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Biomedical subjects

D R Gray

Publications and source records attributed to D R Gray.

At least 19 recordsLinked to original sources
PubMed2000

Immunoassays for pentamidine and related compounds: development of a facile inhibitory ELISA suitable for clinical use.

Aromatic dicationic drugs have a broad spectrum of activity against protozoal and fungal pathogens including Pneumocystis carinii, Leishmania mexicana amazonensis, Cryptosporidium parvum and Cryptococcus neoformans. Pentamidine serves as the exemplar for an extensive collection of newly synthesized related compounds, which have reduced toxicity and a wider range of target organisms. Assays of pentamidine and related compounds have depended on HPLC-tandem mass spectrometry (HPLC-TMS) for the quantitation and identification of drug and metabolites. Immunoassays for pentamidine would have many advantages over the HPLC methods including relative simplicity of assay format and required equipment, convenience in sample preparation and reduction in time and cost of assays. In this report we describe a simple ELISA based immunoassay for pentamidine and pentamidine-like drugs with requisite sensitivity and specificity for use as a clinical assay (EC50 value of about 50 nanomolar). Immunogen was synthesized by coupling the hapten aminopentamidine to ovalbumin (chemically modified to provide an optimal number of -SH groups) using sulfo-MBS. Maleic-anhydride activated ELISA plates were covalently sensitized using the aminopentamidine hapten and used in an inhibitory ELISA assay format whereby the ability of analyte to suppress antibody binding to sensitized plate was measured. The assay detects primarily the phenolic amidine of pentamidine when in a para position and hence can also detect structurally related derivatives of pentamidine of potential interest as new therapeutic agents.

Animals↗
PubMed1999

Impact of therapeutic interchange from pravastatin to lovastatin in a Veterans Affairs Medical Center.

OBJECTIVE: To evaluate the impact of a therapeutic interchange from pravastatin to lovastatin on treatment outcomes, quality of life, patient satisfaction, and costs. STUDY DESIGN: A prospective cohort study of 170 patients switched from pravastatin to lovastatin from September 1997 through November 1997. PATIENTS AND METHODS: The therapeutic interchange program promoting lovastatin as the preferred agent went into effect June 2, 1997 after Merck & Co. was awarded the Veterans Health Administration national contract for 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Patients were switched to lovastatin by either their primary care physician during routine clinic visits or the pharmacist by mail. The following outcomes were measured before and after conversion to lovastatin: lipid values, liver function tests, National Cholesterol Education Program (NCEP) low-density cholesterol (LDL-C) goals achieved, quality of life (QOL) (measured by the Medical Outcomes Study 36-item short-form health survey [SF-36]), medication tolerance (measured with a global symptom survey), patient satisfaction, and cost-minimization analysis. RESULTS: Lipid values and liver function test results were similar for pravastatin and lovastatin treatment. Forty percent of patients achieved NCEP LDL-C goals before and after formulary conversion. There were no significant differences between pravastatin and lovastatin in QOL, medication tolerance, and patient satisfaction. The projected cost savings from this therapeutic interchange was approximately $211,000 annually. CONCLUSION: Therapeutic interchange from pravastatin to lovastatin resulted in substantial cost savings. QOL, patient satisfaction, and achievement of NCEP LDL-C goals were maintained.

Anticholesteremic Agents↗
PubMed1994

Efficacy and safety of controlled-release niacin in dyslipoproteinemic veterans.

OBJECTIVE: To evaluate the safety and efficacy of controlled-release niacin in patients with hyperlipoproteinemia. DESIGN: A retrospective cohort study. SETTING: A Department of Veterans Affairs Medical Center. PATIENTS: A consecutive sample of 969 predominantly elderly male veterans treated for dyslipoproteinemia with controlled-release niacin between October 1988 and October 1991. MAIN OUTCOME MEASURES: Primary outcomes were lipid levels and lipoprotein cholesterol response, alternations in levels of hepatic enzymes and blood chemistry test results, and characterization of niacin-induced hepatotoxicity abstracted from the patient's medical, laboratory, and pharmacy records. RESULTS: 93% (896 of 969) of the cohort was evaluable. Patients (age, 61.7 years [9.4 years], mean [SD]) were treated for 1 to 36 months (13.0 months [9.7 months]) with an average maintenance dose of 1.67 g/d (0.8 g/d). Niacin was discontinued in 48.5% (435 of 896) of the patients primarily because of adverse effects. Poor glycemic control led to discontinuation in 40.6% (43 of 106) of the patients with diabetes mellitus. The lipoprotein response was dose-related and favorable (levels of total cholesterol, -19.1%; low-density lipoprotein cholesterol, -24.0%; high-density lipoprotein cholesterol, +5.7%; and triglycerides, -32.5%). Statistically but not clinically meaningful dose-related increases were seen in levels of liver enzymes and serum glucose (aspartate aminotransferase, +29%; alanine aminotransferase, +23%; alkaline phosphatase, +25%; and glucose, +7%; P = 0.0001). Twenty of 896 (2.2%) and 42 of 896 (4.7%) patients met biochemical criteria for probable and for possible or probable niacin-induced hepatotoxicity, respectively. Predisposing factors included high dose, alcohol use, preexisting liver disease, and concurrent oral sulfonylurea therapy. CONCLUSIONS: Controlled-release niacin is effective in treating dyslipoproteinemia in selected middle-aged and elderly veterans, but approximately one half of patients discontinued the drug because of adverse effects or other causes including noncompliance. Niacin should be avoided in patients with hepatic dysfunction or a history of liver disease, patients with diabetes mellitus, and patients who abuse alcohol. Because controlled-release niacin seems to be more potent than crystalline niacin, product substitution without dose adjustment should be avoided.

