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Diffusion of innovations: anatomical informatics and iPods.

Over the course of many centuries, evolving scientific methods and technologies have advanced the study of anatomy. More recently, such dissemination of innovations has been formally studied in multidisciplinary psychosocial contexts, yielding useful knowledge about underlying principles and processes. We review these precepts and show how diffusion of innovations theory and principles apply to the development and dissemination of anatomical information methods and resources. We consider the factors affecting the late-20th-century dissemination of personal computers and World Wide Web hypermedia into widespread use in anatomical research and instruction. We report on the results of a small experiment in applied diffusion, the development and Internet-based distribution of learning resources for a popular, widely distributed personal media player. With these wearable microcomputer devices already in use by a variety of students, new opportunities exist for widespread dissemination of anatomical information. The continuing evolution of wearable computing devices underscores the need for maintaining anatomical information transportability via standardized data formats.

Anatomy↗

Transient triiodothyronine deficiency. Absence of effect on basal or adrenaline-stimulated carbohydrate and lipid metabolism in man.

Severe stress is accompanied by a fall in circulating triiodothyronine levels as well as increases in secretion of several hormones including adrenaline. The present study was designed to test the hypothesis that the fall in triiodothyronine may counteract in part the catabolic effects of stress hormones such as adrenaline. Transient hypothyroidism was induced by administration orally of sodium ipodate (3 g). Adrenaline infusions (6 micrograms/min for 2 hours) were performed in five healthy men before and four days after ipodate was given. Circulating triiodothyronine levels decreased from 1.7 +/- 0.1 to 1.1 +/- 0.1 nmol/l (p less than 0.001), associated with a small rise in serum thyroxine, but basal circulating concentrations of glucose, the gluconeogenic precursors, NEFA and 3-hydroxybutyrate were unaltered. Circulating insulin, glucagon and growth hormone concentrations were also similar with and without prior ipodate ingestion. Adrenaline infusion produced a rise in blood glucose (4.9 +/- 0.2 to 8.5 +/- 0.4 mmol/l at 60 min), lactate, pyruvate and the lactate: pyruvate ratio, which was unaltered by ipodate. Blood glycerol (0.04 +/- 0.004 to 0.13 +/- 0.03 mmol/l at 30 min), plasma NEFA (0.52 +/- 0.05 to 1.31 +/- 0.17 mmol/l at 30 min) and blood 3-hydroxybutyrate concentrations (0.04 +/- 0.004 to 0.26 +/- 0.07 mmol/l at 50 min) were elevated by adrenaline, with similar responses obtained after ipodate. Ipodate also did not influence the circulating insulin and glucagon response to adrenaline infusion. A transient decrease in circulating triiodothyronine concentrations induced by ipodate does not modulate the hormonal and metabolic response to adrenaline in normal man.

3-Hydroxybutyric Acid↗

Cholangiographic excretion studies. Solu-Biloptin and Biligrafin comparison.

The biliary concentration and output of two cholangiographic agents, Solu-Biloptin (calcium ipodate) and Biligrafin (meglumine iodipamide), were compared in labrador dogs. The maximum output of ipodate was approximately 20 mumol/min compared with 16 mumol/min for iodipamide. The maximum bile iodine concentration with both ipodate and iodipamide was similar (18-20 mgI/Ml) but the molar concentration of ipodate was almost twice that of iodipamide. Iodipamide was found to be much more choleretic, producing 0.025 ml of bile/mumole excreted compared with 0.009 ml/mumole for ipodate. Compared with iodipamide the lower choleretic effect and higher molar concentration of ipodate suggests that hepatic conjugation of the oral agent may permit its excretion in bile salt micelles.

Animals↗

The effect of some iodine-containing radiocontrast agents on iodothyronine secretion from the perfused canine thyroid.

