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Biomedical subjects

K E Muller

Publications and source records attributed to K E Muller.

At least 37 records · Page 2Linked to original sources
PubMed1992

Treatment of progressive membranous glomerulopathy. A randomized trial comparing cyclophosphamide and corticosteroids with corticosteroids alone. The Glomerular Disease Collaborative Network.

OBJECTIVE: To determine if deterioration in renal function could be ameliorated by adding cyclophosphamide to corticosteroid therapy in patients with progressive membranous glomerulopathy. DESIGN: Randomized, controlled treatment trial. Patients were followed for a mean of 29.2 +/- 17.1 months. SETTING: Collaborative network of 120 university and private-practice nephrologists. PARTICIPANTS: Patients with membranous glomerulopathy whose renal function deteriorated (as evidenced by doubling of the serum creatinine level, a 50% fall in the glomerular filtration rate, or a sustained serum creatinine level of greater than 2.0 mg/dL [reciprocal creatinine value, 0.5], or whose nephrotic range proteinuria persisted in association with morbid complications. Of 156 patients with biopsy-proven membranous glomerulopathy, 36 became eligible for randomization. Twenty-six of these 36 patients were randomly assigned to receive one of the two treatments. INTERVENTIONS: Pulse methylprednisolone, oral corticosteroids, and 6 months of intravenous cyclophosphamide or alternate-day corticosteroid therapy alone. MAIN RESULTS: At entry, no statistical differences were found between the treatment groups in duration of renal disease, age, gender, serum creatinine level, 24-hour urine protein excretion, or biopsy stage. The groups showed no difference in mean arterial blood pressure during follow-up. Four of the 13 patients receiving corticosteroids alone and 4 of the 13 patients receiving corticosteroids plus intravenous cyclophosphamide progressed to end-stage renal disease during follow-up. Reciprocal creatinine values tested at 6-month intervals showed no statistical differences between treatment groups at any time point. The log of the 24-hour protein excretion values showed no statistical differences between treatment groups after treatment. The power to detect a substantial improvement in renal function, defined as a doubling of the reciprocal of the serum creatinine, at the 0.05 significance level was 0.92. CONCLUSIONS: Combination therapy with intravenous cyclophosphamide and corticosteroids, when compared with corticosteroid therapy alone, does not improve renal function in patients with progressive membranous glomerulopathy.

Adult↗
PubMed1988

Babble and random-noise masking of speech in high and low context cue conditions.

"Perceptual" masking of speech by multitalker speech (babble) has been widely reported but poorly quantified. Furthermore, the validity of the construct of perceptual masking is questionable. This report describes an experiment using a newly standardized test of speech perception in noise (SPIN) with both babble and spectrally matched random-noise maskers. Classical psychophysical ogive curves were used to model speech recognition as a function of signal-to-noise ratio (S/N). The two maskers yielded speech recognition functions of the same steepness but different locations on the S/N axis. The high-context items of SPIN yielded speech recognition curves with steeper slope and different locations on the S/N axis than the low-context items. These data are used to argue that perceptual masking was not documented (under certain assumptions) and that the superior masking of babble may be explained in purely acoustical terms. Speculations are offered about the possible acoustical differences that could be responsible for the differences in masking effect.

Acoustics↗
PubMed1984

Toluene levels in blood and brain of rats as a function of toluene level in inspired air.

The relationship of toluene concentration in blood and brain to the concentration of toluene in inspired air has not been explicitly studied. Sixty rats were exposed by inhalation to 50, 100, 500, or 1000 ppm toluene for 3 hr. Immediately following exposure, venous blood samples and whole brains were collected and assayed for toluene levels. For several empirical reasons, the natural logarithm (log) of toluene tissue levels were predicted in a linear model from log toluene levels in air. An additional 10 rats were exposed to 550 ppm toluene for 8 hr in order to verify that the 3-hr exposure was sufficient to produce near-asymptotic levels of toluene in blood and brain. Log brain toluene concentration was significantly higher than log blood concentration by an additive constant. The ratio of brain to blood toluene level was estimated as 1.56/1. Three- and eight-hour exposure results did not differ, thus indicating that these results would hold for toluene exposures of 3 hr or greater.

Animals↗
PubMed1984

Toluene blood level following subcutaneous injection of toluene in the rat.

A model of toluene level in blood following subcutaneous injection of toluene mixed with polyoxyethylated-vegetable-oil vehicle was developed. The purpose was to provide a means of predicting dose received for subsequent toxicologic studies for any time and dose combination. The pharmacokinetics were of secondary interest. Using data from 111 rats, a four-parameter equation was devised to predict the time course of toluene blood level from 20-480 min post dosing, for dose levels of 50-1000 mg/kg. Blood concentrations rose at a rate which was independent of dose level. Maximum blood levels were uniquely determined by dose level. Blood levels fell at different rates depending upon dose level. Injection exposure, when compared to inhalation, has the advantages of (a) low expense, (b) low equipment requirements, and (c) simplicity. The disadvantage is, for some experiments, poor temporal stimulation of the normal route of administration, inhalation.

