Biomedical subjects

D J Edwards

Publications and source records attributed to D J Edwards.

At least 55 records · Page 3Linked to original sources

PubMed1995

Skin closure using nylon and polydioxanone: a comparison of results.

Nylon vertical mattress sutures and interrupted subcuticular polydioxanone (PDS) sutures have been used for skin closure. The complications and cosmetic results of each have been noted in a prospective trial of 93 hip wounds. When nylon sutures are used there is an increased incidence of erythema and the final scar is less cosmetically attractive. Interrupted PDS sutures take longer to insert but have few complications and are recommended in both the young and elderly patients.

Adult↗

PubMed1994

Problems in regaining full extension of the knee after anterior cruciate ligament reconstruction: does arthrofibrosis exist?

A total of 194 patients was reviewed after ACL reconstruction using a patellar tendon graft or Leeds-Keio prosthesis supplemented with a MacIntosh lateral substitution. There were five groups of patients: patellar tendon with cast immobilisation in flexion (n = 34); restricted extension but no cast (n = 40); immediate full extension (n = 40); 40); immediate full extension with notch widening (n = 40); Leeds-Keio ligament prosthesis (n = 40). The incidence of a click or a block to extension requiring operation ranged from 59% following cast immobilisation to 2.5% with the Leeds-Keio ligament. The incidence was significantly less when a Leeds-Keio prosthesis was used, and these problems may be associated with biological materials only. Restricting extension after operation significantly increased the loss of extension, confirming the work of others. Loss of extension was due to a mechanical block in all cases examined arthroscopically. All were relieved by arthroscopic surgery, and no case of flexion contracture or arthrofibrosis was encountered. A simple mechanical block to extension caused by a Cyclops lesion should be clearly distinguished from flexion contracture and arthrofibrosis, conditions which are probably extremely rare and overdiagnosed.

Adolescent↗

PubMed1994

Adrenal medullary adaptations and cardiovascular regulation after 6-hydroxydopamine treatment in rats.

Experiments were conducted to assess the pattern of activation of adrenal medullary adrenaline (ADR) and noradrenaline (NA) chromaffin cells following damage to sympathetic neurons with 6-hydroxydopamine (6-HDA, 100 mg/kg per day for 7 days, s.c.). 6-HDA treatment resulted in a sustained elevation in urinary ADR excretion, suggesting that the adrenal medulla was continuously stimulated. Further evidence of neural stimulation of the adrenal medulla was demonstrated by a persistent elevation of adrenal medullary dopamine (DA) content, an indicator of catecholamine synthesis. The increase in synthetic rate was associated with a significantly augmented medullary NA and ADR content. However, NA content was elevated after only 1 day of treatment, whereas, ADR became elevated after the second day, a finding that suggests a differential activation of the two populations of chromaffin cells. Cardiac and kidney NA contents were reduced by 97 and 87%, respectively, and BP increments to stimulation of the thoracolumbar spinal cord of pithed rats (0.5 to 16 Hz) were attenuated by more than 75% by 6-HDA. Moreover, the residual BP responses were abolished by adrenalectomy. Thus the results indicate that the changes in adrenal CA disposition may be related to a greater reliance upon the adrenal medulla to maintain blood pressure (BP) following damage to sympathetic neurons, and further, the findings are consistent with the possibility that ADR and NA chromaffin cells are separately controlled.

Adrenal Medulla↗

PubMed1994

Evaluation of dosage-release formulations on inhibition of drug clearance: effect of sustained- and immediate-release verapamil on propranolol pharmacokinetic parameters.

Limited information exists regarding the influence of dosage-release formulation on inhibition of drug metabolism. Therefore, the purpose of this study was to evaluate the effect of immediate-release (IR) and sustained-release (SR) verapamil on the pharmacokinetic parameters of propranolol in 12 healthy men. IR propranolol, 160 mg, was administered alone (Phase A) and following either IR verapamil, 80 mg t.i.d., (Phase B) or SR verapamil, 240 mg q.d., (Phase C) in a randomized crossover fashion. Of the 12 subjects enrolled, only seven were able to be analyzed secondary to assay interference. Oral clearances for L-propranolol for Phases A, B, and C were 198 +/- 70, 156 +/- 76, and 143 +/- 85 L/h, respectively. Oral clearances for D-propranolol for Phases A, B, and C were 203 +/- 96, 172 +/- 96, and 152 +/- 102 L/h, respectively. No significant differences were observed. However, when the verapamil groups (Phase B and C) were combined and compared to Phase A, a significant decrease in clearance for propranolol isomers was observed. In conclusion, due to the unexpected low numbers of patients evaluated, no significant differences in oral clearance were observed among the three treatment phases. However, there is a trend suggesting that SR verapamil had the greatest effect on propranolol clearance, which may warrant caution when changing from one formulation to another.

