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Biomedical subjects

C E Webb

Publications and source records attributed to C E Webb.

16 recordsLinked to original sources

Impact of alpha-bungarotoxin on transmitter release at the neuromuscular junction of the rat.

The drug, alpha-bungarotoxin (BTX) is believed to be a 'pure' nicotinic antagonist. Hence, use of this drug should avoid the secondary actions associated with other nicotinic antagonists. The hypothesis that the motor nerve terminal responds to the presence of acetylcholine (ACh) by releasing less transmitter was tested by examining the effects of BTX on end-plate potentials (EPPs), miniature end-plate potentials (MEPPs), and quantal release at the rat diaphragm neuromuscular junction. Analysis of EPP and MEPP amplitudes and quantal release demonstrate that BTX significantly increases transmitter release at the onset of tetanic stimulation (50 Hz). Like other nicotinic antagonists, BTX was not able to sustain enhanced quantal release during a brief train of 40 stimuli and resulted in greater decline in EPP amplitude during tetanic stimulation. The data suggests that negative feedback regulation by presynaptic autoreceptors only serves a functional role at the onset of stimulation and that other factors such as transmitter supply or adenosine regulation may serve to dominate transmitter release during maintained tetanic stimulation.

Action Potentials

Variables affecting creatinine clearance prediction.

Patient data were analyzed retrospectively to evaluate the relationship between several body-weight variables and creatinine production and clearance. Data from 722 creatinine clearance determinations in 627 patients older than 12 years were analyzed. Weight variables were actual body weight (ABW), lean body weight (LBW), ideal body weight (IBW), and lean body mass (LBM). Weight-independent and weight-dependent clearance prediction methods were evaluated. Actual creatinine clearance values were compared with these predictions. Use of LBW and IBW produced equivalent estimates of creatinine clearance that were closer to measured values than those obtained with ABW. The use of LBW or IBW was not appropriate in patients less than 60 inches tall nor in morbidly obese patients. Weight-dependent clearance estimation was superior to weight-independent predictions in morbidly obese patients. A new LBM-based clearance estimation formula was derived; it may be useful for patients less than 60 inches tall. The use of LBM, particularly in patients less than 60 inches tall, should be investigated further.

Adult

A multicenter evaluation of variables affecting the predictability of creatinine clearance.

Data from 722 urine collections (627 patients) from 14 medical facilities were used to compare measured creatinine clearance values with clearance estimates calculated using three "urine-free' mathematical formulas. The influence of two patient weight variables (actual weight, lean body weight) and the level of renal function on clearance prediction was assessed. In addition, site parameters (region, facility), time parameters (month, day, day of the week), and patient parameters (age, sex, height, weight, diagnoses) were evaluated for their statistical influence on the relationship between measured clearance and estimates calculated with one of the methods. Strong, statistically significant correlations were observed between clearance values estimated with each prediction method and measured clearances. Although statistical differences were noticed between mean values predicted with each method, these differences were clinically insignificant. Use of lean body weight for calculation of creatinine excretion produced clearance estimates that were significantly lower than those obtained with actual weight and substantially closer to measured clearance values. Among patient variables, age and two specific diagnoses (congestive heart failure and pregnancy), were statistically associated with variability in the relationship between measured and predicted clearance. Interregional and interfacility differences in the measured-predicted clearance relationship, variability associated with the day of the week of collection, and tendency of the urine-free formulas to over-predict clearance support potential inaccuracy of measured clearance determination. The results suggest that inaccuracies in clearance determination, rather than inadequacies of urine-free prediction methods, account for the majority of the observed variability in the relationship.

Age Factors

Multicenter evaluation of six methods for predicting warfarin maintenance-dose requirements from initial response.

Warfarin maintenance-dose requirements predicted by six mathematical methods based on initial response to therapy were compared with patients' actual dose requirements in a multicenter trial. Data were collected for patients who had received an initial regimen of warfarin sodium 10 mg orally every 24 hours for three days and for whom a prothrombin time (PT) had been determined 16-20 hours after the third dose. Patients' individual dose requirements and PT values were recorded during one to three follow-up visits after discharge from one of seven medical centers. Prothrombin ratios (patient PT divided by control PT) calculated on day 4 were used for maintenance-dose prediction by five methods; a sixth method was based on the cumulative warfarin dose-PT response curve up to a PT value of 20 seconds. For 54 men and 30 women who qualified for the study, 197 maintenance-dose-PT response measurements were recorded; 95 in the first four weeks of therapy, 76 during weeks 5-12, and 26 at 6-12 months after initial treatment. Prothrombin ratios were within the therapeutic range (PT 1.5-2.5 times the control value) in 154 observations, and the mean actual warfarin sodium maintenance dose associated with therapeutic response was 7.6 mg/day. For patients with therapeutic prothrombin ratios, dose predictions by the five methods using prothrombin ratios (PRs) correlated significantly with actual dose requirements. The formula that predicted doses numerically closest to the actual dose is as follows: Dose = 11.17 - 21.08 (log PR). Only 45 observations were obtained for the sixth prediction method, and the correlation between actual and predicted doses was not significant. Initial warfarin maintenance-dose requirements can be predicted effectively based on one PT determination after administration of three daily 10-mg doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult