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Biomedical subjects

W L Russell

Publications and source records attributed to W L Russell.

At least 55 records · Page 3Linked to original sources
PubMed1985

First-generation litter-size reduction following irradiation of spermatogonial stem cells in mice and its use in risk estimation.

Litter-size reduction (LSR) is a useful measure of part of the overall F1 radiation-induced damage. Extensive LSR data were obtained as a by-product of specific-locus experiments. Fourteen such experiments involving 158,490 F1 litters have been analyzed for the extent of LSR induced by x- or gamma-irradiation of spermatogonia. Litter sizes were compared between experimental and control groups at about 3 weeks after birth. In order to reduce variability, comparisons were made only with concurrent controls and between groups of litters having mothers of approximately the same age. At the high dose rate of 90 R/min, the LSRs showed a humped dose-response curve. There was a pronounced dose-rate effect, the mutational responses being much less at dose rates of 0.009 R/min and 0.001 R/min. It is estimated that if men were exposed to 1 R of radiation delivered at low linear energy transfer (low LET) and low dose rate, the number of deaths caused by induced dominant mutations among their children before late childhood would be about 19 per million live-born. This can be added to the earlier estimate of an approximately equal number of viable disorders in all body systems as based on dominant skeletal mutations. This gives a total estimate of induced dominant damage, but much of this addition represents death in very early embryonic life that would not be recognized in humans. The LSR data also permit the conclusion that only an extremely small proportion of serious radiation-induced genetic disorders among live-born humans would be expected to result from segmental aneuploidy.

Aneuploidy↗
PubMed1985

Dose-repetition increases the mutagenic effectiveness of N-ethyl-N-nitrosourea in mouse spermatogonia.

In order to maximize the mutagenic effectiveness of N-ethyl-N-nitrosourea in mouse stem-cell spermatogonia, advantage was taken of the fact that these cells can accumulate mutations from repeated doses given over relatively long time periods. Repeated doses (100 mg/kg) of ethylnitrosourea injected intraperitoneally into male mice at weekly intervals were found to allow adequate survival and fertility with total dosages of 300 and 400 mg/kg. The specific-locus mutation frequencies at these dosages were, respectively, 1.8 and 2.2 times that obtained with the maximal practicable single dose of 250 mg/kg. The mutation frequency induced by a 400 mg/kg dosage of ethylnitrosourea is 12 times the maximal mutation frequency achievable with a single exposure to x-rays and 36 times that reported for procarbazine, the most effective chemical mutagen previously known for mouse stem-cell spermatogonia. Ethylnitrosourea is already the mutagen of choice in deliberate attempts to create mouse models for human disease and in any experiments in which a maximal mutation rate is desired. Repeated-dose regimens similar to the ones reported here should increase the efficiency of such studies.

Abnormalities, Drug-Induced↗
PubMed1985

Appendicitis in mature patients.

All patients greater than 50 years of age (N = 96) admitted with a pre- or postoperative diagnosis of acute appendicitis from 1971 to 1980 were reviewed. A comparative series of 91 patients aged 25 to 50 years was similarly reviewed. Noninflammatory diseases of the appendix and incidental appendectomies were excluded. Detailed study of symptoms, clinical presentation, laboratory evaluation, radiographic evaluation, concomitant diseases, hospital course, surgical findings, complications, and mortality were completed. Comparison of patients aged 25 to 50 to patients older than 50 years revealed a statistically significant increased incidence of perforation in the older group (p less than 0.0001). Sixty-five per cent of the older group showed greater incidence of perforation. Further analysis of this series yields the hypothesis that the increased incidence of perforation is related to a significant decrease in the frequency of classic presentation in the greater-than-50 age group, a significant decrease in frequency of correct admission diagnosis and a significant delay between admission and surgical procedure in the older group. A more rapid pathophysiologic progression of appendicitis with increasing age was noted. A much higher percentage of older patients was undiagnosed until the surgical procedure. In this group, there was a longer duration of symptoms, less frequent classic presentation, and decreased frequency of right lower quadrant guarding and tenderness as compared to patients with correct diagnosis prior to surgery. Complications were much more frequent in older patients and higher still in those with perforation. Analysis of findings by decade of life revealed an anticipated high incidence of perforated appendicitis in patients greater than 50, but also showed a continuation of the high incidence of perforation into the decade 40 to 50. There were three deaths in the entire study group (1.6%) all occurring in the older age group with postoperative sepsis.

