Atherogenic effects in a non-human primate of Fusarium moniliforme cultures added to a carbohydrate diet.

Adding less than 0.5% w/w of culture material of strain MRC 826 of the fungus Fusarium moniliforme to a carbohydrate diet low in fat resulted in an atherogenic plasma lipid profile in a non-human primate. Simultaneously increased plasma fibrinogen and activity of blood coagulation factor VII could enhance atherogenesis. This unique potential for promotion of atherosclerosis was probably secondary to chronic hepatotoxicity as indicated by liver fibrosis and elevated cholesterol, albumin and the enzymes AST, ALT, LD, GGT and ALP in serum. The cholesterol and enzymes responded in proportion to the calculated doses of fumonisin mycotoxins in the F. moniliforme MRC 826 cultures. Fumonisins are water soluble and heat stable. Thrombotic, hepatotoxic, carcinogenic and cerebral effects of MRC 826 culture material and fumonisins are well known in non-primates. The estimated fumonisin concentrations tested fall within a range due to natural contamination of human foods. The results suggest that all maize grain products should be analysed for fumonisins.     

Myophosphorylase B deficiency and malignant hyperthermia

A 6-year-old boy was examined with the dual purpose of establishing whether he had malignant hyperthermia (MH) and to investigate his complaint of excessive muscle fatiguability. In the course of such investigations, McArdle's disease was diagnosed, and the patient was also identified as an MH-positive reactor.     

Comparison of oxine and tropolone methods for labeling human platelets with indium-111

The effect of the chelates oxine and tropolone, used to label platelets, on the kinetics of indium-111-(111In) labeled platelets was studied in twelve normal human subjects. Autologous platelets were labeled either in saline with 111In-oxine or in plasma with 111In-tropolone. Mean platelet lifespan was estimated by fitting the disappearance curve of platelets from the circulation to the multiple hit and other mathematical models. The in vivo distribution of platelets was quantitatively imaged with a scintillation camera. The in vivo recovery of 111In-oxine and 111In-tropolone did not differ, and the mean platelet lifespan was also similar (111In-oxine: 230 +/- 29 hr; 111In-tropolone: 226 +/- 13 hr). At equilibrium (90 min after reinjection of labeled platelets) and at the end of platelet lifespan, 111In-oxine and 111In-tropolone radioactivities in the spleen and liver were similar. These results demonstrate that the results of kinetics measured with 111In-oxine or 111In-tropolone do not differ significantly.     

Blood platelet kinetics in normal subjects modelled by compartmental analysis

The purpose of this study was to describe the function of platelets throughout their life span by expressing their in vivo distribution and kinetic behaviour in mathematical terms by using multicompartmental analysis. The distribution of indium-111 labelled platelets in five normal subjects was imaged and quantified with a scintillation camera image processing system. Serial blood samples were also obtained. The data were modelled using the SAAM (Simulation Analysis and Modelling) compartmental computer program. Five models were entertained to evaluate the role of platelets that were either functional or injured during collection and their interaction with the liver, spleen and vascular endothelium. Models were evaluated by comparing F values calculated from the least squares estimate obtained from each model. The Dornhorst function was used to describe the sequestration of platelets in the compartmental model. Results indicated that the data could not be satisfactorily simulated when compartments were included that simulated only functional and sequestered platelets (model 1). It was necessary to include compartments that simulated the kinetics of collection-injured plateles in the liver (model 2) and spleen (model 3). The model that simulated the interaction with the vascular endothelium (model 5) showed a visual but not significant improvement in the fitting of the observed data compared to model 3. The mean organ uptake and range indicated in parentheses were calculated at equilibrium. There were 20% (15%–27%) of the injected platelets in the spleen, 10% (8%–11%) in the liver and 70% (64%–75%) in the circulation. The relatively high accumulation of activity in the spleen was as a result of the slow transit time of the functional platelets through the spleen of 5.1 (3.5–6.0) min compared with the transit time through the liver of 0.33 (0.19–0.50) min. The 9% (5%–12%) collection-injured platelets in the spleen and 10% (5%–16%) in the liver had longer transit times than functional platelets. Platelet sequestration was well simulated with the compartmental model. The mean platelet survival time estimated by the compartmental model and standard curve fitting techniques did not differ significantly. A multicompartmental model and reference range for platelet kinetics have been established and may prove to be clinically useful in platelet disease. Correspondence to: M.G. Lötter     

