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Effect of methylglucamine salts of iocarmic and iothalamic acids on hemodynamics, acid-base equilibrium and coagulation.

The effects of electrolytes, osmolality, pH, PaO2, PaCO2, hematocrit, blood volume and coagulation occurring after a rapid intra-aortic injection of a monomer and a dimer (salts of methylglucamine of the iothalamic and iocarmic acids) were compared. The effects of the monomer agreed with previous results but the effects of the dimer differed from those reported in the literature.

Acid-Base Equilibrium

Uptake of contrast materials by experimental acute myocardial infarctions: a preliminary report.

The concentration of iodine within infarcted and normal myocardium after intravenous administration of contrast material was determined by fluorescence excitation analysis in seven dogs at 48 hours after coronary arterial ligation. The iodine concentration of infarcted myocardial tissue was several times greater than normal myocardium after administration of meglumine/sodium diatrizoate, iodipamide, and an experimental polymer of iothalamic acid.

Acute Disease

Solute excretion during intravenous urography: a comparison of sodium and methylglucamine iothalamates.

The sodium and methylglucamine salts of iothalamic acid were compared as urographic agents. The two drugs were administered intravenously to dogs at a dose of 600 mgI/kg. The outputs and concentrations of the major urinary solutes and the injected solutes were measured to define the differences in renal excretion of sodium and methylglucamine iothalamates. The action of methylglucamine as a relatively inert osmotic diuretic was reconfirmed. When sodium iothalamte was adminstered the tubular reabsorption of sodium and chloride was greater than when methylglucamine iothalamate was used. It is suggested that this reabsorption explains the advantage of sodium-linked agents over methylglucamine-linked agents in urography.

Animals

Study of renal functions by repeated constant infusion of radiotracers before and after initiation of therapy in hypertension or in diabetes mellitus.

Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were simultaneously measured by obtaining an isotopic steady state during a continuous infusion of 125I orthoiodohippurate (OIHA). A good correlation was found between the clearances of Ioth (y) and of inulin or polyfructosan (x) : y = 1.18 X (x) + 8.43 (r = 0.96; P less than 0.001) and between the clearances of OIHA (y') and of PAH (x') : y' = 0.62 X (x') + 21.2 (r = 0.93; P less than 0.001). When renal functions were impaired the use of Ioth was not convenient since the infusion time necessary to reach a radioactive plateau was longer than 3 hours. On the contrary, excellent results were obtained by using OIHA. In this case, the main advantages were the absence of urine collection and the rapid obtention of an isotopic equilibrium. The repeated determination of renal clearances in hypertensive or diabetic patients appears to be useful in the study of changes induced by antihypertensive drugs or insulin. Clearances were slightly improved by clonidine, claimed to be useful in hypertension associated with chronic renal failure. GFR and ERPF were rapidly increased by insure on the metabolic and hemodynamic changes induced by insulin than on the return to normal of glomerular basement membrane permeability.

Adrenergic alpha-Antagonists

Osmotic effect and solubility of amipaque (metrizamide) in the gastrointestinal tract.

Loops of small intestine in seven rabbits were resected with intact pedicle and ligated at both ends after instillation of 0.5 ml of Gastrografin, Urografin 76%, Amipaque 370 mg I/ml, Amipaque 170 mg I/ml or physiologic saline. After half an hour, the amount of fluid in the loops containing Gastrografin and Urografin 76% increases about twice as much as in the loops containing Amipague with the same iodine concentration because of their greater osmolality. The differences between the loops with isotonic Amipaque (170 mg I/ml) and physiologic saline are not significant. Precipitation occurs when sodium and meglumine salts of diatrizoate, metrizoate, iothalamate, iocarmate and ioglycamate are mixed with 0.05 N HCl. No precipitation occurs with Amipaque, not even when the HCl concentration is as high as 1.2 N. Precipitation occurs when Gastrografin is added to gastric juices with low pH, but is not seen with Amipaque should be a suitable contrast medium for gastrointestinal examinations because of its low osmolality and toxicity and good solubility in gastric juice.

Animals

Activation of serum complement by contrast media.

Evidence is presented for the activation of serum complement by contrast media, in vitro and in vivo. Activation as a function of concentration was measured and the increasing order of effectiveness was found to be metrizamide, iothalamate, diatrizoate, acetrizoate, iodipamide and iopanoate. This order is the same as for protein binding and enzyme inhibition. The activation mechanism for iodipamide, and by inference for the other compounds, does not involve gamma-globulin aggregation. Serial daily injections in normal dogs resulted in substantial declines in serum complement over several days. Guinea pigs which were depleted of serum complement with cobra venom factor were found to be no less sensitive to lethal doses of iodipamide than those with normal complement. Implications of these findings are discussed.

Acetrizoic Acid

Error dependent on renal function when monoexponential equation assumed. Serum clearances of 125I-iothalamate and 131I-o-iodohippurate.

An example from the literature has been used to demonstrate errors involved in calculating drug clearance by inappropriate use of the apparent drug distribution volume Vdext. The Vdext is always an overestimate of the true volume of distribution in a multicompartment system, and the degree of overestimation in using it to calculate clearance for such a system will increase as renal function increases. Drug dosages calculated on the basis of overestimated clearance values may give rise to overdosage in normal individuals, or therapeutic failure in severely uremic patients. Problems associated with the use of an oversimplified pharmacokinetic model for clearance calculations are discussed, together with the concept of model-independent calculations.

Humans

Antibiotics and chemotherapeutics in renal lymph. An experimental study in dogs.

Renal lymph concentrations of ampicillin, carbenicillin, cephacetrile, cephaloridine, and nitrofurantoin were determined in a total of 28 dogs during constant infusion of the drugs together with [125I]iothalamate and [131I]o-iodohippurate for simultaneous determination of glomerular filtration rate and effective renal plasma flow. The lymph concentrations of the radiolabeled clearance substances, serving as a standard were compared to those of the antimicrobial agents. The lymph concentrations of the four antibiotics were all significantly lower than the respective simultaneous arterial plasma concentrations. The nitrofurantoin lymph concentrations were equal to the simultaneous plasma concentrations. It is concluded that the renal lymph concentrations of antibiotics and chemotherapeutics do not exceed the simultaneous plasma concentrations unless the urine flow is obstructed.

Ampicillin

Use of the double-isotope, single-injection method for estimating renal function in normal and polybrominated biphenyl-exposed dairy cows.

A method is described for conducting a rapid and efficient renal function test in dairy cattle. The method, adapted from methods used for man and dogs, utilizes radiolabeled 131I-sodium iodohippurate to determine effective renal plasma flow (ERPF) and 125I-sodium iothalamate to determine glomerular filtration rate (GFR). The mean GFR for adult cattle was determined to be 2.8 +/- 0.4 ml/kg/minute with a biological half-life of 35.5 +/- 1.4 minutes. The mean ERPF was found to be 10.5 +/- 1.9 ml/kg/minute with a half-life of 17.9 +/- 0.6 minutes. These values are comparable with those in man, but are lower than values in dogs. A toxcity study was done with dairy cattle exposed to polybrominated biphenyls (PBB). Efforts were made to determine the amount of time required for kidney lesions to develop and, if possible, to delineate the potential site of action of PBB. Apparently PBB do not affect GFR or ERPF, even though they produce nephrotoxic effects. Potential mechanisms to explain these results are described.

Animals