Acute Disease↗
PubMed1985

Extracranial carotid vascular disease: detection by real time B-mode ultrasonography.

Real time B-mode ultrasonography is a currently popular technique used to screen patients with suspected carotid vascular disease and identify those who need cerebral angiography. From September 1981 through February 1983, 1,205 patients had carotid ultrasonography in the Vascular Laboratory at Erlanger Medical Center. Retrospective review of these patients identified 260 who also had cerebral angiography. In these 260 patients, 517 arteries were studied with ultrasound and then compared to angiographic results, using the angiograms as control. In this study, there was a technical success rate of 89% for all ultrasonic procedures done. With positive disease considered as stenosis of more than 40%, the overall accuracy was 79%, sensitivity was 81%, and specificity was 77%. The false-positive rate was 14% and the false-negative rate 7%. Carotid ultrasonography accurately detected total vessel occlusion in 91% of such cases. Ultrasonic studies were not consistently accurate in the detection of ulcerative plaques where compared to angiographic results.

Auscultation↗
PubMed1985

Utilization and wide clinical implementation using the wick catheter for compartment pressure measurement.

A series of 71 patients was identified and studied over a period of 30 months. Twenty-five patients underwent fasciotomy, all but one patient had a compartment pressure finding of more than 30 millimeters of mercury. Sixteen patients underwent fasciotomy on the basis of pressure measurement alone. Patients with a pressure measurement of less than or equal to 30 millimeters of mercury and those with an absence of clinical findings were spared fasciotomy. Continued accumulation of data in various patient groups should yield specific comments and observations using this important adjunctive technique.

Adolescent↗
PubMed1985

An electronic technique for compartment pressure measurement using the wick catheter.

Compartmental pressure measurement through an electromechanical process can be readily, accurately and inexpensively accomplished with standard hospital equipment. Best results will be obtained when personnel familiar with the set up and continued use of pressure monitoring equipment are assigned for the care and recording of data. The most frequently encountered problems associated with this technique are improper settings or inadequate calibration of pressure monitors and stopcocks or thrombosis of the wick catheter itself.

Catheterization↗
PubMed1984

Effect of antacids on predicted steady-state cimetidine concentrations.

The purpose of this study was to evaluate effects of antacids on predicted steady-state concentrations of cimetidine. Ten healthy volunteers received in random order one week apart, cimetidine and cimetidine and antacid suspension. Blood was obtained at specified times and analyzed for cimetidine. Bioavailability was assessed by comparison of peak concentration, time to peak concentration, area under the curve, and time spent over 0.5 micrograms/ml. Single-dose data were extrapolated to steady-state using computer simulation. Concurrent administration of antacid suspension reduced parameters of bioavailability approximately 30%. When steady-state conditions were simulated, concentrations of cimetidine greater than or equal to 0.5 micrograms/ml were maintained for the entire dosing interval in seven of 10 subjects. These data suggest that temporal separation of cimetidine and antacid suspension may be unnecessary.

Adult↗
PubMed1984

Dose-dependent kinetics of theophylline in adults with pulmonary diseases.

The incidence of dose-dependent pharmacokinetics of theophylline was retrospectively investigated in adults with pulmonary disease receiving continuous aminophylline infusions. Twenty-one of 180 successive admissions to medical intensive care units with a diagnosis of chronic obstructive pulmonary disease, asthma, or respiratory failure met the criteria of two steady-state serum theophylline concentrations on two different doses. Of these, 14 patients continued to smoke, whereas 7 had never smoked or had stopped greater than 1 year prior to admission. No statistical difference existed between the mean systemic clearances of theophylline at the two different doses, using either total body weight or ideal body weight. Only 1 of the 21 patients met the criteria for dose dependency of a greater than or equal to 50% reduction in clearance with dosage increase. Six of eight subjects with decreased clearance on the higher dose were nonsmokers. In contrast, all nine with augmented clearance following dosage increase were smokers. Four were considered to have proportional changes. In general, nonsmoking patients tended to have greater changes in serum theophylline concentration than in dosage. Conversely, smoking patients demonstrated smaller changes in concentration. The relationship of smoking status and dose-dependent theophylline elimination is discussed.

Adult↗
PubMed1984

Comparison of the predictions of one- and two-compartment microcomputer programs for long-term tobramycin therapy.

