PubMed Health⌕ Search

Biomedical subjects

J B Douglas

Publications and source records attributed to J B Douglas.

At least 19 recordsLinked to original sources
PubMed1993

Rapid determination of maintenance heparin infusion rates with the use of non-steady-state heparin concentrations.

OBJECTIVE: To compare heparin dosage adjustment using only activated partial thromboplastin time (APTT) with a method using non-steady-state heparin concentrations (HCs) to rapidly achieve and maintain an APTT ratio greater than or equal to 1.5 times baseline throughout the first 24 hours of therapy. DESIGN: Randomized, blind, parallel comparison of an empiric dosing method based only on APTT with a dosing method based on the calculation of heparin clearance using non-steady-state HCs. SETTING: A private community teaching hospital. The patient, physician, nurses, and investigators were blinded to the dosing method. Only the clinical staff pharmacist, who received the consult and made all dosage adjustments, was not blinded. PATIENTS: All patients requiring heparin for the treatment of thromboembolic disease were evaluated for potential inclusion in the study. Patients were enrolled in the study if they had a clinical diagnosis of deep venous thrombosis confirmed by objective means such as venography or ultrasonography. Patients were excluded if they had active bleeding, platelet dysfunction, thrombocytopenia, severe hepatic disease (total bilirubin > 25.7 mumol/L), renal disease, or evidence of stroke. Patients were also excluded if they were receiving heparin prior to enrollment. MAIN OUTCOME MEASURE: Maintenance of an APTT ratio greater than or equal to 1.5 times baseline throughout the first 24 hours of heparin therapy. RESULTS: Thirty-four patients were enrolled in the study; 17 in each group. The groups were not significantly different with regard to gender, age, baseline APTT, or mean loading dose (p > 0.5). Mean initial infusion rates for the control and HC groups were 1042 +/- 194 and 1071 +/- 143 units/h, respectively (p > 0.5). After the first rate adjustment at 4 hours, the difference achieved significance at 1032 +/- 232 and 1367 +/- 317 units/h for the control and HC groups, respectively (p < 0.01). At 12 hours, 18.8 percent of the patients in the control group were subtherapeutic; by 24 hours, 33.3 percent were subtherapeutic. No patients became subtherapeutic in the HCs group during the first 24 hours. CONCLUSIONS: This study demonstrates that, in contrast to standard heparin dosing methods, the use of non-steady-state HCs allows patients with deep venous thrombosis to rapidly achieve and maintain therapeutic APTT ratios throughout the critical first 24 hours of therapy.

Female↗
PubMed1992

Altered heparin pharmacodynamics in patients with pulmonary embolism.

Heparin clearance and pharmacodynamic response were examined in 12 patients being treated for deep venous thrombosis (DVT, 6 patients) or pulmonary embolism (PE, 6 patients). A loading dose of 70 units/kg was administered to DVT patients and 100 units/kg to PE patients followed by an initial infusion rate of 15 or 25 units/kg/h for DVT or PE patients, respectively. Heparin clearance was determined at 4, 12, and 24 h after initiating heparin therapy. The mean heparin clearance in the DVT group was 2,164 +/- 1,024 ml/h at 4 h, 2,591 +/- 1,239 ml/h at 12 h, and 2,795 +/- 1,863 m/h at 24 h. The PE patients had clearances of 1,775 +/- 494, 2,004 +/- 321, and 2,843 +/- 1,000 ml/h at 4, 12, and 24 h, respectively. The difference between the two groups was not statistically significant (p greater than 0.50). The activated partial thromboplastin time (aPTT) was used as a measure of heparin effect. The maximum effect (EMAX) and concentration required to attain 50% of the maximum effect (EC50) were determined for each group using the Lineweaver-Burke linearization method. The mean EMAX and EC50 for the DVT patients were 130 +/- 40.99 s and 1.01 +/- 0.70 units/ml, respectively. For the PE patients, the mean EMAX was 418 +/- 200 s and the mean EC50 was 4.32 +/- 2.81 units/ml. The difference between both groups for each parameter was statistically significant (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-Response Relationship, Drug↗
PubMed1991

An unusually proximal deletion on the short arm of chromosome 3 in a patient with small cell lung cancer.

The tumors of patients with small cell lung carcinoma (SCLC) frequently exhibit the loss of alleles at polymorphic loci on the short arm of chromosome 3. We report the genotype analysis of six SCLC patients obtained using 15 chromosome 3 probes that identified 19 restriction fragment length polymorphisms (RFLPs). Five of the six patients were reduced to homozygosity in the tumor DNA at every informative 3p locus, and thus did not serve to delineate the deletion. However, the RFLP analysis of the tumor DNA of the sixth patient demonstrated both heterozygous and hemizygous loci on 3p and allowed the definition of an interstitial deletion that extends proximal to the D3S2 locus at 3p14.2-p21 to include at least 3p13-p14. The exclusion of the D3F15S2 locus from the deleted region, observed in this patient, is an uncharacteristic feature of SCLC deletions. This deletion includes the location of D3S30 and D3S4, and thus serves to map these loci within the proximal half of chromosome 3.

