Biomedical subjects

D E Martin

Publications and source records attributed to D E Martin.

At least 37 records · Page 2Linked to original sources

PubMed1998

SK&F107647: a synthetic hematoregulatory peptide in patients with solid tumor malignancies: a phase I trial.

SK&F107647 is a synthetic hematoregulatory peptide (HP) increases both the number and function of progenitor cells, enabling improved survival after lethal myelosuppression, lethal fungal infection, and lethal herpes simplex virus infection in murine models. This Phase I single-blind placebo-controlled dose-rising crossover trial examined the efficacy of SK&F107647 in patients who had incurable solid tumor malignancies. Sixteen patients were treated. Six adverse events in 3 patients were considered to be possibly related to SK& F107647; all were mild to moderate in nature (mild nervousness and agitation at 0.01 ng/kg, moderate fever and mild nausea at 0.1 ng/kg, elevated hepatic enzymes at 0.1 ng/kg, and mild vomiting at 1.0 ng/kg). Plasma half-life was 2.44 hours (+/-1.07 standard deviation). The observed area volume of distribution was 16.7 L (+/-7.7 standard deviation) and clearance was 5.04 L/hour (+/-1.83 standard deviation). When administered as a single 2-hour intravenous infusion at doses ranging from 0.01 to 100 ng/kg, SK&F107647 is safe and well tolerated.

Adjuvants, Immunologic↗

PubMed1998

Effects of a functional knee brace for ACL insufficiency during treadmill running.

PURPOSE: To assess the effects of a functional knee brace (FKB) for anterior cruciate ligament insufficiency (ACLI) on physiological and perceptual parameters during treadmill running. METHODS: Thirteen ACLI subjects (time since injury, 5.8 +/- 5.3 yr), performed an incremental test to exhaustion and two constant load 20-min tests, one at an intensity below lactate threshold (bLT), and the other at an intensity above LT (aLT) each with and without their FKB. RESULTS: Bracing had no effect on peak variables except for higher ratings of perceived exertion at the legs (RPE-L) at the velocities associated with a blood lactate concentration [HLa] of 4.0 mM and at peak. Bracing had no effect when exercising at bLT but did significantly alter the metabolic profile developed during the performance of the aLT tests (83 +/- 0.03% VO2peak). In particular, FKB resulted in elevated blood [HLa] (23%), VO2 (4%), VE (12%), VCO2 [corrected] (7%), and VE/VO2 (7%). HR and slow component VO2 did not differ between the brace and no brace aLT tests. RPE-L and RPE-knee were significantly elevated during aLT when the brace was worn. Suspected mechanisms include alterations in muscle recruitment patterns and/or occlusion. CONCLUSIONS: When ACLI individuals wear a FKB during high intensity straight-ahead running exercise of long duration, physiological parameters are affected.

Adolescent↗

PubMed1998

Effect of ranitidine on the pharmacokinetics of orally administered eprosartan, an angiotensin II antagonist, in healthy male volunteers.

OBJECTIVE: To assess the effect of ranitidine on the pharmacokinetics of eprosartan in healthy male volunteers. DESIGN: Single-center, randomized, open-label, two-period, period-balanced, crossover study. PATIENTS: Seventeen healthy men aged 19 to 43 years. INTERVENTION: In each period (separated by a > or = 7 d washout), subjects received a single 400-mg oral dose of eprosartan alone, or a single oral dose of eprosartan 400 mg and ranitidine 150 mg on day 4 after 3 days of ranitidine 150 mg twice daily. Serial pharmacokinetic samples were obtained for up to 24 hours following eprosartan dosing. MAIN OUTCOME MEASURES: Plasma and urine eprosartan concentrations during each treatment session. RESULTS: Eprosartan maximum concentration (Cmax), the AUC from time-zero to the last quantifiable concentration (AUC0-t), and renal clearance (Cl(r)) values were approximately 7%, 11%, and 4% lower, respectively, when administered with ranitidine compared with eprosartan alone. The 95% CIs for the ratio of eprosartan plus ranitidine compared with eprosartan alone were 0.81 to 1.07, 0.77 to 1.03, and 0.64 to 1.43, for Cmax, AUC0-t, and Cl(r), respectively, indicating no statistically significant difference between regimens. CONCLUSIONS: Repeated doses of ranitidine did not have a marked effect on the single-dose pharmacokinetics of eprosartan.

