Plasma tumor necrosis factor and mortality in critically ill septic patients

Tumor necrosis factor (TNF) cachectin has been implicated as an important host mediator responsible for shock and multiple organ failure (MOF) observed during sepsis. Using a sensitive enzyme-linked immunosorbent assay, we measured plasma TNF levels in 43 septic patients suffering from a broad range of diseases. Measurements were taken on the day that sepsis was diagnosed. Eleven patients had detectable TNF plasma levels ranging from 10 to 100 pg/ml (TNF-positive group); in 32 patients circulating TNF could not be detected (TNF-negative group). The groups did not differ significantly as to age, underlying disease, percentage positive bacteremia and bacteriologic profile, sepsis score, and extent of MOF. Eight (73%) of 11 TNF-positive patients died from sepsis during ICU stay, vs. 11 (34%) of 32 TNF-negative patients (p less than .05). This study demonstrates that sepsis is accompanied by detectable circulating TNF in 25% of the cases, and for these patients mortality is twice that for comparable TNF-negative patients.     

A simplified method of counting microorganisms in studying human autoflora

Formulae for the calculation of the count of microorganisms isolated from natural bacterial biocenoses of a child's body have been derived. The authors suggest a variant of simplified drip method for the computation of microorganism colonies in solid media. The described method helps cut down the nutrient media consumption at least 3-fold and is time-saving.     

Value of continuous monitoring of the electrocardiogram in asymptomatic subjects

The authors analysed the prevalence of atrioventricular conduction defects and sinus node dysfunction by Holter monitoring in three population groups with similar clinical characteristics: 50 controls (Group I), 17 physically fit subjects with an atrioventricular conduction defect on the resting ECG which was usually asymptomatic (Group II), and 48 professional pilots who were also physically fit but who had no conduction defects on resting ECG (Group III). The 24 hour recordings showed: --a similar incidence of sinus dysrhythmias and atrioventricular conduction defects in the three groups although the frequency of low degree block was a little higher in sportsmen; --a preponderance of the association of first degree block and nocturnal Luciani-Wenckebach periods, sometimes with episodes of Mobitz II block; --the absence of progression to high-degree atrioventricular block. Holter monitoring would therefore seem to be a good method of detecting and following up abnormalities of sinus node function and atrioventricular conduction defects in asymptomatic patients. In addition, it gives a qualitative and quantitative assessment of the recorded changes and provides a means of monitoring their evolution.     

Effect of estrogen on calcium homeostasis and pituitary hormones in the growing chick

An experiment was carried out to investigate the effect of a range of estradiol (E2) doses (0.1-6.5 micrograms/g body wt/day) on vitamin D metabolism and the plasma levels of growth hormone (GH) and prolactin (PRL) in the growing chick. Doses of 0.5-0.7 microgram/g E2, which are insufficient to raise the plasma calcium level, did induce an increase in growth rate, an increase in 25-hydroxyvitamin D 1 alpha-hydroxylase (1-hydroxylase) and 24-hydroxylase activities, and an increase in plasma GH level. These parameters leveled off or fell over the dose range 1-2 micrograms/g E2 but there was evidence of a second peak in 1-hydroxylase activity at 6 micrograms/g E2. At this high dose rate, the plasma Ca level rose to 8 mM, as it does in the laying hen; 24-hydroxylase activity, growth rate, and plasma GH and plasma PRL levels all decreased. It was concluded that the dose response to estrogen in the growing chick is not linear and, in the case of 1-hydroxylase activity, may even be biphasic.     

Hospital charges: analysis and comparison

The validity of studies comparing charges between hospitals is threatened by differences in hospital case mix and severity of illness within diagnoses. The method presented here uses readily available Blue Cross claims data to make interhospital comparisons of charges.     

Cervical cytology in a community laboratory

A retrospective analysis of the results of 27,801 cervical smears from one year in a community laboratory was undertaken. This represented 23,820 individual patients. Abnormalities were seen in 9.3% of patients. Three point seven percent of patients had benign abnormalities, 5.5% had cervical intraepithelial neoplasia and 0.1% had major abnormalities. The incidence of cervical epithelial abnormality was highest in the 15-34 age group but major abnormalities were seen most often in the 55+ age group. Human papillomavirus was more commonly seen in the youngest age group. The presence of inflammation was reported in 65% of the smears. Thirty percent of smears had no endocervical cells and 0.6% were grossly inadequate. Fifteen percent of patients had repeat smears and 3% of total smears were judged unnecessary. Forty two point six percent of patients less than 55 years of age in the laboratory population base had a smear but only 7.9% of those over 55.     

