Toe temperature versus transcutaneous oxygen tension monitoring during acute circulatory failure

Measurements of toe temperature and transcutaneous PO₂ (P_tcO₂) have been both suggested for non-invasive assessment of peripheral blood flow in acute circulatory failure. The underlying principle of the two methods is that cutaneous vasoconstriction occurs early when tissue perfusion is altered. In 15 patients, we compared the two measurements during cardiogenic shock (27 measurements) or septic shock (29 measurements). Toe-ambiant temperature gradient and P_tcO₂ correlated well together (r=0.66, p(0.001) especially in hyperkinetic septic shock (r=0.79, p(0.001). In cardiogenic shock, toe-ambiant temperature correlated well with cardiac index (r=0.63), stroke index (r=0.64) and oxygen transport (r=0.65), and these correlations were stronger than for P_tcO₂. In septic shock, both techniques were poor indicators of blood flow indexes but P_tcO₂ rather correlated with arterial pressure (r=0.66) and left ventricular work (r=0.66). Trend evaluation of data revealed in cardiogenic shock that the increase in toe temperature usually preceded the increase in P_tcO₂. Since measurement of P_tcO₂ is technically more complicated, correlates less well with standard hemodynamic parameters and later reflects cardiovascular improvement, it has no advantage over measurement of toe temperature in circulatory shock. In cardiogenic shock, measurements of toe temperature can reliably track cardiac output changes. In septic states, however, non-invasive assessment of skin perfusion is of limited interest.     

A comparative study on the diagnostic value of prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA) in patients with carcinoma of the prostate gland

Serum prostatic-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined simultaneously in 241 patients presented to the Urology Department. The patients consisted of 140 prostatic carcinoma patients (34 newly diagnosed and 106 previously treated) and 101 patients with benign prostatic hypertrophy (BPH). Prostatic acid phosphatase was measured by two different methods, an enzymatic method (PAP-EA, Boehringer) with tartrate inhibition and an immunoenzymetric assay (PAP-IEMA, Hybritech). The concentration of prostatic specific antigen in serum was measured using a recently introduced immunoradiometric assay (PSA-IRMA, Hybritech). Receiver operating characteristic curves were constructed to compare the diagnostic value of the different tests at different cutoff values. The diagnostic efficiencies of the PAP-EA and the PAP-IEMA appeared to be similar. A better diagnostic efficiency for PSA compared to PAP was found independent of the cutoff value. The upper-normal limit of 2.7 micrograms/l for PSA, as suggested by the manufacturer and mentioned in the literature introduces too many false-positive results. We therefore selected 10 micrograms/l as the upper-normal limit for PSA (sensitivity 57%, specificity 88%). Combined sensitivity found for PAP + PSA was 37% with a specificity of 97%. A literature survey is included to allow better comparison with data published elsewhere.     

Evidence for nitric oxide participation in down-regulation of CYP2B1/2 gene expression at the pretranslational level

Septic or inflammatory stimuli suppress drug metabolism by cytochrome P-450 in the liver, presumably at the pretranslational level. We have shown previously that nitric oxide is responsible at least in part for the inhibition by bacterial lipopolysaccharide of phenobarbital-induced CYP2B1/2 activity in vivo. This was attributed to the interaction of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report that endogeneous nitric oxide also contributes to LPS-induced suppression of CYP2B1/2 in vivo by down-regulating the expression of CYP2B1/2 protein and mRNA.     

FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

Comparison of Ampicillin-Sulbactam and Ticarcillin-Clavulanic Acid in Patients With Chronic Renal Failure: Effects of Differential Pharmacokinetics on Serum Bactericidal Activity

