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Biomedical subjects

D J Edwards

Publications and source records attributed to D J Edwards.

177 records · Page 10Linked to original sources
PubMed1972

Aromatic acids derived from phenylalanine in the tissues of rats with experimentally induced phenylketonuria-like characteristics.

1. Aromatic acids were extracted from brain and liver of rats with phenylketonuria-like characteristics produced by administration of phenylalanine, either alone or in combination with p-chlorophenylalanine. The metabolism of the aromatic acids in these tissues was measured by gas chromatography. 2. At 1h after an intraperitoneal injection of l-phenylalanine (1g/kg) in 23-day-old rats, the phenyl-lactate concentration was 2.2mug/g in the liver and 0.43mug/g in the brain, and the concentration of o-hydroxyphenylacetate was 0.26mug/g in the liver. 3. Phenylacetate concentrations in brain and liver were 0.26 and 0.14mug/g respectively. 4. Suckling rats produced phenyl-lactate less rapidly than weanling rats, but accumulated higher concentrations in longer-term experiments. 5. Intraperitoneal injections of phenyl-lactic acid showed that this compound could directly penetrate the blood-brain barrier, and could produce similar brain/liver ratios of phenyllactate to those found after phenylalanine injection. 6. Qualitative and quantitative similarities in urinary excretion of aromatic acids between the rats used in this study and human patients with uncontrolled phenylketonuria indicate that a patient with a circulating phenylalanine concentration of the order of those achieved in the experimental animal may have aromatic acid concentrations in brain and liver comparable with those found in the rats used in the present study.

Animals↗
PubMedDate not supplied

Adrenal medullary catecholamine secretion patterns in rats evoked by reflex and direct neural stimulation.

Epinephrine (EPI) and norepinephrine (NE), secretion patterns evoked by reflex (to hypotension and hypoglycemia) and direct neural stimulation of the adrenal medulla were measured in pentobarbital anesthetized male Sprague-Dawley rats. Secretion rates were determined by collecting adrenal venous blood. Baseline catecholamine secretion was similar in innervated and denervated glands indicating that there was little tonic sympathetic neural drive to the medulla. Both hydralazine-induced hypotension and insulin-induced hypoglycemia significantly increased catecholamine secretion with the secretion of EPI predominating. Similarly, in response to stimulation of the splanchnic nerve, frequency-related increments in EPI and NE were elicited with EPI release being greater than NE at all frequencies. However, the magnitude of the increase in secretion during splanchnic stimulation at frequencies above 1 hz greatly exceeded the release achieved by reflex stimulation. The results indicate that despite the fact that the stimuli of hypotension and hypoglycemia are integrated by different centers in the brain, the pattern of adrenal release is similar.

Adrenal Medulla↗
PubMedDate not supplied

Transcultural nursing: a view of the Russian health care system.

In October 1991, I visited Russia, Hungary, and Czechoslovakia as a member of a delegation of orthopaedic nurses. The 30 delegates were assembled under the Citizen Ambassador Program of People to People International. Our focus was a sharing of information about orthopaedic nursing practice and the cultural influences related to health care practice. This article reflects my experiences and observations in St. Petersburg and Moscow as far as the facilities visited, patient population, nursing management, treatment modalities, equipment, ancillary departments, nurses' educational preparation, and the nurses' roles within the health care system.

Czechoslovakia↗
PubMedDate not supplied

Endometrial cancer metastasis presenting as a grossly swollen toe.

Metastasis to the peripheral skeleton, especially in the face of low stage disease, is rare. This report describes the case of a 77-year-old lady with stage IC disease who underwent curative total abdominal hysterectomy and bilateral salpingo-oopherectomy 2 years prior to presenting with a painless gigantism of her fourth toe. A histologic diagnosis of dedifferentiated endometrial metastasis with sarcomatous differentiation was made following amputation of the toe. Osseous metastasis to bone is discussed in the context of endometrial carcinoma and the literature reviewed. This paper reports the first case of endometrial carcinoma metastasis presenting as gross swelling of a toe.

