Comportement des acides aminés plasmatiques libres chez des chiens normaux et des chiens pancréatectomisés après administration intraveineuse rapide de l-leucine

Resume L'injection intraveineuse rapide de l-leucine entraîne chez les chiens normaux une hypoglycémie, une chute du taux plasmatique du potassium et du phosphore inorganique, une hyperaminoacidémie initiale fort transitorie, et une l'hypoaminoacidémie survenante après. Chez les chiens traités au préalable par chlorpropamide l'hypoglycémie, l'hypokaliémie et l'hypoaminoacidémie entraînées par l'injection de leucine sont plus marquées - à différent degré; par contre la fugace hyperaminoacidémie et l'hypophosphatémie sont du même rang que dans le groupe précédent. Chez les chiens pancréatectomisés, l'injection rapide de leucine provoque un abaissement minime de la glycémie et n'influence pas le taux plasmatique du potassium; chez ces animaux la chute du taux des acides aminés dans le plasma est inférieure par rapport aux animaux sains, tandis que l'hyperaminoacidémie initiale et l'hypophoshatémie sont les mêmes.L'injection intraveineuse rapide de la l-valine et de l-alanine aux chiens normaux entraîne un abaissement de la glycémie et de la kaliémie inférieur en comparaison avec les mêmes effects de la leucine, lors que l'hypophosphatémie est du même rang. Ces acidesaminés provoquent également un accorissement initial de la concentration d'autres acidesaminés dans le plasma, montrant des différences en comparaison avec les modifications faisantes suite à l'injection de la leucine. La l-valine produit également un abaissement secondaire du taux de certains acides-aminés, tandis que l'on n'observe pas ce phénomène après l'injection de l-alanine. Dans la discussion on a évoqué la possibilité d'une influence de la leucine alimentaire sur l'utilisation des hydrates de carbone et des protéines digérés.

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Summary The quick intravenous administration of l-leucine produces in normal dogs a hypoglycemia, a decrease of potassium and of inorganic phosphorus, an initial and very transient increase of blood aminoacid plasma values and afterwards a decrease of blood aminoacids. In dogs previously treated with chlorpropamide, the decrease of glycemia, kaliemia and aminoacidemia are more evident, and in different degrees: on the contrary the transient decrease of blood aminoacids and the decrease of blood phosphorus are of he same degree as the other group's. In pancreatectomized dogs the quick administration of leucine produces a very small decrease of glycemia and it does not affect the potassium plasma values: in these animals the fall of the aminoacids in plasma is inferior to the one that happens in healthy animals, while the initial hypoaminoacidemia and hypophosphatemia are of the same degree.The quick intravenous administration of l-valine and l-alanine in normal dogs produces a decrease of glycemia and kaliemia inferior compared with the same effects of leucine, while the hypophosphatemia is of the same degree. Valine and alanine produce an initial increase of the aminoacid blood levels too, showing afterwards some differences from the changes that take place after the leucine administration. L-valine produces a secondary decrease of some aminoacid levels too, while such phenomenon cannot be observed after l-alanine injection. During the discussion, the possibility that food leucine may affect the utilization of carbohydrates and digested proteins is taken into consideration.

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Zusammenfassung Die rasche i.v. Injektion von l-Leuzin verursacht bei normalen Hunden eine Hypoglykaemie, Abfall des Plasmaniveaus von K und inorganischem P, anfaengliche, rasch voruebergehende Hyperaminoazidaemie und darauffolgende Hypoaminoazidaemie. Bei den zuvor mit Chlorpropamid behandelten Hunden sind die Hypoglykaemie, Hypokaliaemie und die Hypoaminoazidaemie — mit unterschiedlichem Grad — ausgepraegter; hingegen sind die voruebergehende Hyperaminoazidaemie sowie die Hypophosphataemie gleichen Grades, wie bei der vorhergehenden Gruppe. Bei den pankreatektomierten Hunden bewirkt die rasche Leuzin-Injektion einen minimalen Abfall des Blutzuckers und beeinflusst nicht das Plasmaniveau von K. Bei diesen Tieren ist der Abfall des Plasmaniveaus der Aminosaeuren geringer als bei gesunden Tieren, waehrend die anfaegliche Hyperaminoazidaemie und Hypophosphataemie die gleichen sind.Die rasche i.v. Injektion von l-Valin und l-Alanin bewirkt bei den normalen Hunden einen Abfall des Blutzuckers und der Kaliaemie, der geringer ist als der von Leuzin hervorgerufene, waehrend die Hypophosphataemie gleichen Grades ist. Diese Aminosaeuren rufen auch eine anfaengliche Erhoehung der Konzentration der anderen Aminosaeuren im Plasma hervor und offenbaren somit Unterschiede in Bezug auf die nach Leuzin-Injektion auftretenden Veraenderungen. Das l-Valin produziert ferner einen sekundaeren Abfall des Niveaus einiger anderer Aminosaeuren, waehrend man dieses Phaenomen nach l-Alanin-Injektion nicht beobachtet. In der Diskussion wird auf die Moeglichkeit eines Einflusses des alimentaeren Leuzins auf die Verwertung der verdauten Kohlehydrate und der Proteine hingewiesen.

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Resumen La inyección endovenosa rápida de l-leucina en perros normales determina una hipoglicemia, una caída del nivel plasmático del potasio y del fósforo inorgánico, una hiperaminoacidemia inicial my transitoria y una sucesiva hipoaminoacidemia. En los perros previamente tratados con clorpropamida, la hipoglicemia, la hipocaliemia y la hipoaminoacidemia son más marcadas, en grados diversos; en cambio, la fugaz hiperaminoacidemia y la hipofosfatemia son del mismo grado que en el grupo precedente. En los perros pancreatectomizados, la inyección rápida de leucina provoca una mínima disminución de la glicemia y no influye sobre el nivel plasmático del potasio; en estos animales, la caída del nivel plasmático de los aminoácidos es inferior a la de los animales sanos, mientras la hiperaminoacidemia inicial y la hipofosfatemia son las mismas.La inyección endovenosa rápida de l-valina y de l-alanina en perros normales determina una menor disminución de la glicemia y de la caliemia en comparación con los mismos efectos de la leucina, mientras la hipofosfatemia es del mismo grado. Estos aminoácidos provocan igualmente en el plasma un aumento inicial en la concentración de los otros aminoácidos, mostrando algunas diferencias con respecto a las modificaciones que se verifican después de la inyección de leucina. La l-valina también produce una reducción secundaria del nivel de algunos aminoácidos, mientras dicho fenómeno no se observa después de inyectar la l-alanina. En la discusión se illustra la posibilidad de influencia de la leucina alimenticia en la utilización de los hidratos de carbono y de las proteínas digeridas.

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Riassunto L'iniezione endovenosa rapida di l-leucina determina in cani normali una ipoglicemia, una caduta del livello plasmatico del potassio e del fosforo inorganico, una iperaminoacidemia iniziale, molto transitoria, ed una successiva ipoaminoacidemia. Nei cani trattati preventivamente con cloropropamide, l'ipoglicemia, l'ipokaliemia e l'ipoaminoacidemia sono più marcate, in gradi diversi; in cambio la fugace iperaminoacidemia e l'ipofosfatemia sono dello stesso grado del gruppo precedente. Nei cani pancreatectomizzati, l'iniezione rapida della leucina provoca un abbassamento minimo della glicemia e non influenza il livello plasmatico del potassio; in questi animali la caduta del livello plasmatico degli aminoacidi è inferiore a quanto avviene negli animali sani, mentre la iperaminoacidemia iniziale e l'ipofosfatemia sono le stesse.L'iniezione endovenosa rapida della l-valina e della l-alanina nei cani normali determina un abbassamento della glicemia e della kaliemia inferiore in confronto agli stessi effetti della leucina, mentre l'ipofosfatemia è dello stesso grado. Questi aminoacidi provocano ugualmente un aumento iniziale nella concentrazione degli altri aminoacidi nel plasma, mostrando quindi delle differenze rispetto alle modifiche che si verificano dopo l'iniezione di leucina. La l-valina produce ugualmente un abbassamento secondario del livello di alcuni aminoacidi, mentre tale fenomeno non si osserva dopo l'iniezione della l-alanina. Nella discussione viene ricordata la possibilità d'influenza della leucina alimentare sull'utilizzazione degli idrati di carbonio e delle proteine digerite.