The effects of the iodine-containing radiocontrast agents ipodate, iopanoic acid, and iothalamate on the secretion of T4, T3, and rT3 were studied using perfused canine thyroid lobes. The experiments were performed as paired comparisons, with one thyroid lobe acting as a control. At 10(-5) M, the two agents used for cholecystography (ipodate and iopanoic acid) inhibited the TSH-stimulated secretion of T3 [ipodate, 69 +/- 8% of control (P less than 0.05); mean +/- SE; n =4] and rT2 [iopanoic acid 59 +/- 9% (P less than 0.01); iopanoic acid, 61 +/- 9% (P less than 0.05)], whereas T4 secretion was not significantly altered. Iothalamate (10(-3)M), an agent predominantly excreted through the kidneys, did not alter T4, T3, or rT3 secretion. This pattern is compatible with an inhibitory effect on intrathyroidal T4 deiodination to T3 and rT3 by ipodate and iopanoic acid, similar to the inhibition of T3 deiodinases in peripheral tissues by these compounds. At a concentration of 10(-3) M, ipodate induced a hitherto unrecognized pattern of thyroid hormone secretion: a very rapid, sustained and reversible inhibition of the secretion of all three iodothyronines. The mechanism behind this response remains to be elucidated.

Animals↗

Inhibition of hepatic binding of thyroxine by cholecystographic agents.

Subsequent to studies indicating that cholecystographic agents and sulfobromophthalein (BSP) inhibit uptake of thyroxine (T(4)) by rat liver slices, the effect of such compounds on hepatic storage of T(4) in man has been examined. After intravenous administration of [(125)I]T(4) to five normal subjects, hepatic radioactivity, estimated by external gamma counting, rose to a peak in approximately 4 h and then declined in parallel with serum radioactivity. When a 6-g dose of the cholecystographic agent, tyropanoate (Bilopaque), was administered orally 3 d later, estimated hepatic extravascular radioactivity fell 50-60% within 4 h and then rose toward the pretyropanoate value. Concomitant with the fall in hepatic radioactivity, serum radioactivity rose 57-70%, as did stable T(4) levels in serum, suggesting that hormone discharged from the liver entered the serum. Both uptake of T(4) and discharge by tyropanoate were much less in two patients with liver disease. Ipodate (Oragrafin), 12 g orally in two subjects, caused much smaller changes in hepatic and serum radioactivity. However, ipodate also caused a doubling of the percent free T(4) in the serum as judged by equilibrium dialysis, and the ratio of hepatic radioactivity to free [(125)I]T(4) in serum declined markedly after ipodate, similar to the fall in hepatic:serum (125)I ratios after tyropanoate. BSP, 20 mg/kg i.v. in three subjects, caused a smaller change; the decline in hepatic T4 content averaged 19%. We conclude that these organic anions, tyropanoate, ipodate, and BSP, all can displace T(4) from the liver. The results imply a link between T(4) transport and organic anion transport, and indicate a mechanism for altering hepatic T(4) content in man that could be the site of physiologic regulation or of disease. A method is described whereby analysis of the change in hepatic and plasma radioactivity after tyropanoate could be employed to estimate hepatic T(4) content in diverse clinical circumstances.

Adult↗

Roentgenographic contrast agents inhibit triiodothyronine binding to nuclear receptors in vitro.

The ability of roentgenographic contrast agents to inhibit binding of [125I]T3 to nuclear receptors was studied during incubation of rat liver nuclei or nuclear extracts in vitro and after ip administration of the agents in vivo. Ipodate, iodipamide, iopanoic acid, and diatrizoate inhibited binding of [125I]T3 in vitro. The most potent inhibitor was ipodate, which produced 50% inhibition of binding at 1.2 X 10(-4) M. When given orally in acute in vivo experiments, ipodate did not diminish binding to liver nuclear receptors. Ipodate appeared to inhibit in vivo metabolism of [125I]T3.

Animals↗

Basal oxygen uptake: a new technique for an old test.

