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Biomedical subjects

J R Horn

Publications and source records attributed to J R Horn.

At least 19 recordsLinked to original sources
PubMed1996

Use of prokinetic agents in special populations.

The use of prokinetic agents by pediatric patients, geriatric patients, and patients taking other drugs that may affect or be affected by the prokinetic agent is reviewed. The use of such agents to treat motility disorders has expanded over the past few years. These agents may be administered to patients who have special physiologic considerations, have other diseases, or require concomitant drug therapy. The appropriate use of prokinetic agents in these groups requires an understanding of the unique dosage considerations that may be necessary to ensure safe, effective therapy.

Age Factors↗
PubMed1996

Lack of in vitro interaction between heparin and nitroglycerin.

Nitroglycerin has been reported to reduce activated partial thromboplastin time (aPTT) values in patients treated with concurrent heparin and nitroglycerin. However, in vivo studies have yielded conflicting results. In this in vitro evaluation, nitroglycerin was added to samples of pooled plasma from normal volunteers in concentrations of 0, 1, 10, 50, 100, 150, and 200 ng/mL. Preservative-free heparin was then added to the samples to produce final concentrations of 0, 0.3, and 0.6 U/mL. Activated partial thromboplastin time (aPTT) was determined for each sample using a single reagent. There were no significant differences in aPTT values among increasing nitroglycerin concentrations for any of the three levels of heparinization. No direct effect of nitroglycerin on the anticoagulant effect of heparin was observed, as measured by aPTT.

Blood Coagulation↗
PubMed1996

Mixed-effect modeling for detection and evaluation of drug interactions: digoxin-quinidine and digoxin-verapamil combinations.

Mixed-effect modeling has been suggested as a possible tool to detect and describe drug interactions in patient populations receiving drug combinations for the treatment of disease states. The mixed-effect modeling program, NONMEM, was used to measure the effects of the well-known digoxin-quinidine and digoxin-verapamil drug interactions in 294 patients receiving oral digoxin as hospital inpatients. Fourteen percent of the population took either quinidine or verapamil concurrently with digoxin (mean quinidine dose = 857 +/- 397 mg/day, verapamil = 261 +/- 110 mg/day). Two regression models for digoxin oral clearance were used. Model 1 used the knowledge that digoxin is eliminated by both renal and nonrenal routes (TVCL = ClNR+m.CrCl, where TVCL is the population digoxin oral clearance, ClNR is the nonrenal clearance, and m is the slope of the line that relates creatinine clearance (CrCl) to digoxin clearance); model 2 used a more conventional regression approach with a simple series of multipliers. For both models, quinidine administration decreased population digoxin oral clearance by approximately 45% and verapamil therapy decreased population digoxin oral clearance by approximately 30%. These values are similar to those found by traditional drug interaction studies conducted in small patient or normal subject populations. Mixed-effect modeling can detect clinically relevant drug interactions and produce information similar to that found in traditional pharmacokinetic crossover study designs.

Adult↗
PubMed1995

Comparison of the costs associated with medical and surgical treatment of obesity.

BACKGROUND: We compared the long-term costs and outcomes of gastric bypass versus medical therapy (very low-calorie diet plus weekly behavioral modification) for obese patients. METHODS: A successful outcome was defined as the loss of at least one third of excess weight that was maintained for the duration of the study. A minimal cost was assigned: $3000 for medical and $24,000 for surgical treatment. A cost per pound of weight lost for all patients successfully monitored was calculated. The Federal Trade Commission recently asked all weight loss programs to report this cost for patients at least 2 years after therapy. RESULTS: A total of 201 patients entered surgical and 161 entered medical therapy. The surgical group was initially heavier (mean body mass index [kg/m2] +/- SE = 49.3 +/- 0.6 versus 41.2 +/- 0.7, p < 0.01), but each group's lowest mean body mass index was similar (31.8 versus 32.1, respectively). A significantly higher percentage of patients in the surgical versus the medical group were still successful at year 5: 89% versus 21%. The cost per pound lost for medical therapy exceeded the cost of surgical therapy in the sixth posttreatment year (both more than $250/pound). CONCLUSIONS: Surgical treatment appears to be more cost-effective at producing and maintaining weight loss. It is imperative that long-term follow-up studies be funded to definitely establish this finding.

Adolescent↗
PubMed1995

Drug interactions with antibacterial agents.

