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Biomedical subjects

R Dean

Publications and source records attributed to R Dean.

At least 37 records · Page 2Linked to original sources
PubMed1995

The pharmacokinetics and cardiovascular pharmacodynamics of HP 749 (besipirdine HCl) and metabolite P86-7480 in the conscious monkey.

HP 749 was absorbed slowly in the conscious monkey after single oral doses (10, 20, and 40 mg/kg), with gradual metabolism to the N-despropyl metabolite, P86-7480. The tmax was 2 to 4 hours after dosing, with nonlinear increases in Cmax and the AUC0-4th for HP 749. The calculated elimination half life (t1/2) after oral administration was 7.4 +/- 2.1 hours; however, absorption appeared to influence the terminal phase because the t1/2 after intravenous administration of 10 mg/kg was 1.5 hours. Plasma concentration of HP 749 2 minutes after intravenous bolus was 26.08 micrograms/mL. The HP 749 was rapidly distributed (t1/2 alpha = 0.064 +/- 0.033 hours) after intravenous administration, and displayed a VZ of 2.6 +/- 0.85 L/kg. The CL of HP 749 was 20.8 +/- 6.9 mL/min/kg, whereas renal clearance (CLR) of unchanged drug was only 0.13 +/- 0.04 mL/min/kg. Thus, only about 1% of the administered dose was excreted unchanged by the kidney. The P86-7480 also was rapidly distributed and eliminated after an intravenous bolus, but was less extensively distributed than HP 749. HP 749 administered either as an intravenous bolus or orally caused a significant pressor effect soon after dosing. A significant tachycardia resulted from intravenous administration, but not after oral administration of the drug. An intravenous bolus of P86-7480 (0.1 mg/kg) resulted in an immediate increase in MAP and decreased heart rate. The duration of these cardiovascular events was significantly shorter after intravenous administration of P86-7480 than with intravenous or oral administration of the parent drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Intravenous morphine pharmacokinetics in pediatric patients with sickle cell disease.

To examine the pharmacokinetics of parenteral opioids, such as morphine, in patients with sickle cell disease, we determined the plasma morphine clearances in 18 patients (aged 6 to 19 years) who were receiving continuous intravenous infusions, and the pharmacokinetics of morphine in an additional six patients after single intravenous doses. Plasma morphine clearances ranged from 6.2 to 59.1 ml min-1 kg-1 (35.5 +/- 12.4, mean +/- SD) during steady-state infusions. There was a negative correlation between clearance values and age over the age range studied (p = 0.013). A significant difference (p = 0.042) was also observed in clearance values between patients who had serious adverse symptoms (23.4 +/- 10.7 ml min-1 kg-1) and those who had less serious symptoms (36.3 +/- 6.4 ml min-1 kg-1) when morphine was given at high dosage rates (> or = 0.15 mg kg-1 hr-1). Pharmacokinetic modeling of plasma morphine concentrations adequately fit a two-compartment model with a short initial distribution phase (mean half-life = 4.5 minutes) and a rapid terminal elimination half-life (77.6 +/- 19.2 minutes). These findings suggest that considerable individualization of morphine dosing may be necessary to achieve optimal analgesia and minimal adverse effects in these patients.

Adolescent↗
PubMed1995

Surgical workshop on liver surgery using isolated perfused livers in moulded casts of the upper abdomen.

The basic training in liver surgery on isolated perfused livers used at the workshop in the First Surgical Course of the Alps--Adriatic Hepatobiliary School is presented. The methods for the excision, preservation, perfusion and preparation of the liver are described, as is the manner of manufacturing the upper abdomen moulded casts, into which an isolated perfused liver is placed for training. The methods proved to be sufficiently successful, enabling participants to perform basic liver surgery like an intraoperative ultrasound investigation, as well as liver dissection techniques, liver suturing, segmental resection and even hepatectomy. Some technical improvements are proposed for future surgical workshops, such as washing out the blood from the liver, and a triple perfusion.

Abdomen↗
PubMed1994

Absorption of therapeutic drugs by barrier gels in serum separator blood collection tubes. Volume- and time-dependent reduction in total and free drug concentrations.