The effect of halothane, enflurane and isoflurane on the circulation

This study, in open-chested dogs, sought to explore the relationship between whole-body oxygen delivery and oxygen consumption during anaesthesia, using increasing concentrations of halothane, enflurane and isoflurane. Results indicate that the cardiac index and oxygen delivery became critical at less than 1 MAC (minimal alveolar concentration of anaesthetic) for the three commonly used vapours. Halothane caused the least depression of contractility, but the stroke volume was reduced by the well-maintained afterload at 1 MAC. Enflurane and isoflurane were associated with more depression of contractility, but the cardiac output was maintained by an increase in heart rate in the case of isoflurane and reduced mean arterial pressure during the use of enflurane.     

Kinetics of In-111-platelets in the baboon: II. In vitro distribution and sites of sequestration

The kinetics and sites of sequestration of a fully representative population of In-111-platelets were determined in 11 baboons. The in vivo method of quantification with computer assisted scintillation camera image analysis was validated by sacrificing 5 baboons and measuring and comparing the distribution of organ radioactivity. Recovery of platelets in the circulation was 87% +/- 7, and their mean survival time was 147 hr +/- 15. The mean splenic platelet pool was 16.0 +/- 1.9. At equilibrium 15.8% +/- 2.9 of the In-111-platelets were in the hepatic blood pool. Senescent platelets were destroyed in the reticulo-endothelial system. The major sites of sequestration were: liver (37.6% +/- 6.0), and the spleen (23.3% +/- 4.6). The bone marrow sequestrated 14.4% +/- 1.7 of the labelled platelets, and 15.5% +/- 4.0 were present in various other tissues. We conclude that the in vivo method of In-111-quantification is accurate. Senescent platelets are mainly sequestrated in the reticuloendothelial tissue, with the liver, spleen and the bone marrow important sites of sequestration.     

Effects of pentoxifylline on cytokine profiles and left ventricular performance in patients with decompensated congestive heart failure secondary to idiopathic dilated cardiomyopathy

Patients with severe heart failure have plasma cytokine concentrations that are more than twofold greater than those in patients with moderate heart failure. Although pentoxifylline, an immunomodulatory agent that inhibits tumour necrosis factor-alpha (TNF-alpha) production, improves pump function in mild-to-moderate heart failure, its effects on advanced heart failure have not been determined. In a prospective, randomized, double-blind, placebo-controlled study we compared the effects of 1-month therapy with pentoxifylline (400 mg 3 times daily) (n = 9) and placebo (n = 9) on left ventricular systolic function and dimensions as well as on plasma TNF-alpha (picograms per milliliter), interleukin-10 (IL-10), and the apoptosis-signaling receptor Fas/Apo-1 in patients with idiopathic dilated cardiomyopathy and advanced heart failure. All patients had New York Heart Association functional class IV heart failure, required intravenous inotropic agents for >72 hours at the beginning of the study, and received diuretics, digoxin, and an angiotensin-converting enzyme inhibitor for the duration of the study. Marked increases in TNF-alpha and Fas/Apo-1 concentrations were noted in the 18 patients compared with patients with functional class II to III heart failure and controls (p <0.001). Baseline characteristics were the same between the pentoxifylline and placebo groups. Pentoxifylline administration resulted in reduced TNF-alpha and Fas/Apo-1 concentrations, and an increase in ejection fraction at 1 month (p <0.05 compared with baseline and with placebo), effects that were not observed in the placebo-treated group. These data suggest that pentoxifylline may be a useful adjunct to conventional therapy in patients with severe heart failure.