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Rapport présenté pendant le 1° Congresso Nazionale della Società Italiana di Diabetologia, le 16 févriér 1966 à Catania.     

Spectral representation--analyzing single-unit activity in extracellularly recorded neuronal data without spike sorting

One step in the conventional analysis of extracellularly recorded neuronal data is spike sorting, which separates electrical signal into action potentials from different neurons. Because spike sorting involves human judgment, it can be subjective and time intensive, particularly for large sets of neurons. Here we propose a simple, automated way to construct alternative representations of neuronal activity, called spectral representation (SR). In this approach, neuronal spikes are mapped to a discrete space of spike waveform features and time. Spectral representation enables us to find single-unit stimulus-related changes in neuronal activity without spike sorting. We tested the ability of this method to predict stimuli using both simulated data and experimental data from an auditory mapping study in anesthetized marmoset monkeys. We find that our approach produces more accurate classification of stimuli than spike-sorted data for both simulated and experimental conditions. Furthermore, this method lends itself to automated analysis of extracellularly recorded neuronal ensembles. Additionally, we suggest ways in which these representations can be readily extended to assist in spike sorting and the evaluation of single-neuron peri-stimulus time histograms.     

Osteochondritis dissecans of the temporomandibular joint

A case is reported of a 43-year-old female patient presenting bilateral osteochondritis dissecans (OCD) of the temporomandibular joint (TMJ), in different stages for each side, associated with avascular necrosis (AVN) of the right condyle. Additionally observed was anterior disk displacement without reduction for both sides. We have proposed an adaptation of the previous classification of OCD for cases affecting the TMJ. We have also stressed the fundamental role of panoramic radiography on the diagnosis of stage 3 and stage 4 OCD of the TMJ. In relation to MRI, we have recommended sagittal (slice thickness of 2 mm) and coronal (slice thickness of 1 mm) fast spin-echo proton density-weighted sequences to better identify bone lesions (stage 1 and 2) and also localize osteochondral loose bodies; and coronal (slice thickness of 1 mm) fat-suppressed fast spin-echo T2 weighted sequence to better evaluate OCD (stable or unstable) and the features of the occasionally associated AVN (acute or chronic).     

Issues arising from the prenatal diagnosis of some rare trisomy mosaics--the importance of cryptic fetal mosaicism

OBJECTIVES: To add to the knowledge of fetal mosaicism, confined placental mosaicism (CPM), and uniparental disomy (UPD), in rare trisomies detected at prenatal diagnosis. METHODS: The origin of rare trisomy mosaics, mostly (8/11) seen in amniocytes, was examined in 11 cases by follow-up karyotyping and the study of microsatellite inheritance. RESULTS: Of the rare trisomies presented, three were mosaic trisomy 16 (two of which were CPM), and the remainder comprised single cases of mosaic trisomies of 8, 9, 10, 11, 12, 14, 5 and 15--the last two being CPM. Cases varied in parental derivation and meiotic versus post-zygotic origin but no case involved UPD. There was evidence for cryptic fetal mosaicism in three cases (5, 7, 11)--involving chromosomes 11, 14 and 16. CONCLUSIONS: These cases contribute further data to phenotypes associated with rare trisomies and the relative influences on the phenotype of CPM, UPD and fetal mosaicism. From sparse published data, we estimate that approximately 10% of apparent CPM cases for a rare trisomy (i.e. aneuploid CVS, normal amniocytes) may actually be cryptic fetal mosaics undetected in cultured amniocytes. In many cases, this cryptic mosaicism may be of limited clinical significance, but in others, the associated phenotypic effects may be obvious. There is no general approach to resolve this issue; the finding of even a few similar aneuploid cells in different amniocyte culture vessels may be clinically significant. It may be useful to study such an amniocyte culture with FISH with the relevant centromeric probe. Careful follow-up is recommended, particularly for infants where apparent correction of autosomal trisomy has occurred.     