Study Objectives . To evaluate the pharmacodynamic antibacterial activity of ticarcillin-clavulanic acid (T-C) and ampicillin-sulbactam (A-S) combinations against reference bacterial strains in patients with end-stage renal disease maintained on long-term hemodialysis. Design . Randomized, crossover, controlled study. Setting . National Institutes of Health-funded general clinical research unit in a Veterans Administration Medical Center. Patients . Nine adult men with end-stage renal disease maintained on long-term hemodialysis. Two subjects did not complete the study due to problems of vascular access, and another withdrew for personal reasons. Interventions . On a nondialysis day, each subject was randomly administered either T-C 3.1 g or A-S 3 g as a slow intravenous infusion over 30 minutes. Serial blood samples were collected for measurement of antibiotic serum concentrations and determination of serum bactericidal titers. Following a washout period, the study was repeated with the alternative antibiotic combination. Measurements and Main Results . The mean observed apparent β-half-life of clavulanic acid was substantially shorter than that for the other three drugs. The bactericidal activity of both A-S and T-C against non-β-lactamase-producing (Nβ-LP) strains of S. aureus and E. coli was consistently high, as indicated by geometric mean SBTs of at least 1:5 at 24 hours. Against β-lactamase-producing (β-LP) S. aureus, the geometric mean SBTs for A-S were at least 1:25 throughout the study period, while the geometric mean SBTs for T-C decreased over 24 hours from 1:29 to 1:6. Against β-LP E. coli, the bactericidal activities for both A-S and T-C were poor, with geometric mean peak SBTs of only 1:6 and 1:3, respectively. The geometric mean SBT for T-C against this E. coli strain had declined to 1:1 at 6 hrs. Conclusion . Increasing the dosing interval for T-C in patients with end-stage renal disease may lead to periods of insufficient clavulanic acid to protect ticarcillin from β-lactamase degradation.     

Flip side of synaptic plasticity: Long-term depression mechanisms in the hippocampus

There is growing interest in the phenomenon of long-term depression (LTD) of synaptic efficacy that, together with long-term potentiation (LTP), is a putative information storage mechanism in mammalian brain. In neural network models, multiple learning rules have been used for LTD induction. Similarly, in neurophysiological studies of hippocampal synaptic plasticity, a variety of activity patterns have been effective at inducing LTD, although experimental paradigms are still being optimized. In this review the authors summarize the major experimental paradigms and compare what is known about the mechanisms of LTD induction. Although all paradigms appear to initiate a cascade of events leading to an elevated level of Ca²⁺ postsynaptically, the extent to which these paradigms involve common expression mechanisms has not yet been tested. The authors discuss several critical experiments that would address this latter issue. Numerous questions about the properties and mechanisms of LTD(s) in the hippocampus remain to be answered, but it is clear that LTD has finally arrived, and will soon be attracting attention equal to its flip side, LTP. © 1994 Wiley-Liss, Inc.     

Dexfenfluramine in the treatment of severe obesity: a placebo-controlled investigation of the effects on weight loss, cardiovascular risk factors, food intake and eating behaviour.

Dexenfluramine, an effective and safe serotoninergic drug with anorectic and possible food-selection-tuning properties, was investigated in a placebo-controlled study of 1 year's duration in severe and refractory obesity. The aim of the study was to assess weight loss, and changes in cardiovascular risk factors, food intake and eating behaviour. Dexfenfluramine- and placebo-treated patients achieved a similar weight loss (greater than 10% of initial weight, by 39.5 and 30.0%, greater than 20% of initial overweight by 42.1% and 32.5% and greater than 10 kg by 41.4 and 33.3%, respectively, of the initial cohorts). Furthermore, the decreases in weight (10.7 vs. 8.0 kg), in body mass index (3.9 vs. 2.9 kg m2) and in waist/hip ratio (0.04 vs. 0.02) were not significantly different. After discontinuation of the drug, the increase in weight (2.8 vs. 1.0 kg) was significantly higher in the dexfenfluramine-treated group. Except for a borderline better effect on glucose of dexfenfluramine, both groups showed similar beneficial changes in food intake and cardiovascular risk factors. Eating behaviour in response to emotional and external stimuli was comparable in the two groups, but placebo-treated patients had to restrain their eating more in order to achieve the same weight loss. Notwithstanding the fact that weight losses and an associated amelioration of health-risk factors were of similar magnitude in dexfenfluramine- and placebo-treated patients, dexfenfluramine might have a useful role in promoting a less stressed adherence to prolonged restriction of energy intake in the severe and refractory obese subject.