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A Picone

Publications and source records attributed to A Picone.

At least 37 records · Page 2Linked to original sources

Surfactant replacement in the treatment of sepsis-induced adult respiratory distress syndrome in pigs.

OBJECTIVE: To evaluate the efficacy of treating sepsis-induced adult respiratory distress syndrome (ARDS) by instillation of exogenous surfactant in a porcine endotoxin model. DESIGN: Prospective trial. SETTING: Laboratory at a university medical center. SUBJECTS: Fifteen hybrid pigs, weighing 15 to 20 kg. INTERVENTIONS: Pigs were anesthetized and surgically prepared for hemodynamic and lung function measurements. Animals were randomized into three groups: a control group (group I; n=4) that received sham Escherichia coli lipopolysaccharide (endotoxin); an endotoxin group (group II; n=6) that received endotoxin (25 micrograms/kg); and an endotoxin + surfactant (Infasurf, ONY, Amherst, NY) instillation group (group III; n=5) that received endotoxin (25 micrograms/kg) followed by surfactant (100 mg/kg) instillation; all groups were studied for 6 hrs after the start of endotoxin injection. At necropsy, lung water and surfactant function (Wilhelmy balance) were measured and the right middle lung lobe was fixed for histologic analysis. Surfactant function was expressed as the surface tension at the minimum trough area. MEASUREMENTS AND MAIN RESULTS: Surfactant treatment (group III) significantly (p<.05) decreased venous admixture (group III = 41.5 +/- 9.1%; group II = 61.6 +/- 4.7%), PaCO2 (group III = 46.6 +/- 1.3 torr [6.2 +/- 0.2 kPa]; group II = 54.4 +/- 2.6 torr [7.25 +/- 0.34 kPa], and surface tension minimum (group III = 8.8 +/- 1.8 dyne/cm; group II = 20.0 +/- dyne/cm), as compared with endotoxin without treatment (group II) 6 hrs after endotoxin infusion. However, surfactant instillation did not significantly improve PaO2 (group III = 62.8 +/- 6.8 torr [8.4 +/- 0.9 kPa2]; group II = 50.3 +/- 3.7 torr [6.7 +/- 0.49 kPa]) or reduce the amount of pulmonary edema (group III = 7.1 +/- 0.39 ratio; group II = 6.8 +/- 0.24 ratio) seen 6 hrs following endotoxin injection. Histologic analysis showed that endotoxin caused edema accumulation around airways and pulmonary vessels, and a large increase in the number of marginated leukocytes with or without surfactant treatment. Surfactant treatment significantly increased the total number of leukocytes in the pulmonary parenchyma. CONCLUSIONS: We conclude that endotoxin caused lung injury typical of ARDS as demonstrated by pulmonary edema, an increase in PaCO2, and a decrease in PaO2, a decrease in static lung compliance and inhibition of surfactant function. Exogenous surfactant treatment effected only moderate improvements in lung function (i.e., reduced venous admixture and restored surfactant function) in this sepsis-induced ARDS model.

Animals↗

Pulmonary surfactant function following endotoxin: effects of exogenous surfactant treatment.

In a porcine model of endotoxin-induced adult respiratory distress syndrome (ARDS) we tested the hypothesis that the severity of lung injury would vary with the concentration of endotoxin and that reestablishment of normal surfactant function with exogenous surfactant would vary with the severity of lung injury. The therapeutic effects of exogenous surfactant treatment on pulmonary surfactant function have varied greatly in animal models of ARDS. This has created discrepancies in the literature that may be due in part to a difference in the severity of the pulmonary lesion. Yorkshire pigs were anesthetized, placed on a ventilator, and surgically prepared for hemodynamic and lung function measurements. Pigs received either 25 (25LPS) or 50 (50LPS) micrograms/kg of Escherichia coli lipopolysaccharide (LPS) followed by exogenous surfactant (SURF, 100 mg/kg) instillation, and were randomized into five groups: Control = sham LPS (n = 4); 25LPS (n = 6); 50LPS (n = 6); 25LPS + SURF (n = 5); and 50LPS + SURF (n = 6). Treatments were followed by histological and surfactant function evaluation. Histological evaluation showed the hallmarks of ARDS. Pulmonary surfactant function assessed by surfaced tension minimum (Ymin) was significantly (P < .05) elevated in both the 25LPS (20.2 +/- 2, dyne/cm) and 50LPS (19 +/- 3, dyne/cm) groups as compared with the Control group (10 +/- 1, dyne/cm). Exogenous surfactant reduced Ymin in the 25LPS + SURF group (9 +/- 2 dyne/cm, p < .05 vs. 25LPS) but not in the 50LPS + SURF group (20 +/- 1 dyne/cm, p < .05 vs. Control and 25LPS + SURF). Surfactant treatment was more effective in reestablishing normal surfactant function in animals subjected to a low dose of endotoxin, compared with animals receiving a higher dose.

Animals↗

Quantification of the oesophageal peristaltic reflex in man.

