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Biomedical subjects

W A Edwards

Publications and source records attributed to W A Edwards.

14 recordsLinked to original sources
PubMed1987

Systemic absorption of endotracheally administered aminoglycosides in seriously ill patients with pneumonia.

A study was performed with 10 hospitalized patients to determine the percentage of an aminoglycoside dose (tobramycin or gentamicin) that is absorbed systemically after being instilled into the endotracheal tube at steady state. All patients were on respirators, had indwelling urinary catheters, and had creatinine clearances estimated to be greater than or equal to 40 ml/min. Tobramycin or gentamicin (40 mg) was instilled every 4 h directly into the endotracheal tube. Nine patients also received systemically a different aminoglycoside from that administered through the endotracheal tube. Urine was collected over a 4-h dosing interval at steady state (after at least 5 doses of the drug). The amount of aminoglycoside excreted over the 4-h interval was measured and expressed as percentage of the dose administered over that period. The range of percentage of dose absorbed was 1.5 to 34%, with a mean of 16.7 +/- 11.4% standard deviation and a median of 16.5%. The coefficient of variation was 68%. Levels of the endotracheally administered aminoglycoside in serum were measured, and all were less than 1.0 microgram/ml. While a large degree of variability in absorption was observed in this study, significant amounts of aminoglycosides could be absorbed in some patients. However, levels apparently did not accumulate in sera of patients with adequate renal function, and an empirical dosage reduction in intravenous aminoglycoside should not be necessary with the addition of endotracheally instilled aminoglycoside in patients with creatinine clearances greater than 40 ml/min.

Absorption↗
PubMed1985

Cimetidine clearance in the obese.

Six subjects with normal weight (mean weight = 62 kg) and six obese subjects (mean weight = 140 kg) were given a single intravenous cimetidine infusion of 600 mg over 10 to 15 minutes. Both groups of subjects had normal serum creatinine levels and were matched with respect to age, desirable body weight, height, renal function, and sex. Compared with subjects of normal weight, obese subjects had higher cimetidine systemic (1147 and 637 ml/min) and renal (808 and 318 ml/min) clearances. Volume of distribution at steady state was of the same order for the two groups (82 and 84 L), but the t 1/2 was shorter in the obese group (1.2 and 1.9 hr). Obese subjects had lower cimetidine sulfoxide serum concentrations and greater cimetidine sulfoxide renal clearance (856 and 509 ml/min). Cimetidine systemic clearance and cimetidine sulfoxide renal clearance values were of the same order in the two groups when normalized by the value of weight raised to the 0.76 and 0.5 powers. Under the assumptions of an average weight of 70 kg and that average serum concentrations produced by cimetidine, 300 mg iv every 6 hours, are appropriate, people with normal renal function and body weight usually receive 48 mg/day/weight0.76. This same dosage in obese individuals with normal serum creatinine values should result in the same average steady-state serum concentrations. In our obese subjects, the mean cimetidine dose would have been approximately 500 mg iv every 6 hours.

Adult↗
PubMed1983

Influence of weight on aminoglycoside pharmacokinetics in normal weight and morbidly obese patients.

Aminoglycoside pharmacokinetics were determined in 30 normal weight patients and 30 morbidly obese patients (greater than 90% overweight). All had normal renal function and a gram-negative infection (documented by cultures, fever and elevated white blood cell counts) which was treated only with aminoglycoside antibiotics. The normal weight and morbidly obese patients were matched with respect to the following criterion: age, sex, ideal body weight (IBW), serum creatinine, site of infection, and type of aminoglycoside antibiotic (gentamicin, tobramycin, or amikacin). The results were similar for all 3 drugs. Average half-life was 2 h for both the morbidly obese and normal weight patients. The mean volumes of distribution and clearances were significantly larger in the morbidly obese (23.3 l and 135.8 ml/min for gentamicin, 29.9 l and 162.4 ml/min for tobramycin, and 26.8 l and 157.3 ml/min for amikacin) than in normal weight patients (17.0 l and 95.9 ml/min for gentamicin, 18.3 l and 101.3 ml/min for tobramycin, and 18.6 l and 99.2 ml/min for amikacin). As a result of altered aminoglycoside pharmacokinetics, morbidly obese patients required significantly larger mean doses (540 mg/d for gentamicin, 690 mg/d for tobramycin and 1970 mg/d for amikacin) when compared to the normal weight patients (380 mg/d, 420 mg/d and 1420 mg/d, respectively; p less than 0.005) in order to achieve comparable serum concentrations.