To assess the metabolic effects of T4 and T3, we measured serum total T4 (TT4), free T4 (FT4), total T3 (TT3), TSH, and basal oxygen uptake (VO2) in eight normal subjects in the basal state and after treatment with L-T3 (T3) and sodium ipodate for 2 weeks. T3 treatment resulted in a rise of serum TT3 from a baseline of 137 +/- 16 (+/- SE) to a peak of 239 +/- 15 ng/dl. Serum TT4 declined from 8.14 +/- 0.56 to 6.08 +/- 0.43 micrograms/dl, FT4 from 1.59 +/- 0.13 to 1.03 +/- 0.05 ng/dl, and TSH from 1.74 +/- 0.24 to 0.56 +/- 0.16 microU/ml. Basal VO2 increased from 2.66 +/- 0.11 to 3.15 +/- 0.09 ml/kg X min. Ipodate, on the other hand, led to a lower serum TT3 concentration (102 +/- 21 ng/dl), higher serum TT4 and FT4 (9.59 +/- 0.5 micrograms/dl and 1.91 +/- 0.13 ng/dl, respectively), and elevated TSH (3.64 +/- 0.14 microU/ml). Basal VO2 was reduced to 2.44 +/- 0.06 ml/kg X min. Linear regression analysis revealed an excellent positive correlation between serum TT3 and basal VO2 (n = 25; r = 0.747; P less than 0.001) and a significant negative correlation between serum TT3 and TSH (n = 26; r = -0.526; P less than 0.01). Serum TT4 and FT4 correlated negatively with VO2 and positively with serum TSH. The higher T4 level during ipodate treatment was associated with lower VO2 and higher TSH, and vice versa when T4 was suppressed while receiving T3. When ipodate was given concomitantly with T3 to five subjects, only the effects of T3, characterized by increased VO2 and decreased TSH, were evident. These data indicate that both basal VO2 and serum TSH are sensitive indices of thyroid hormone activities. The latter gives only the directional change (hyper- or hypothyroidism), while the former more accurately quantitates the magnitude of the derangement. Moreover, it appears that in man, T3, and not T4, is the primary hormone that regulates thermogenesis and TSH secretion.

Adult↗

Influence of industrial pollutants on thyroid function in Channa punctatus (Bloch).

A 30 day exposure of C. punctatus to sublethal levels of phenol, ammonia, mercuric chloride, cadmium chloride and a mixture of the four resulted in an overall activation of guaiacol peroxidase and depression of iodide peroxidase (IPOD) activity and blood T4 titre. Interestingly enough, in case of 15 day ammonia and 1 day mercury exposures, an increase of IPOD activity was accompanied by a decrease in T4 titre. In general, phenol, mercury, cadmium and the mixture of pollutants were found to inhibit LP activity by 56% to 85% while ammonia inhibited lysosomal protease (LP) activity by 70%. Alterations in acid phosphatase (AP) activity indicate changes in the lysosomal membrane characteristics caused by these toxicants. Considering the concomitant alterations in IPOD, T4, LP and AP it is surmised that thyroid function in C. punctatus is influenced by the pollutants by two pathways, one via IPOD pathway affecting T4 synthesis and the other via lysosomal pathway affecting T4 release.

Ammonia↗

The effect of diet and fasting on gallbladder opacification during oral cholecystography in dogs as measured by computed tomography.

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.

Administration, Oral↗

The effects of amiodarone on serum thyroid hormones and hepatic thyroxine 5'-monodeiodination in rats.

