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Biomedical subjects

R D Moore

Publications and source records attributed to R D Moore.

At least 163 records · Page 9Linked to original sources
PubMed1986

Increased risk of renal dysfunction due to interaction of liver disease and aminoglycosides.

To determine if aminoglycoside use and liver disease interact to cause an increased risk for renal dysfunction, data from 179 hospitalized patients who had been enrolled in a prospective, randomized trial of nafcillin/tobramycin versus cefotaxime were analyzed. The cefotaxime-treated patients served as a control group not receiving an aminoglycoside. Renal dysfunction occurred in seven of 88 (8 percent) given cefotaxime and 37 of 91 (41 percent) given tobramycin (p less than 0.001), in 11 of 29 (38 percent) with liver disease and 33 of 150 (22 percent) without liver disease (p less than 0.08), and occurred in 11 of 15 (73 percent) with both liver disease and tobramycin use and in 0 of 14 (0 percent) with liver disease and cefotaxime use (p less than 0.001). By logistic regression analysis, the relative odds of renal dysfunction developing during tobramycin treatment in a patient were 6.0 (95 percent confidence interval: 3.8 to 9.5). The relative odds of renal dysfunction developing in a patient receiving tobramycin and having liver disease were 31.8 (95 percent confidence interval: 19.7 to 51.4). This analysis demonstrates an interaction between tobramycin use and liver disease for increasing the risk of renal dysfunction.

Aminoglycosides↗
PubMed1986

Studies of risk factors for aminoglycoside nephrotoxicity.

The epidemiology of aminoglycoside-induced nephrotoxicity is not fully understood. Experimental studies in healthy human volunteers indicate aminoglycosides cause proximal tubular damage in most patients, but rarely, if ever, cause glomerular or tubular dysfunction. Clinical trials of aminoglycosides in seriously ill patients indicate that the relative risk for developing acute renal failure during therapy ranges from 8 to 10 and that the attributable risk is 70% to 80%. Further analysis of these data suggests that the duration of therapy, plasma aminoglycoside levels, liver disease, advanced age, high initial estimated creatinine clearance and, possibly, female gender all increase the risk for nephrotoxicity. Other causes of acute renal failure, such as shock, appear to have an additive effect. Predictive models have been developed from these analyses that should be useful for identifying patients at high risk. These models may also be useful in developing insights into the pathophysiology of aminoglycoside-induced nephrotoxicity.

Acute Kidney Injury↗
PubMed1986

A model for predicting nephrotoxicity in patients treated with aminoglycosides.

We have previously identified risk factors for nephrotoxicity in 204 patients receiving aminoglycosides. We added data on an additional 134 patients from the University of Chicago who were treated for longer periods (13.1 +/- 9.4 days) to determine if duration of therapy was also a risk factor. In the combined populations, nephrotoxicity developed in 59 (17.5%) of 338 patients, and duration of therapy was the factor most strongly associated with nephrotoxicity (P less than .0001). A new predictive model was developed that was then tested prospectively on 175 consecutive medical and surgical patients who had plasma levels of aminoglycoside measured. The new model accurately identified 14 of 15 patients with nephrotoxicity (sensitivity = 93%) and 106 of 160 without nephrotoxicity (specificity = 66%). A bedside scoring system accurately identified high-risk and low-risk patients. We believe these data add to the understanding of the clinical correlates of aminoglycoside nephrotoxicity and aid in the identification of high-risk patients.

Aminoglycosides↗
PubMed1986

Underdiagnosis of alcoholism by residents in an ambulatory medical practice.

