Hemodynamic effects of medical antishock trousers during mechanical ventilation

Purpose

To compare the hemodynamic effects of medical antishock trousers (MAST) inflation in mechanically ventilated patients with normal and poor left ventricular function.

Methods

Twelve patients requiring respiratory support were divided into two groups according to baseline transesophageal echocardiography (TEE) measurements: normal left ventricular dimensions and fractional area of contraction (FAC=61 ± 5%) (n=7) and dilated cardiomyopathy with reduced FAC (21 ± 1%) (n=5). All patients were studied when two successive levels of load (mild load by inflation of the leg compartment of MAST at 50 cmH₂O and high load by adding the abdominal compartment of MAST inflated at 30 cmH₂O) were applied. Global left ventricular systolic function was assessed on the TEE transgastric short-axis view. End-systolic wall stress (ESWS) was used as an indicator of left ventricular afterload.

Results

Total respiratory, lung and chest wall compliances were reduced by 48%, 51% and 27% respectively at the high load level (P < 0.05). Whereas no hemodynamic changes occurred at mild load, the high load level produced an increase in left ventricular afterload as evidenced by concomitant increases in diastolic arterial blood pressure (66 ± 6 to 79 ± 6 mmHg,P < 0.05) and ESWS (69 ± 12 to 74 ± 12 Kdyn·cm^?2·m^?2,P < 0.05). In patients with dilated cardiomyopathy, this increase in afterload impaired the left ventricular systolic function and end-systolic area increased (19.0 ± 2.5 to 21.4 ± 2.9 cm²·m^?2,P < 0.05) while FAC decreased (22 ± 2 to 16 ± 2%,P < 0.05). Left ventricular end-diastolic area remained unchanged during the study in both groups.

Conclusion

MAST inflation impairs respiratory mechanics and global left ventricular systolic function in cardiac patients without changes in left ventricular preload.     

Leucoéncephalopathie multifocale progressive

Summary A young woman presented a mixed congenital and familial immunodeficiency syndrome consisting in an absence of IgA and lowered levels of IgG and IgM, with a defect in cellular immunity. She had a mild malabsorption syndrome with slight alterations of the jejunal mucosa. Non-caseating tuberculoid granulomata were found in skin lesions, in lymph nodes and in the spleen. At age 27 the patient died of a neurological disease of 4 months duration. Autopsy revealed a very widespread demyelinating process involving mainly the right cerebellar hemisphere but also most of the pons and left cerebellum, with the typical morphologic characters of PML. In the hemispheres lesions were limited to microscopical microglial nodules with discrete demyelination. A review of 86 published cases of PML revealed 9 other cases in which lesions showed a strong predilection for the subtentorial territories. This sampling allows for the assumption that some 11% of the cases of PML have this particular lesion distribution. Other pertinent features of this case are briefly discussed.

     

Succinylcholine does not worsen bupivacaine-induced cardiotoxicity in pentobarbital-anaesthetized dogs

The intravascular injection of a large dose of bupivacaine induces electrophysiological cardiac impairment, mainly by slowing ventricular conduction velocity, and haemodynamic depression, by a decrease in myocardial contractility. When cardiotoxicity occurs, succinylcholine rapidly stops convulsions. However, the possible interactions between bupivacaine and succinylcholine on cardiac electrophysiology and haemodynamic status have never been investigated. Thus, we used an experimental electrophysiological model involving closed-chest dogs. Three groups (n = 6) of pentobarbital-anaesthetized dogs were given 0.2 mg.kg-1 atropine iv. Dogs in Group 1 were given saline. The others received 4 mg.kg-1 bupivacaine iv over ten seconds. Dogs in Group 2 were then given saline and those in Group 3 were then given 2 mg.kg-1 succinylcholine iv from one to two minutes after the administration of bupivacaine. The following electrophysiological variables were measured: heart rate represented by RR interval (RR), PR, atria-His (AH), and His-ventricle (HV) intervals, QRS duration, and QT interval corrected for heart rate (QTc). The following haemodynamic variables were measured: mean aortic pressure (MAoP), the peak of the first derivative of left ventricular pressure (LV dP/dt max), and LV end diastolic pressure (LVEDP). Comparison between Groups 1 and 2 showed that bupivacaine induced more than 100% HV interval lengthening and QRS widening (P less than 0.01), prolonged QTc interval by more than 25% (P less than 0.01), and decreased LV dP/dt max by more than 50% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of cell surface receptor-altering agents on the binding and biological activity of 12-O-tetradecanoylphorbol-13-acetate in isolated epidermal cells

Isolated epidermal cells were incubated with a variety of compoundsknown to interfere with or alter the ultrastructure of cellsurface receptors, and the ability of 12-O-tetradecanoyl-phorbol-13-acetate(TPA) to bind to these cells and induce epidermal ornithinedecarboxylase (ODC) activity was investigated. The - and ß-adrenergicantagonists, phentolamine and propranolol, and the cholinergicantagonist, atropine, which competed effectively for the bindingreceptors of [³H]dihydro--ergocryptine, [³H]dihydroalprenolol,and [¹⁴C]acetylcholine, did not inhibit the induction of ODCactivity by TPA or the specific binding of [³H]TPA to the cells.Neuraminidase treatments caused a time- and dose- related releaseof sialic acid from the cells and enhanced the stimulatory effectof cholera toxin on basal and TPA-induced ODC activities asmuch as the monosialoganglioside GM₁. Neuraminidase and theother membrane-altering agents, fucosidase, galactosidase, galactoseoxidase, phospholipases A2 and C, and NaIO₄, were used aloneand/or in various combinations in our studies. All treatmentstested inhibited the specific binding of several ¹²⁵I-labeledhormones and epidermal growth factor to the cells. In contrast,none of these treatments was able, in the same cell system,to affect either the binding or the biological activity of TPA.Therefore, these results suggest that the primary interactionof TPA at the plasma membrane level as well as its biologicaleffect in the intact cell do not proceed through adrenergicor cholinergic receptors and do not require the integrity ofthe cell surface glycoconjugates and phospholipids. In addition,the inhibitory effect of retinoic acid on TPA-induced ODC activityremained unaffected by some of the above treatments, suggestingthat retinoic add is unlikely to interfere with TPA interactionsat the plasma membrane level.     

The effects of antiinflammatory steroids on the response of the guinea-pig isolated ileum to acetylcholine,histamine, nicotine, 5-hydroxytryptamine and electrical stimulation

Summary High concentrations of antiinflammatory steroids (2.5–40 g/ml) reversibly inhibited the electrically induced contractions of the guinea-pig isolated ileum. At 40 g/ml they also reversibly inhibited contractions clicited by acetylcholine, histamine, nicotine and 5-hydroxytryptamine. PGE₁ (2.5 ng/ml), PGE₂ (2.5 ng/ml) and PGF₂ (25 ng/ml) antagonized these effects.The inhibition of contractions elicited by direct agonists were less pronounced than those elicited by indirect or partly indirect agonists. The inhibitory effect of steroids may be related to non-specific actions on biological membranes. An overall sensitization of the smooth muscle by PG's may explain their antagonism to inhibition by steroids.     

Reliability of the Dominic-R: A Young Child Mental Health Questionnaire Combining Visual and Auditory Stimuli

Reliability of the Dominic-R, a. questionnaire combining visual and auditory stimuli, was tested in 340 community children aged 6 to 11 years. Test-retest reliability of symptoms of, and of symptom scores of, DSM-III-R disorders including simple phobias, separation anxiety disorder, overanxious disorder, depression/dysthymia, attention deficit/ hyperactivity disorder, oppositional defiant disorder, and conduct disorder was assessed. Most symptoms yielded kappas greater than .40, and ICCs ranged from .74 to .81. In conclusion, reliability of the Dominic-R compares favourably with that of other child assessment questionnaires.     

