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Biomedical subjects

D Ilfeld

Publications and source records attributed to D Ilfeld.

At least 19 recordsLinked to original sources
PubMed1992

Bioequivalence of quinidine in two sustained-release preparations.

The bioequivalence of two sustained-release preparations of quinidine bisulphate from Teva (Israel) and from Astra (Sweden) was assessed in an acute, single-dose randomized cross-over study in seven healthy subjects. There was no significant difference in time to peak, peak serum concentration, area under the concentration time curve from 0 to infinity, and the fraction absorbed between quinidine bisulphate 500 mg from Teva and from Astra. In addition, quinidine bisulphate 250 mg from Teva was compared with the short-acting quinidine sulphate 200 mg. The quinidine bisulphate from Teva had a significantly P less than 0.025) decreased peak serum concentration and an increased time to peak compared with the short-acting quinidine sulphate, although these two drugs are similar for the area under the curve from 0 to infinity. Our pharmaceutical records show that 85% of outpatients receiving quinidine are given the sustained-release quinidine bisulphate. However, only 36% of the outpatients prescribed sustained-release quinidine bisulphate are appropriately prescribed for twice-daily treatment. Thus the quinidine bisulphate from Teva is a sustained-release preparation with bioequivalence to the reference sustained-release preparation and can be administered twice daily.

Administration, Oral↗
PubMed1986

Effect of cimetidine on digoxin disposition in peptic ulcer patients.

Cimetidine inhibits the renal tubular secretion of creatinine and digoxin is partly excreted by the same pathway. In order to investigate a possible interaction between the two drugs, a randomized cross-over acute study has been conducted. Six patients with duodenal ulcers were given a single dose of digoxin (Dig) 0.75 mg i.v. with and without oral cimetidine 1200 mg/day. Cimetidine significantly reduced creatinine clearance from 157 to 132 ml/min. There was no significant difference in inulin clearance, 99.2 vs 97.5 ml/min, Dig elimination half life 53.9 vs 56.9 h, apparent volume of distribution 11.3 vs 11.6 l/kg, systemic clearance 2.42 vs 2.35 ml/min/kg, renal clearance 1.48 vs 1.62 ml/min/kg or urinary excretion of digoxin 49.5 vs 51.6% of dose without or with cimetidine. These results suggest that cimetidine does not influence the disposition of digoxin.

Adult↗
PubMed1986

Correlation of Fc gamma receptors on peripheral blood mononuclear cells and survival in patients with metastatic breast cancer.

Patients with carcinomas have elevated levels of Fc receptors for IgG (Fc gamma R) on their peripheral blood mononuclear cells (PBMC). The purpose of the present study was to determine whether there is a correlation between Fc gamma R levels on PBMC and survival in patients with metastatic breast cancer. Binding assays were performed on PBMC using 125I-labeled fibrinogen complexed with rabbit IgG (or as a control F(ab')2) anti-human fibrinogen. Twenty-two metastatic breast cancer patients had significantly (p less than 0.001) elevated Fc gamma R levels as compared to either 22 breast cancer patients receiving adjuvant chemotherapy following mastectomy without clinical evidence of tumor, or to 34 non-malignant controls. Significantly more metastatic patients with elevated Fc gamma R levels died at 6 months (p less than 0.001) as compared to those with low levels. A direct correlation between Fc gamma R levels and hazard probability was found (correlation coefficient = 0.3321, p less than 0.005). These results raise the possibility that Fc gamma R levels on PBMC from metastatic breast cancer patients may be clinically useful as a prognostic marker of disease activity.

Adult↗
PubMed1985

Correlation of a quinidine-induced platelet-specific antibody with development of thrombocytopenia.

The rapidity by which drug-dependent antiplatelet antibodies can develop is not known, since patients are only studied during or after the episode of thrombocytopenia. This report describes the development of quinidine-induced immune thrombocytopenia in a healthy volunteer during a drug study. The thrombocytopenia developed within two weeks of initiation of quinidine therapy. During the thrombocytopenic episode, but not before receiving the drug, the patient had an IgG antiplatelet antibody that bound to control platelets in the absence of the drug. This antibody was absent when the drug was discontinued and the platelet count rose. The patient's acute serum also induced the release of serotonin from control platelets, and the reaction was enhanced by quinidine. This indicates that drug-dependent antiplatelet antibodies can develop rapidly and supports the hypothesis that quinidine-induced thrombocytopenia is due to a quinidine-dependent platelet-specific IgG.

Adult↗
PubMed1985

Reduction of serum theophylline levels by terbutaline in children with asthma.

We studied the effect of oral terbutaline on serum theophylline levels in 12 children with asthma. Sustained-release theophylline (10 mg/kg twice a day) was given with placebo or terbutaline (0.075 mg/kg three times a day) in a chronic, randomized, double-blind, crossover design. The trough serum theophylline concentration fell from 13.8 +/- 4.0 to 10.8 +/- 3.6 micrograms/ml and the peak expiratory flow rate increased from 285 +/- 30 to 310 +/- 29 L/min after terbutaline. Further investigation is needed to clarify the mechanism of action by which terbutaline decreases serum theophylline levels.

Asthma↗
PubMed1985

Effect of in vitro colchicine and oral theophylline on suppressor cell function of asthmatic patients.

Extrinsic asthmatic patients have been reported to have a deficiency of concanavalin A (Con A)-induced suppressor cell function. We tested whether in vitro colchicine and oral theophylline can correct this immunoregulatory abnormality. Asthmatic patients' mononuclear cells were incubated with Con A and/or colchicine and then suppression of proliferation was measured by coculture of these cells with healthy volunteers' mononuclear cells and phytohaemagglutinin. The Con A induced suppressor cell function of 29 theophylline treated patients (26 +/- 16%, mean +/- s.d.) was significantly (P less than 0.002) increased as compared to 21 untreated patients (12 +/- 10%) but significantly (P less than 0.01) decreased as compared to 45 healthy volunteers (39 +/- 17%). A pharmacological concentration (10(-8) M) of colchicine had no significant effect on Con A-induced suppressor cell function of 19 untreated patients (from 12 +/- 9% to 9 +/- 22%) but significantly (P less than 0.05) increased Con A-induced suppressor cell function of 20 theophylline treated patients (from 26 +/- 17% to 36 +/- 19%). Thus asthmatic patients have decreased Con A-induced suppressor cell function which is partially corrected by oral theophylline and almost completely corrected by oral theophylline plus in vitro colchicine. This synergistic effect raises the possibility that oral colchicine together with theophylline may be useful in treating patients with extrinsic asthma.

Adolescent↗
PubMed1984

In vitro correction of a deficiency of Con A-induced suppressor cell function in primary biliary cirrhosis by a pharmacological concentration of colchicine.

Patients with primary biliary cirrhosis (PBC) have been previously reported to have immunoregulatory abnormalities. We tested the effect of in vitro colchicine on PBC patients' suppressor cell function in order to determine whether colchicine can correct their suppressor cell deficiency. PBC patients' mononuclear cells were cultured for 44 h with concanavalin A (Con A) as well as with or without colchicine at a pharmacological concentration (10(-8)M) or at a suprapharmacological concentration (10(-5)M) and then tested for their ability to suppress proliferation of phytohaemagglutinin stimulated healthy volunteers' mononuclear cells. Eleven PBC patients had significantly (P less than 0.001) decreased suppressor cell function (12 +/- 15%, mean +/- s.d.) as compared to 37 healthy volunteers (43 +/- 12%). The suprapharmacological concentration of colchicine did not significantly affect the PBC patients' suppressor cell function (16 +/- 15%). In contrast, in the nine PBC patients tested with the pharmacological concentration of colchicine, their suppressor cell function was increased to 40 +/- 20% which was significantly different than without colchicine (P less than 0.01) or with the suprapharmacological concentration of colchicine (P = 0.02) but not significantly different than healthy volunteers. Thus, in vitro colchicine at a pharmacological concentration corrects PBC patients' deficiency of Con A-induced suppressor cell function raising the possibility that oral colchicine might be clinically useful as an immunomodulating drug in PBC.

Aged↗
PubMed1984

Effect of colchicine on T cell subsets of healthy volunteers.

We examined the effect of oral colchicine (1-2 mg/day) on four healthy volunteers' T cell subsets. Colchicine significantly (P less than 0.01) decreased the mean (+/- SD) percent of OKT3+ total T cells (from 70 +/- 16 to 47 +/- 13), OKT4+ helper/inducer T cells (from 44 +/- 9 to 24 +/- 6), and OKT8+ suppressor/cytotoxic T cells (from 27 +/- 7 to 17 +/- 7), but did not significantly affect the OKT4:OKT8 ratio (from 1.64 +/- 0.21 to 1.48 +/- 0.45) or concanavalin A-induced suppressor cell function (from 44 +/- 9% to 47 +/- 13%). Thus, colchicine non-selectively decreased the circulating helper/inducer and suppressor/cytotoxic T cells.

Adult↗
PubMed1983

Effect of colchicine on immunoregulatory abnormalities in familial Mediterranean fever.