Aged↗
PubMedDate not supplied

Prospective comparison of ceftriaxone and cefotaxime for the short-term treatment of bacterial meningitis in children.

The effectiveness and safety of ceftriaxone and cefotaxime in the short-term treatment of primary bacterial meningitis were compared using a prospective, randomized, multicenter study design. Children between the ages of 6 weeks and 16 years received either ceftriaxone as a single dose (100 mg/kg on the first day followed by 75 mg/kg/day) or cefotaxime as four divided doses (200 mg/kg/day) for 4-7 days. A total of 82 patients (44 ceftriaxone, 38 cefotaxime) with documented bacteria in the CSF were studied. In patients receiving ceftriaxone, full recovery occurred in 79.5% while a further 13.7% recovered with neurologic sequelae. Full recovery was observed in 71.1% of children treated with cefotaxime with sequelae in a further 23.6% (no statistically significant differences between drugs). The time to clinical improvement and resolution of fever (3-4 days) was also similar for both drugs. All but 1 of the 82 patients studied had negative CSF cultures within 24 h of the beginning of therapy consistent with the excellent penetration into the CSF (trough concentrations of 2.7 mg/l for both drugs at the end of therapy). No differences were observed in the incidence of clinically significant adverse events. Ceftriaxone and cefotaxime are both effective in the treatment of bacterial meningitis. Ceftriaxone offers an advantage in case of administration since it is administered as a single daily dose.

Adolescent↗
PubMedDate not supplied

The use of cold therapy in the postoperative management of patients undergoing arthroscopic anterior cruciate ligament reconstruction.

In this prospective, randomized study we assessed the use of cold therapy after arthroscopic anterior cruciate ligament reconstruction. Seventy-one patients were randomly allocated, without the knowledge of the single surgeon, to one of three groups: Group I had an ice water-filled CryoCuff fitted in the operating theater after surgery, Group II had room temperature water in the CryoCuff, and Group III patients had no CryoCuff. Patients were well matched for age, sex, and associated surgery. An independent observer measured blood loss, analgesic use, range of motion, and visual analog pain scores postoperatively. There were no differences between any of the three groups regarding the variables measured. The use of cold therapy devices as an adjunct to the postoperative management of these patients must be questioned.

Adolescent↗
PubMedDate not supplied

Radiographic changes in the knee after meniscal transplantation. An experimental study in a sheep model.

Meniscal transplantation has been suggested as an alternative to total meniscectomy, which is now known to lead to long-term osteoarthritic degeneration of the knee joint. To evaluate the success of meniscal transplantation, we divided 28 sheep knees into 4 groups: total meniscectomy, allograft, autograft, and control. After a mean postoperative time of 21.4 months, we radiographed the excised knee joints in a loaded state and graded the radiographs for osteoarthritic changes. The knees with meniscectomies, allografts, and autografts showed significantly more degenerative changes than the control knees. However, there were no statistically significant differences between these three groups. The results of this study suggest that meniscal allograft transplantation does not protect the knee against degenerative changes.

Animals↗
PubMedDate not supplied

Vancomycin protein binding in patients with infections caused by Staphylococcus aureus.

The protein binding of vancomycin has been reported to range from less than 10 percent to 82 percent. We examined the binding of vancomycin in 34 patients (14 intravenous drug abusers, 10 burn patients, and 10 control patients) with Staphylococcus aureus infections. Blood samples were collected serially over an 8- or 12-hour dosing interval following a one-hour infusion. In vitro studies were also performed using albumin solutions of varying concentrations. Binding characteristics were determined through ultrafiltration with vancomycin concentrations analyzed for fluorescence polarization immunoassay. The unbound fraction of vancomycin ranged from 0.41 to 0.77 with a mean of 0.54 +/- 0.08. Unbound fractions was significantly correlated with serum albumin concentration (r = -0.344, p less than 0.046) and renal clearance (r = 0.394, p less than 0.021) but not with total body clearance or volume of distribution. In vitro data also showed an association between albumin concentration and unbound fraction (r = -0.94, p less than 0.017). Although vancomycin protein binding changes with serum albumin, this finding may have limited clinical significance.