Antibacterial drugs, such as quinolones, macrolides, rifampin, isoniazid, and trimethoprim-sulfamethoxazole, can interact with other drugs in a wide variety of clinically significant ways. They are frequently administered with other prescription and nonprescription medications. Antibacterial agents may interact by causing a change in the pharmacokinetics or pharmacodynamics of a second drug. In other cases, the antimicrobial may be affected by the action of another drug. Interactions involving antimicrobials often result from alterations in the absorption of the antimicrobial from the gastrointestinal tract or changes in the hepatic metabolism or renal elimination of the drugs concurrently administered. While certain classes of antibacterial drugs are known to interact with many other drugs, the interaction potential of most classes of antimicrobials is not uniform among members of the class. This diversity in interaction potential provides the clinician with an opportunity to avoid potential interactions by means of appropriate drug selection. An understanding of the common, clinically significant drug interactions involving antibacterial agents will enable the physician to avoid unnecessary adverse drug reactions.

4-Quinolones↗
PubMed1994

Acute effects of sublingual nitroglycerin on hepatic blood flow in healthy volunteers.

Duplex sonography was used to assess the effects on hepatic blood flow after administering 0.6 mg nitroglycerin (NTG) sublingually to ten healthy volunteers. The study was a randomized, placebo-controlled, cross-over study in which subjects were studied on three separate occasions. Each visit involved administering either placebo or NTG followed by estimation of blood flow through a particular branch of the hepatic artery, portal vein, and hepatic vein every minute for 15 minutes after NTG and placebo administration. Two hours later, subjects were crossed over to the other treatment and the same vessel branch was again examined for 15 minutes. Total blood flow increased 7% in the portal vein and 27% in the hepatic vein during NTG treatment, but did not change significantly in the hepatic artery. Vascular resistance was increased in the hepatic artery and decreased in the portal and hepatic veins after NTG. Qualitatively, flow changed dramatically in the hepatic vein after NTG with the disappearance of normal retrograde flow. The results indicate that nitroglycerin effects hepatic blood flow through the portal and hepatic veins with a decrease in vascular resistance in the portal and hepatic veins and an increase in resistance in the hepatic artery.

Administration, Sublingual↗
PubMed1994

Liver blood flow, antipyrine clearance, and antipyrine metabolite formation clearance in patients with chronic active hepatitis and alcoholic cirrhosis.

Duplex scanning was used to measure liver blood flow (hepatic artery and main branches of the portal and hepatic veins) in six healthy subjects, five cirrhotic patients, and six hepatitis patients. Antipyrine clearance and formation clearances to its metabolites were also measured. Compared with healthy control subjects, cirrhotic patients had a lower hepatic vein blood flow (-76%, P < 0.05). This was due primarily to a lower portal vein blood flow (-36%, NS). A statistically significant difference in liver blood flow between patients with hepatitis and normal subjects was not detected. Antipyrine half-life, clearance, and the area under the serum drug concentration vs time curve were significantly different in cirrhotic patients compared with the healthy subjects (mean +/- s.d.-healthy controls: t1/2 = 13.7 +/- 3.0 h, CL = 30.0 +/- 8.6 ml h-1 kg-1, AUC = 549 +/- 139 mg l-1 h; cirrhotic patients: t1/2 = 32.4 +/- 1.7 h, CL = 12.3 +/- 2.1 ml h-1 kg-1, AUC = 1061 +/- 218 mg l-1 h; P < 0.008). Antipyrine half-life, clearance, and the area under the serum drug concentration vs time curve were not significantly different in hepatitis patients compared with the healthy subjects (hepatitis patients: t1/2 = 14.3 +/- 3.7 h, CL = 29.3 +/- 8.5 ml h-1 kg-1, AUC = 498 +/- 142 mg l-1 h). The volume of distribution of antipyrine was similar in all three groups of subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Influence of dietary sodium restriction on lipid metabolism.