Alleles↗
PubMed1990

Pharmacokinetics and pharmacodynamics of heparin during hemodialysis: interpatient and intrapatient variability.

Heparin pharmacokinetics and pharmacodynamics were studied in 17 patients undergoing hemodialysis, once a week for 4 weeks in order to evaluate intrapatient variability over time. A single bolus injection of heparin was administered directly into the circulation immediately prior to the start of hemodialysis in doses ranging from 3000 to 12,000 U. Blood samples were obtained to determine activated coagulation times (ACT) and heparin concentrations (HC). Combined zero- and first-order elimination was seen in each of the 4 weeks. The half-life of heparin decreased from beginning to end of hemodialysis during each week, with the percentage of decrease from the start of dialysis ranging from 70-74%, indicating concentration-dependent elimination. Since the zero-order component did not appear to be clinically significant, first-order elimination was assumed. A linear decline in ACT over the time of the dialysis period was also seen during each week. A profile of ACT versus HC was generated for each patient as well as for the mean data to assess the relationship of HC to response. An excellent correlation was found for both individual patient data and mean data. In the third week the patients were randomized to receive standard treatment or an individualized dose. They were then crossed over to the opposite group in the fourth week to see if this relationship between ACT and HC would be useful in predicting heparin dose. These profiles were used to individualize the dose during either the third or fourth week of the study. No significant differences were noted between actual and predicted ACT. A significant degree of interpatient variability was demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Heparin pharmacokinetics during hemodialysis.

The disposition of heparin was studied in 21 chronic hemodialysis patients. Heparin was administered as a bolus injection in doses of 3,000-12,000 U. Combined zero and first-order elimination was demonstrated, with heparin half-life declining by 74% over 3.5 h during dialysis. Assumption of a first-order pharmacokinetic model of elimination resulted in a mean difference of 0.001 U/ml between actual and predicted heparin concentrations. Mean first-order pharmacokinetic parameters were: half-life, 117 min; heparin volume of distribution (V), 68 ml/kg; clearance, 28 ml/min. A high degree of interpatient variability was also observed. A comparison of V and plasma volume (PV) revealed V to be significantly greater than PV (p less than 0.001), indicating distribution outside the plasma compartment. When compared to blood volume, there was no significant difference (p greater than 0.1), indicating that blood volume may be used to approximate V. The nonlinear component of the elimination process is not clinically significant within the range of therapeutic plasma concentrations used during hemodialysis, but the high degree of interpatient variability indicates that dosage individualization may be useful.

Adult↗
PubMed1989

Clinical career ladders: the Moses H. Cone Memorial Hospital.

A competence- and achievement-based advancement program developed for pharmacists at The Moses H. Cone Memorial Hospital, a 530-bed community teaching hospital, is described. In 1985 pharmacy management recognized the need to provide an incentive program to reward achievements by staff clinical pharmacists, recognize their increased responsibilities, and increase the department's ability to retain qualified practitioners. Adding another rung to the existing administrative career ladder was not desirable, so a new job category, pharmacist II, was created. Employees are evaluated for promotion to pharmacist II on the basis of tenure, performance, and elective professional and service activities. A point system is used to objectively score achievements; to be promoted, an employee must accumulate 50 points during a two-year period. The number of staff pharmacists who can advance is limited not arbitrarily but rather by the application of challenging criteria. Employees are responsible for submitting documentation of their achievements to a review committee, which meets quarterly to evaluate applications and award points. Of 13 applicants since 1985, 10 have been promoted. Because of problems in evaluating the performance of pharmacist II employees, providing them time to conduct research, and incorporating specialty practice areas into the program, plans are being made to institute a more structured career ladder system with separate managerial, clinical, and educational tracks. A competence- and achievement-based advancement program with a single step was an improvement over the former system but lacked the balance and comprehensiveness offered by more structured career ladder programs.

Career Mobility↗
PubMed1987

The effect of oral cimetidine on total and unbound serum lidocaine concentrations in patients with suspected myocardial infarction.