The stability of seven commonly monitored therapeutic drugs in serum was examined following storage in Vacutainer SST and Corvac serum separator blood collection tubes. Significant decreases (ranging from 5.9% to 64.5%) in the measured concentrations of phenytoin, phenobarbital, lidocaine, quinidine, and carbamazepine were observed, as a function of both time and sample volume, when serum was stored in Vacutainer SST serum separator blood collection tubes. In contrast, measured concentrations of theophylline and salicylate did not change under identical specimen storage conditions. No significant changes in the concentrations of phenytoin, phenobarbital, carbamazepine, theophylline, quinidine, and salicylate were observed when serum was stored in Corvac serum separator blood collection tubes. Only serum lidocaine concentrations decreased (ranging from 31.5% to 72.6%, depending on sample volume) after storage in Corvac tubes for 24 hours. The apparent decreases in serum concentrations of therapeutic drugs in both Vacutainer SST and Corvac tubes were most pronounced when small volumes (200-500 microL) of serum remained in contact with the barrier gels for prolonged periods of time (> 2-6 hours). These decreases were due to absorption of drugs by the barrier gels, as demonstrated by the recovery of drugs following chemical extraction of the barrier gels with methanol. For phenytoin and phenobarbital, the reduction in total drug concentrations also resulted in a proportional decrease in free drug concentrations and was dependent on the extent of protein binding by the drug. None of the therapeutic drugs used in this study were adversely affected by prolonged storage in standard red top Vacutainer blood collection tubes without barrier gels. The data suggest that serum separator blood collection tubes should be used with extreme caution for therapeutic drug monitoring, particularly when reduced sample volumes or prolonged specimen storage may be required.

Absorption↗
PubMed1994

Albendazole inhibits Pneumocystis carinii proliferation in inoculated immunosuppressed mice.

Albendazole, a benzimidazole derivative widely used for treating helminth infections, was successfully used to treat and prevent development of Pneumocystis carinii pneumonia in transtracheally inoculated immunosuppressed mice. For treatment, 3 weeks postinoculation, albendazole at 300 and 600 mg/kg of body weight per day was administered in food for 3 weeks. For prophylaxis, albendazole was begun on the same day as inoculation at 300 mg/kg/day for 7 days, and then the dose was reduced to 150 mg/kg/day for 35 additional days. With these regimens, albendazole was effective both for treatment and prophylaxis. Both dexamethasone-immunosuppressed and L3T4+ monoclonal antibody-immunosuppressed mouse models were used, and albendazole inhibited P. carinii infection in both.

Albendazole↗
PubMed1994

Cellular distribution of 125I-endothelin-1 binding in rat kidney following in vivo labeling.

Endothelin-1 (ET-1) receptors have previously been demonstrated in the rat kidney by in vitro autoradiography and in cultured renal cell lines by radioreceptor assay, but the precise cellular localization of these receptors under in vivo conditions remains to be determined. We performed electron microscopic autoradiography on rat kidney following intravenous administration of 125I-labeled ET-1. In vivo autoradiographs revealed binding patterns identical to those previously demonstrated following in vitro labeling. Light microscopic autoradiography showed that silver grains occurred exclusively overlaying glomeruli and peritubular capillaries in the cortex, inner stripe of the outer medulla, and the inner medulla. At the electron microscopic level, ET-1 binding was specifically localized to the fenestrated endothelium of glomerular and peritubular capillaries, and to a lesser extent to the vasa recta. No significant grains were seen on mesangial or visceral epithelial cells; nor were any seen on the cells of proximal tubule, the thick and thin limbs of the loop of Henle, the medullary collecting ducts, and renal interstitial cells. These results indicate that the endothelial cells of glomerular and peritubular capillaries are the primary target for the circulating ET-1 in the rat kidney and suggest an autocrine and/or paracrine function of locally synthesized ET-1 in vivo in both physiological and pathophysiological states.

Animals↗
PubMed1992

Bilateral atrial appendectomy abolishes increased plasma atrial natriuretic peptide release and blunts sodium and water excretion during volume loading in conscious dogs.