Acrylates↗

PubMed1997

Eprosartan, an angiotensin II receptor antagonist, does not affect the pharmacodynamics of glyburide in patients with type II diabetes mellitus.

The potential for eprosartan, a nonbiphenyl tetrazole angiotensin II receptor antagonist, to affect the 24-hour plasma glucose profiles in type II diabetic patients treated with glyburide was investigated in this randomized, placebo-controlled, double-blind (eprosartan-placebo phase only), two-period, period-balanced, crossover study. All patients received a stable oral dose (3.75-10 mg/day) of glyburide for at least 30 days before the first dose of double-blind study medication was administered. Patients were randomized to receive either 200-mg oral doses of eprosartan twice daily or matching oral placebo doses concomitantly with glyburide for 7 days during each treatment period. After a minimum washout period of 14 days, patients were crossed over to the alternate treatment. Serial samples to measure glucose concentrations in plasma were collected over a 24-hour period on the day before administration of eprosartan or placebo and again on day 7. Mean glucose concentrations were comparable between treatment groups before administration of eprosartan or placebo. The point estimate (90% confidence interval) for the ratio of the average mean 24-hour plasma glucose concentrations of eprosartan + glyburide to placebo + glyburide after 7 days of administration was 0.96 (0.90, 1.01). Eprosartan did not significantly alter the 24-hour plasma glucose profile in patients with type II diabetes mellitus who were previously stabilized on glyburide.

Acrylates↗

PubMed1997

Effect of fluconazole on the pharmacokinetics of eprosartan and losartan in healthy male volunteers.

OBJECTIVE: To investigate the effect of steady-state fluconazole administration on the disposition of eprosartan, losartan, and E-3174. METHODS: Sixteen healthy male subjects received 300 mg eprosartan every 12 hours, and 16 received 100 mg losartan every 24 hours on study days 1 to 20. All 32 subjects received 200 mg fluconazole every 24 hours beginning on day 11 and continuing through day 20. Serial blood samples were collected over one dosing interval on study days 10 and 20 for measurement of plasma concentrations of eprosartan, losartan, and E-3174 (the active metabolite of losartan). RESULTS: There was no significant difference in eprosartan area under the concentration-time curve from time 0 to time of last quantifiable concentration [AUC(0-t)] or maximum concentration (Cmax) when administered alone and with fluconazole. After concomitant administration with fluconazole, losartan AUC(0-t) and Cmax were significantly increased 66% and 30%, respectively, compared with those values for losartan alone. The AUC(0-t) and Cmax for E-3174 were significantly decreased 43% and 56%, respectively, after administration of losartan with fluconazole. CONCLUSIONS: Fluconazole significantly increases the steady-state AUC of losartan and inhibits the formation of the active metabolite of losartan, E-3174. In contrast, fluconazole administration has no effect on the steady-state pharmacokinetics of eprosartan.

Acrylates↗

PubMed1997

Relevance of oral intake and necessity to void as ambulatory surgical discharge criteria.

Discharge criteria used in the outpatient setting of a 500-bed academic medical center were evaluated by nursing staff in two ambulatory units to determine validity in identifying patient readiness for discharge. Criteria categories include temperature, circulation, activity and mental status, pain, bleeding, voiding, and oral intake. The hospital course and post-discharge course of a convenience sample of 248 ambulatory subjects was drawn from consecutive patients. Post-discharge recovery outcomes identified by the telephone assessment included recovery, complications, necessity of further medical treatment, and the need to return to a medical facility. The descriptive results showed the safety of the seven discharge criteria. Voiding and oral intake were related to prolonged stays in the ambulatory units. Approval was granted by the Hospital Policy Board to relax discharge criteria, and make voiding and oral intake optional for patients. A stage II follow-up study of 1,582 patient subjects was conducted using the new criteria of voluntary voiding and oral intake. The average ambulatory stay was reduced 50 minutes after voiding and oral intake were made optional.

