Nasal administration of anti-CD3 monoclonal antibody modulates effector CD8+ T cell function and induces a regulatory response in T cells in human subjects.

Background: Parenteral anti-CD3 Mab (OKT3) has been used to treat transplant rejection and parental administration of a humanized anti-CD3 Mab (Teplizumab) showed positive effects in diabetes. Nasal administration of anti-CD3 Mab has not been carried out in humans. Nasal anti-CD3 Mab suppresses autoimmune diseases and central nervous system (CNS) inflammation in animal models.

Reproductive factors and lower extremity arterial occlusive disease in women.

Background: Reproductive variables affecting sexual hormone levels seem to be significant for atherosclerosis, a major cause of morbidity of the vessels of the lower extremities such as lower extremity arterial occlusive disease (LEAOD). We quantify a direct relationship between reproductive variables including age at regular and premature menopause and the incidence of severe LEAOD among post-menopausal women.

Methods And Results: Questionnaires were administered to 269 female amputees with LEAOD, 224 patients who underwent total joint replacement due to osteoarthritis and 88 healthy women.

Pharmacodynamics of racemic and S(-)-atenolol in humans.

The cardiovascular actions of racemic atenolol (RSATN) have been well characterized in humans, but the actions of S(-)-atenolol (SATN) when administered alone are unknown. In this study, responses of heart rate (HR) and Doppler-derived aortic blood flow profiles to upright treadmill exercise were compared after oral administration of 50 mg SATN and 100 mg RSATN in eight healthy, adult, male volunteers. After a single-blind, placebo run-in period, subjects were randomly allocated in a double-blind, crossover fashion to receive SATN and RSATN.

Single dose pharmacokinetics of (S)-atenolol administered orally as a single enantiomer formulation and as a racemic mixture (Tenormin).

The purpose of this study was to describe the pharmacokinetics of and heart rate and blood pressure responses to (S)-atenolol (SATN) and (R)-atenolol (RATN) after oral administration of (S)-atenolol and (R,S)-atenolol (Tenormin) in man. Eight male subjects were given single oral doses of 50 mg of SATN as a single enantiomer formulation (SEF) and 100 mg of Tenormin (TMN) using a randomized, double-blind, 2-period, complete crossover study design. Subjects performed exercise tolerance tests (Bruce Protocol) before and 2, 4, 6, 8, 12, and 24 h after drug administration.

Pharmacokinetics of quinidine in male patients. A population analysis.

Quinidine pharmacokinetic behaviour was evaluated in 139 adult hospitalised men receiving oral quinidine therapy. A total of 391 serum quinidine concentrations were measured by enzyme immunoassay for routine clinical purposes. The NONMEM programme was used to examine the relationship between quinidine pharmacokinetics and several potential covariates.

Absolute bioavailability and dose proportionality of betaxolol in normal healthy subjects.

The absolute bioavailability and dose proportionality of betaxolol [(+/-)-1-(p-[2-cyclopropylmethoxy)ethyl]phenoxy]-3- (isopropylamino)-2-propanol hydrochloride], a cardioselective beta-adrenergic antagonist effective in the treatment of angina and hypertension, was studied in 12 healthy male subjects using a four-way crossover Latin Square design. Each subject received a 10-mg iv dose administered by constant-rate infusion over a period of 30 min and three oral doses (10, 20, and 40 mg). Blood and urine were collected over a 48-h period and analyzed for betaxolol using gas-liquid chromatography with electron capture detection.

Clinical assessment of a two-compartment Bayesian forecasting method for lidocaine.

The predictive performance of a two-compartment Bayesian forecasting method for lidocaine (L) was evaluated concurrently with lidocaine therapy in 46 hospitalized patients; 14 of these patients presented with congestive heart failure (CHF). Using an HP-85 microcomputer, demographic and dose-concentration information obtained during continuous lidocaine therapy was used to forecast subsequent lidocaine concentrations. One lidocaine concentration was obtained within each of the three intervals following initiation of lidocaine infusions: I1 (1-6 h), I2 (6-12 h), and I3 (greater than 12 h).

Evaluation of a Bayesian regression-analysis computer program using non-steady-state phenytoin concentrations.

The predictive performance of a Bayesian regression-analysis computer program that uses non-steady-state phenytoin data was evaluated. Forty patients receiving phenytoin or phenytoin sodium who had two or more non-steady-state serum concentrations were selected for study. Additional serum concentrations and dosing data were collected as they became available, but no effort was made to control the number or timing of serum concentration determinations.

Captopril modifies the hemodynamic and neuroendocrine responses to sodium nitroprusside in hypertensive patients.