Aged↗
PubMed1993

Lower limb ischaemia in the octogenarian: is limb salvage surgery worthwhile?

Vascular surgeons are being asked to manage vascular disease in an increasingly elderly population, and advanced age may be considered a relative contraindication to limb salvage surgery with an amputation seeming the preferred option. We present a review of 50 patients over the age of 80 years, presenting with ischaemic rest pain, ulceration or gangrene of the lower extremity. Six patients were treated conservatively, four of whom died during the same admission. Only two patients proved suitable for transluminal angioplasty as the sole curative procedure. Twelve patients (24%) underwent primary amputation with a perioperative mortality of 3/12 (25%). Five patients (10%) had an iliac bypass procedure, and 25 patients (50%) were considered suitable for infrainguinal bypass. Of the latter group 14 had femoropopliteal bypasses, and 11 had femorodistal bypasses with an overall perioperative mortality of 3/25 (12%). Mortality at 6 months was high (33%) and was similar in both the grafted and amputation groups. Patients having reconstruction fared well in terms of independent mobility, use of long-term care, and length of hospital stay. Patients over 80 years of age with critical ischaemia should not be denied the opportunity of vascular reconstruction.

Age Factors↗
PubMed1992

Chlorpropamide-induced hyponatremia in the veteran population.

OBJECTIVE: To determine the incidence and possible risk factors associated with chlorpropamide (CPA)-induced hyponatremia in the veteran population. DESIGN: Retrospective cohort study. SETTING: Federal tertiary care medical center. PATIENTS: Veterans receiving CPA from our facility with at least one serum sodium concentration below 135 mmol/L within the past year were eligible. A randomly selected control group consisting of patients taking CPA with normal sodium concentrations was also chosen. One hundred forty-five of 799 patients who had received CPA were included in the study. RESULTS: The average daily dose of CPA was 425 +/- 207 mg (+/- SD). The incidence of hyponatremia associated with CPA was 7.1 percent (57/799 patients). The majority of patients were mildly hyponatremic (48/57 patients, 84 percent) with serum sodium concentrations between 130 and 134 mmol/L. The incidence of CPA-induced syndrome of inappropriate antidiuretic hormone was 2.1 percent. Concurrent angiotensin-converting enzyme (ACE) inhibitor use was identified as a risk factor; thiazide diuretic use was not. CONCLUSIONS: The incidence of hyponatremia related to CPA use in elderly veterans is consistent with other reports in the literature. ACE inhibitors may be a predisposing factor for CPA-induced hyponatremia.

Aged↗
PubMed1992

Documentation and assessment of pharmacist-initiated drug therapy interventions.

In conclusion, the development of an efficient system to document pharmacist-initiated drug therapy interventions has been successful. The system has been incorporated into the pharmacy quality assurance program and is being used to evaluate the provision of pharmaceutical care. Finally, the system has been incorporated into the clinical services drug-use evaluation program and is being used to evaluate individual physician prescribing practices.

California↗
PubMed1990

Promotion of extended-release niacin tablets at a Veterans Affairs medical center.

