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A Nespoli

Publications and source records attributed to A Nespoli.

30 records · Page 2Linked to original sources

The cardiorespiratory impairment in cirrhosis and sepsis. An experimental interpretation using octopamine infusion.

The effects of octopamine on systemic and pulmonary circulation and on respiratory parameters have been studied in ten O2 100% breathing pigs. A rise in cardiac index (CI) due to an increase in the dynamics of the left ventricle and a progressive hypoxemia, notwithstanding the hyperventilation, was found. The decrease in arterial O2 tension was due to a rise in the pulmonary shunt fraction (QS/QT). The statistical analysis of cardiorespiratory parameters demonstrated that the high flow state linked with a non-Starling mechanism was the causing factor of a ventilation: perfusion ratio (VA/QT) decrease, which led to the rise in QS/QT. Also, a decrease in the lung compliance simultaneous to the increased blood flow was observed. It is suggested that octopamine may play a role in the pathogenesis of the cardiorespiratory hemodynamic impairment of cirrhosis and sepsis where high levels of this false neurotransmitter were observed.

Animals↗

Pathologic synergy in cardiovascular and respiratory compensation with cirrhosis and sepsis. A manifestation of a common metabolic defect?

Multivariable physiologic studies of cardiovascular, respiratory, and metabolic functions were performed in 341 patients (884 studies). Eighty patients had cirrhotic liver disease, 64 had sepsis, 87 had nonseptic cariogenic syndromes, and 110 had nonseptic general surgical or traumatic injury. The group with cirrhosis had the highest cardiac index and ejection fraction. When compared with the group with nonseptic surgery or trauma, vascular tone was reduced in the patients with cirrhosis or sepsis and was lowest in patients with both conditions. Ventricular function was good in the groups with cirrhosis or sepsis, due to the additive effect in reducing vascular tone that allowed ejection fraction to increase, but caused the ratio of alveolar ventilation to perfusion (VA/QT) to fall, resulting in a greater perfusion of a decreased pulmonary vascular bed. The falls in vascular tone and VA/QT in patients with cirrhosis or sepsis result from the reduced oxygen consumption that occurs due to metabolic imbalance (B state). This B state seems to reflect a hepatic inability to metabolize aromatic amino acids, so that levels of tyrosine, phenylalanine, and the false neurotransmitter octopamine increase. These mechanisms are pathologically synergistic when sepsis and cirrhosis occur together.

Amino Acids↗

Pathogenesis of hepatic encephalopathy and hyperdynamic syndrome in cirrhosis. Role of false neurotransmitters.

We sought to determine whether false neurotransmitters (FNTs) play an important role as determinants not only of hepatic encephalopathy but also of hyperdynamic syndrome in cirrhosis. A combined biochemical and hemodynamics study of 55 bleeding cirrhotic patients was made. We evaluated the aromatic and aliphatic branched-chain amino acids and octopamine serum levels as well as the hemodynamic measurements. The results show that there is a correlation between levels of serum octopamine and aromatic amino acids and hepatic coma: the higher the octopamine level, the deeper the hepatic coma. There is also a correlation between aromatic amino acids and cardiac index and total peripheral resistance. Furthermore, when a narrowing of arteriovenous difference in oxygen occurs and oxygen consumption decreases, there is an increase not only in the level of aromatic amino acids, but also in octopamine level, suggesting an important linkage between hemodynamic and metabolic impairment.

Adolescent↗

Death after portal decompressive surgery. Physiologic state, metabolic adequacy, and the sequence of development of the physiologic determinants of survival.

Detailed serial cardiovascular and respiratory physiologic studies were carried out in 80 patients with cirrhotic liver disease, including 45 cirrhotic patients who underwent portal decompressive surgery on an urgent or elective basis. In surgical cases, death could be predicted from the first postoperative day's pattern of response. Predictors of death were an increase in percent of pulmonary shunt due to a redistribution of the increased pulmonary blood flow, and a disproportionate fall in vascular tone, which permits an increased cardiac ejection fraction even when significant myocardial depression occurs. The etiology of the vascular tone defect seems related to the rise in levels of the false neurotransmitter octopamine, which are shown to increase as oxygen consumption falls in the patho-physiologic hyperdynamic B state, presumably due to a block in the oxidative metabolism of aromatic amino acids.

Esophageal and Gastric Varices↗

[Effects of octopamine on pulmonary circulation of the pig].

The perfusion of octopamine in pig produces an increase of cardiac output with decrease of pulmonary vascular resistances. The changes in lung circulation depend by a direct action of this drug on nervous control of vascular walls because when the pulmonary shunt increase the effect is not correlated to changes a pattern of breathing.

Animals↗

Pre-operative IL-2 immunoprophylaxis of cancer recurrence: long-term clinical results of a phase II study in radically operable colorectal cancer.

This study evaluates retrospectively the outcome of 20 colorectal cancer patients radically operated (M/F 13/7; primary/recurrent 15/5; Dukes B=11; C=6; D=3) who received pre-operative IL-2 (18,000, 000 IU/daily s.c. for 3 days) and the outcome of 40 colorectal cancer (primary/recurrent 40/0) patients age, sex and stage-matched radically operated, as control group. After a median follow-up of 72 months, in the IL-2 pre-operative group we observed 6/20 recurrences (30%) vs. 19/40 (47.5%) in controls. Mean and median disease-free period in patients who relapsed were respectively 21 months and 20.5 months (range 6-36) in IL-2 group vs. 14.1 and 12 months in the control group (range 3-34). After a 5-year follow-up, 4/20 (20%) IL-2 treated patients were dead vs. 19/40 control patients (47.5%) (log-rank chi2=3.7, p=0.05). Pre-operative IL-2 administration is safe, active in preventing post-operative lymphocytopenia and seems to improve the clinical outcome in radically operated colorectal cancer patients.