Amiodarone (2-n-butyl-3,4'-diethylaminoethoxy-3', 5'-diiodobenzoyl-benzofurane) is an antiarrhythmic drug which increases serum T4 and rT3 levels in patients and lowers serum T3 levels. To investigate its effects on T4 metabolism and its cardiac action, we fed amiodarone to male Fisher rats at doses of 5, 15, and 45 mg/kg BW X day; controls received potassium iodide for 4-7 weeks, and another group received sodium ipodate. At 4 weeks, amiodarone caused a dose-dependent increase in the serum T4 concentration and a slight reduction of serum TSH without a change in the serum T3 concentration. These changes were not present at 7 weeks. Sodium ipodate raised serum T4 concentrations at both times. Rats treated with T4 (150 micrograms/kg BW X day) to suppress thyroidal secretion of hormone and with amiodarone (15 mg/kg) had marked reduction of serum T3 concentrations compared with controls receiving T4 without amiodarone. Liver homogenates from rats treated with amiodarone showed marked reduction on T4 5'-monodeiodinase activity in a dose-related manner. Amiodarone added to liver homogenates in vitro at concentrations of 0.001-1 mM did not inhibit T3 production from T4, whereas ipodate added in vitro (0.01-1 mM) did inhibit T3 production. Rats treated with amiodarone showed a lowering of the resting heart rate and a reduction of the increment in heart rate after iv isoproterenol administration. The cardiac Ca++ myosin ATPase activity was reduced in rats receiving amiodarone (45 mg/kg) compared with that in controls. The data indicate that rats treated with amiodarone have reduced peripheral conversion of T4 to T3 owing to impaired hepatic T4 5'-monodeiodinase activity. In addition, these rats have slowing of heart rate and reduction of cardiac Ca++ myosin ATPase activity. These findings are consistent with the hypothesis that amiodarone blocks some effects of thyroid hormone on the heart, but additional studies are needed to test this hypothesis.

Amiodarone↗

Effects of cholecystographic agents and sulfobromophthalein on binding of thyroid hormones to serum proteins.

A number of interactions between thyroid hormones and cholecystographic agents have previously been demonstrated. In the present study we show that cholecystographic agents also interfere with the binding of thyroid hormones to serum proteins. A commercial kit (Tri-Tab) was used in which the uptake of labeled hormone from serum by a silicate adsorbent tablet is measured. In the presence of cholecystographic agents or sulfobromophthalein (BSP), the amount of labeled hormone bound to adsorbent increased in a dose-dependent fashion, reflecting displacement from protein-binding sites. The order of potency was BSP greater than ipodate greater than iopanoate greater than tyropanoate. Displacement of hormone was confirmed by a second methodology in which graded amounts of unlabeled T4 were added to the system. This allowed a Scatchard analysis to be performed for binding sites on T4-binding globulin. The cholecystographic agents and BSP caused displacement of the Scatchard slopes, again demonstrating interference with binding to serum protein sites. A method is described in which the change in Scatchard slope produced by an inhibitor is employed to compute the association constant between T4-binding sites on T4-binding globulin and the inhibitors. The values were: BSP, 14.6 X 10(3) M-1; ipodate, 4.7 X 10(3) M-1, iopanoate, 2.2 X 10(3) M-1; and tyropanoate, 0.1 X 10(3) M-1. Because of these relatively low values and the rapidity with which these agents are normally cleared from serum, it seems likely that effects on free hormone levels would be transient and of small magnitude during routine cholecystography. Also, ipodate, in the 1 g/day dose that has been employed experimentally to treat hyperthyroidism, should have a negligible effect on protein binding. On the other hand, when high levels of these compounds are used in experimental settings to study other aspects of thyroid hormone metabolism, changes in protein binding can occur and confound interpretation of results.

Blood Proteins↗

[Treatment of neonatal hyperthyroidism with calcium iopodate].

BACKGROUND: Treatment of hyperthyroidism in those neonates born to mothers with Grave's disease is difficult. Calcium ipodate, an agent for oral cholecystography, inhibits extra-thyroid conversion of T3 to T4 and diminishes thyroid secretion. CASE REPORTS: Two neonates with clinical manifestations and biological findings of hyperthyroidism were given calcium ipodate orally, 400 mg every 3 days, from day 26 to 50 for the first patient and from day 9 to 18 for the second in association with a beta blocker. Clinical manifestations disappeared within 2 days and circulating levels of T3 and T4 were normalized within 2-5 days. CONCLUSIONS: This treatment was effective and well-tolerated in both patients and in three others previously reported; it should be confirmed in a larger number of patients and controlled by measuring levels of antibodies directed against thyrotropin-releasing hormone receptors in order to avoid relapse after cessation of treatment as seen in our second patient.

Adrenergic beta-Antagonists↗