Effect of bacterial purified antigenic fractions on natural defence mechanisms

The in vitro ability of bacterial purified antigenic fractions to interfere with the immune system has been investigated on human mononuclear cells from peripheral blood. Exposure of purified monocytes to the drug at concentrations from 1 to 1000 micrograms/ml, for different periods from 0 to 18 h, significantly increased cell-mediated cytotoxicity against TU5 target cells. Moreover, monocytes exposed for 1 to 18 h to drug concentrations from 0.1 to 1000 micrograms/ml released significant amounts of tumor necrosis factor alpha in a dose-dependent manner in the culture supernatants. The drug was also tested on natural killer (NK) cell activity; mononuclear cells exposed to antigenic fractions for different periods showed a significant increase of NK cytotoxic activity against K562 target cells after 3 and 6, but not 0 and 18 h. Active concentrations were from 1 to 100 micrograms/ml, higher and lower doses being ineffective. Bacterial purified antigenic fractions thus have some ability to interfere in vitro with mechanisms of cytolysis mediated by cells and soluble factors.     

Prediction of steady state bioequivalence relationships using single dose data II-nonlinear kinetics

Two nonlinear pharmacokinetic models were simulated to investigate the relationship between single and multiple dose bioequivalency parameters for drugs such as phenytoin and propranolol which exhibit either saturable elimination kinetics or a capacity limited first pass effect. Mean Tmax, Cmax and area under the plasma-concentration time curve values from 0 to infinity (AUC 0-infinity) were compared after a single and multiple dose(s) of a test or reference drug. The aim was to determine if there were systematic changes in the limits of the single dose confidence interval at steady state that would limit the usefulness of confidence intervals following a single dose in accurately predicting bioavailability following multiple dosing. The 90 per cent confidence interval expressed as a percentage of the reference mean for Tmax, Cmax, and AUC 0-infinity showed model dependent changes from single to multiple dosing in response to the level of data error and changes in absorption. Changes in clearance also seemed to have a marked effect on the observed limits of the single and multiple dose confidence intervals especially for Cmax which showed a characteristic change in the intervals as a function of the clearance ratio. The model used to describe phenytoin had confidence intervals for Cmax and AUC 0-infinity from single to multiple dosing that were similar to that seen for the experimental data. However, the model predictions for Tmax confidence intervals following single and multiple dosing was at variance with the experimental data for formulations A and B.     

Sodium reabsorption by the Henle loop in humans

In a previous study, we described a new method [3] to measure Na reabsorption by each segment of the human nephron independently. Reabsorption was expressed as equivalent volumes of solute-free water (CH2O) generated by the loop of Henle (CH2O-HL) and by the distal tubule (CH2O-DT), and dissipated by back diffusion (BD) across collecting ducts (CH2O-BD). These data were obtained during maximal water diuresis (MWD). The present study was undertaken to calculate CH2O-HL by experiments performed during maximal antidiuresis (MA). For this purpose, a new theoretical approach was devised, described by algebraic equations which allowed calculations of segmental transport during MA alone, where only CH2O-HL could be calculated independently. The study was performed on 14 normal volunteers who were studied twice by clearance measurements, firstly during MWD and again during MA. In each experiment, clearance periods were performed during baseline conditions and during the administration of furosemide (0.7 mg/kg bolus injection followed by 0.06 mg/kg/min maintenance infusion). From the values measured during either condition, segmental reabsorption was calculated. During MWD, CH2O-HL averaged 19.4 + 10.4, during MA 20.4 + 8.0 ml/min/GFR X 100; p greater than 0.05. The paired measurements were significantly correlated (r = 0.80; p less than 0.01). These data demonstrate that CH2O-HL obtained with the original theory is a reproducible result that can be confirmed with independent measurements obtained during different experimental conditions. Thus, measurements of segmental Na transport in the human nephron are feasible and can contribute important informations on disease states.