The possible increase in total and low-density lipoprotein cholesterol following severe restriction of dietary NaCl was reported in 1990 and and 1991 from three experiments, one in the United States and two in Germany. Each of these experiments lasted only 1 week. To evaluate the clinical side effects we analyzed data collected from patients who completed a course of NaCl-restricted weight reduction at the Duke Diet and Fitness Center. Observations of lipid changes are not available for periods of less than 3 weeks; however, we were able to collect data on lipid and lipoprotein changes from 556 participants 25 days after they were referred for weight reduction. Total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels returned to normal in the majority of obese patients. In our slightly longer observation period in patients on a 1000 mg NaCl restricted diet we found no evidence of hyperlipidemic side effects. We believe that the hyperlipidemia resulting from severe sodium restriction in non-hypertensive, normal-weight individuals is not relevant to the problem of nonpharmacological and diuretic treatment of obese hypertensive patients. In clinically healthy, normal-weight, normotensive individuals severe salt restriction serves no practical or therapeutic purpose.

Cholesterol↗
PubMed1992

Accuracy of duplex scanning for measurement of arterial volume flow.

This study examined the accuracy of duplex ultrasound measurements of volume flow in a baboon model. Volume flow (Vf) through the external iliac artery was calculated from measurements of blood velocity averaged over several cardiac cycles (time-averaged velocity [TAV]) and vessel cross-sectional area (A) measured from the B-mode image: Vf = TAV x A. Fourteen anesthetized baboons were studied with a duplex scanner with a 7 MHz imaging transducer and 5 MHz pulsed Doppler. B-mode ultrasound measurements of external iliac artery diameters (2.5 +/- 0.2 mm) were used for calculation of cross-sectional area. Timed blood collections obtained through a cannula inserted into the common femoral artery and TAV measurements were obtained simultaneously during 6 to 15-second intervals. These measurements were repeated three to five times per animal with different flow rates each time. Flow rates ranged from 56 to 280 ml/min (170 +/- 54 ml/min). Average velocity was 55 +/- 17 cm/sec. There was no significant difference between the two methods of volume flow measurement (Student t test). Linear regression analysis revealed a high degree of correlation (r = 0.90, slope 0.95, and p = 0.0001). The absolute percentage error was 13% +/- 8%. Volume flow measured by duplex scanning correlates highly with timed blood collections. This method has potential application for the evaluation of diseased arteries and bypass grafts whose rates of flow and waveform patterns are similar to those of this experiment.

Animals↗
PubMed1991

The effects of oral nifedipine on hepatic blood flow in humans.

Duplex ultrasonography was used to measure changes in hepatic blood flow in 13 healthy volunteers after they received single doses of 10 mg oral nifedipine and placebo. Blood flow was measured in the hepatic artery and branches of the portal and hepatic veins at baseline and 0.3, 0.6, 1, 1.5, 2, 3, 4, and 5 hours after drug administration. Cardiac output was also measured at baseline and 1, 2, and 3 hours after dosing. Blood flow initially increased in all three vessels 0.6 hour after administration of nifedipine (29%, 56%, and 31% in the hepatic artery, hepatic vein, and portal vein, respectively) compared with placebo. Flow rapidly returned to baseline in the hepatic artery and hepatic vein, whereas it appeared to remain elevated through 3 hours in the portal vein. Nifedipine administration resulted in an increase in cardiac output of 26%, 22%, and 14% above placebo at 1, 2, and 3 hours, respectively. No significant differences were detected in the systolic, diastolic, or mean arterial blood pressures after nifedipine or placebo. This study demonstrates that nifedipine increases hepatic blood flow in a transient nature and systemic hemodynamic parameters do not necessarily reflect specific organ responses. The nifedipine-induced change in blood flow should be considered when nifedipine is coadministered with high-clearance drugs, because systemic availability may be increased.

Administration, Oral↗
PubMed1991

Disposition of drugs in cystic fibrosis. II. Hepatic blood flow.

To determine whether the increased clearance of high extraction-ratio drugs in cystic fibrosis is caused by an increase in hepatic blood flow, the blood flow in main branches of the hepatic vein and portal vein was measured by use of noninvasive duplex ultrasound scanning in 10 adult subjects with cystic fibrosis and in 10 healthy age-, gender-, and height-matched control subjects. No statistically significant differences between subjects with cystic fibrosis and control subjects were detected in either the hepatic vein (217 +/- 103 ml/min for subjects with cystic fibrosis versus 211 +/- 135 ml/min for control subjects) or the portal vein (205 +/- 114 ml/min for subjects with cystic fibrosis versus 190 +/- 101 ml/min for control subjects) blood flows. These data indicate that a large (greater than or equal to 100%) increase in the clearance of high extraction-ratio drugs in patients with cystic fibrosis is unlikely to be primarily caused by an increase in hepatic blood flow. It is probable that alternative mechanisms such as enhanced secretory or metabolic pathways account in large part for increases in clearance of high extraction-ratio drugs.