A program to modify the prescribing of antilipemic agents by promoting the use of extended-release niacin tablets is described. Between December 1987 and August 1988, pharmacists at a 1188-bed Veterans Affairs medical center observed a large increase in the number of outpatient prescriptions for antilipemic agents. In an attempt to control costs, a program to promote the use of extended-release niacin tablets for treating hyperlipemia was conducted during August and September 1988. Various educational materials on niacin were distributed to physicians. A display on therapy of hyperlipemia was featured at the monthly drug fair, and articles on niacin were presented during a journal club meeting of ambulatory-care clinicians. Pharmacists succeeded in having extended-release niacin tablets placed on the formulary in September. Data on the number of prescriptions filled for antilipemic agents were collected before and after the niacin promotional program. The number of prescriptions filled for extended-release niacin 500-mg tablets increased steadily during a six-month study period after the program ended; the number of prescriptions filled for regular niacin decreased by 50%. As prescribing of extended-release niacin increased, prescribing of colestipol, gemfibrozil, and probucol declined. The promotional program was well received by most of the medical staff. A program of education and formulary management successfully changed physician prescribing habits for antilipemic agents.

Cost Control↗
PubMed1988

Gentamicin bioavailability and single-dose pharmacokinetics in spinal cord injury.

The rate and completeness of absorption of gentamicin from muscle (healthy and paralyzed) and gentamicin disposition kinetics following a single intravenous infusion were studied in nonobese, healthy male volunteers with functionally complete, chronic (greater than one year duration) spinal cord injury (SCI) and in able-bodied controls. Pharmacokinetic parameters were derived using compartmental and model-independent analyses. The absolute bioavailability of gentamicin was complete and did not differ from control values using both model-independent (LAGRAN) and model-dependent (ADAPT) analyses. The rate of gentamicin absorption in patients with SCI was, however, significantly slower, with a mean absorption time of 2.55 h compared with 0.96 h in able-bodied controls (p less than or equal to 0.05). Mean volume of distribution steady-state (Vssd) of gentamicin was demonstrated to be 33-47 percent greater in spinal cord injury than in controls (p less than 0.05). We conclude that the absorption of gentamicin from paralyzed muscle is significantly impaired, and in conjunction with an increase in Vssd results in delayed, decreased peak serum levels in patients with SCI.

Adult↗
PubMed1987

Workload measurement of a clinical pharmacy residency program.

The types of activities performed by four clinical pharmacy residents and the amount of time spent on each activity were studied using a workload measurement system. A workload measurement system was developed to record all activities performed by pharmacy residents. The system included 50 activities that were grouped under 11 general headings; residents' time was divided among 10 major areas of service. The following data were collected and analyzed each month during the six-month study period: units of work, weighted units of work, total productive hours, total service hours, and productivity. The residents participated in 39 of 50 clinical pharmacy activities. Activities performed most frequently included nursing-home-care-unit drug reviews, drug monitoring, and rounds. The most time-consuming activities were clinical education, administration, and drug-use review. Productivity ranged from 80 to 115% and was influenced by residents' assigned rotations. A workload measurement system for quantifying the time spent by residents performing various clinical pharmacy activities provided objective data that were used to restructure a clinical pharmacy residency program.

California↗
PubMed1986

Treatment of gynecomastia with tamoxifen: a double-blind crossover study.

Benign asymptomatic or painful enlargement of the male breast is a common problem, postulated to be due to an increased estrogen/testosterone ration or due to increased estrogenic or decreased androgenic stimulation via estrogen or androgen receptor interactions. Treatment at present consists of analgesic medication or surgery. However, treatment directed against the preponderance of estrogenic stimulation would seem to represent a more specific form of therapy. In the present double-blind crossover study, one-month courses of a placebo or the antiestrogen tamoxifen (10 mg given orally bid) were compared in random order. Seven of ten patients experienced a decrease in the size of their gynecomastia due to tamoxifen (P less than 0.005). Overall, the decrease for gynecomastia for the whole group was significant (P less than 0.01). There was no beneficial effect of placebo (P greater than 0.1). Additionally, all four patients with painful gynecomastia experienced symptomatic relief. There was no toxicity. The reduction of breast size was partial and may indicate the need for a longer course of therapy. A followup examination was performed in eight out of ten patients nine months to one year after discontinuing placebo and tamoxifen. There were no significant changes from the end of the initial study period except for one tamoxifen responder who developed a recurrence of breast tenderness after six months, and one nonresponder who demonstrated an increase in breast size and a new onset of tenderness after ten months. Therefore, antiestrogenic treatment with tamoxifen may represent a safe and effective mode of treatment for selected cases of cosmetically disturbing or painful gynecomastia.

Administration, Oral↗
PubMed1985

Gentamicin disposition kinetics in humans with spinal cord injury.

