Utility of radioisotopic filtration markers in chronic renal insufficiency: simultaneous comparison of 125I-iothalamate, 169Yb-DTPA, 99mTc-DTPA, and inulin. The Modification of Diet in Renal Disease Study

Assessment of glomerular filtration rate (GFR) with inulin is cumbersome and time-consuming. Radioisotopic filtration markers have been studied as filtration markers because they can be used without continuous intravenous (IV) infusion and because analysis is relatively simple. Although the clearances of 99mTc-diethylenetriamine-pentaacetic acid (DTPA), 169Yb-DTPA, and 125I-iothalamate have each been compared with inulin, rarely has the comparability of radioisotopic filtration markers been directly evaluated in the same subject. To this purpose, we determined the renal clearance of inulin administered by continuous infusion and the above radioisotopic filtration markers administered as bolus injections, simultaneously in four subjects with normal renal function and 16 subjects with renal insufficiency. Subjects were studied twice in order to assess within-study and between-study variability. Unlabeled iothalamate was infused during the second half of each study to assess its effect on clearances. We found that renal clearance of 125I-iothalamate and 169Yb-DTPA significantly exceeded clearance of inulin in patients with renal insufficiency, but only by several mL.min-1.1.73m-2. Overestimation of inulin clearance by radioisotopic filtration markers was found in all normal subjects. No differences between markers were found in the coefficient of variation of clearances either between periods on a given study day (within-day variability) or between the two study days (between-day variability). The true test variability between days did not correlate with within-test variability. We conclude that the renal clearance of 99mTc-DTPA, 169Yb-DTPA, or 125I-iothalamate administered as a single IV or subcutaneous injection can be used to accurately measure GFR in subjects with renal insufficiency; use of the single injection technique may overestimate GFR in normal subjects.     

The Effect of High-Dose Ascorbate Supplementation on Plasma Lipoprotein(a) Levels in Patients With Premature Coronary Heart Disease

Study Objective . To determine the efficacy of high-dose ascorbate supplementation in lowering lipoprotein(a) [Lp(a)] levels in patients with premature coronary heart disease (CHD). Design . Randomized, double-blind, placebo-controlled trial. Setting . Outpatient clinic. Patients . Forty-four patients with documented premature CHD. defined as confirmed myocardial infarction and/or angiographically determined stenosis of 50% or greater in at least one major coronary artery before age 60 years. Interventions . Patients were block randomized on the basis of age, gender, and screening Lp(a) concentrations to receive ascorbate 4.5 g/day or placebo for 12 weeks. Measurements and Main Results . High-dose ascorbate was well tolerated and produced a marked elevation in mean plasma ascorbate levels (+1.2 mg/dl; p<0.001). Multiple linear regression analysis revealed no significant effect of supplementation on postintervention Lp(a) levels (p=0.39) in a model that included treatment group assignment, and baseline Lp(a) levels. Conclusions . Our findings do not support a clinically important lowering effect of high-dose ascorbate on plasma Lp(a) in patients with premature CHD.     

Primary lymphoma of the mandible with diffuse widening of the mandibular canal: report of a case

A case of primary non-Hodgkin's lymphoma (NHL) of the mandible with unusual radiographic presentation is reported. The panoramic radiography revealed diffuse widening of the right mandibular canal with ill-defined margins and absence of edge sclerosis. Computed tomography showed infiltration of the superior portion of the canal with involvement of the vestibular cortex of the bone and of the alveolar ridge. Correspondence to: M. Bertolotto     

Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers

Zolmitriptan (Zomig^TM) is a 5HT_1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg+diazepam 10 mg, zolmitriptan 5 mg+diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination.     

Selected monoclonal antibodies can increase the accuracy of cytodiagnosis of neoplastic effusions of cryptic origin expanded in a short term culture.

The use of a selected panel of monoclonal antibodies (MoAb) to tumor associated antigens (TAA) in immunocytochemical (IIC) tests has been shown, in a preliminary study, to be a powerful diagnostic tool for the identification of the primary solid tumor causing metastatic effusion. Despite this improvement in a minority of neoplastic fluids a number of different causes may still determine false negative (FN) immunocytochemical diagnoses. The aim of the present study was to confirm the diagnostic accuracy of this panel of MoAb. This was done by analyzing in IIC tests a larger number of effusions and by evaluating whether the expansion in short term culture of those fluids with an uncertain malignant morphology could provide an adequate cellular substrate for immunocytodiagnosis. The analysis of 314 effusions confirmed the results of the pilot study and demonstrated that the combination of short term culture and immunocytochemical assays can further increase the sensitivity of this novel diagnostic procedure from 84.3% to 95.3%.     

Indapamide inhibits endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat

Summary— Experiments were designed to determine whether or not indapamide, an antihypertensive agent with vasodilator properties, inhibits endothelium-dependent contractions. Rings of aortae with and without endothelium from spontaneously hypertensive rats (SHR) were suspended in conventional organ chambers for the measurement of isometric force. Acetylcholine and adenosine diphosphate-β-S in the presence of a nitric oxide synthase inhibitor, caused endothelium-dependent contractions, which were inhibited by indapamide. The compound (10⁻⁴M) also slightly reduced the contractions of rings without endothelium evoked by U-46,619, which activates thromboxane-endoperoxide receptors. These results demonstrate that indapamide inhibits endothelium-dependent contractions in the SHR aorta, and suggest that the inhibition is due, at least in part, to the action of the drug on the hypertensive vascular smooth muscle.