliance need a short preoperative regime.

Five randomly chosen patients with thyrotoxicosis were administered 1 gm of the oral cholecystographic agent iopanoic acid daily for 21 days. There was a marked fall in T3 levels by 75% of the pretherapy value by 96 hr; values remained normal over the 21-day period. T4 values fell significantly by seven days of therapy, and the decreased values were sustained. FT3 and FT4I also showed corresponding decreases in value. All subjects showed clinical improvement by both subjective and objective criteria. During therapy, escape from the effect of iopanoic acid was not encountered. However, after stopping the drug for 2-4 wk, the patients' iodine-131 uptake become as high as the pretherapy level, enabling them to undergo radioiodine treatment for thyrotoxicosis. The treatment strategy can be aimed at achieving quick euthyroidism and in planning radioiodine treatment as early as possible in high risk patients. This treatment may also be useful in preoperative control of thyrotoxicosis.

A hidden pool of rT3 production represents a source of rT3 that is minimally reflected in circulating rT3 levels. To test for the existence of such a source of rT3 production in man, varying doses of the generalized deiodinase inhibitor iopanoic acid (IA) were administered to four hyperthyroxinemic subjects. The doses employed included low-IA (0.5-g load, then 0.5 g/day for 5 days), mid-IA (1.0-g load, then 1.0 g/day for 5 days), and high-IA (3.0-g load, then 3.0 g/day for 5 days). Each patient received 25 microCi [125I]rT3, iv, in the high T4 state and on day 3 of each IA dosing regimen. Serial blood and urine samples were obtained to determine serum rT3 clearance rates and the urinary thyronine metabolite patterns. Although total serum rT3 values were increased by all IA dosages (P less than 0.001), rT3 was lower with high-IA administration (P less than 0.02) than with low- or mid-IA regimens. Low-IA decreased rT3 clearance to 33 +/- 2 L/day (P less than 0.005), while increasing the daily rT3 production to 76 +/- 8 nmol/day (P less than 0.04) compared to the control values (150 +/- 10 L/day and 53 +/- 8 nmol/day, respectively). Mid-IA also reduced rT3 clearance (23 +/- 4 L/day; P less than 0.005) without changing rT3 production (50 +/- 10 nmol/day), while high-IA reduced both rT3 clearance (21 +/- 2 L/day; P less than 0.005) and production (39 +/- 9 nmol/day; P less than 0.04). Intravenously administered tracer rT3 could not be detected in the urine in the high T4 state, but rT3 could not be detected in the urine in the high T4 state, but was prominent after IA administration. It is concluded that a hidden pool of rT3 production exists in vivo in man. Further, low dose IA serves as a selective inhibitor of liver and kidney deiodinase systems, allowing reflection of this hidden rT3 pool in the blood and urine. It would appear that hypertrophy of this hidden pool of rT3 production occurs in high T4 states and may account for the majority of the unrecognized deiodinative metabolites of T4 generated in hyperthyroxinemia.

The effect of fasting on gallbladder opacification during oral cholecystography was studied in 10 normal volunteers using 2 oral cholecystographic agents, iopanoic acid and sodium tryopanoate. Radiographs made 15 hours after ingestion of the contrast agents revealed good opacification of the gallbladder in all subjects when iopanoic acid was administered with a meal and when sodium tyropanoate was administered in the fasting state; in only 2 subjects when iopanoic acid was given in the fasting state; in 3 when given in the fasting state with ox bile; and in 3 when sodium tyropanoate was given with a meal.

A 48-year-old woman had severe symptomatic thrombocytopenia three times in 13 months. Each episode followed ingestion of iopanoic acid. The interval between drug ingestion and onset of symptoms was 40, 12, and 8 hours. Resolution to normal platelet counts occurred in 6, 5, and 8 days. The third thrombocytopenic crisis occurred while the patient was receiving maintenance steroid therapy, given because the initial diagnosis was idiopathic thrombocytopenic purpura. Incubation of platelet-rich plasma with the patient's serum caused platelet lysis if either the patient or the donor serum obtained after ingestion of iopanoic acid was present in the mixture.

Three patients are described with unusual collections of cholecystographic contrast material in the right upper abdomen medial and posterior to the gallbladder, in a characteristic "incomplete ring" configuration. Subsequent barium examinations of the upper gastrointestinal tract proved each of these collections to represent contrast material trapped in active duodenal ulcer craters. This cholecystographic sign, though uncommon, is believed to be fairly specific for duodenal ulcer. Recognition of the "incomplete ring" sign should prompt the radiologist to obtain barium studies necessary to confirm the presence of ulcer.