Adolescent↗
PubMed1990

Estimation of hepatic blood flow in branches of hepatic vessels utilizing a noninvasive, duplex Doppler method.

The measurement of hepatic blood flow by indirect methods such as indocyanine green clearance has several limitations. The duplex Doppler offers the potential for noninvasive, real-time measurement of blood flow and has been employed in the evaluation of arterial disease in a variety of vascular beds. We evaluated Doppler ultrasound estimation of blood flow in branches of the hepatic artery, hepatic vein, and portal vein in 12 healthy subjects on two separate days. In vitro accuracy of the scanner was assessed using phantom targets of known diameter and velocity. Blood velocity and vessel diameter measurements were obtained five times over a period of 2 hours. No significant differences were seen in velocity or blood flow measurements within or between days. The interday coefficients of variation, which include intrasubject variability, were 10-15% and 14-20% for velocity and blood flow measurements, respectively. This study demonstrates the potential utility of Doppler ultrasound to detect intrinsic, drug, or disease-induced changes in hepatic blood flow.

Adult↗
PubMed1990

Single and multiple doses of oral cimetidine do not change liver blood flow in humans.

Liver blood flow was measured in 10 healthy men for 6 hours after single (300 mg) and multiple (300 mg every 6 hours for 5 days) oral doses of cimetidine. Blood flow measurements were determined in the superior mesenteric and hepatic arteries and in the intrahepatic branches of the portal and hepatic veins by use of a duplex Doppler ultrasound technique. Compared with baseline measurements obtained before drug administration, cimetidine treatment did not change blood flow in any of the four blood vessels. Cimetidine serum concentrations and pharmacokinetic parameters were similar to those reported in other studies conducted in healthy adults. The findings of this study indicate that single and multiple 300 mg doses of oral cimetidine do not change liver blood flow.

Administration, Oral↗
PubMed1990

Therapeutic drug monitoring reduces toxic drug reactions: a meta-analysis.

Therapeutic drug monitoring (TDM) is commonly employed to optimize the dosing of certain drugs, including digoxin, aminoglycosides, theophylline, and phenytoin. Studies were reviewed in order to (a) evaluate the effect of TDM on the occurrence of toxic drug reactions (TDRs) and (b) identify factors that may modify or invalidate the relationship. In 14 studies, monitored patients suffered fewer toxic drug reactions than nonmonitored patients (odds ratio = 0.35, 95% confidence interval, 0.13 to 0.89). The average effect size was larger in studies that utilized a control group for comparisons rather than a before-and-after study design. TDM appeared to be most beneficial for patients taking theophylline or digoxin. Issues that must be addressed in future TDM service evaluations include (a) study design, (b) adverse patient selection, (c) insufficient sample size, (d) incomplete or inconsistent description of the TDM service, and (e) incomplete, inconsistent, or absent description of criteria for reporting TDRs.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1989

Glipizide pharmacokinetics: effects of age, diabetes, and multiple dosing.

Aging and disease may contribute to alterations in drug pharmacokinetics. The purpose of this study was to determine the effects of aging, the presence of NIDDM, and multiple dosing on the pharmacokinetics of glipizide, an oral hypoglycemic drug. Ten healthy young men (under age 25), ten healthy older men (over age 65) and 15 older diabetic men ingested a single 5 mg tablet of glipizide after an overnight fast. Blood samples for measurement of serum glipizide were obtained over the next 24 hours. The study was repeated in the diabetics after 2 weeks of daily therapy. The mean values for Tmax (range 2.0-2.5 hours), Cmax (385-465 micrograms/l), and t1/2 (4.0-4.2 hours) were not significantly different in the three populations after single doses of glipizide. Several subjects in each population had slow absorption, with peak concentrations delayed for up to 12 hours. Only one elderly diabetic subject had evidence of drug accumulation at steady state. AUC, Cl, Vss and V area were not significantly different in the three populations or at steady state, but there was a trend for AUC to be smaller and each of the other parameters to be increased in the older diabetics. The young subjects had a significantly higher fp (0.83%) than either of the two elderly groups (0.55-0.64%), but Cl int did not differ between groups. Age, diabetes, and multiple dosing appear to have little effect on the pharmacokinetics of glipizide and should have little influence on the clinical response to this drug.

Adult↗