Dynastab S: A new concept for high energy fractures of the distal tibia

Background. High energy fractures of the distal tibia ("pylon fractures") usually result in severe reduction of the range of motion of the superior ankle joint. If there is severe soft tissue trauma coexisting with the fractures, the possibilities for surgical treatment are limited. Our study examined the suitability of the DYNASTAB S external fixator (for ankle joint stabilization). Material and methods. We studied 25 adult patients (15 men, 10 women), treated from April 2001 to March 2003, to whom the DYNASTAB-S stabilizer was applied for an average of 10.5 weeks. Results. In all patients bone union was achieved, with a good range of motion in the talo-crural joint. All patients tolerated the applied treatment well. The average hospital stay was 9 days. There were 2 cases of transient inflammatory reaction of the skin around the screws, and 1 case of algodystrophy syndrome, which resolved after physical treatment combined with pharmacotherapy. Conclusions. The Dynastab S external fixator is very successful in the treatment of fractures with poor prognosis in traditional methods of conservative and surgical treatment, providing bone union and good functional efficiency of the superior ankle joint. The use of the mechanical joint imitating the movement of the injured ankle joint allows for early joint rehabilitation without loss of stability of the fracture. Adaptation of the device to the operated limb is excellent. The Dynastab S external fixator can be recommended for wider use in the treatment of pylon fractures.     

Moderate increase in intraabdominal pressure attenuates gastric mucosal oxygen saturation in patients undergoing laparoscopy

BACKGROUND: Perioperative disturbances of microvascular blood flow and oxygenation in the intestinal tract have been hypothesized to play an important role in development of the multiple organ dysfunction syndrome. Herein, increased intra-abdominal pressure (IAP) has been identified as a key factor in the initiation of the pathophysiologic cascade. The authors hypothesized that increasing the IAP by intraperitoneal insufflation of carbon dioxide attenuates microvascular oxygen saturation in gastric mucosa. They tested this hypothesis in a prospective, observational study in 16 patients scheduled to undergo elective diagnostic laparoscopy. METHODS: The authors continuously assessed microvascular oxygen saturation in gastric mucosa by reflectance spectrophotometry. Simultaneously systemic oxygen saturation, heart rate, arterial blood pressure, and ventilation-derived variables were measured noninvasively. During general anesthesia and controlled mechanical ventilation, baseline values were obtained. Thereafter, the IAP was increased to 8 and 12 mmHg, respectively, followed by a control period after desufflation. RESULTS: The increase in IAP from baseline to 8 mmHg decreased microvascular oxygen saturation in gastric mucosa from 69+/-7% (mean +/- SD) to 63+/-8% at 8 mmHg IAP (P <0.05), with a further significant reduction to 54+/-13% at 12 mmHg IAP (P <0.01). Microvascular oxygen saturation in gastric mucosa recovered rapidly to baseline level (66 +/- 10%) after release of increased IAP. In striking contrast to regional mucosal oxygen saturation, systemic oxygenation did not change with either of the interventions. CONCLUSIONS: The results suggest that increasing intraabdominal pressure to moderate levels, commonly applied to induce a surgical pneumoperitoneum, decreases gastric mucosal oxygen saturation.     

Transcervical-subxiphoid-videothoracoscopic "maximal" thymectomy--operative technique and early results

Background

The operative technique of a transcervical-subxiphoid-videothoracoscopic “maximal” thymectomy without sternotomy is described and the early results of the follow-up of patients operated on are analyzed.

Methods

One-hundred “maximal” transcervical-subxiphoid-videothoracoscopic thymectomies were performed for nonthymomatous myasthenia gravis during a recent 32-month period (from September 1, 2000 to May 8, 2003). Patient characteristics, complications, pathologic findings, and the results of follow-up were analyzed.