The disposition kinetics of gentamicin, an aminoglycoside antibiotic, were studied in seven tetraplegic and six paraplegic volunteers. The volume of distribution of gentamicin in l/kg of body weight varied in a statistically significant way from values of this parameter measured in normal subjects. The elimination of gentamicin in spinal man proceeded in a log-linear fashion accurately characterized by a one compartment open-model with a half-life of approximately 2 hours. The clinical significance of altered disposition kinetics and an increased intersubject variability in gentamicin disposition in spinal man as compared to normal subjects is unknown. The existence of these observed differences in pharmacokinetic parameters, however, emphasizes the need to define individual pharmacokinetic profiles and individualize dosing regimens in spinal man. The data presented are supportive of the hypothesis that spinal man constitutes a discreet therapeutic population.

Adult↗
PubMed1985

Retrospective evaluation of a pharmacist-managed warfarin anticoagulation clinic.

The effectiveness of a pharmacist-managed warfarin anticoagulation clinic in maintaining therapeutic prothrombin times and preventing hospitalizations secondary to inadequate control of anticoagulation was evaluated. Patients who had received warfarin sodium for at least one year before being referred to the anticoagulation clinic were studied using retrospective chart reviews. Clinical pharmacists provided patient education, monitored patients for hemorrhagic and thromboembolic complications, and adjusted warfarin sodium dosage to maintain therapeutic prothrombin times. The patients' primary physicians retained responsibility for overall care and were consulted by pharmacists regarding complications of anticoagulation and patient unreliability. The percentage of patients requiring hospitalization (39% versus 4%) and the percentage of prothrombin times outside the therapeutic range (35.8% versus 14.4%) were significantly higher during the preclinic phase (before referral to the clinic) than during the clinic phase. Eight patients were hospitalized for hemorrhagic complications and four for thromboembolism during the preclinic phase; only one hospitalization for hemorrhage occurred during the clinic phase. The warfarin anticoagulation clinic staffed by specially trained pharmacists provided improved therapy compared with treatment received by patients before their referral to the clinic.

Adult↗
PubMed1984

Warfarin interaction with erythromycin.

The drug interaction between warfarin and erythromycin is not well known. We report a case in which erythromycin was observed to markedly potentiate warfarin anticoagulation, resulting in hemorrhage in a patient treated for Legionella pneumonia. The morbidity of this drug interaction is enhanced in elderly patients who have infection accompanied by anorexia and/or fever and who are receiving intravenous erythromycin. The well-documented, temporal relationship established erythromycin as the interacting drug.

Drug Interactions↗
PubMed1983

Effects of low-dose antihypertensive therapy in elderly patients with predominant systolic hypertension.

Patients over 60 years of age (M = 70 years) with the predominant systolic form of essential hypertension (systolic blood pressure greater than 160 mm Hg; diastolic blood pressure less than 100 mm Hg) were treated with a combination of low doses of the diuretic chlorthalidone and the centrally-acting sympatholytic agent clonidine. In this randomized double-blind study, patients received either active treatment (n = 14) or placebo (n = 16). Baseline systolic blood pressure in the treatment group averaged 172 mm Hg and was controlled (fall in systolic blood pressure to less than 140 mm Hg or by at least 10%) in 13 of the 14 patients; in eight patients, control was achieved with a single daily dose (given at night) of the clonidine (.1 mg)-chlorthalidone (15 mg) combination. The active drug was significantly superior to placebo in decreasing systolic blood pressure. Changes measured in the standing position did not differ from those in the supine position. Side effects were mild and transient for both the placebo and the treatment groups. Low-dose combination therapy appears to be a highly effective approach for the management of older patients with predominant systolic hypertension of mild-to-moderate degree.

Aged↗
PubMed1983

Combined diuretic and sympatholytic therapy in elderly patients with predominant systolic hypertension.

It has been speculated that the convenience and palatability of low-dose combination antihypertension treatment might enhance therapeutic effectiveness and compliance, especially in elderly patients. To test this possibility, patients over 60 years of age with predominant systolic hypertension were treated with a combination of a diuretic, chlorthalidone, and the centrally acting inhibitor of sympathetic activity, clonidine. The results of active treatment in these patients (n = 13) were compared with those of a placebo (n = 11). Active therapy with low doses of chlorthalidone and clonidine (usually once daily) controlled blood pressure (systolic pressure less than 140 mm Hg) in 12 of the 13 patients without inducing orthostatic hypotension. Administration of placebo did not result in significant changes in blood pressure. The diuretic-clonidine combination induced only small decreases in serum potassium levels and small increases in uric acid; no significant changes in creatinine clearance were observed. Both active and placebo therapy were tolerated without significant side effects. This study reveals that combined therapy with low doses of chlorthalidone and clonidine is effective, convenient, and palatable in controlling blood pressure in elderly patients with predominant systolic hypertension and supports the idea that treatment with sympathoinhibitory and volume-depleting agents is appropriate for this form of hypertension.

Aged↗