The atrial appendages contain most of the atrial natriuretic factor (ANF) in the mammalian heart, and atrial appendage mechanical function predicts ANF secretion during volume loading. To demonstrate the crucial role of the atrial appendages in ANF release, we first measured hemodynamics and changes in plasma ANF after injection of 1,000 ml i.v. normal saline in conscious dogs and again after bilateral atrial appendectomy; we next measured changes in renal function using infusions of atriopeptin 24 to achieve plasma levels corresponding to levels achieved during volume loading; and we lastly measured renal function during acute volume expansion and also after atrial appendectomy. Plasma ANF increased from 65 +/- 11 to 246 +/- 54 pg/ml after volume loading but did not increase after atrial appendectomy. Atrial appendectomy did not alter the tachycardia or hemodynamic effects of volume loading. Infusion of 10 ng/kg/min atriopeptin 24 increased plasma ANF from 50 +/- 9 to 234 +/- 54 pg/ml, increased urine output 34 +/- 10%, and increased sodium excretion 62 +/- 10% in dogs with intact atrial appendages. Renal function was compared in dogs before atrial appendectomy: 20, 40, and 60 minutes after volume loading, urine flow rate increased by 5.9 +/- 0.5, 6.9 +/- 0.4, and 4.4 +/- 0.8 ml/min, while sodium excretion increased by 717 +/- 60, 839 +/- 84, and 582 +/- 57 mueq/min. After atrial appendectomy urine flow rate increased 2.1 +/- 0.7, 2.7 +/- 0.7, and 2.0 +/- 0.6 ml/min, and sodium excretion increased only by 327 +/- 110, 324 +/- 77, and 340 +/- 92 mueq/min (p less than 0.01) during volume loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

T.A.C.

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Anesthesia, Local↗
PubMed1991

Effect of dietary manipulation on c-myc RNA expression in adipose tissue, muscle and liver of broiler chickens.

The effects of dietary restriction on the relative steady state levels of cellular myc (c-myc) mRNA in abdominal adipose tissue, breast muscle and liver of chickens were determined. Fasting was found to increase c-myc RNA expression in adipose tissue (p less than 0.01). This increase returned to normal levels after refeeding. Muscle and liver in fasted birds did not show changes in c-myc that differed from controls. Serum concentrations of glucose, triglyceride (TG), free fatty acids (FFA) and insulin-like growth factor (IGF-I) were compared to levels of c-myc found in control birds. In adipose tissue, c-myc levels were negatively correlated with serum glucose, TG and IGF-I, while in muscle a positive correlation with serum glucose and TG was found. Data suggest that c-myc is involved in the metabolic changes occurring in fat cells under fasting conditions.

Adipose Tissue↗
PubMed1991

Isolation of DNA from blood.

A rapid, economical method of DNA isolation from blood was developed that yields DNA suitable for Southern analysis and polymerase chain reactions without organic solvent extractions. Bovine DNA was prepared from peripheral leukocytes and nuclei using pronase E digestion and ethanol precipitation. This isolation method readily adapts to multiple samples. The DNA is characterized by high yield, solubility, lack of protein contamination, and ease of restriction endonuclease digestion.

Animals↗
PubMed1991

Prediction of free phenytoin levels based on [total phenytoin]/[albumin] ratios. Potential errors with hypoalbuminemia.

Therapeutic monitoring of the pharmacologically active (free drug) fraction of protein-bound medications (e.g., phenytoin) represents a major diagnostic challenge in clinical and laboratory medicine. While free drug levels may be beneficial in many clinical situations, current methods for predicting free phenytoin concentrations are unreliable and not recommended for general use. The authors have demonstrated a linear relationship (r2 = 0.98) between serum levels of total and bound phenytoin in 56 patients with seizure disorders. No significant correlations were observed when total phenytoin and albumin levels were compared independently to measured concentrations of free phenytoin or percent free phenytoin. A good correlation (r2 = 0.89) existed between free phenytoin levels and [total phenytoin]/[albumin] ratios in patients with normal or elevated albumin levels, but significantly weaker correlations were found in patients with hypoalbuminemia. Thus, [total phenytoin]/[albumin] ratios may have clinical value in predicting free phenytoin levels in uncomplicated patients without hypoalbuminemia.

Humans↗
PubMed1991

Displacement of phenytoin from serum protein carriers by antibiotics: studies with ceftriaxone, nafcillin, and sulfamethoxazole.

Increased concentrations of free phenytoin in serum, attributable to the displacement of this anticonvulsant by other drugs, e.g., valproic acid and salicylic acid, have been reported. We observed in vitro and in vivo displacement of phenytoin by the antibiotics ceftriaxone, nafcillin, and sulfamethoxazole. In vitro studies demonstrated statistically significant (P less than 0.05) increases in free phenytoin after the addition of specific antibiotics to patients' sera and to phenytoin-supplemented sera from controls. Concentrations of free phenytoin in vivo, predicted by an equation we have found to be accurate for albumin concentrations greater than or equal to 32 g/L, were consistently underestimated in patients receiving concomitant therapy with the antibiotics studied. The concentrations of free phenytoin decreased towards the predicted values when the antibiotic therapy was discontinued. We conclude that ceftriaxone, nafcillin, and sulfamethoxazole can displace phenytoin from the usual protein carriers found in serum, in vitro and in vivo.

Carrier Proteins↗