A retrospective study of patients receiving tobramycin compared the accuracy of predictions of actual trough serum concentrations using two commercially available microcomputer software programs. Twelve patients met the study criteria of intravenous tobramycin treatment for more than 10 days with serum concentration monitoring within the first 5 days and after 10 days of therapy. No patients received dialysis. Twenty-five serum concentrations were compared. Predictions within 0.2 microgram/ml were considered clinically "exact." No significant differences were found by chi-square analysis for any of the four possible choices (p less than 0.3). One of the programs, distributed by Dista Pharmaceuticals, offers a one-compartment model, a two-compartment model, and a two-compartment prenephrotoxic option. SIMKIN, a program marketed by Medical Engineering, Inc., uses a two-compartment model. Overall, the predictions errors were small, but occasionally were clinically significant. Further evaluation of microcomputer programs for therapeutic drug monitoring is necessary to document their impact on predicting drug efficacy and toxicity.

Adult↗
PubMed1984

Inadequacy of FDA dosing guidelines for intravenous theophylline.

The ability of a dosing regimen of intravenous theophylline to achieve therapeutic serum theophylline concentrations was evaluated. Intravenous theophylline was administered to 25 adult patients with acute bronchospasm using dosing guidelines 20 percent higher than FDA recommendations. The dose of theophylline was determined by assignment to one of four clinical categories. Blood samples for determination of serum theophylline concentrations were collected 12 and 24 hours after initiation of a constant infusion. Differences between mean observed and target theophylline concentrations did not achieve statistical significance. All patients in categories 1 and 2 achieved therapeutic concentrations of theophylline. Most of those with subtherapeutic levels were smokers suffering from multiple diseases. We conclude that current FDA recommendations for dosing intravenous theophylline are unreliable for routine use in category 3 and 4 patients. Further work is necessary to evaluate these recommendations in pediatric and category 1 and 2 patients.

Adult↗
PubMed1984

Therapeutic substitution: has its time arrived?

Therapeutic substitution refers to substitution by the dispenser of a drug product that is not chemically identical but is therapeutically equivalent to the product prescribed, pursuant to guidelines established by the hospital P & T Committee. Until recently, the extent to which this concept has been adopted by hospitals across the country was unknown. Late in 1980, we conducted a nationwide survey of hospital pharmacies to learn more about therapeutic substitution. This paper reviews some of the issues involved, some of the findings of our study, and the pros and cons of therapeutic interchange. It also provides an update as to some of the recent changes that are occurring in therapeutic substitution procedures.

Data Collection↗
PubMed1983

Evaluation of the "condition correction factor" method of estimating theophylline clearance.

The predictive ability of the "condition correction factor" method of estimating total body theophylline clearance as proposed by Powell et al. was evaluated in 22 acutely ill hospitalized patients. Actual theophylline clearance was calculated while the patient was on a constant infusion of aminophylline with serum theophylline concentrations obtained at steady-state conditions. Independently, theophylline clearance was estimated for each patient using condition correction factors. The relationship between actual and estimated total body theophylline clearance was evaluated using multiple regression analysis and correlation testing. The data failed to demonstrate any significant positive correlation between actual and estimated theophylline clearance data. Because of this poor correlation, the use of one of the clearance estimation methods incorporating two serum theophylline concentrations obtained early in therapy is preferable, although less convenient. All estimates of clearance must be considered only as guides for individualization of therapy. Serum concentration monitoring and clinical response of the patient must be considered prior to adjustment of dosage.

Adult↗
PubMed1983

Drug usage in newborn intensive care units.

A national survey of neonatal intensive care units (NICUs) was undertaken to obtain information concerning drug usage, dosages, methods of administration, incidence of drug-induced phlebitis, and drug reference sources. Antimicrobial agents are the most frequently used drugs in NICUs. Dosages reported by NICUs generally agreed with dosage recommendations by the manufacturer and literature citations. A 10% estimate of phlebitis was the consensus report by NICUs. Calcium gluconate was implicated most often as causing phlebitis, and most NICUs reported that drugs are not mixed with hyperalimentation solutions. The Pharmacy and Therapeutic Committee should review drug dosages in neonates and establish policies for intravenous drug administration methods and rates to ensure uniform initial doses and to provide a consensus among clinicians using these medications.

Data Collection↗