To determine if clinically effective doses of the antihypertensive agent captopril affected the neuronal release of norepinephrine or baroreflex sensitivity, changes in plasma norepinephrine concentration and heart rate were related to the changes in mean arterial pressure seen during the intravenous infusion of stepwise incremental doses of sodium nitroprusside before and during captopril treatment in eight hypertensive men with normal or low plasma renin activity. At all times, significant linear correlations were found between the decrease in mean arterial pressure and the dose of sodium nitroprusside, the increase in heart rate and the decrease in mean arterial pressure, and the increase in plasma norepinephrine concentration and the decrease in mean arterial pressure. When the subjects were treated with captopril (25 mg t.

Measurement of lidocaine free concentration.

Since lidocaine exhibits significant variation in serum protein binding, the availability of a practical method for measuring free lidocaine concentration could contribute to the optimization of individual lidocaine dosage regimens. Fifty serum samples from patients receiving lidocaine were partitioned by ultrafiltration and equilibrium dialysis. The lidocaine concentration in the ultrafiltrate was measured using an enzyme multiplied immunoassay (EMIT) and a gas-liquid chromatographic assay (GLC).

Experience with intrainstitutional clinical evaluations of newly marketed preparations as a basis for drug-product selection to hospital formularies.

The decision to admit a new drug-product formulation (NDPF) to a hospital pharmacy formulary is a difficult task, particularly when minimal pharmacokinetic or clinical efficacy data are available. To provide objective information to the Pharmacy and Therapeutics (P&T) Committee, we implemented a procedure to evaluate these NDPFs at our institution. This procedure, termed clinical evaluation, was initiated at our institution in 1981.

Comparative assessment of in vitro inactivation of gentamicin in the presence of carbenicillin by three different gentamicin assay methods.

Inactivation of gentamicin (G) is known to occur secondarily to the formation of complexes with certain beta-lactam antibiotics. However, aminoglycosides in the presence of aminoglycoside-beta-lactam complexes may not be recognized uniformly by all assay methods. We tested this hypothesis by using mixtures of G plus carbenicillin (C), with and without the addition of penicillinase, in pooled sera under several in vitro conditions: at 25 and 35 degrees C and at low and high C concentrations.

Chronic acetazolamide intoxication.

Severe acidosis associated with acetazolamide therapy is rare. We report the first case in which plasma and whole blood acetazolamide concentrations were measured. A 61 year-old patient receiving oral acetazolamide for treatment of glaucoma presented with a 7 day history of declining mental status.

Decrease in theophylline clearance after the administration of erythromycin to a patient with obstructive lung disease.

It has been demonstrated previously that erythromycin can inhibit the total body clearance of theophylline, resulting in elevated serum theophylline concentrations. The overall incidence of this interaction and the population at risk have not been elucidated fully. Recent investigations have suggested that such an interaction is doubtful and that patients in whom this occurrence was suspect developed alterations in theophylline disposition secondary to worsening pulmonary function, not from erythromycin therapy alone.

Endogenous generation of hydralazine from labile hydralazine hydrazones.

The hypothesis that the pharmacologically active hydralazine hydrazones (HH) are endogenously hydrolyzed to parent hydralazine (H) was tested in a series of in vitro and in vivo systems. The stable hydrazones H alpha-ketoglutaric acid hydrazone and H pyruvic acid hydrazone did not hydrolyze to H in vitro (buffer or plasma), were inactive in vivo and did not generate urinary metabolites of parent H. By contrast, the labile HH, H acetaldehyde hydrazone and acetone hydrazone (HAH) generated H in vitro.

Route and rate of hydrallazine administration as determinants to its hypotensive effect in rabbits.

1. The cardiovascular responses to varying doses of hydrallazine were studied in renal hypertensive rabbits. 2.

Quantitative analysis of hydralazine pyruvic acid hydrazone, the major plasma metabolite of hydralazine.

A specific, high-performance liquid chromatographic technique for the measurement of hydralazine pyruvic acid hydrazone is described. This method utilized reversed-phase chromatography for the separation of this hydrophilic metabolite of hydralazine from other fluid constituents present in serum, plasma, or urine of human volunteers and rabbits receiving hydralazine. Detection of the compound of interest is accomplished spectrophotometrically at 250 nm.

Pharmacokinetics and cardiovascular effects in rabbits of a major hydralazine metabolite, the hydralazine pyruvic-acid hydrazone.

The hydrazone of hydralazine and pyruvic acid (HPH) has been recognized as a quantitatively important metabolite of hydralazine in human plasma. We evaluated the disposition of [14C] HPH after its i.v.

Phenytoin cumulation kinetics.

Four male subjects were given phenytoin orally in single or twice-daily doses. Subjects were on 2 or 3 different dosing rates from 260 to 600 mg phenytoin sodium daily. Predose blood samples were obtained almost daily.

Compendium of drug abuse jargon.

Drug abuse slang is an originative and a protean language,which poses the problem of identification and definition of terms. This compilation of nomenclature provides an extensive list to serve as a resource for the busy family physician, who frequently deals with drug abuse problems.