In this study, we prospectively evaluated the effect of oral cimetidine on serum lidocaine concentrations in 6 patients with suspected myocardial infarction. Compared to baseline lidocaine levels, total lidocaine concentrations increased by 8.2 +/- 7.8% at 6 hours, 16.4 +/- 9.0% at 12 hours and 27.9 +/- 9.4% at 24 hours after two doses of oral cimetidine. Unbound lidocaine concentrations increased by 14.3 +/- 4.1% at 6 hours, and 18.3 +/- 10.3% at 24 hours after cimetidine. In patients with myocardial infarction (3), total lidocaine concentrations increased by 24.2 +/- 10.4%, whereas unbound lidocaine increased by 8.9 +/- 10.2% at 24 hours. Therefore, increases in total lidocaine concentrations after cimetidine administration were considerably less than those previously reported and empiric dosage reductions of lidocaine in patients receiving cimetidine may not be appropriate.

Administration, Oral↗
PubMed1987

Heparin dosage adjustment in patients with deep-vein thrombosis using heparin concentrations rather than activated partial thromboplastin time.

In patients with deep-vein thrombosis, heparin dosage adjustment based on measurement of heparin concentrations in whole blood was compared with conventional dosage adjustment based solely on activated partial thromboplastin time (APTT) measurement. Initially, all patients were given i.v. bolus doses of heparin sodium 70 units/kg followed by continuous infusion of 16 units/kg/hr. Seventeen patients (group 1) had their initial heparin dosages adjusted according to the results of the APTT value four hours after the start of heparin therapy; subsequent adjustments were made to maintain APTT values within the therapeutic range of 1.5 to 2.5 times the patient's baseline control. Fifteen patients (group 2) had heparin dosage adjusted four hours after the start of heparin infusion, based on apparent heparin clearance using the two-point method of Chiou et al., to maintain whole-blood heparin concentrations of 0.3 to 0.6 units/mL. APTT values less than 1.5 times control occurred in about 12% of group 1 patients at 8, 12, and 24 hours and in 11 of 17 (65%) for at least one value during the study. In group 2 patients, no APTT values were less than 1.5 times control. The patients in group 2 had faster symptomatic improvement and shorter hospital stays. Heparin dosing based on measurement of whole-blood heparin concentrations and application of a practical two-point pharmacokinetic model was superior to dosing based on APTT values.

Adult↗
PubMed1986

Effect of pharmacist intervention on control of resistant hypertension.

The effect of a pharmacist's clinical intervention on blood pressure control in ambulatory adults with resistant hypertension was studied. Twenty patients of an internal medicine clinic who had diastolic blood pressures greater than 96 mm Hg on two consecutive visits and antihypertensive regimens consisting of two or more agents were entered in the study between November 1, 1980, and February 1, 1981. After asking each patient 15 questions about hypertension and its treatment, the pharmacist counseled the patient about antihypertensive therapy, obtained a medication history, and discussed diet. The patient's blood pressure was measured, and the pharmacist evaluated the appropriateness of the patient's antihypertensive regimen (based on compliance, adverse reactions, and regimen complexity) and possible reasons for the poor response to treatment. The pharmacist then recommended drug therapy to the physician; stepped care including hydrochlorothiazide, reserpine, and hydralazine was used when possible. Patients' mean age was 56 years. Most did not know the names of their medications or understand their dosage schedules. Eight patients had severe hypertension (193/124 +/- 23/4 mm Hg), five had moderate hypertension (161/109 +/- 20/2 mm Hg), and seven had mild hypertension (171/100 +/- 29/0 mm Hg). Factors contributing to poor blood pressure control were noncompliance and adverse drug effects. After five to eight months of follow-up, mean blood pressures for patients with severe, moderate, and mild hypertension were, respectively, 140/92 +/- 23/10 mm Hg, 131/92 +/- 8/6 mm Hg, and 137/88 +/- 26/3 mm Hg; the mean for each group was significantly different from baseline. In this study, pharmacists intervened successfully with patients and physicians to enhance blood pressure control through drug therapy.

Antihypertensive Agents↗
PubMed1984

Fatty acid synthesis in brown adipose tissue of the Mongolian gerbil (Meriones unguiculatus): influence of acclimation temperature on synthesis in brown adipose tissue and the liver in relation to whole-body synthesis.

Fatty acid synthesis was measured in vivo with 3H2O in Mongolian gerbils acclimated at different temperatures. At 31 degrees C the highest rate of synthesis was in the liver, and the liver accounted for approximately one half of whole-body synthesis. At 20 and 40 degrees C, the highest synthesis rate (per g tissue) occurred in brown adipose tissue, and this tissue was estimated to account for some 15% of whole-body synthesis at both these temperatures. In contrast to other rodent species whole-body fatty acid synthesis in the Mongolian gerbil was lower in cold-acclimated than warm-acclimated animals, despite the cold-induced increase in energy intake.

Acclimatization↗