Alcoholism is a widespread illness which in its early stages can be treated effectively. It is important, therefore, that medical residents be able to diagnose alcoholism prior to end-stage disease and organ damage. To assess the ability of residents to diagnose alcoholism, a survey was conducted of 95 patients from the ambulatory care internal medicine practice of the Johns Hopkins Hospital. The patients' alcohol consumption was measured by a self-report questionnaire, and the patients answered an alcoholism questionnaire, the responses to which have been shown to correlate with alcoholism. The questionnaire contains four questions, one each on cutting down on alcohol consumption, annoyance at criticism of alcohol consumption, guilty feelings about alcohol consumption, and use of alcohol early in the day. The answers to the questionnaire were compared with the residents' diagnoses of alcoholism on the medical record. Alcoholism was diagnosed by the residents in only 11 of the 20 patients (55 percent) who had given three or more yes answers on the alcoholism questionnaire and in only 14 of the 31 patients (45 percent) who had given two or more yes answers. (Yes answers indicate that patients suffer from alcoholism.) The residents' diagnosis of alcoholism correlated with signs of physical damage or dependence. These results demonstrate a moderate underdiagnosis of alcoholism by residents in the ambulatory care setting and suggest that diagnosing alcoholism in early stages of the disease should be made a part of the training curriculum.

Alcohol Drinking↗
PubMed1986

Moderate alcohol consumption and coronary artery disease. A review.

An inverse association between moderate alcohol consumption and coronary artery disease has been demonstrated in epidemiologic studies of diverse design. These include ecologic correlations, case-control, longitudinal and clinical studies. The consistency, strength and independence of the inverse relationship argues persuasively for a causal association. These data also suggest that both abstention and heavy alcohol use are associated with an increased risk for coronary artery disease. The effect of moderate alcohol consumption on lipoprotein and apolipoprotein levels is a biologically plausible and likely mechanism for this inverse association. Alcohol consumption elevates HDL cholesterol, although it is unclear whether the HDL subfractions HDL-2 and HDL-3 are beneficially altered. Recent evidence, however, suggests that the apolipoproteins may be more important indicators of coronary artery disease, and moderate alcohol consumption does beneficially alter these proteins. Alcohol may also affect coronary artery disease by other mechanisms, which may include fibrinolytic activity, coagulation, blood pressure, coronary vasoreactivity, and sociobehavioral factors.

Adult↗
PubMed1986

Cefotaxime vs nafcillin and tobramycin for the treatment of serious infection. Comparative cost-effectiveness.

To evaluate the cost-effectiveness of cefotaxime sodium at a dosage of 12 g/day vs nafcillin sodium and tobramycin sulfate for the treatment of serious infection, the hospital and physician charges of patients enrolled in a prospective, randomized, clinical trial were analyzed. For 187 patients receiving therapy empirically, mean hospital charges for the interval in which the trial antibiotics were used were $3,550 +/- $1,740 for cefotaxime and $3,160 +/- $1,990 for nafcillin and tobramycin. After adjusting for cost-generating factors, charges for cefotaxime were greater than for nafcillin and tobramycin, but the difference was not significant. For 107 patients with clinically or bacteriologically documented infection, mean charges were $3,980 +/- $1,800 for cefotaxime and $4,170 +/- $1,780 for nafcillin and tobramycin. Adjusted charges did not differ. Incremental charges for cefotaxime per additional response were $1,630 in all patients and -$820 in patients with clinically or bacteriologically documented infections.

Bacterial Infections↗
PubMed1985

Lack of evidence for interaction between tobramycin and shock in their effect on renal function.

We sought to determine whether there was an interaction between aminoglycoside use and shock in their effect on renal function among seriously ill patients suspected of having gram-negative sepsis. Serial serum creatinine determinations were used to estimate changes in creatinine clearance rates in 179 patients entered onto a prospective randomized trial of tobramycin-nafcillin versus cefotaxime. A 25% decline in estimated creatinine clearance was considered to be clinically important. Univariate chi-square analysis showed that both shock (P less than 0.01) and tobramycin use (P less than 0.001) were independently associated with decline in estimated creatinine clearance. A two-way analysis of variance showed that both shock (F = 10.44, P less than 0.01) and tobramycin use (F = 42.6, P less than 0.001) continued to be significantly associated with renal dysfunction in the presence of each other, but there was no significant interaction between shock and tobramycin in their effect (F = 0.62, P less than 0.43). A multiple logistic regression with an interaction term representing the occurrence of shock and tobramycin use simultaneously yielded similar results. Our study provided no analytic evidence supporting the existence of an interaction between shock and aminoglycoside use in their effect on renal function.

