Angiogenic/lymphangiogenic factors and adaptation to extreme altitudes during an expedition to Mount Everest.

AIM: To analyse the correlation between production of angiogenic [vascular endothelial growth factor A (VEGF-A) and interleukin 8 (IL-8)] and lymphangiogenic factors (VEGF-C and D) and adaptation to high altitude (>8000 m). Erythropoietin (EPO) served as a positive control. METHODS: We analysed the percentage of oxygen saturation and the plasmatic contents of VEGF-A, C, D, IL-8 and EPO in seven mountaineers and four Sherpas during an expedition to Mount Everest. Acute mountain sickness was also evaluated using the Lake Louise score. RESULTS: Whereas VEGF-A, IL-8, VEGF-C and EPO were transiently up-regulated at 5000 m and decreased at the highest altitudes, VEGF-D remained elevated throughout the ascent. Sherpas had increased basal levels of VEGF-A, C, IL-8 and EPO and up-regulation of all the tested factors when they passed the altitude at which they lived. CONCLUSION: Our data suggest that expression of angiogenic and lymphangiogenic factors is up-regulated directly or indirectly by altitude-dependent hypoxia. Both factors could be involved in a mechanism of adaptation to high altitudes.

[Transvascular fluid exchange disturbed by capillary injuries]. / Situations où les échanges liquidiens sont perturbs par des lésions capillaries.

Fluid exchange disorders due to capillary lesions are numerous and their extent depends on the underlying disease as well as the capillary structure of the affected organ. The inflammatory cascade, triggered by sepsis or reperfusion injury, is mediated by several humoral mediators and activated blood cells. These include pro-inflammatory cytokines, arachidonic acid, proteases, oxygen free radicals, polymorphonuclears, procoagulant, complement and fibrinolytic system. The interaction between these mediators leads to a loss of endothelial integrity, a loss of basment membrane and a disruption of the interstitial matrix, with wasting of the endothelial cytoskeleton. The alteration in permeability induces transcapillary exudation of water and protein in the interstitial space, leading to organ dysfunction, mainly the lungs and splanchnic organs. Nitric oxyde, by modulating the response of the endothelium to the cellular interaction may protect against capillary injury. Capillary "stress lesions" following microvascular hypertension are the physiological basis of neurogenic or high altitude pulmonary oedema, and overinflation injury from mechanical ventilation. The anatomic specific features of the cerebral capillaries resulted in the well known concept of blood brain barrier with it's changeing morphology. Under the effect of humoral mediators and cellular interactions, the endothelial cells are able, via a calcium-mediated mechanism, to contract and to modify capillary permeability, leading to vasogenic oedema.

Intraoperative glycaemic control in non-insulin-dependent and insulin-dependent diabetes.

We have compared intraoperative glycaemic control, insulin requirements and metabolic and endocrine variables in 40 non-insulin-dependent diabetic patients (NIDDM) and 40 insulin-dependent diabetic patients (IDDM) undergoing general anaesthesia for elective procedures. Two i.v. insulin regimens were used: continuous i.v. infusion (group A: 1.25 u.h-1) and repeated i.v. boluses (10 u./2 h). Blood concentrations of glucose were measured every 15 min from just before induction of anaesthesia until 2 h after surgery. Plasma lactate and pyruvate concentrations, ketone bodies, C-peptide and counter-regulatory hormones were also measured. Glycaemia did not differ significantly in the two types of diabetes, regardless of the insulin therapy used. The amounts of insulin administered were similar in NIDDM and IDDM. There was no significant difference for other metabolic variables. Plasma concentrations of growth hormone (GH) increased significantly during surgery, especially in IDDM patients, but this change did not alter intraoperative glycaemic control. We conclude that mean glycaemic control, insulin requirements and development of ketone bodies in NIDDM and IDDM patients did not differ during the operative period, regardless of the insulin regimen used. Therefore, during the operative period, it is not necessary to modify the insulin regimen according to the type of diabetes. The consequences of increased plasma GH concentrations on glycaemic control in IDDM patients after operation are unknown.

Economia transfusional en cirugía cardíaca, rol de la aprotinina y el ácido tranexámico / Reduction of homologous transfusion requirements with aprotinin or tranexamic acid in cardiac surgery

Las pérdidas hemorrágicas y las necesidades de transfusión sanguínea homólogas son comparadas en tres grupos de pacientes operados en Cirugía Cardíaca bajo Circulación Extra-Corpórea (CEC), recibiendo aprotinina (grupo A), ácido tranexámico (grupo T) o formando el grupo control (grupo C). El protocolo randomizado prospectivo y abierto, fue aprobado por el Comité de Etica del Hospital. El estudio comprende 100 pacientes. Los tres grupos son comparables en edad, sexo, patología, duración de la CEC y del clampaje aórtico. El grupo A recibió 500.000 UIK de aprotinina a la inducción de la anestesia, más 500.000 UIK/hora durante la CEC. El grupo T recibió 15 mg/kg de ácido tranexámico en dos veces; a la inducción de la anestesia y al fin de la CEC. El grupo C no recibió ningún antifibrinolítico. El volumen total de pérdidas drenadas en el período postoperatorio, fue menos importante en el grupo A (486 + 340 ml) y en el grupo T (482 + 345 ml) que en el grupo C (819 + 573 ml) p < 0,01. El número de pacientes transfundidos fue más importante en el grupo C (20/32) que en grupo A (12/33) y el grupo T (11/35) p < 0,05. La aprotinina y el ácido tranexámico reducen en 40 por ciento las pérdidas hemorrágicas en el postoperatorio de cirugía cardíaca bajo CEC. Las necesidades transfusionales fueron reducidas en un 50 por ciento en los grupos A y T comparados con el grupo C. (AU)

Economia transfusional en cirugía cardíaca, rol de la aprotinina y el ácido tranexámico / Reduction of homologous transfusion requirements with aprotinin or tranexamic acid in cardiac surgery

Las pérdidas hemorrágicas y las necesidades de transfusión sanguínea homólogas son comparadas en tres grupos de pacientes operados en Cirugía Cardíaca bajo Circulación Extra-Corpórea (CEC), recibiendo aprotinina (grupo A), ácido tranexámico (grupo T) o formando el grupo control (grupo C). El protocolo randomizado prospectivo y abierto, fue aprobado por el Comité de Etica del Hospital. El estudio comprende 100 pacientes. Los tres grupos son comparables en edad, sexo, patología, duración de la CEC y del clampaje aórtico. El grupo A recibió 500.000 UIK de aprotinina a la inducción de la anestesia, más 500.000 UIK/hora durante la CEC. El grupo T recibió 15 mg/kg de ácido tranexámico en dos veces; a la inducción de la anestesia y al fin de la CEC. El grupo C no recibió ningún antifibrinolítico. El volumen total de pérdidas drenadas en el período postoperatorio, fue menos importante en el grupo A (486 + 340 ml) y en el grupo T (482 + 345 ml) que en el grupo C (819 + 573 ml) p < 0,01. El número de pacientes transfundidos fue más importante en el grupo C (20/32) que en grupo A (12/33) y el grupo T (11/35) p < 0,05. La aprotinina y el ácido tranexámico reducen en 40 por ciento las pérdidas hemorrágicas en el postoperatorio de cirugía cardíaca bajo CEC. Las necesidades transfusionales fueron reducidas en un 50 por ciento en los grupos A y T comparados con el grupo C.

Investigations about a direct neurotensin-dopamine interaction by nuclear magnetic resonance study, synaptosomal uptake of dopamine, and binding of neurotensin to its receptors.

Interactions between dopamine and neurotensin can occur at various levels of the dopaminergic pathways. By using different approaches in vitro, we investigated the proposed hypothesis that neurotensin might bind to dopamine in the synaptic cleft. Nuclear magnetic resonance spectra of neurotensin were not modified by the addition of dopamine, and no nuclear Overhauser effect was detected. Synaptosomal uptake of [3H]dopamine in the presence of neurotensin did not lead to any modifications of the kinetic constants of the uptake. Neurotensin binding was not modified by the addition of dopamine. These results did not confirm the suggestion that neurotensin can form a complex with dopamine.

Reduced peptide bond pseudopeptide analogues of neurotensin.