Adult↗

Predictive value of a pathophysiological score in the surgical treatment of perforated diverticular disease.

Resection is the preferred method of perforated diverticular disease treatment compared to conservative treatment. However, the immediate or deferred timing of bowel continuity restoration for advanced degrees of peritoneal contamination is debatable. This is a retrospective study designed to identify operative mortality predictors and guidelines for safe primary anastomosis. A pathophysiological score (acute physiology and chronic health evaluation, APACHE II) was applied to 135 consecutive patients who had undergone surgery for acute inflammatory complication of diverticular disease. A multivariate analysis was used to identify prognostic factors such as age, chronic diseases, neoplastic cancer, Acute Physiology Score (APS), Hinchey's classification and APACHE II scores. Seventy patients underwent primary resection and anastomosis, 35 underwent Hartmann's procedure and 15 conservative treatment. There was a significant correlation between operative mortality and increasing disease severity based on Hinchey's classification, APS and APACHE II scores. The multivariate analysis proved APACHE II scores to be the only prognostic factor of operative mortality. Both single and multivariate analysis of variance failed to identify a factor significantly associated with surgical and/or medical postoperative complications. APACHE II scores were the best predictor for operative mortality in patients with diverticular disease complications, but none of the classification criteria used was effective in predicting postoperative complication. Patients with phlegmonous sigmoiditis can be safely treated with primary resection and anastomosis. Conservative treatment should not be considered an effective method for diverticular disease. A prospective trial comparing resection with and without colostomy should be done for local and diffuse purulent peritonitis treatment. Hartmann's procedure is seen to be the only indicator for faecal peritonitis.

APACHE↗

Abrogation of surgery-induced decline in circulating dendritic cells by subcutaneous preoperative administration of IL-2 in operable cancer patients.

Surgery-induced immunosuppression is characterized by a decline in lymphocyte count, particularly T lymphocyte number. In addition, preliminary studies have shown that the postoperative period is also characterized by a decline in the number of circulating dendritic cells (DC), whose fundamental anticancer role has been recently demonstrated. Previous studies had already shown that the preoperative injection of IL-2 may completely abrogate surgery-induced lymphocytopenia, whereas its eventual influence on DC system during the perioperative period is still unknown. The present study was performed to evaluate the influence of IL-2 preoperative immunotherapy on the perioperative changes in circulating DC number in patients affected by colorectal cancer. The study included 14 consecutive patients, who were randomized to be treated with or without IL-2 presurgical immunotherapy (12 million IU/day for 3 days subcutaneously). Circulating immature and mature cells were evaluated before surgery and at days 3 and 7 of the postoperative period. The detection was made by FACS using monoclonal antibodies against CD123 and CD11c to recognize immature and mature DC, respectively. Surgery induced a significant decline in the mean number of both immature and mature DC. The pre-surgical administration of IL-2 completely abrogated surgery-induced decline in immature DC cell amount. Moreover, mature DC mean number was diminished only at day 3 of the postoperative period, since the value observed at day 7 was not significantly lower than that found before surgery. This preliminary study shows that surgery-induced immunosuppression is characterized also by a significant decline in the mean number of both immature and mature DC. Moreover, this study would suggest that the preoperative immunotherapy with IL-2 may counteract surgery-induced failure of DC system. Because of the fundamental antitumor role of DC, this evidence could have a prognostic impact on the clinical course of the neoplastic disease.

Aged↗

Surgery-induced decline in circulating dendritic cells in operable cancer patients: a possible explanation of postoperative immunosuppression.

BACKGROUND/AIMS: The recent advances in the immunobiology of tumor have demonstrated the essential role of dendritic cells in anticancer immunity. Dendritic cells activate anticancer immunity by secreting interleukin-12 and by activating T helper lymphocytes, with the following production of interleukin-2. Since surgery-induced immunosuppression has been proven to be associated with a decline in the blood levels of both interleukin-2 and interleukin-12, it could depend at least in part on a transient deficiency of dendritic cells system. Unfortunately, at present there are no data about changes in circulating dendritic cell number during the postoperative period. This preliminary study was performed to evaluate the influence of surgery on dendritic cell number in the peripheral blood. METHODOLOGY: The study included 14 consecutive operable gastrointestinal tract cancer patients, who were evaluated before and at day 7 of the postoperative period. The control group consisted of 50 healthy subjects. Immature (CD 123+) and mature (CD 11+) dendritic cell subsets were measured by FACS and monoclonal antibodies. RESULTS: Cancer patients showed a significantly lower mean number of immature dendritic cells with respect to that found in controls. The mean number of mature dendritic cells was also lower in patients than in controls, without, however, significant differences. Finally, surgery induced a statistically significant decline in the mean number of both immature and mature dendritic cells, and the decrease was particularly pronounced for immature dendritic cells. CONCLUSIONS: In addition to the well-demonstrated surgery-induced lymphocytopenia, this preliminary study shows that the surgical treatment may determine a significant decrease in circulating immature and mature dendritic cells. Because of the fundamental role of dendritic cells in regulating the immune responses, surgery-induced decline in circulating dendritic cells number could play a role in determining the immunosuppressive status, which characterizes the postoperative period.

Adult↗