Animals↗
PubMed1984

Recommendations for appropriate statistical practice in toxicologic experiments.

Appropriate statistical practice in toxicologic research is reviewed. The problem centers on the antagonistic needs to discover toxic effects and avoid false indictments of harmless compounds. Specific problems which distort error rates include having many dependent variables, conducting many tests on a variable, data snooping, lack of statistical power and 5) violations of statistical assumptions. Solution strategies include top down planning, designing efficient experiments, balancing type I and type II error rates, selecting hypotheses and 5) using appropriate statistical analysis methods. Top down planning and the "leapfrog" design strategy are particularly emphasized.

Research Design↗
PubMed1981

Effects of age and body lead burden on CNS function in young children. I. slow cortical potentials.

The effects of body Pb burden on slow cortical potentials were studied in 63 children aged 13-75 months. Slow wave (SW) voltage during sensory conditioning varied as a linear function of blood lead (PbB) level. The slope of this function, moreover, changed systematically with age. For children under 5 years of age, SW voltage tended to be positive at low PbBs and to be negative above 30 micrograms/dl. For children over 5 years of age, SW voltage tended to be negative at low PbBs and to be less negative (or positive) above 30 micrograms/dl. These results provide evidence of altered CNS function at the lowest Pb effect level ever reported.

Aging↗
PubMed1981

Effects of age and body lead burden on CNS function in young children. II. EEG spectra.

This study explored the effects of age and PbB upon EEG power spectra and various measures of hemispheric laterality in children, aged 13-75 months, watching a display (cartoon). The following are the principle conclusions: (1) The delta- and theta-band amplitude decreased with age. (2) When only bilaterally synchronized EEG between P3 and P4 was considered, the amplitude of P3 was estimated as greater than P4 in all frequency bands and for all ages. Previous reports have not shown lateral EEG dominance in children below 75 months. (3) When lateral dominance measures consider only the relationship between synchronized EEG at P3 and P4, bilateral communality in the delta band increased with age. (4) Increased PbB generally produced an increase in the relative amplitude of synchronized EEG between P3 and P4 in all frequency bands. This was true for PbB levels well below 15 micrograms/dl, among the lowest level PbB effects previously reported. No clinical or behavioral effects of PbB values have been reported below 15 micrograms/dl. It appears to be theoretically and practically important to understand the functional significance of bilaterally synchronized activity. The signal processing of the CNS can be explored using these methods. Greater understanding of these data would help define the extent and etiology of PbB effects on the CNS

Aging↗
PubMedDate not supplied

Guidelines for managing datasets, programs and printouts in scientific research.

This paper presents guidelines and naming conventions to assist in managing datasets, programs and printouts for small to medium sized research projects. First, the limits and nature of the type of project are considered. A number of definitions are included to help further specify the problem. Four main areas are addressed. First, a consistent set of rules for naming programs and datasets is presented. Next, techniques for storing and archiving the programs and datasets are presented, using the naming conventions just developed. Third, rules for printout management are given, based on the naming rules. Finally, the documentation of all components of the project is discussed. Although trivial to implement, adherence to the naming rules provides a sound basis for a high quality, easy-to-use documentation system.

Computers↗
PubMedDate not supplied

Effect of low level carbon monoxide on compensatory tracking and event monitoring.

Experiments by Putz et al. concerning the effect of carbon monoxide (CO) exposure on compensatory tracking and monitoring in healthy young men were replicated. Task and procedural variables were reproduced as closely as practical. Subjects were exposed to either room air or 100 ppm CO. Mean carboxyhemoglobin (COHb) levels in the high CO exposure groups were 5.1% for Putz et al. (70 ppm exposure), and 8.24% for the present study (100 ppm exposure). In both studies elevated COHb produced a statistically significant increase over time in log mean absolute deviation scores (tracking error) with respect to control groups. The magnitude of the effect was smaller in the present study, perhaps because of subtle methodological or training differences between studies. The relationship between task difficulty and magnitude of CO-induced dysfunction remains unresolved. In contrast to Putz et al., no statistically significant effect of COHb in monitoring behavior was found. The failure to replicate this feature of may reflect the large differences in baseline performance, and higher variance in the present study.

Adult↗
PubMedDate not supplied

Absence of symptoms with carboxyhemoglobin levels of 16-23%.

It has been generally accepted that carboxyhemoglobin levels between 10-20% produce mild headaches, dizziness and/or nausea. Experimental double blind exposures of 18 healthy, nonsmoking young men at rest to 7,000-24,000 ppm CO, designed to elevate COHb to 15-20% in 3-5 minutes, were followed by exposure to 232 ppm CO designed to maintain COHb level for a total of 130 minutes. Resulting COHb values were 16-23%. These COHb values did not produce significantly more symptoms (as reported in an open-ended questioning) than reported in the control group (n = 23). Subjects were especially queried about headache, dizziness and nausea. The symptoms which were previously reported in clinical studies of CO poisoning may have resulted from CO exposure in combination with (a) exposure to other substances, (b) stress due to the event that precipitated medical attention or (c) higher COHb levels before the first blood sample was taken.