The effect of colchicine on immunoregulatory T lymphocytes in children with familial Mediterranean fever (FMF) was studied. Concanavalin A (Con A)-induced suppressor cell function was significantly (P less than 0.0001) decreased in five untreated FMF patients (15 +/- 3%, mean +/- s.e.) as compared to six age matched paediatric controls (46 +/- 3%) and eight healthy adults (49 +/- 4%). When the five untreated FMF patients' mononuclear cells were pre-incubated in vitro with Con A plus 10(-5) M colchicine, their suppressor cell function was significantly increased (52 +/- 10%, P less than 0.01). Similarly, oral colchicine treatment (0.5 mg twice daily) significantly (P = 0.02) increased the five FMF patients' Con A-induced suppressor cell function to levels (34 +/- 6%) that were not significantly (P greater than 0.05) different than the paediatric controls or the healthy adults. The percentage of OKT8+ cells (but not OKT3+ or OKT4+ cells) was significantly (P less than 0.0001) decreased in 10 untreated FMF patients (16.0 +/- 0.9) as compared to 10 paediatric controls (27.6 +/- 2) or 10 healthy adults (25.7 +/- 0.6). The 10 untreated FMF patients had a significant (P less than 0.002) increase in the OKT4/OKT8 ratio (2.41 +/- 0.13) as compared to 10 FMF patients treated with 0.5 mg twice daily of colchicine (1.81 +/- 0.08), 10 pediatric controls (1.47 +/- 0.2), or 10 healthy adults (1.78 +/- 0.11). Colchicine appears to have corrected the FMF patients' elevated OKT4/OKT8 ratio by both decreasing the percentage of OKT4+ cells and increasing (but only partially correcting) the percentage of OKT8+ cells. Thus FMF patients have a suppressor cell deficiency in which colchicine treatment corrects their deficiency of Con A-induced suppressor cell function and their elevated OKT4/OKT8 ratio. This raises the possibility that colchicine might be potentially useful as an immunomodulating drug in treating patients with autoimmune or allergic diseases associated with a suppressor cell deficiency.

Adolescent↗
PubMed1982

Correction of a suppressor cell deficiency and amelioration of familial Mediterranean fever by hemodialysis.

We tested the clinical and immunoregulatory effects of peritoneal dialysis and hemodialysis on a patient with familial Mediterranean fever (FMF), amyloidosis, and chronic renal failure. His frequency of FMF attacks during maintenance hemodialysis (no attacks in 21 months) was significantly less than during conservative medical therapy (10 attacks in 14 months, P less than 0.00002) or during intermittent peritoneal dialysis (3 attacks in 4 months, P less than 0.004). His mean (+/-SE) percentage suppressor cell function was significantly (P less than 0.001) higher during hemodialysis (53 +/- 5) than during conservative medical therapy (4 +/- 3) or during peritoneal dialysis (2 +/- 7) and was similar to the healthy untreated volunteers (46 +/- 3). This suggests that his suppressor cell deficiency may be associated with the pathogenesis of his disease. One possible mechanism by which hemodialysis ameliorates FMF may be the correction of a suppressor cell abnormality.

Adult↗
PubMed1982

Nonspecific suppressor cell activity and lymphocyte response to beta-lactoglobulin in cow's milk protein hypersensitivity.

beta-Lactoglobulin (BLG) is clinically the most frequent allergen in cow's milk protein hypersensitivity (CMPH). We therefore assessed its in vitro blastogenic effect on lymphocytes of patients suffering from CMPH. Twenty-two patients aged from 1 to 20 months were investigated. beta-Lactoglobulin produced a significantly (p less than 0.00003) higher blastogenic response in lymphocytes of patients with CMPH (mean stimulation index 7.7 +/- 0.7 SEM) than in 26 age-matched controls (2.7 +/- 0.4). This response was age related, being most marked in infants up to 5 months of age. Lymphocyte proliferation following stimulation with BLG can be a useful in vitro test in the diagnosis of CMPH. Because of this augmented lymphocyte response, we considered the possibility of a related defect in immune suppression. Nonspecific concanavalin A-induced suppressor cell activity was assessed in the above patient and control populations. Concanavalin A-induced suppressor cell activity was significantly (p less than 0.05) reduced in patients with CMPH. This too was most marked in the first few months of life. We suggest that the development of CMPH may be due to delayed maturation of a suppressor cell population.

Concanavalin A↗
PubMed1982

Hydrocortisone reverses the suppression of immunoglobulin synthesis by concanavalin A-activated spleen cell supernatants.

Supernatants of concanavalin A (Con A)-activated human spleen cells have been previously shown to inhibit polyclonal immunoglobulin (Ig) biosynthesis by pokeweed mitogen (PWM)-stimulated human spleen and peripheral blood mononuclear cells. In the present study, hydrocortisone was added at the beginning of in vitro culture to determine whether it might influence the immunoregulation of polyclonal IgG, IgA and IgM biosynthesis by PWM-stimulated human spleen and peripheral blood mononuclear cells. Hydrocortisone (10(-5) m) mildly increased (15 +/- 9%; mean +/- s.e.m.) polyclonal Ig biosynthesis when added to PWM-stimulated human mononuclear cells. The addition of supernatants from Con A-activated human spleen cells to PWM-stimulated human spleen and peripheral blood mononuclear cells significantly (P less than 0 . 001) suppressed (94 +/- 2%) polyclonal Ig biosynthesis. In contrast, when hydrocortisone (10(-5) m) was added together with Con A supernatants to PWM-stimulated cells, there was no significant suppression (6 +/- 13%) of polyclonal Ig synthesis. Thus, one mechanism by which hydrocortisone can influence Ig biosynthesis is by blocking the suppressive effect of a soluble suppressor factor secreted by Con A-activated human spleen cells.

Antibody-Producing Cells↗