Adult↗
PubMedDate not supplied

Electrophysiologic and electrocardiographic pharmacodynamics of cocaine.

To determine and describe relationships between plasma cocaine concentrations and electrophysiologic and electrocardiographic effects, 10 anesthetized dogs with normal intact hearts received a continuous 3-hour infusion of cocaine 0.11 mg/kg/minute (total dose 20 mg/kg). Data were collected as part of a randomized, blinded, placebo-controlled study investigating the effects of cocaine on ventricular fibrillation threshold. Every 30 minutes during infusion of cocaine or placebo and for 3 hours after discontinuation of the infusion, heart rate and mean arterial pressure were determined, effective refractory period (ERP) was measured, and QRS duration and PR, QTc, and JTc intervals were recorded. At the time of each 30-minute measurement, arterial blood was obtained to determine plasma cocaine concentrations. Hysteresis curves were observed for cocaine-induced increases in ERP and PR interval. The effects of cocaine on QRS duration and QTc and JTc intervals were not well described by tested models. Pharmacodynamic modeling techniques may be used to describe relationships between plasma cocaine concentrations and specific cardiovascular effects of cocaine. Further study is required to determine applicability of this model for prediction of cocaine's cardiovascular effects in humans.

Animals↗
PubMedDate not supplied

The influence of multiple dosing and age on the pharmacokinetics and pharmacodynamics of glipizide in patients with type II diabetes mellitus.

STUDY OBJECTIVES: To determine the pharmacokinetics and pharmacodynamics of glipizide after a single dose and 12 weeks of dosing in patients with type II diabetes mellitus, and evaluate the influence of aging. DESIGN: Comparison of single and multiple doses of glipizide. SETTING: University-affiliated outpatient internal medicine clinic and diabetes care unit. PATIENTS: Twenty patients (11 men, 9 women, mean age 55.2 +/- 9.9 yrs) with type II diabetes mellitus who were currently receiving oral hypoglycemic agents or were hyperglycemic with diet. INTERVENTIONS: A 24-hour pharmacokinetic evaluation of glipizide was assessed after a 5-mg dose at the start of therapy and after 12 weeks of therapy. Pharmacokinetic parameters were assessed using compartmental population analysis techniques. Glipizide pharmacodynamic evaluation was assessed by serum glucose, insulin, and C-peptide responses during a 4-hour Sustacal tolerance test performed at baseline before instituting glipizide therapy, with the first 5-mg dose, and at week 12 of therapy. Glipizide dosages were titrated to a targeted goal of fasting plasma glucose of 7.8 mmol/L or less or to reach maximum daily doses of 40 mg. MEASUREMENTS AND MAIN RESULTS: No significant differences in time to peak concentration, apparent volumes of distribution for the central and peripheral compartments, apparent oral clearance from the central compartment, distributional clearance between the central and peripheral compartments, or terminal elimination half-life were observed with a single dose and long-term dosing. The mean +/- SD terminal elimination half-lives were 9.67 +/- 5.6 and 9.35 +/- 4.6 hours after a single dose and 12 weeks, respectively. Fasting plasma glucose concentrations decreased from 12.3 +/- 3.6 mmol/L before the first dose of glipizide to 9.2 +/- 1.7 mmol/L after 12 weeks of treatment. The values for area under the serum concentration-time curve from zero to 4 hours for glucose (AUC0-4.glucose) were significantly reduced at week 12 (baseline 49.8 +/- 15.6, week 12 37.8 +/- 9.8 mmol/L/hr). Glipizide provoked an increase in serum insulin and C-peptide concentrations (AUC0-4.insulin: baseline 698 +/- 327, single dose 954 +/- 461, long-term dosing 945 +/- 600 pmol/L/hr). No significant change in insulin response was observed between single and multiple doses. No age-related differences in the pharmacokinetic parameters or the pharmacodynamic responses of glipizide were observed. CONCLUSIONS: Long-term dosing and aging have little effect on the pharmacokinetic profile of glipizide. In addition, glipizide stimulates insulin secretion to a similar extent following glucose challenge after a single dose and long-term administration.

Adult↗