Adolescent↗
PubMedDate not supplied

The effects of low-level carbon monoxide exposure upon evoked cortical potentials in young and elderly men.

The neurophysiological effects of acute, low-level carbon monoxide (CO) exposure are not well known. This experiment investigated the effects of a 5% carboxyhemoglobin level upon two indices of neurophysiological function, reaction time and the late positive component of the visual evoked potential in young and elderly men. Results indicated (1) no effects of CO upon any of the neurophysiological indices and (2) greater absorption of CO by young than by elderly men. These results, along with those of other studies, indicate that acute, low-level CO exposure is probably not neurotoxic, in normal, healthy men.

Adolescent↗
PubMedDate not supplied

Compensatory tracking in humans with elevated carboxyhemoglobin.

A total of seventy-four men divided into five groups performed a compensatory tracking task for 4 hr with group mean carboxyhemoglobin (COHb) levels of 0.9, 5.6, 6.1, 11.4 or 16.6%. In all but one group, COHb was formed in approximately 5 min by having the subject breathe a high concentration of carbon monoxide (CO) from a Douglas bag. An appropriate low level of CO in the exposure/test chamber maintained the elevated COHb for the 4-hr duration of the experiment. A slow COHb formation group, not exposed to CO during bag breathing, which was only exposed to low-level CO in the exposure/testing chamber, served as a positive control. Even though mean tracking error scores increased in a nearly monotone manner as a function of COHb, the effects were not statistically significant. Even at the highest dose, the increase in tracking error was small. The increased mean error score due to rapid formation was virtually the same as that due to slow formation.

Adult↗
PubMedDate not supplied

Dose-effects functions for carboxyhemoglobin and behavior.

Literature on dose-effects functions of carboxyhemoglobin (COHb) and human behavior is internally inconsistent. A recent study was performed to describe such a function for tracking behavior in humans (7). No significant effects were found, however, even for COHb levels up to ca. 17%. The present review and analysis of published data was undertaken to attempt to reduce uncertainty about COHb dose-effects functions. Dose-effects data from six laboratory animal operant behavior studies were reviewed. Maximum COHb levels ranged from 33 to 59%. Data were converted to a common metric and dose-effects functions were fitted. The preferred function was nonlinear, with a shallow slope, indicating small effects (if any) for COHb levels less than ca. 20%. As COHb increased further, the slope of the function became progressively steeper. Review of the human dose-effects function publications for COHb and behavior revealed that no significant findings had survived the test of direct or partial replication. Other studies found no significant effects. A dose-effects curve was fitted to the human data from one study (7) and compared to the laboratory animal curves. Extrapolation of the human curve was used to suggest that the dose-effects curves for humans and laboratory animals were of similar form and that effects of COHb on behavior in man are small or absent below ca. 20%. It is also possible that some uncontrolled variables are affecting the results so that COHb produces effects only some of the time. No conclusion can be drawn from the body of literature due to the divergence of results.

Animals↗
PubMedDate not supplied

Increasing scientific power with statistical power.

A survey of basic ideas in statistical power analysis demonstrates the advantages and ease of using power analysis throughout the design, analysis, and interpretation of research. The power of a statistical test is the probability of rejecting the null hypothesis of the test. The traditional approach to power involves computation of only a single power value. The more general power curve allows examining the range of power determinants, which are sample size, population difference, and error variance, in traditional ANOVA. Power analysis can be useful not only in study planning, but also in the evaluation of existing research. An important application is in concluding that no scientifically important treatment difference exists. Choosing an appropriate power depends on: a) opportunity costs, b) ethical trade-offs, c) the size of effect considered important, d) the uncertainty of parameter estimates, and e) the analyst's preferences. Although precise rules seem inappropriate, several guidelines are defensible. First, the sensitivity of the power curve to particular characteristics of the study, such as the error variance, should be examined in any power analysis. Second, just as a small type I error rate should be demonstrated in order to declare a difference nonzero, a small type II error should be demonstrated in order to declare a difference zero. Third, when ethical and opportunity costs do not preclude it, power should be at least .84, and preferably greater than .90.

Data Interpretation, Statistical↗
PubMedDate not supplied

Neurophysiological effects of 30 day chronic exposure to toluene in rats.

Long-Evans hooded rats were exposed to 1000 ppm toluene or 0 ppm toluene 6 hr/day, 5 days/week for 30 days. Following removal from the exposure conditions (18-26 hr) flash-evoked potentials were recorded to paired light flashes and pentylenetetrazol (PTZ) seizure properties were examined. No alterations were found in the response to the first flash, but alterations in the recoverability of the nervous system were demonstrated by significant latency shifts in the response to the second of the paired flashes, using first flash latencies as covariates. No significant alterations were found in PTZ seizures. The data indicated that at these exposure levels toluene produced a small but significant alteration in brain function, even after toluene had been completely metabolized.

Animals↗