Fifteen healthy volunteers underwent a randomized trial of oral cholecystography (OCG) using 5 different combinations of contrast agents given as 2 consecutive doses: Telepaque (iopanoic acid) given with food (TF) or without food (T), Bilopaque (sodium tyropanoate) given without food, and a combination of both agents (TF-B). The density of gallbladder opacification was judged visually on a scale of 1+ to 4+ and quantitatively by a densitometric method. Comparison of gallbladder opacification on the first and second days of the study revealed 52 of 75 (70%) combinations (TF-T, TF-TF,T-T, TF-B, B-B) resulted in improved opacification, 17% in equal opacification, and 13% in worse opacification on day 2. The TF-B combination showed the highest number (9) of excellent (grade 4+) results and the lowest number (2) of poor (grade 1+ and 2+) results, gave the best opacification in 8 volunteers, and had the highest average density difference (0.32) between first- and second-day opacifications. The TF-TF combination was the next most effective, and the T-T combination was the least effective. The results indicate that OCG in 2 consecutive doses is superior to single-dose OCG, and that a combination of TF-B or TF-TF will provide the greatest gallbladder opacification. The TF-B combination is recommended because of better patient tolerance.

A comparative trial was made between two oral cholecystographic agents, iocetamic acid (Cholebrin) and iopanoic acid (Telepaque), Fifty patients were given Cholebrin and another 50 were given Telepaque by random allocation. The cholecystographic qualities of the two contrast media showed no significant difference. It was noted that contrast medium within the bowel at the time of the investigation tended to be homogeneous rather than granular with Cholebrin, and the significance of this is discussed. Gastrointestinal side-effects were common with both contrast media, but there was a significantly lower incidence of diarrhoea with Cholebrin than with Telepaque. Various biochemical parameters of hepatic and renal function were measrued in 40 random patients and showed no clinically significant alteration following ingestion of the contrast media.

Radiographs and CT images taken during oral cholecystography in dogs were interpreted in an independent, blind fashion by three radiologists on two occasions and visual assessment of gallbladder density compared to the actual CT values. While there was significant intra- and inter-observer variation, the mean scores for the observers' interpretations of both radiographs and prints correlated well with the actual CT values (p less than 0.05). In five out of six comparisons between first and second readings, the observers gave a lower score on the second reading. The considerable variation reflects the problems inherent in subjective evaluation of agents that produce small but measurable differences in radiographic density. Studies involving such subjective data have to be carefully designed in order to obtain meaningful results.

A dynamic infusion method, originally developed for the pharmacokinetic studies of Iodoxamic acid, was applied to the kinetic studies of the biliary excretion of another cholecystographic agent, iopanoic acid. This dynamic method has an important advantage in that the pharmacokinetic parameters involved in the hepatic uptake or biliary excretion can be evaluated from a single infusion experiment. Using the equilibrium dialysis technique, iopanoic acid was found to be highly bound to the plasma proteins. A linear relationship was found when the logarithm of unbound plasma concentration of iopanoic acid was plotted vs. the logarithm of its blood concentration. When the biliary excretion rates of iopanoic acid were fitted by a computer to the Michaelis-Menten equation against its unbound plasma concentration, the average Vm value was found to be 0.85 micron/kg/min and the average Km value was found to be 0.253 micron. Iopanoic acid was found to exist in monkey blood as unchanged species and in the bile mainly as the ester glucuronide.

The conventional manner of preparing ambulatory patients for oral cholecystography with six tablets of iopanoic acid yields results which are essentially equal to those obtained by single-visit oral cholecystography (two-day preparation with 12 tablets of iopanoic acid). Also, it is more convenient for patients and referring physicians. The conventional method of preparation is recommended for hospitalized patients as well.

We report a case of severe thrombocytopenia following oral cholecystography with iopanoic acid, a widely used contrast medium. A bone marrow aspirate showed increased numbers of megakaryocytes, suggesting a thrombocytopenia due to enhanced peripheral destruction of platelets; this examination was not reported in the previously described two cases. Although hematological reactions due to iopanoic acid are very rare, it would be wise to question patients regarding any preceding drug-induced purpura before proceeding with oral cholecystography.

Oral cholegraphy is one of the most accurate procedures in diagnostic radiology. Nevertheless it is not without shortcomings. To achieve an enhancement of its reliability the biochemical and physiological processes involved in an ultimately sufficient biliary-tract opacification are analysed. From these theoretical considerations some conclusions are drawn which could be important for the improvement of oral cholegraphy and which appeared to be worth testing in practice.

To determine the influence of diet and fasting on gallbladder opacification during oral cholecystography, 10 dogs were studied in a blind, random fashion, giving single or two consecutive doses of iopanoic acid, sodium tyropanoate, or sodium ipodate while the animals were fasting, on a normal diet, or on a low-fat diet. Gallbladder density was determined by CT to eliminate the bias created by subjective interpretation of radiographs. For maximum, first-dose gallbladder opacification during clinical cholecystography, iopanoic acid should be given with a meal and sodium ipodate while the patient is fasting; diet makes no difference with sodium tyropanoate. For maximum opacification with two consecutive doses, iopanoic acid may be given with a meal or during fasting, while sodium ipodate and sodium tyropanoate should be administered during fasting.