The peristaltic reflex represents the basis of peristalsis and has two components, ascending contraction above and descending relaxation below the site of distension. Studies of the two components of the reflex in the human oesophagus performed by concurrent monitoring of oesophageal body and lower oesophageal sphincter (LOS) motility are lacking. We investigated the peristaltic reflex in eight healthy volunteers (aged 19-25 years; five male, three female) by two series of eight graded (3-10 mL) balloon distensions performed 11 cm above the LOS, monitoring motor activity in the oesophageal body both above and below the balloon and in the LOS (sleeve sensor). During balloon distension both ascending contraction, as assessed by contractile activity above the balloon, and descending relaxation, as assessed by LOS relaxation, increased linearly with increasing inflation volumes (r = 0.6 and r = 0.8, respectively, both P < 0.0001). The threshold for descending relaxation was lower than that for ascending contraction. The contractile response of the body below the balloon was always lower than above the balloon and occurred with a higher (P < 0.05) frequency at 6 and 7 mL compared to 3, 4 and 10 mL. After balloon deflation an oesophageal contraction, usually accompanied by an LOS contraction, occurred with increasing frequency as the balloon volume increased. Our experimental model allows detailed assessment of the two components of the peristaltic reflex in the human oesophagus in vivo and should prove useful in future studies on the physiology and pathophysiology of this reflex.

Adult↗

Effect of morphine and naloxone on motor response of the human esophagus to swallowing and distension.

The effect of morphine on esophageal motility has been little explored. In eight healthy volunteers, we studied the effect of intravenous morphine (100 micrograms/kg) followed 60 min later by intravenous naloxone (80 micrograms/kg) and of intravenous naloxone alone (80 micrograms/kg) on the esophageal motor response to swallowing and 30-s intraluminal distensions(4, 6, 8, and 10 ml) during two separate experiments. Morphine increased (P < 0.01) the velocity but did not alter the amplitude or duration of primary peristalsis, and it decreased the duration and magnitude of swallow-induced lower esophageal sphincter (LES) relaxation (P < 0.01). It also markedly increased contractile activity below the balloon at high distending volumes (P < 0.05) and decreased the magnitude of distension-induced LES relaxation (P < 0.05) but did not affect contractile activity above the balloon. All effects were reversed by naloxone. The latter alone did not influence the esophageal response to swallowing or distension. The conclusions are that 1) morphine exerts effects on the response of the human esophagus to swallowing and intraluminal distension that are consistent with an action at the level of the inhibitory neural pathways, 2) these effects occur through opioid receptors, and 3) endogenous opioids do not seem to control esophageal motility, at least through mu-receptors.

Adult↗

Transgenic mice carrying the human KRAS oncogene under the control of a thyroglobulin promoter: KRAS expression in thyroids analyzed by in situ hybridization.

We have previously generated transgenic mice bearing a molecular construct obtained by fusing the rat thyroglobulin promoter with the human Kirsten ras oncogene (KRAS). These mice showed thyroid abnormalities, although at very low incidence and after a long latency period. A six-month thyrotropin (TSH) stimulation of thyroid glands, followed by a two-month suspension, induced a significant increase in the number of lesions in transgenic mice as compared with a nontransgenic control group. Our goal was to follow the progression and the reversion of the tumorigenesis process in relationship with the levels of expression of the KRAS in this experimental model. In situ hybridization was used to detect expression of KRAS mRNA in sections of thyroids of the various groups of mice. A positive hybridization was observed in follicular cells of TSH-stimulated transgenic mice, whereas no expression could be appreciated in control nontransgenic mice. A positive signal was also observed in thyroid glands excised from transgenic mice after the 2-month suspension of treatment; however, the number of expressing cells was decreased compared with transgenic mice killed immediately after 6 months of a goitrogen regimen. Finally, every cell in the single thyroid carcinoma observed after the two-month suspension was positive for the transgene mRNA. This study further strengthens the role of the expression of mutated KRAS in the early stages of thyroid follicular cell transformation and indicates that when the expression of the mutated KRAS becomes independent of exogenous TSH stimulation, this event coincides with a further progression towards tumorigenesis.

Adenoma↗

Protamine-induced pulmonary venoconstriction in heparinized pigs.