Results

The study group included 83 women and 17 men. The mean age was 29.8 years (range, 10-69 years). The mean preoperative duration of myasthenia was 2.73 years (range, 3 months to 17 years). The preoperative Osserman score was I-III, 27 patients were taking steroids preoperatively. Eleven operations were performed by two teams working simultaneously and 89 operations were performed by one surgeon including four combined thymectomy-thyroid operations in patients with myasthenia and thyroid nodules. The mean operative time for two-team approach thymectomies was 159.09 minutes (range, 140-170 minutes) and the mean operative time for the thymectomy performed by one surgeon was 199.41 minutes (range, 150-270 minutes) (p = 0.0004). There was a 15.0% (15 out of 100) postoperative morbidity and no mortality. Foci of ectopic thymic tissue were found in 71.0% of the patients and were most prevalent in the perithymic fat (37.0%) and in the aorta-pulmonary window (33.0%). The mean weight of the specimen was 78.4 g (range, 14.5-253.0 g). In 48 patients followed-up for 12 months, the improvement rate was 83.3%, the no improvement rate was 14.6%, and 1 patient died during the follow-up period. Complete remission rates were 18.8% and 32.0% after 1 and 2 years of follow-up, respectively.

Conclusions

We conclude that the “maximal” transcervical-subxiphoid-videothoracoscopic thymectomy is a safe operative technique, avoiding a sternotomy, performed partly in an open fashion with the extensiveness comparable with the transsternal extended and “maximal” thymectomies. The two-team approach helps to reduce the operative time. However, because of the limited time of follow-up it is too early for the final assessment of the long-term results of this method in the treatment of myasthenia gravis.     

Polyhydroxylated 2-styrylchromones as potent antioxidants

Four polyhydroxylated 2-styrylchromones, structurally related to flavones and cinnamic acid, have been studied. An SC derivative with OH groups only at positions 3' and 4' on the styryl moiety and another SC bearing an additional OH group at position 5 on the benzopyrone ring were more potent inhibitors of the Cu2+-induced peroxidation of LDL than the flavonoid quercetin. Fluorescence and absorption spectroscopies suggested that one LDL particle may bind 40 SC molecules. A pulse radiolysis study in pH 7 buffered micellar solutions of neutral TX100 and positively charged CTAB demonstrated that one-electron oxidation by *Br2-, *O2- and tryptophan radicals (8Trp) depends strongly on the micellar microenvironment. All SCs were readily oxidized by *O2- in CTAB micelles (rate constants: 6-18 x 10(6) M(-1) s(-1)). In TX100 micelles only the SC derivative with OH groups in position 3' and 4' reacted with *O2- (rate constant: 1.1 x 10(6) M(-1)s(-1)). In CTAB, electron transfer to *Trp radicals was observed for all SCs with rate constants > or =3.2 x 10(7) M(-1) s(-1). In TX100 micelles, this reaction occurred solely with the derivative bearing OH groups only at positions 3' and 4'.     

Association after linkage analysis indicates that homozygosity for the 46C-->T polymorphism in the F12 gene is a genetic risk factor for venous thrombosis

In a family-based study called GAIT (Genetic Analysis of Idiopathic Thrombophilia) that included a genome-wide scan we demonstrated that a polymorphism (46C-->T) in the F12 locus jointly influences variability of plasma (Factor XII) FXII levels and susceptibility to thrombotic disease. It then became germane to determine the prevalence of the 46C-->T polymorphism and its relative risk of thrombotic disease. We followed up evidence for genetic linkage with a case-control study, including 250 unrelated consecutive Spanish patients suffering from venous thrombotic disease and 250 Spanish subjects matched for sex and age as a controls. We measured FXII levels and genotyped the 46C-->T polymorphism, as well as a number of classical risk factors for thrombotic disease.We confirmed that individuals with different genotypes for this polymorphism showed significant differences in their FXII levels. Most importantly, the mutated T allele in the homozygous state (genotype T/T) was associated with an increased risk of thrombosis (adjusted OR of 4.82; 95% CI 1.5-15.6), suggesting that the polymorphism itself is an independent risk factor for venous thromboembolism. This study confirms that the 46C-->T polymorphism is a genetic risk factor for venous thrombosis in the Spanish population. In addition, our results confirm that a genome-wide scan coupled with a classical case-control association study is an extremely valuable approach to identify DNA variants that affect complex diseases.