Pseudopeptide analogues of the C-terminal hexapeptide of neurotensin (H-Arg-Arg-Pro-Tyr-Ile-Leu-OH) were obtained by replacing each peptide bond by the reduced peptide bond CH2NH. The resulting analogues were then examined for their ability to inhibit binding of labeled neurotensin to new-born mouse brain membranes and for stimulation of guinea pig ileum contraction. Replacement of the Ile12-Leu13, Tyr11-Ile12, Pro10-Tyr11 and Lys9-Pro10 peptide bonds resulted in about 2000-, 3400-, 200- and 3400-fold losses, respectively, in binding affinity and 400-, 750-, 250- and 300-fold losses, respectively, in biological activity. Replacement of both Arg8 and Arg9 by lysine led to an analogue exhibiting the same pharmacological profile as the C-terminal hexapeptide of neurotensin. Interestingly, replacement of the Lys8-Lys9 peptide bond by the CH2NH bond produced an analogue exhibiting the same affinity for neurotensin receptors, but 10 times more potent in stimulating guinea pig ileum contraction. N-terminal protected analogues (by the Boc group) showed decreased potency as compared with their amino-free corresponding compounds.

Reduced peptide bond pseudopeptide analogues of neurotensin: binding and biological activities, and in vitro metabolic stability.

A series of pseudopeptide analogues of neurotensin was produced by systematically replacing the five peptide bonds in neurotensin-(8-13) with CH2NH (psi, reduced) bonds. All these analogues were synthesized with a free amino terminus (H derivatives) and with a N-terminal tert-butyloxycarbonyl group (Boc derivatives). The compounds were screened in vitro for agonist or antagonist activity and for metabolic stability by testing (1) their ability to inhibit the binding of radiolabelled neurotensin to homogenates of newborn mouse brain; (2) their ability to contract isolated guinea-pig ileum preparations; and (3) their degradation in the presence of rat brain homogenates. All the analogues bound to the mouse brain neurotensin receptor and all exhibited agonist activity in the guinea-pig ileum assay. Only the H- and Boc-[psi 8,9] derivatives were at least as potent as their parent compounds neurotensin-(8-13) and Boc-neurotensin-(8-13) in the binding and biological assays. All the other pseudopeptide analogues with reduced bonds at position 9-10, 10-11, 11-12 and 12-13 showed a marked reduction in potency ranging from 2 to 4 orders of magnitude. All the derivatives that were protected at their N terminus either by the presence of a Boc group or by the presence of a reduced bond at position 8-9 and 9-10 were slowly degraded by rat brain homogenates. The other derivatives were, in contrast, quite rapidly degraded. There was a good correlation between binding and biological potencies for those analogues that were resistant to degradation. Interestingly, the degradation-resistant H-[psi 8,9] compound exhibited higher binding and biological potency then neurotensin. It is therefore expected that this analogue will produce highly potent and long-lasting neurotensin-like effects in vivo, and preliminary experiments indicate that this is indeed the case.

[Thrombocytopenia induced by heparin and cardiac surgery with extracorporeal circulation]. / Thrombopénie induite par l'héparine et chirurgie cardiaque sous circulation extracorporelle.

A case of mitral and aortic valvular replacement combined with double coronary artery bypass grafting is reported in a 64-year-old woman who presented with a history of heparin-induced thrombocytopenia. The use of a conventional dose of heparin did not induce the formation of a plasma platelet-aggregation factor. The necessity of postoperative anticoagulation was ensured by the prescription of antivitamin K, started on the morning of the operative day.

[An experimental and clinical study of a new intubation tube with a foam-filled cuff]. / Etude expérimentale et clinique d'une nouvelle sonde d'intubation à ballonnet en mousse.

An experimental and clinical study of an endotracheal tube with a foam-filled cuff has been carried out. The experimental study showed that, during inspiration, the cuff was insufflated through the "T piece" connecting the cuff in the inspiratory limb of the ventilator circuit, preventing inspiratory leak. The intracuff pressure was equal to airway pressure. During expiration the gas insufflated into cuff leaked out through the "T piece" and intracuff pressure rapidly returned to zero. When N2O in 50% O2 was used for one hour, intracuff pressure did not increase. Twenty patients intubated with a foam-filled cuff tube, for ENT surgery, have been studied. The mean intubating time was 151 min +/- 36 and two patients were intubed, respectively, 26 hours and 28 hours. No complications were noted, 24 hours after extubation, during laryngeal fibroscopic control. Only two patients had light edema of the vocal cords and three of them had a light inflammation of the subglottic mucosa, without sore throat. No tracheal ischaemic damage nor tracheal mucosal inflammation were observed.