Ambulatory Surgical Procedures↗

PubMed1997

Lack of effect of eprosartan on the single dose pharmacokinetics of orally administered digoxin in healthy male volunteers.

AIMS: To study the effect of eprosartan, a nonbiphenyl tetrazole angiotensin II receptor antagonist, on digoxin pharmacokinetics in a randomized, open-label, two period, period balanced crossover study in 12 healthy men. METHODS: Each subject received a single 0.6 mg oral dose of digoxin (Lanoxicaps 0.2 mg/capsule, Glaxo Wellcome) alone or following 4 days of dosing with eprosartan 200 mg orally every 12 h. Each study period was separated by a 14 day washout interval. Serial blood samples were obtained for up to 96 h after each digoxin dose for determination of digoxin pharmacokinetics. The effect of eprosartan on digoxin pharmacokinetics was assessed through an equivalence-type approach using AUC(0, t') as the primary endpoint. RESULTS: For AUC(0, t'), the ratio of digoxin+eprosartan: digoxin alone was 0.99 with a 90% confidence interval (CI) of [0.90, 1.09]. For Cmax, the ratio was 1.00 with a 90% CI of [0.86, 1.17]. tmax was similar for both regimens. Both regimens were safe and well tolerated. CONCLUSIONS: Based on AUC and Cmax data, it can be concluded that eprosartan has no effect on the pharmacokinetics of a single oral dose of digoxin.

Acrylates↗

PubMed1997

Paroxetine does not affect the cardiac safety and pharmacokinetics of terfenadine in healthy adult men.

Potent CYP3A4 inhibitors such as ketoconazole can cause dangerous increases in plasma concentrations of the H-1 antagonist terfenadine. In light of recent reports that the selective serotonin reuptake inhibitor antidepressants may be weak CYP3A4 inhibitors, this study was designed to investigate the effects of paroxetine on the pharmacodynamic and pharmacokinetic profile of terfenadine. Twelve healthy male volunteers participated in a randomized open-label, two-period, steady-state crossover study. Terfenadine (60 mg twice daily for 8 days) was administered alone and with paroxetine at steady state (20 mg once daily for 15 days, with terfenadine on days 8 through 15). Extensive electrocardiogram monitoring was conducted throughout, and terfenadine and carboxyterfenadine pharmacokinetics were assessed at the end of each treatment period. One subject withdrew because of adverse experiences related to paroxetine, but the other 11 subjects completed the study uneventfully. On the final day of coadministration, the rate-corrected QT interval (QTc) was unaltered compared with terfenadine dosed alone; maximum QTc values (mean [SEM]) were 404 (4) and 405 (5) msec, respectively. Terfenadine pharmacokinetics were also unchanged; geometric mean steady-state area under the curve (AUC)tau values were 30.0 ng.hr/mL during coadministration compared with 30.8 ng.hr/mL when dosed alone (p > 0.05). The corresponding Cmax values were 3.68 and 3.64 ng/mL (p > 0.05). There was, however, a small (on average 17-20%), unexplained reduction in the steadystate Cmax and AUCtau of carboxyterfenadine during coadministration with paroxetine. In conclusion, paroxetine does not affect the pharmacokinetics or cardiovascular effects of terfenadine. The small reduction in carboxyterfenadine plasma concentrations is unlikely to be important clinically.

Adult↗

PubMed1997

Role of hyperpronation as a possible risk factor for anterior cruciate ligament injuries.