Analysis of Variance↗
PubMed1984

Association of aminoglycoside plasma levels with therapeutic outcome in gram-negative pneumonia.

To determine the association of aminoglycoside plasma levels with therapeutic outcome in gram-negative pneumonia, the case reports of 37 patients from four prospective, randomized, controlled trials of gentamicin, tobramycin, and amikacin were analyzed. Twenty (54 percent) of these patients had a favorable outcome. Patients with maximal one-hour postinfusion (peak) levels of 7 micrograms/ml or greater for gentamicin and tobramycin or 28 micrograms/ml or greater for amikacin more often had successful outcomes (14 of 20, 70 percent) than those with levels less than this (six of 19, 32 percent) (p less than 0.006). Patients with overall mean peak levels of 6 micrograms/ml or greater for gentamicin and tobramycin or 24 micrograms/ml or greater for amikacin more often had successful outcomes than those with levels less than this (six of 17, 35 percent) (p less than 0.04). The initial patient temperature, serum urea nitrogen/creatinine ratio, initial polymorphonuclear leukocyte count, and age were also associated with outcome; but by multivariate analysis, achieving an adequate peak concentration was the most important discriminating factor. These results suggest the potential importance of achieving adequate aminoglycoside levels in patients with gram-negative pneumonia.

Adult↗
PubMed1984

Risk factors for the development of auditory toxicity in patients receiving aminoglycosides.

Risk factors for the development of auditory toxicity in patients receiving aminoglycosides were determined from the analysis of 135 patients enrolled in three prospective, randomized, double-blind clinical trials of gentamicin, tobramycin, and amikacin. Auditory toxicity, defined as a decrease in auditory acuity of greater than or equal to 15 dB, occurred in 30 patients (22.3%). Patients with auditory toxicity underwent therapy for a longer period, were more likely to be bacteremic, and had, on the average, a higher temperature (P less than 0.05). Using stepwise discriminant analysis, we selected these factors with liver dysfunction and the serum urea nitrogen:serum creatinine ratio in a function that accurately discriminates between toxic and nontoxic patients. Factors not adding significantly to the predictive accuracy of the equation were plasma aminoglycoside levels, aminoglycoside type, furosemide use, diabetes, age, sex, renal function, initial auditory acuity, hematocrit value, and shock. This analysis may be important both for determining the pathophysiology of auditory toxicity and for the prognostic stratification of patients receiving aminoglycosides in clinical trials.

Amikacin↗
PubMed1984

The association of aminoglycoside plasma levels with mortality in patients with gram-negative bacteremia.

To determine the association of aminoglycoside levels with mortality from gram-negative bacteremia, we analyzed the case reports of patients from four prospective, randomized, and controlled clinical trials of gentamicin, tobramycin, and amikacin. Twelve (13.5%) of 89 patients died. One (2.4%) death occurred in 41 patients with early (1-hr postinfusion) peak concentrations of greater than 5 micrograms/ml of gentamicin and tobramycin and of greater than 20 micrograms of amikacin/ml; nine deaths (20.9%) occurred in 43 patients with lower concentrations. Five (8.3%) deaths occurred in 60 patients with mean peak concentrations for the entire course of therapy of greater than 5 micrograms/ml of gentamicin and tobramycin and of greater than 20 micrograms of amikacin/ml; five (20.8%) deaths occurred in 24 patients with lower concentrations. Stepwise discriminant analysis showed that therapeutic early peak concentration was a significant factor in the presence of three other factors: severity of underlying illness, peak temperature, and initial leukocyte count. The results suggest the importance of achieving adequate early aminoglycoside levels in patients with gram-negative bacteremia.