Adult↗

PubMed1994

Vancomycin pharmacokinetics in a patient population: effect of age, gender, and body weight.

The effects of age, gender, and body weight on the pharmacokinetics of vancomycin were examined using data collected as part of routine therapeutic drug monitoring in patients. One thousand eighty-five sets of steady-state peak and trough serum concentrations obtained from 704 different patients were used to calculate elimination rate constant (k), volume of distribution (V), and clearance (Cl) using a one-compartment model. The median half-life of vancomycin was 6.5 h. Clearance was significantly correlated with creatinine clearance as estimated using the Cockcroft-Gault equation [Cl = 0.771 (Clcr) + 18.9; r = 0.63]. V averaged 0.69 L/kg ideal body weight (IBW) with increased values in females, patients over age 60, and obese patients. V ranged from 0.58 L/kg IBW in normal weight males under age 40 to 1.17 L/kg IBW in obese females over age 60. V was not different in underweight patients and those of normal weight (43.8 vs. 44.4 L). Regression analysis indicated that V was more predictable in women than in men and that vancomycin distributed into excess body weight (EBW) to a greater extent in women. However, the correlation coefficients from multiple regression analysis of V with IBW, EBW, and age did not exceed 0.60, and the high root mean square error values of 11-15 L suggest considerable variability in V is not accounted for by these factors alone. Despite these limitations, dosing of vancomycin may be improved by adjusting initial estimates of V for patient age, gender, and obesity.

Adult↗

PubMed1994

Periosteal stripping in achondroplastic children. Little effect on limb length in 10 cases.

We present a prospective study of the results of periosteal stripping and division in 10 achondroplastic children. A single limb (femur and tibia) was operated on and the change in actual length of each bone and the percentage change in growth compared to that of the non-operated limb was measured by scanogram. The mean absolute increase in growth was small, measuring 3 mm for the femur and 2 mm for the tibia. There was no measurable growth difference after 18 months. This method of increasing limb length in achondroplastic children prior to definitive and extensive lengthening procedures is not recommended.

Achondroplasia↗

PubMed1993

Evaluation of the pharmacokinetic and pharmacodynamic interaction between quinidine and nifedipine.

Quinidine and nifedipine appear to be subject to metabolism by the same isozyme of cytochrome P-450. In addition, both drugs have been reported to alter the pharmacokinetics of other compounds. To investigate a potential interaction, 10 healthy subjects (five male, five female) received quinidine sulfate (200 mg orally), nifedipine (20 mg orally), or the combination of both drugs every 8 hours for 4 doses using a randomized, cross-over study design with a 2-week washout period between treatments. Drug concentration, heart rate, and mean arterial pressure were measured at frequent intervals after the final dose. Quinidine concentrations were unchanged by the co-administration of nifedipine. Nifedipine area under the curve (AUC0-8) increased 36.6% from 333 to 455 micrograms.hr/L (P < .05) after quinidine administration. Heart rate was significantly higher in the nifedipine-quinidine treatment at 0.5, 1.0, 1.5, and 2.0 hours when compared with either drug alone. The maximum increase in heart rate (17.9 beats/minute) occurred at 0.5 hours after nifedipine administration and was significantly correlated with serum concentrations at that time (r = .78). These results suggest that quinidine inhibits nifedipine metabolism, and this pharmacokinetic interaction results in enhanced pharmacologic response.

Administration, Oral↗

PubMed1993

Trough concentrations of cyclosporine in blood following administration with grapefruit juice.