Reversal of heparin anticoagulation with protamine may be associated with acute pulmonary vasoconstriction. The specific site of pulmonary vasoconstriction has not been determined. This study was designed to determine the site of protamine-induced pulmonary vasoconstriction and the role of nitric oxide (NO) after protamine injection. Pigs were anesthetized and instrumented with catheters for monitoring pulmonary arterial, systemic arterial, and central venous pressures. Pulmonary capillary pressure was estimated using the arterial occlusion concept, while left atrial pressure was estimated from the equilibrium wedge pressure. Hemodynamic measurements were made during baseline, before and after heparin (200 U/kg), at peak pressure response after protamine injection (2 mg/kg), and 10 and 30 min thereafter. In the control group, pulmonary vascular resistance (PVR) values during baseline and after heparin were identical (2.7 +/- 0.4 mm Hg.L-1.min-1). At peak protamine response (1-2 min) PVR increased to 8.0 +/- 1.6, but returned to baseline value after 10 min (2.8 +/- 0.3) and remained stable for 30 min (2.2 +/- 0.3). The increase in PVR after protamine was primarily due to an increase in venous resistance from 1.0 +/- 0.2 to 4.9 +/- 1.4 mm Hg.L-1.min-1, and a much smaller increase in arterial resistance from 1.7 +/- 0.3 to 3.4 +/- 0.6 mm Hg.L-1.min-1. A second group was treated with nitrow-L-arginine (LNA, 20 mg/kg) to inhibit NO release, and then heparin and protamine were administered as in the first group. Heparin had no effect on pressures, but protamine increased PVR by the same magnitude as in Group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PCNA/cyclin and P-glycoprotein as prognostic factors in locally advanced breast cancer. An immunohistochemical, retrospective study.

AIMS AND BACKGROUND: The aim of the present study was to determine, retrospectively, whether the immunohistochemical expression of two biologic markers of aggressively, P-glycoprotein (P-gp) and PCNA/cyclin (PCNA), could be related to response to chemotherapy and prognosis in locally advanced breast cancer. METHODS: PC 10 Mab was used to determine the proliferation index (PCNA) and C-219 Mab to determine P-gp in 25 locally advanced breast carcinomas subjected to preoperative chemotherapy with MDR-related drugs. RESULTS: P-gp and PCNA were expressed in 76% and 100% of the tumors, respectively. No case of high P-gp expression was associated with good chemosensitivity, and all P-gp-negative cases showed the best chemotherapeutic response. P-gp and PCNA were both highly expressed in patients who developed local-regional or distant metastases. No recurrence was associated with a negative or low P-gp score. CONCLUSIONS: Statistical analysis showed that high P-gp expression was related to a poor response to chemotherapy and a short disease-free survival. A high PCNA score was not found to be significant for predicting chemosensitivity or survival.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Alveolar variant of infiltrating lobular carcinoma of the breast with stromal osteoclast-like giant cells.

An alveolar variant of infiltrating lobular carcinoma of the breast in which a prominent feature was the presence of numerous osteoclast-like giant cells in a richly vascularized stroma is described. A similar stromal reaction has previously been reported in 46 breast carcinomas of various histologic types, but only once in a pure infiltrating lobular carcinoma. The fine needle aspiration cytological and histological appearances and the immunohistochemical and ultrastructural features of this tumor are reported. Our study confirms the histiocytic nature of the multinucleated giant cells and their similarity to normal osteoclasts.

Adult↗

[Bone echinococcosis].

Hydatidosis of the bone is a rare form of human echinococcosis. Due to the clinical, diagnostic, therapeutic and prognostic problems involved, the costal and occipital locations are of particular interest. Both are rare and differ from visceral locations in that they are always "primary" and have the capacity to destroy the bone matrix and infiltrate the adjacent tissues. The course of the disease is particularly slow and without specific signs and symptoms so that it can look like any bone condition. Laboratory tests are frequently negative and not wholly specific. While some authors claim that the radiological picture is of no diagnostic significance, others state that it offers pathognomonic signs. Diagnosis will be obtained through the combined assessment of clinical, radiological, laboratory and anamnestic data. Provenance from a rural area should reinforce the suspicion. Surgery, whether radical or conservative, is the key factor in treatment though local recurrences are common. Better results are obtained by combining surgery with Mebendazole for pre and postoperative prophylaxis. Large doses over a long period will give a better clinical course and reduce the incidence of recurrences. The prognosis is good for both sites as long as surgical treatment is given in good time.

Adult↗

[Muscular and subcutaneous hydatidosis].

Among unusual echinococcus cysts, muscular hydatidosis merits particular attention. Careful analysis of the statistics provided by the literature shows that the condition is not all that rare: its incidence varies from 0.5 to 4.7%, making it less common than hepatic or pulmonary cysts but more frequent than cysts of the kidneys, bone, pancreas, spleen or mesenterium. There are disagreements about the percentage distribution in the various muscular districts but it seems that the incidence gradually decreases as we go from the muscles of the torso and the root of the limbs to the distal extremities. The Palermo University case series includes 6 cases of which 5 muscular and one in the connective tissue. Of the 4 muscular cases, only one is to be considered secondary. For the purposes of correct preoperative diagnosis we should not neglect either anamnestic data or laboratory tests. Though the latter are not specific they are helpful for differential diagnosis from other muscular neoformation. Exploratory centesis that must be performed very cautiously in order to prevent dissemination appears to be more specific. Radiography and ultrasound examinations permit the direct study of cystic formations and a general assessment of the possibility of multiple hydatid locations. The only possible treatment is surgical. Though total removal of the cyst is the operation of choice, this is not always possible if the cyst is very big and adhering to other structures. In this case the procedure to be adopted is sterilisation and aspiration of the content, removal of the membrane and treatment of the pericystium.(ABSTRACT TRUNCATED AT 250 WORDS)

Echinococcosis↗