Aminoglycosides↗
PubMed1983

Importance of unbound phenytoin serum levels in head trauma patients.

Total (bound + unbound) and unbound phenytoin serum concentrations were measured in ten male comatose head trauma patients and ten male epileptic patients. Serum biochemistry and complete blood cell counts were normal for both groups, except albumin concentrations were below normal in the head trauma patients for nutritional reasons. Total phenytoin concentrations were 6.8 +/- 1.8 mcg/ml for the head trauma patients and 14.5 +/- 3.0 mcg/ml for the epileptic patients (p less than 0.0002) even though phenytoin doses were similar. However, unbound phenytoin concentrations were within the therapeutic range of 1 to 2 mcg/ml for both groups and were not significantly different. Had only the total concentrations been measured, phenytoin doses might have been increased inappropriately in the head trauma patients. The reason head trauma patients had therapeutic unbound concentrations despite lower total concentrations was that the unbound per cent of phenytoin was higher in these patients (21 +/- 3.2%) than in the epileptic patients (10 +/- 1.3%, p less than 0.0002).

Adult↗
PubMed1982

Anergy in high-risk surgical patients: the role of parenteral nutrition.

The finding of delayed hypersensitivity on skin testing has been used to predict the outcome following operations, traumas or severe illnesses and has been correlated with nutritional status in some reports. To test these hypotheses, we did weekly skin tests with a battery of four antigens on 98 high-risk patients referred to the nutritional support service. Anergy persisted or developed in 72 patients, whereas 26 patients remained or became reactive. These two groups were comparable in number of days in hospital, age and amount and duration of parenteral nutrition. Infectious complications (68 percent versus 23 percent, P<.001), sepsis (35 percent versus 12 percent, P<.01) and mortality (33 percent versus 0 percent, P<.001) were more prevalent in anergic than in reactive patients. There was no correlation between nitrogen balance studies and skin test results. In most instances conversion of skin test results occurred as a consequence of appropriate surgical care rather than nutritional support. Whereas nutritional support is required in these high-risk patients, anergy should not be the sole indicator for giving nutritional support or delaying an operation.

Adolescent↗
PubMed1981

A comparison of patient drug regimens as viewed by the physician, pharmacist and patient.

This study sought to determine the completeness and congruence of records for drugs ordered and received by outpatients. The setting was a large outpatient medical facility that was part of a large multispecialty hospital. It was found that a listing of current drugs orders (prepared by physicians) and a listing of current prescription drugs consumed (prepared from pharmacy drug profiles) each agreed 73 per cent of the time with a list of 107 prescription drugs actually consumed by 26 study patients. Lists were compared based on drug name, strength and directions for use. Further, the physician and pharmacy lists correlated with one another 70 per cent of the time, indicating a substantial degree of inconsistent as well as incomplete drug records within the same setting. In another comparison involving medical chart drug notations and pharmacy drug profiles, a complete match or drug name, strength and directions for use occurred in 39 per cent of the cases, while a match on drug name only occurred 64 per cent of the time. The highest degree of congruence occurred between hospital discharge medication notes and outpatient drug profile records. Based on the results of this study, the common assumption that drug records in such settings are congruent and complete appears unwarranted.

Drug Information Services↗
PubMed1980

Randomized prospective evaluation of cimetidine and antacid control of gastric pH in the critically ill.