Components of grapefruit juice have been shown to inhibit CYP3A4 activity, the enzyme involved in cyclosporine metabolism. Eleven medically stable patients (seven males, four females) receiving cyclosporine following kidney transplantation were instructed to take their usual dose of cyclosporine with water for 1 week (Phase 1), with grapefruit juice (8 ounces) for 1 week (Phase 2) and again with water for 1 week (Phase 3). Trough blood samples were obtained at the end of each phase for measurement of cyclosporine concentration using a specific monoclonal whole blood radioimmunoassay. Cyclosporine trough concentrations averaged 116.9 +/- 51.6 ng ml(-1) in the first phase, 145.3 +/- 44.7 ng ml(-1) with grapefruit juice (P < 0.05 compared with the first and third phases) and 111.2 +/- 56.1 ng ml(-1) in the third phase. Cyclosporine concentrations increased in 8 of 11 patients when given with grapefruit juice (mean increase 32%; range -4 to 97%) and declined in 10 of 11 when subjects resumed taking cyclosporine with water (mean decrease 27%). These results suggest that grapefruit juice increases trough concentrations of cyclosporine in blood, possibly by inhibiting pre-hepatic gut wall metabolism, and could be useful in optimizing therapy with this drug.

Adult↗

PubMed1993

Bioavailability of syrup and tablet formulations of cefetamet pivoxil.

Two studies examining the bioavailability of cefetamet pivoxil in healthy male subjects were conducted. In the first, the bioavailabilities of the 250-mg (M250) and M500 tablet formulations of cefetamet pivoxil to be marketed were compared with that of a tablet used in clinical trials. All products were given with food at a dose of 500 mg. In the second study, the bioavailability of the syrup formulation was evaluated under both fasting and nonfasting conditions and compared with that of the M500 tablet formulation given with food. The absolute bioavailabilities of the M500 and M250 tablets (55.0% +/- 8.0% and 55.7% +/- 7.0%, respectively) were not significantly different from that of the clinical-trial formulation (49.8% +/- 8.5%). The newer tablet formulations exhibited faster absorption as evidenced by higher peak concentrations (3.8 [M500] and 3.9 [M250] mg/liter compared with 3.2 mg/liter for the clinical-trial formulation), a shorter time to peak concentration, and a shorter mean absorption time. The syrup formulation was found to have significantly lower absolute bioavailability (37.9% +/- 6.0%) compared with that of the M500 tablet (58.4% +/- 9.0%) when both were given with food. Food had no significant effect on the bioavailability of the syrup, which averaged 34.0% +/- 8.6% under fasting conditions, although absorption was delayed by food (mean absorption time increased from 2.2 to 3.9 h). This contrasts with the results of previous studies documenting significant increases in tablet bioavailability with food. Despite the lower bioavailability of the syrup, unbound-cefetamet concentrations are expected to remain above the MICs for 90% of the strains tested for susceptible organisms for approximately 10 h of the usual 12-h dosing interval with both syrup and tablet formulations of cefetamet pivoxil given with food.

Administration, Oral↗

PubMed1993

Plasma concentrations of inorganic sulfate in Alzheimer's disease.

Recent reports have suggested that plasma concentrations of inorganic sulfate may be lower in patients with Alzheimer's disease (AD). We measured sulfate concentrations in 10 patients with AD and found an average concentration of 0.28 mM, which was not significantly different from the mean concentration in age-matched controls (0.32 mM) or young healthy controls (0.27 mM). These results indicate that plasma sulfate concentrations are not altered in AD and that previous reports suggesting altered metabolism of sulfur-containing xenobiotics in neurodegenerative diseases should be reevaluated.

Adult↗

PubMed1992

Crystal structure of a chimeric Fab' fragment of an antibody binding tumour cells.

The crystal structure of a chimeric Fab' fragment of a monoclonal antibody is presented. The Fab' comprises the murine light chain and heavy chain variable domains of the carcinoma-binding antibody B72.3 fused to the constant domain of human kappa, and the first constant domain and hinge domain of human gamma 4, respectively. A model for the Fab' has been determined by molecular replacement and refined to a resolution of 3.1 A with an R-factor of 17.6%. The additional residues that distinguish a Fab' from a Fab fragment are seen to be disordered in the crystals. The H3 hypervariable loop is short and adopts a sharp hairpin turn in a conformation that results from an interaction between the lysine side-chain of H93 and the main-chain carbonyl group of H96. The remaining hypervariable loops display conformations similar to those predicted from the canonical structures approach, although loop H2 is apparently displaced by a salt-bridge formed between H55 Asp and the neighbouring H73 Lys. These and other features of the structure likely to be important in grafting the hypervariable loops to an otherwise human framework are discussed.