Adult↗
PubMed1984

Risk factors for nephrotoxicity in patients treated with aminoglycosides.

Risk factors for nephrotoxicity in patients treated with aminoglycosides were determined from the case records of 214 patients in two prospective, randomized clinical trials of gentamicin and tobramycin. Nephrotoxicity, defined as a 50% or greater fall in calculated creatinine clearance, developed in 30 patients (14.1%). Patients with nephrotoxicity had higher initial calculated creatinine clearances, were more often women, and were more likely to have liver disease. Using stepwise discriminant analysis, these factors were selected with the initial 1-hour post-dose aminoglycoside level, patient age, and shock. An equation was generated that was accurate in discriminating between patients with and without nephrotoxicity when validated in an independent population. Factors that did not add significantly to the equation were diabetes, dehydration, serum bicarbonate, bacteremia, urinary tract infection, gentamicin or tobramycin use, duration of therapy, total aminoglycoside dose, or the use of clindamycin, furosemide, or cephalothin.

Aged↗
PubMed1984

Comparative cost effectiveness of gentamicin and tobramycin.

Gentamicin and tobramycin were compared for cost effectiveness in the treatment of adult patients with serious infections in a general medical service. We used data from a randomized double-blind trial in which the only observed difference between the clinical effects of these aminoglycosides was the incidence of nephrotoxicity (26% with gentamicin and 12% with tobramycin). According to 1984 cost data, the combined average drug and nephrotoxicity costs per patient were $127 for tobramycin and $72 for gentamicin. An extensive sensitivity analysis--varying frequency and cost of nephrotoxicity, dialysis requirements, aminoglycoside acquisition costs, and length of hospitalization--showed gentamicin to be more cost effective than tobramycin, unless hospitalization is prolonged by an average of at least 15 days for patients with severe nephrotoxicity or at least 3 days for all patients with moderate or severe nephrotoxicity.

Adult↗
PubMed1983

Effects of streptozotocin diabetes and fasting on intracellular sodium and adenosine triphosphate in rat soleus muscle.

The hypothesis that part of the insulin transduction system consists of a co-ordinated stimulation of the Na pump and of Na-H exchange by the hormone (Moore, 1981) requires that insulin plays a physiological role in the regulation of intracellular Na+. Moreover, this model predicts that in hypoinsulinaemic states, such as diabetes and fasting, intracellular pH and intracellular ATP levels would be depressed. The present study tests the hypothesis that in hypoinsulinaemic states intracellular Na+ is increased and intracellular ATP is decreased by measuring these parameters in soleus muscles removed from both diabetic and fasted rats. When rats were made diabetic by injection of streptozotocin (SZ) plasma insulin significantly decreased by 24 hr and plasma glucose and triglyceride levels increased. Intracellular Na+ was significantly elevated by 48 hr after injection of SZ. The elevation ranged from 18 to 48% and persisted for the duration of the experimental observation (up to 28 days). Intracellular ATP decreased significantly by the seventh day after SZ injection and remained depressed by about 24% for the duration (35 days) of the observation. In one series, a significant negative correlation was seen between plasma insulin levels and intracellular Na+ of both SZ-diabetic animals and their controls. Intracellular Na+ also significantly increased when hypoinsulinaemia was induced by fasting. Again, intracellular ATP did not decrease until after the elevation of intracellular Na+. After 72 hr of fasting, intracellular ATP was still decreased in spite of normal plasma glucose levels. Insulin therapy of SZ diabetic rats restored intracellular ATP and plasma glucose to normal, but did not restore intracellular Na+ to normal levels. The results confirm two predictions of the 'insulin transduction system model (Moore, 1981). Most strongly supported is that part of the model which indicates that the Na pump is regulated by physiological levels of insulin. This is especially convincing since hypoinsulinaemia produced by a non-pharmacological procedure, fasting, was associated with an increase in intracellular Na+.

Adenosine Triphosphate↗