OBJECTIVE: The purpose of this study was to examine the relationship between hyperpronation and the occurrence of noncontact injury to the anterior cruciate ligament (ACL). DESIGN AND SETTING: Subjects were categorized as either ACL injured (ACLI) or ACL uninjured (ACLU). All ACLI subjects received their injuries from a noncontact mechanism. To justify using the ACLI subjects' uninjured legs as representative of their preinjury state, a t test was used to compare the differences between the left and right foot for the ACLU group on both measurements. Based on the results of the t test, a regression analysis was performed to determine whether group membership could be predicted from navicular drop. All measures were performed in a university athletic training room. SUBJECTS: Fourteen ACLI subjects (age = 21.07 +/- 0.83 yr, ht = 174.81+/-8.29 cm, wt = 72.32+/-13.47 kg) and 14 ACLU subjects (age = 21.14+/-2.03 yr, ht = 177.35+/-11.31 cm, wt = 72.99+/-14.81 kg) participated. MEASUREMENTS: Hyperpronation was assessed via the navicular drop test and the calcaneal stance test. RESULTS: No significant difference (p > .05) between feet for the navicular drop test was found. However, there was a significant difference (p < .05) between feet for the calcaneal stance test, and, thus, this measure was not used in the regression analysis. Using the navicular drop score, the regression analysis was unable to predict group membership. CONCLUSIONS: Hyperpronation as measured by the navicular drop test was not a predictor of ACL injury, and, thus, may not be a predisposing factor to noncontact ACL injuries.

Journal Article↗

PubMed1996

Effects of ofloxacin on the pharmacokinetics and pharmacodynamics of procainamide.

Procainamide is a class I antiarrhythmic agent that undergoes active tubular secretion through the organic cation transport system, with approximately 50% of a dose excreted in the urine as unchanged drug. The remainder is metabolized to an active metabolite, n-acetyl procainamide (NAPA). Ofloxacin is a fluoroquinolone antibiotic that is excreted in the urine as unchanged drug via active tubular secretion and glomerular filtration. To test the hypothesis that ofloxacin may interfere with the renal elimination of procainamide, 9 healthy volunteers were randomly assigned to receive 1 g of oral procainamide as a single dose with or without pretreatment with 400 mg of ofloxacin twice a day for 5 doses. Blood and urine samples were obtained and pharmacokinetic parameters for procainamide were determined for each treatment period. Standard 12-lead and signal-averaged electrocardiographic recordings were used for pharmacodynamic analysis. The mean area under the concentration-time curve (AUC) and peak plasma concentration (Cmax; mug/mL) for procainamide increased by 27% and 21%, respectively, and the plasma clearance for procainamide decreased by an average of 22% with coadministration of ofloxacin. Ofloxacin did not significantly influence the pharmacokinetics of NAPA, nor were pharmacodynamics of procainamide significantly affected by coadministration of ofloxacin. These results suggest that procainamide concentrations should be monitored closely when coadministered with ofloxacin.

Administration, Oral↗

PubMed1996

Interspecies pharmacokinetics of a novel hematoregulatory peptide (SK&F 107647) in rats, dogs, and oncologic patients.

PURPOSE: To study the pharmacokinetics of SK&F 107647, a novel hematoregulatory agent, in rats, dogs, and patients with non-lymphoid solid tumor malignancy. METHODS: Sprague Dawley rats and beagle dogs (n = 6 each; 3 M, 3 F) were given 25 mg/kg of SK&F 107467 as an iv bolus injection, and patients (n = 6; 4 M, 2 F) received 100 mg/kg as a 2 hour iv infusion. Plasma samples were assayed for drug using either HPLC (rat and dog) or RIA (human). RESULTS: In each species the plasma clearance (CL) of SK&F 107647 was low in relation to hepatic blood flow, and the volume of distribution (Vd ss) was reflective of distribution to extracellular body water. The plasma CL in humans was near that of average glomerular filtration rate. Using allometric equations for interspecies scaling (Y = a.W(b)), body-weight normalized human pharmacokinetic data were reasonably predicted using either the body weight normalized rat or the dog data. The allometric exponents (b) for CL, Vd(ss), and T(1/2) of SK&F 107647 were 0.63, 0.94, and 0.29, respectively. CONCLUSIONS: Use of a limited pool of available animal data allowed for reasonable predictions of human pharmacokinetics of SK&F 107647.

