Nathalie Nagy

Supratentorial Pilocytic Astrocytomas, Astrocytomas, Anaplastic Astrocytomas and Glioblastomas are Characterized by a Differential Expression of S100 Proteins

The levels of expression of the S100A1, S100A2, S100A3, S100A4, S100A5, S100A6 and S100B proteins were immunohistochemically assayed and quantitatively determined in a series of 95 astrocytic tumors including 26 World Health Organization (WHO) grade I (pilocytic astrocytomas), 23 WHO grade II (astrocytomas), 25 WHO grade III (anaplastic astrocytomas) and 21 WHO grade IV (glioblastomas) cases. The level of the immunohistochemical expression of the S100 proteins was quantitatively determined in the solid tumor tissue (tumor mass). In addition twenty blood vessel walls and their corresponding perivascular tumor astrocytes were also immunohistochemically assayed for 10 cases chosen at random from each of the four histopathological groups. The data showed modifications in the level of S100A3 protein expression; these modifications clearly identified the pilocytic astrocytomas from WHO grade II‐IV astrocytic tumors as a distinct biological group. Modifications in the level of S100A6 protein expression enabled a clear distinction to be made between low (WHO grade I and II) and high (WHO grade III and IV) grade astrocytic tumors. Very significant modifications occurred in the level of S100A1 protein expression (and, to a lesser extent, in their of the S100A4 and S100B proteins) in relation to the increasing levels of malignancy. While the S100A5 protein was significantly expressed in all the astrocytic tumors (but without any significant modifications in the levels of malignancy), the S100A2 protein was never expressed in these tumors. These data thus indicate that several S100 proteins play major biological roles in human astrocytic tumors.

Optimal adrenergic support in septic shock due to peritonitis.

Background The authors evaluated optimal adrenergic support using norepinephrine, dopamine, and dobutamine in a clinically relevant model of septic shock. Methods Twenty-eight mature, female, anesthetized sheep (weight, 30.5 ± 3.6 kg) underwent cecal ligation and perforation and were randomized into four groups of seven animals to be treated with norepinephrine, dopamine-norepinephrine, dobutamine-norepinephrine, or no adrenergic agent. In all groups, lactated Ringers solution was administered to restore cardiac filling pressures to baseline. In the norepinephrine group, norepinephrine (0.5–5 &mgr;g · kg−1 · min−1) was titrated to maintain mean arterial pressure between 75–85 mmHg. In the dopamine-norepinephrine group, dopamine was given first, and norepinephrine was added only when mean arterial pressure remained below 75 mmHg despite the infusion of 20 &mgr;g · kg−1 · min−1 dopamine. In the dobutamine-norepinephrine group, dobutamine was started at the same time as norepinephrine and titrated up to 20 &mgr;g · kg−1 · min−1 to get a 15% increase in cardiac output. Results The dobutamine-norepinephrine group had greater cardiac output; superior mesenteric blood flow, oxygen delivery (Do2), and oxygen consumption (&OV0312;o2); and lower blood lactate concentration and partial pressure of carbon dioxide (Pco2) gap than the controls did. Cumulative urine output was significantly higher in the dobutamine-norepinephrine group than in the other groups. Survival time was significantly longer in the dobutamine-norepinephrine (24 ± 4 h), dopamine- norepinephrine (24 ± 6 h), and norepinephrine (20 ± 1 h) groups than the control group (17 ± 2 h;P < 0.05 vs. other groups), and significantly longer in the combined dopamine-norepinephrine and dobutamine-norepinephrine groups (24 ± 5 h) than in the norepinephrine alone group (P < 0.05). Histologic examination of lung biopsies revealed less severe lesions in the dobutamine-norepinephrine group than in the control and norepinephrine alone groups. Anatomic alterations in the lung, liver, and small intestine were less severe in the dobutamine-norepinephrine group than in the other groups. Conclusions In this prolonged septic shock model, association of norepinephrine with either dopamine or dobutamine resulted in the longest survival and the least severe pulmonary lesions. The combination of dobutamine with norepinephrine was associated with a better myocardial performance, greater Do2 and &OV0312;o2, lower blood lactate concentration and Pco2 gap, and less anatomic injury.

Use of low tidal volume in septic shock may decrease severity of subsequent acute lung injury

Recent studies have indicated that protective lung strategies may improve outcomes in acute lung injury. We hypothesized that the use of a lower tidal volume early during septic shock may protect against the subsequent development of acute lung injury. Fourteen fasted, anesthetized, invasively monitored, mechanically ventilated, female sheep (26.4 ± 4.5 kg) underwent cecal ligation and perforation to induce sepsis. Sheep were then randomized to ventilation with low (6 mL/kg) or high (12 mL/kg) tidal volumes. A positive end-expiratory pressure of 10 cmH2O was applied in each case. Ringer’s lactate was titrated to maintain pulmonary artery occlusion pressure at baseline levels. No vasoactive agents or antibiotics were used. Survival time was longer in the low- than in the high-tidal-volume group (21.8 ± 2.4 vs. 17.6 ± 4.1 h, respectively, P < 0.05). The times to develop hypotension and anuria were longer in the low-tidal-volume group (18.1 ± 3.1 vs. 12.0 ± 2.8 h, P < 0.05, and 17.6 ± 1.6 vs. 14.1 ± 3.8 h, P < 0.05). Although the Pao2/Fio2 tended to be lower in the low- than in the high-tidal-volume group (P = 0.06), postmortem examination showed a lower lung tissue wet/dry ratio in the low- than in the high-tidal-volume group (7.1 ± 0.5 vs. 9.1 ± 0.7, P < 0.05). A low-tidal-volume ventilation strategy applied early during septic shock may be beneficial in terms of reducing the amount of lung edema and prolonging survival time.

Determination of growth fraction and cell density to evaluate the potential growth of human oligodendroglial and astrocytic tumours

Abstract The object of this work was Purpose: to develop a methodology that enables net tumour growth, a balance between actual tumour growth and tumour cell loss, to be approximately evaluated. Methods: The methodology proposed relies on detecting the growth fraction immunohistochemically by means of MIB-1 antibody labelling combined with cell density determination, carried out on 5-μm-thick Feulgen-stained histological sections with computer-assisted microscopy. The series investigated included 25 oligodendrogliomas (OLG-II), 9 anaplastic oligodendrogliomas (OLG-III), 13 astrocytomas (AST), 14 anaplastic astrocytomas (ANA) and 8 mixed oligoastrocytomas (OLG-AST). Results: The results show that the biological characteristics of some cases were in total accordance with their histopathological diagnoses. This was the case for the “weakly proliferating weakly dense” OLG-II and AST-II tumours, and for the “highly proliferating highly dense” OLG-III and AST-III ones. In contrast, the biological characteristics of some cases seemed to contradict the histopathological case labels. This was the case for the “highly proliferating highly dense” OLG-II and AST-II tumours, the biological aggressiveness of which would be undervalued on the basis of the morphology-based grading system alone, and also for the “weakly proliferating weakly dense” OLG-III and AST-III tumours, the aggressiveness of which would be overvalued. Conclusions: Combining the determinations of the MIB-1 and the cell density variables appears to be satisfactory in terms of the cell kinetic characterization of glial tumours as a complement to the prognostic information given by a morphology-based grading system alone.