Amino Acid Sequence↗

PubMed1992

Amphetamine or haloperidol 2 weeks earlier antagonized the plasma corticosterone response to amphetamine; evidence for the stressful/foreign nature of drugs.

We inquired whether a single exposure to amphetamine (AM) or haloperidol (HALO) could modify the plasma corticosterone (CORT) response to a second injection of AM 2 weeks later. Male rats were injected with 4 mg/kg d-AM sulfate and tested for water intake for 5 h before sacrifice. Overall, AM induced water intake but none of the pretreatments altered this effect. By contrast, preexposure to AM, HALO or its vehicle 2 weeks earlier prevented the elevation of plasma CORT obtained when AM was administered without pretreatment. A combined pretreatment of HALO or its vehicle with AM produced an even greater blockade of AM-induced CORT elevation. Manipulations which prevented AM-induced drinking reduced the effectiveness of AM pretreatment in attenuating AM-induced elevation in CORT, suggesting that the pretreatment may have been sensitizing the effectiveness of a coping response--drinking--in reducing the CORT effect. Our findings also indicate that a dopamine agonist (AM), a dopamine antagonist (HALO) and a nonspecific stressor (acidic vehicle) can all induce the same, long-lasting action on CORT. This strongly suggests that the effects of AM and HALO in this instance cannot be explained in terms of their pharmacological actions, which are opposite to one another, but instead relate to their properties as stressful/foreign agents to the organism.

Amphetamine↗

PubMed1992

Fractures of the distal clavicle: a case for fixation.

We present a series of 43 Neer type 2 fractures of the distal one-third of the clavicle. These displaced fractures are associated with a high incidence of non-union. In those patients treated non-operatively there was a higher incidence of local complications, residual shoulder dysfunction and non-union than in those treated by open reduction and internal fixation. We recommend that type 2 fractures should be treated by open reduction and internal fixation.

Adolescent↗

PubMed1992

One brief exposure to a psychological stressor induces long-lasting, time-dependent sensitization of both the cataleptic and neurochemical responses to haloperidol.

Rats were exposed for 10 minutes to one of several enclosures graded in novelty. In one experiment they were then simply sacrificed and plasma corticosterone determinations made in order to obtain an index of the relative stressfulness of these enclosures. In a second experiment the animals received haloperidol and were tested for catalepsy, 2 hours or two weeks following the novel experience. The most novel experience, exposure to a black box, resulted in the highest corticosterone levels and was the only one of our pre-treatments to induce significant enhancement of catalepsy as well as alteration of nucleus accumbens dopamine levels, 2 weeks--but not 2 hours--later. These findings indicate that brief exposure of adult animals to a psychological stressor can induce a long-term alteration in both behavioral and neurochemical responses to a drug and that this effect requires a minimum level of stress to get started and once triggered gets stronger with the passage of time.

Animals↗

PubMed1992

Contrasting effects of fluconazole and ketoconazole on phenytoin and testosterone disposition in man.

Nine healthy male subjects received oral fluconazole 400 mg daily, ketoconazole 200 mg twice daily or no treatment for 6 days according to a randomized, cross-over design. A single 250 mg oral dose of phenytoin suspension was administered on day 5 and serum phenytoin concentrations were measured over the following 48 h. Serum testosterone concentrations were measured for 10 h after each dose of phenytoin. Ketoconazole had no significant effect on phenytoin concentrations while the mean AUC(0,48) for phenytoin was significantly higher with fluconazole (195.2 +/- 47.8 micrograms ml-1 h) than control (146.3 +/- 49.6 micrograms ml-1 h). At 48 h, the serum phenytoin concentration averaged 1.72 micrograms ml-1 under control conditions and 3.99 micrograms ml-1 with fluconazole (132% increase). AUC(0,10) for testosterone was 42% lower than control after ketoconazole administration (P less than 0.05) but increased by 33% from 55.6 +/- 9.4 ng ml-1 h (control) to 73.8 +/- 12.6 ng ml-1 h with fluconazole. AUC(0,10) values for the testosterone precursors androstenedione and 17 alpha-hydroxyprogesterone were significantly higher in the fluconazole treatment phase as were concentrations of luteinizing hormone. The mechanism and clinical significance of the increase in testosterone concentration caused by fluconazole remains to be determined.