Low-grade astrocytomas in children: evolving management strategies

Developments in imaging and in neurosurgical techniques over the past decade have substantially altered the management of children with low-grade astrocytoma. Indications for surgery have become more clearly defined, and a larger proportion of children undergo complete or subtotal resection than in the past. Fewer receive adjuvant therapy, even though the options in this regard are more numerous now and theoretically likely to result in less morbidity than conventional external beam radiotherapy.

This review will address in particular the correlations between location, imaging appearance, and behavior that need to be more widely appreciated, and present recommendations regarding the management of these tumors.     

Preclinical in vivo antitumor activity of vinflunine, a novel fluorinated Vinca alkaloid

Vinflunine, or 20′,20′-difluoro-3′,4′-dihydrovino‐relbine, is a novel Vinca alkaloid obtained by hemisynthesis using superacidic chemistry. The most impressive structural modification of this vinorelbine derivative was the selective introduction of two fluorine atoms at the 20′ position, a part of the molecule previously inaccessible by classic chemistry. The antitumor activity of vinflunine was evaluated against a range of transplantable murine and human tumors. Vinflunine exhibited marked activity against murine P388 leukemia grafted i.v. when given i.p. in single or multiple doses according to various schedules or in single i.v. or p.o. doses. Increases in life span achieved with vinflunine, as assessed by T/C ratios, ranged from 200% to 457% and proved markedly superior to those of 129–186% obtained with the other Vinca alkaloids tested. Against s.c.-implanted B16 melanoma, multiple i.p. administration of vinflunine proved active in terms of both survival prolongation and tumor growth inhibition, with optimal T/C values and relative areas under the tumor growth curves (rAUC) being 24% and 36%, respectively. The extent of this activity was superior to that noted for vinorelbine under the same experimental conditions. Growth inhibition of human tumor xenografts LX-1 (lung) and MX-1 (breast) was also observed following four weekly i.p. injections of vinflunine as reflected by optimal T/C values of 23% and 26%, respectively, and significant differences in the rAUCs noted for treated versus control animals. It was also noticeable that vinflunine induced considerably more prolonged inhibitory effects on tumor growth than did vinorelbine. These results demonstrate that vinflunine is well tolerated and is definitively active against a range of experimental animal tumor models. Vinflunine activity has been documented in terms of both survival prolongation and tumor growth inhibition, with definite superiority over vinorelbine being shown in each tumor model evaluated. Received: 13 July 1997 / Accepted: 21 October 1997     

Antimicrobial activity of myotoxic phospholipases A2 from crotalid snake venoms and synthetic peptide variants derived from their C-terminal region.

A short peptide derived from the C-terminal region of Bothrops asper myotoxin II, a Lys49 phospholipase A(2) (PLA(2)), was previously found to reproduce the bactericidal activity of its parent molecule. In this study, a panel of eight PLA(2) myotoxins purified from crotalid snake venoms, including both Lys49 and Asp49-type isoforms, were all found to express bactericidal activity, indicating that this may be a common action of the group IIA PLA(2) protein family. A series of 10 synthetic peptide variants, based on the original C-terminal sequence 115-129 of myotoxin II and its triple Tyr-->Trp substituted peptide p115-W3, were characterized. In vitro assays for bactericidal, cytolytic and anti-endotoxic activities of these peptides suggest a general correlation between the number of tryptophan substitutions introduced and microbicidal potency, both against Gram-negative (Salmonella typhimurium) and Gram-positive (Staphylococcus aureus) bacteria. Peptide variants with high bactericidal activity also tended to be more cytolytic towards skeletal muscle C2C12 myoblasts, thus limiting their potential in vivo use. However, the peptide variant pEM-2 (KKWRWWLKALAKK) showed reduced toxicity towards muscle cells, while retaining high bactericidal potency. This peptide also showed the highest endotoxin-neutralizing activity in vitro, and was shown to functionally interact with lipopolysaccharide (LPS) using a chimeric bacteria model. The bactericidal and anti-endotoxic properties of pEM-2, combined with its relatively low toxicity towards eukaryotic cells, highlight it as a promising candidate for further evaluation of its antimicrobial potential in vivo.