One hundred forty-four critically ill patients admitted to an intensive care setting were randomly assigned to cimetidine or antacid treatament groups. Gastric pH was monitored hourly. One hundred twenty-three (85%) patients demonstrated a fall in pH to less than 4 and were considered to require prophylaxis. Prophylaxis was considered adequate if the measured pH could then be maintained at greater than or equal to 4. Fifty-eight patients received antacids alone, the average requirement being 41 cc/hour. Sixty-five patients received cimetidine. Seventeen (26%) of the cimetidine prophylaxis patients failed to raise their pH and were than placed on hourly administration of antacid with successful elevations of pH to greater than or equal to 4 in all cases on an average supplementary dose of 53 cc/hour. Risk factors, including sepsis, hypotension, head injury, respiratory failure, degree of trauma, and age, were not statistically different in the two treated groups. Using these same criteria, responders to cimetidine could not be differentiated from nonresponders. All patients were protected from significant stress bleeding while on this study. Significant complications of either treatment were minimal. Antacids offered consistent protection against gastric acidity and were 100% effective. A routine schedule of 300 mg every six hours of cimetidine was effective in only 47% of patients, and the maximum dose of cimetidine was effective in only 74% of patients. Hourly measurement of intragastric pH is required for monitoring the response to prophylaxis of stress bleeding in severely ill patients.

Adult↗
PubMed1975

Homocystinuria due to cystathionine synthase deficiency. Studies of nitrogen balance and sulfur excretion.

Apparent nitrogen balances and urinary sulfur excretions were determined for normal subjects, seven cystathionine synthase-deficient patients, and a single cystathioninuric patient on semisynthetic diets containing low-adequate amounts of methionine and very low amounts of methionine and very low amounts (12 mg daily, or less) of cystine. The amounts of supplemental cystine required to prevent abnormally high nitrogen or sulfur losses were determined. The five cystathionine synthase-deficient patients who had low residual activities of this enzyme detected in fibroblast and/or liver extracts did not lose more nitrogen or sulfur on diets virtually devoid of cystine than did the normal subjects. These results suggest that the widely expressed opinion that cystine is an essential amino acid for cystathionine syntase-deficient patients requires modification. Residual enzyme activity of only a few percent of normal may obviate such a cystine requirement. These results are compatible with, and lend support to, the working hypothesis which states that the pyridoxine response in cystathionine synthase-deficient patients is mediated by an increase in the residual activity of the affected enzyme.

Adolescent↗
PubMed1970

Homocystinuria due to cystathionine synthase deficiency: the effect of pyridoxine.

We investigated the effect of pyridoxine administration in three patients with homocystinuria due to cystathionine synthase deficiency. The drug decreased the plasma concentration and urinary excretion of methionine and homocystine and the urinary excretion of homolanthionine and the homocysteine-cysteine mixed disulfide. Urinary cystine rose somewhat. Oral methionine tolerance tests before and during the patients' response to pyridoxine indicated that during response they remained deficient in their capacity to convert the sulfur of methionine to inorganic sulfate, although this capacity increased somewhat. During pyridoxine response only, the methionine loads caused increased homocystinuria. There was no indication that pyridoxine stimulated an alternate pathway of metabolism. The values for specific activity of cystathionine synthase in liver biopsy specimens from two patients in pyridoxine response were 3 and 4% of the mean control value. When these patients were not receiving pyridoxine, comparable values were 2 and 1%, respectively. The hepatic enzyme activity of the mutant patients was similar to normal enzyme activity with respect to trypsin activation, heat inactivation, and stabilization by pyridoxal phosphate. Approximate estimates were made of the relation between total body capacity to metabolize methionine and hepatic cystathionine synthase activity. These estimates suggested that because of the large normal reserve capacity of cystathionine synthase, a few per cent residual activity is sufficient to metabolize the normal dietary load of methionine. Thus, small increases in residual capacity may be of major physiological importance. However, many liver biopsies would be required to establish unequivocally that such changes were due to the administration of a particular therapeutic agent rather than to biological variation. All the data in the present study are consistent with the interpretation that pyridoxine does act by causing an increase in residual cystathionine synthase activity.

Adult↗
PubMedDate not supplied

Use of op site as an occlusive dressing for total parenteral nutrition catheters.

A retrospective study of standard hyperalimentation catheter dressing compared to the use of Op Site has demonstrated that Op Site is cost and time effective and is efficacious for attaining a low catheter sepsis rate. It is easy for nursing personnel to apply and comfortable for the patients to wear. Op Site may be contraindicated in diaphoretic patients.

Adolescent↗