Administration, Oral↗

PubMed1992

The pharmacokinetics of new oral cephalosporins in children.

Differences in the pharmacokinetic parameters of cephalosporins between children and adults may be predictable on the basis of the level of maturation of the physiologic processes involved in drug disposition. It appears that the most important of these factors (gastrointestinal, renal and hepatic function) are reasonably mature by the age of 1 year. As a result, the primary difference between adults and children relates to size and body composition. Comparable bioavailability is expected in children and adults. However, absolute values for systemic clearance (ClS) and volume of distribution (VSS) will be lower in children. It has been suggested that ClS in children is reduced in proportion to body surface area. This may also be true for the VSS of the cephalosporins since they distribute primarily into the extracellular fluid space which has been shown to be similar in children and adults when adjusted for surface area. If both ClS and VSS are proportional to surface area, half-life will be similar in adults and children. Data with cefetamet generally support these principles. Clearance normalized for body surface area averaged 69.3 ml/min/m2 in children aged 3-7 years, 64.9 ml/min/m2 in children of 8-12 years and 68.9 ml/min/m2 in adults. The VSS remained somewhat smaller in children than adults even after correction for surface area. Bioavailability and elimination half-life in children were similar to values in adults. Data with other new cephalosporins are limited, but differences between children and adults in bioavailability and half-life appear to be insignificant.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1991

One experience with 'lower' or 'higher' intensity stressors, respectively enhances or diminishes responsiveness to haloperidol weeks later: implications for understanding drug variability.

This laboratory has previously shown that acute exposure to a variety of brief stressful events can have a very long-lasting influence on subsequent responsiveness to pharmacological and non-pharmacological stressors. In some cases the response to these agents is enhanced, while in others it is diminished: the common denominator being that in each instance the influence of the initial stressor grows stronger with the passage of time. Here, we identify one factor that determines which time-dependent effect is manifest. In 3 separate experiments, male rats were subjected to a single exposure to stressors of either lower or higher intensity and their effects on haloperidol-induced catalepsy and dopamine and dihydroxyphenylacetic acid levels in the nucleus accumbens and medial frontal cortex, measured either 1-2 h or 2 weeks later. The stressors were either environmental (needle jab or 1 h of immobilization), metabolic (200 or 750 mg/kg, i.p. of 2-deoxy-D-glucose), or no effect on haloperidol-induced catalepsy when stressors preceded such behavioral testing by 1-2 h. By contrast, when the interval was 2 weeks, the lower-intensity stressors all increased haloperidol catalepsy, whereas the higher-intensity stressors decreased the same response. In other words, a process that progressed with the passage of time was observed regardless of whether sensitization or diminution of haloperidol's action occurred. In contrast to the uniform bipolar behavioral effects observed, depending on the intensity of the prestressor, the neurochemical findings failed to show any evidence of bipolarity whatever.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

Effects of a three-year exercise program on motor function and cognitive processing speed in older women.

This study evaluated the effects of a three-year exercise program on motor performance and cognitive processing speed of previously sedentary older women, ages 57-85. Variables tested were simple and choice reaction time (CRT), balance, sit and reach flexibility, shoulder flexibility, and grip strength. Subjects participated three times a week in exercise performance classes designed to meet American College of Sports Medicine guidelines. Results indicate that performance was significantly improved on all measures during the course of the study (p less than .01) except for the sit and reach test (SRT), where significance was approached (p less than .027), but not reached. A comparison of the exercise subjects with a comparable group of nonexercising control subjects revealed significant interactions between treatment and time on all variables except CRT and grip strength. Pretest to posttest scores of the exercise subjects tended to improve over the three-year period, whereas the scores of the control subjects declined. Improved reaction time indicated exercise is effective in reversing or at least slowing ceratin age-related declines in motor performance and in speed of cognitive processing.

Aged↗