Adjuvants, Immunologic↗

PubMed1996

Retrospective evaluation of graded stress examination of the ankle.

Stress radiography of the ankle commonly is used to evaluate talar tilt in patients with a history of inversion ankle sprains. Manual and instrumented procedures have been variously described in the literature. No reports have documented normative talar tilt as measured using the Telos ankle stress device in a large clinical population. In addition, little has been done to examine the value of using graded displacement forces compared with a single displacement force. Bilateral Telos examinations from 113 consecutive patients taken during a 4-year period were evaluated for this study. No measurable talar tilt was observed in 65.8% of the ankles in this study. Talar tilt ranged from 1.7 degrees to 24.9 degrees in injured ankles. In patients with quantifiable talar tilt, all had greater talar tilt at the 15 kPa force than at all other forces. Because of the variability in talar tilt in injured and comparison ankles, clinical conclusions regarding injury severity cannot be made on measured talar tilt alone. The analysis suggests that inversion stress examination is helpful in documenting gross talar instability, but the discriminant value of the procedure to determine the anatomy and severity of lateral ligament injury is tenuous.

Adolescent↗

PubMed1996

Hot and cold whirlpool treatments and knee joint laxity.

OBJECTIVE: To examine the influence of clinical applications of heat and cold on arthrometric laxity measurements of the knee. DESIGN AND SETTING: The knee joint was submersed 4 inches above the patella in hot and cold whirlpools containing water of 40 degrees C and 15 degrees C for 20 minutes. A control was also performed to provide a neutral temperature comparison group. SUBJECTS: Eight males and 7 females with no history of knee injury. MEASUREMENTS: The knee was maintained at 20 degrees flexion and tibial rotation at either 15 degrees of internal rotation, 15 degrees of external rotation, or a neutral measurement with a modified KT-1000 knee arthrometer equipped with an LCCB-50 strain gauge that allowed for the digital display of the applied distraction forces. Order of testing was counterbalanced. Subjects underwent each condition once, with each trial on separate days. Two 2-factor repeated measure analyses of variance were performed to test effects of temperature on knee laxity for the dependent measure (laxity at 89N and at maximal displacement forces). RESULTS: There was no thermal effect on displacement at 89N nor at maximal distraction (p > .05). A difference was found with respect to test position, with external rotation showing a greater displacement than internal rotation (p < .05). CONCLUSIONS: There was no evidence that hot or cold whirlpool treatments alter knee laxity as assessed with the KT-1000. Rotation of the tibia does affect the magnitude of displacement of the knee. Further research is needed to determine if these findings can be applied to ACL-deficient or ACL-reconstructed knees.

Journal Article↗

PubMed1996

Alternatives to the closing base wedge osteotomy.

The closing base wedge osteotomy remains a viable option in treating hallux valgus deformities with high intermetatarsal angles; however, the procedure can be technically difficult to perform and has been associated with a fair number of potential complications. As a result, a variety of osteotomies have been introduced and modified over the years that may serve as alternatives. Though all procedures possess complications, several of these alternatives do offer some significant advantages over the closing base wedge osteotomy.

Hallux Valgus↗

PubMed1995

Effect of ACL Reconstruction and Tibial Rotation on Anterior Knee Laxity.

The anterior cruciate ligament (ACL) is the primary restraint to anterior translation of the tibia on the femur. Research suggests that resistance to anterior translation changes as the tibia is rotated internally and externally. This study assessed the degree to which ACL reconstruction and tibial rotation affects anterior knee laxity. Nine subjects with ACL lesions and functional instabilities participated in the study. Subjects were measured 1 to 10 days before surgery and 6 to 8 months after ACL reconstruction using the KT-1000 knee arthrometer. A mechanical leg stabilizer was used to assess anterior translation at 20 degrees of knee flexion in three positions: internal rotation of 15 degrees , neutral, and external rotation of 15 degrees . Subjects were measured at 89 and 67 N of anterior force. Data were analyzed with a three-factor (test x position x force) repeated measures ANOVA. Following surgery, reduction in laxity (mm) for the three positions (internal rotation, neutral, and external rotation) was 1.9, 2.8, and 3.4, respectively, at 89 N and 1.5, 2.0, and 2.6, respectively, at 67 N. The degree of reduction in laxity (presurgery to postsurgery) was dependent upon rotation and force, and was greatest in external rotation and least in internal rotation pre- to postsurgery. We concluded that ACL reconstruction using a patellar tendon graft significantly decreased anterior tibial translation at all three positions, but a greater amount of reduction was observed postsurgically at the externally rotated position. This supports the theory that mechanical blocks and secondary restraints such as a taut mid-third of the iliotibial tract may interfere with clinical laxity tests in some positions of tibial rotation. Fixing the tibia in an externally rotated position may decrease the effect of secondary restraints and improve sensitivity in testing for ACL laxity.

Journal Article↗

PubMed1994

Glucose emergencies: recognition and treatment.

Millions of Americans have pathologies related to glucose regulation. Many of these individuals have diagnosed diabetes. There are, however, countless others who are unaware that they have glucose regulation disorders. Athletic trainers may find themselves called upon to work with individuals with documented and undocumented disorders. The purpose of this article is to define three primary glucose emergencies (diabetic ketoacidosis, diabetic hyperosmolar state, and hypoglycemia) and discuss the treatment for each. Attention is focused on signs and symptoms which allow the athletic trainer to differentiate between the conditions.

Journal Article↗

PubMed1994

Emergency medicine and the underage athlete.

Most high school and some collegiate athletes are legal minors. In civil matters, the law treats minors (usually individuals under the age of 18 years) uniquely. Limitations exist on a minor's ability to enter into contracts, make determinations regarding medical care, and bear responsibility for personal actions. Medical professionals are often unclear on matters relating to the provision of medical care to minors. The purpose of this discourse is to present selected legal issues in the context of two fictional case studies. Case 1 presents issues regarding the definition of emergency medical conditions and the related emergency medical doctrine. Case 2 provides an example of an acute medical concern which fails to fall under emergency medical classification but rather provides a context for discussing the mature minor doctrine. Both cases are analyzed in light of these doctrines in addition to other pertinent legal considerations.

Journal Article↗

PubMed1991

Thiopental as an adjunct to hypothermia for EEG suppression in infants prior to circulatory arrest.

Fifteen infants were studied to evaluate the effect of profound hypothermia (16 degrees C to 18 degrees C) and hypothermia plus thiopental on the electroencephalogram (EEG) prior to circulatory arrest. Mean patient age and weight were 5.5 +/- 1.2 months and 4.9 +/- 0.3 kg, respectively. After core cooling on cardiopulmonary bypass (CPB), all patients received thiopental, 8 mg/kg, 5 minutes prior to circulatory arrest. Satisfactory EEG recordings were obtained for 9 patients, and serum thiopental concentration was measured in 12 patients. Hypothermia (mean venous return temperature, 17.8 degrees C +/- 1.6 degrees C) alone was associated with persistent cerebral electrical activity in 8 of 9 patients (89%). The addition of thiopental, 8 mg/kg, produced an isoelectric EEG in 6 of these 8 patients (75%). Mean circulatory arrest duration was 44 +/- 4 minutes. EEG activity resumed after reinstitution of CPB in all patients. Serum thiopental concentration at the end of CPB was negligible. It is concluded that hypothermia alone often may not produce EEG isoelectricity, and that the associated cerebral metabolic activity may be suppressed by adjunctive use of thiopental.

Blood Proteins↗