Search PubMed⌕ Search

Biomedical subjects

F Cavaliere

Publications and source records attributed to F Cavaliere.

At least 19 recordsLinked to original sources

Hypoalbuminaemia does not impair Diprifusor performance during sedation with propofol.

BACKGROUND: About 98% of plasma propofol is bound to albumin. We investigated if severe hypoalbuminaemia may affect the accuracy of a target-controlled infusion (TCI) device, the Diprifusor, during sedation in critically ill patients. METHODS: Ten critically ill hypoalbuminaemic patients (<24 g litre(-1)) and 10 critically ill normoalbuminaemic patients (>32 g litre(-1)) were included in this study. They underwent sedation with propofol, aimed at a Ramsey sedation score of 4-5. The Diprifusor was used to achieve target propofol plasma concentrations that ranged between 0.6 and 1.5 mg litre(-1). Propofol concentration was measured by high-performance liquid chromatography 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h and 8 h after starting TCI. The accuracy of TCI was evaluated by calculating performance errors [PE=100x(measured concentration-predicted concentration)/predicted concentration], absolute and relative individual median performance errors (MDAPE and MDPE) and divergence (the slope of individual regression lines between PEs and time). RESULTS: PEs [median (range)] were -7 (-65, 79) in hypoalbuminaemic patients and -2 (-53, 188) in normoalbuminaemic patients; absolute PEs were 21 (1, 79) and 22 (0, 188). No significant difference was observed between the two groups. MDPE, MDAPE and divergence values were also similar. In most patients the accuracy of TCI increased with time because higher PE values were observed during the first 30 min. CONCLUSIONS: Hypoalbuminaemia does not affect the accuracy of Diprifusor during sedation with propofol in critically ill patients.

Adult↗

Microglia response and P2 receptor participation in oxygen/glucose deprivation-induced cortical damage.

In the present work, we used a unique cortical/striatal/subventricular zone organotypic model in order to analyze the role of resident microglia in oxygen/glucose deprivation and to check the presence and modulation of several P2 receptors in the cortex. Immunofluorescence with the microglial marker OX42 and pharmacological experiments with indomethacin indicate that activation and recruitment of microglia after the insult is linked to cellular loss, mainly in the cortex. The confocal analysis with OX42 shows that, among the P2 receptors tested, P2X4, and P2X7 are expressed on microglia, while P2X1 and P2Y(1-2-12), although present in the slices, did not co-localize, whereas P2X6 is not detected. The upregulation of P2X4 and P2X7 on microglia and the toxic effect that different P2 agonists exert on cortical slices during oxygen/glucose deprivation indicate that a purinergic mechanism is related to the microglia activity; the protective effect of the P2 antagonist TNP-ATP is also described. In order to better understand the relationship between P2 receptors and OGD-activated microglia, we induced oxygen/glucose deprivation in co-cultures of organotypic slices and N9 microglia cell line. The presence of the N9 (which expresses P2X4 and P2X7 protein) in the cultures increases the damage in the cortex by 40% and the use of P2 antagonist PPADS reduced the cell damage due to the N9 activation. Our results show that microglia recruitment after a metabolic impairment is associated with cellular loss and that P2X4 and P2X7, are involved in microglia activity. The neuroprotective action exerted by TNP-ATP and PPADS and the possible use of purinergic antagonist in the pharmacological treatment of oxygen/glucose deprivation is also addressed.

Adenosine Triphosphate↗

Anesthesiologic preoperative evaluation of drug addicted patient.

Even if there are few scientific data about preoperative management of drug addict patients, a careful anesthesiology evaluation facilitates the prevention of interactions between drugs and anaesthetics and avoids intraoperative and postoperative complications. Moreover it is important to earn the confidence of patient in order to know the abuse substances consumed and the frequency of consumption. This knowledge is necessary to the anaesthetist in order to manage possible withdrawal syndromes or overdose, which are the two greatest dangers for a drug addict patient during the hospital stay.

Anesthesia↗

Squamous and adenosquamous cell carcinomas of the gallbladder.

Squamous and adenosquamous cell carcinomas (ASC and SCC) are rare subtypes of gallbladder cancer, traditionally considered more aggressive and with a poorer prognosis than adenocarcinoma. We report about two patients affected by an advanced squamous cell carcinoma of the gallbladder. Both had a large tumour in the gallbladder fossa region with infiltration of the liver. Surgical resection was radical in one, but palliative in the other. pTNM was T3 N0 M0, G3, R0 in the former and T3 N0 M0, G2 R1 in the latter. Patients died for local recurrence after 12 and 5 months, respectively. Natural history, clinical findings, prognosis and outcome of this rare gallbladder tumour are discussed on the basis of a review of the English literature. In conclusion, an aggressive and radical surgical treatment of advanced squamous and adenosquamous cell gallbladder carcinomas seems to be indicated for their low proclivity to distant spreading.

Aged↗

Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study.

PURPOSE: The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival. PATIENTS AND METHODS: A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded. RESULTS: The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P <.001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators. CONCLUSION: The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.

Adolescent↗

Negative differential conductance induced by spin-charge separation.

Spin-charge states of correlated electrons in a one-dimensional quantum dot attached to interacting leads are studied in the nonlinear transport regime. With nonsymmetric tunnel barriers, regions of negative differential conductance induced by spin-charge separation are found. They are due to a correlation-induced trapping of higher-spin states without magnetic field and are associated with a strong increase in the fluctuations of the electron spin.

Journal Article↗

TNFa-based isolated hyperthermic limb perfusion (HILP) in the treatment of limb recurrent melanoma: update 16 years after its first clinical application.

Hyperthermic Limb Perfusion (HILP) with Tumor Necrosis Factor alpha (TNFalpha) and interferon gamma (IFNgamma) was pioneered by Liénard and Lejeune in 1988. TNFalpha was empirically employed at a dosage of 3-4 mg that is ten times the systemic maximum tolerated dose (MTD). Sixteen years after its first clinical application more than 300 patients have been treated and some clarifications can be made regarding three major questions: the real role of IFNgamma, the TNFalpha dose and eligibility criteria for patient selection. A randomized phase II study has demonstrated that IFNgamma does not increase significantly the efficacy but does increase side-effects. Experimental and clinical results seem to indicate that patients with bulky melanoma disease can really benefit from TNFalpha HILP carried out with only 1 mg.

Animals↗

Liposomal doxorubicin in the perfusional treatment of advanced soft tissue limb sarcoma.

Liposome-containing doxorubicin has been employed in the treatment of advanced soft tissue limb sarcoma during hyperthermic perfusion. A phase I-II study was carried out starting with a standard dose of 10 mg//L of limb volume, the dosage was escalated with 2 mg for each triplet of patients. The maximum tolerable (MTD) dose was established as the amount able to cause a grade IV limb reaction at least in two out of three patients, the temperature level remained unchanged (41.5 degrees C). The grade of limb reaction ranged between I-II (mild edema and erythema). Only in two patients treated with 18 mg/L of limb volume was a grade IV limb reaction observed, therefore MTD at a temperature of 41.5 degrees C is 16 mg. A good tumor response was observed in 29% of the patients, partial response in 71%. The tumor shrinkage after perfusion permitted conservative surgery in 91% of the cases.

Adult↗

Systemic and haemodynamic toxicity after isolated limb perfusion (ILP) with TNF-alpha.

The aim of this study was to evaluate the systemic and haemodynamic postoperative effects of ILP with medium-low dose of TNF alpha in patients diagnosed with primary or recurrent limb melanoma or sarcoma, and to compare the resulting toxicity with Systemic Inflammatory Response Syndrome (SIRS). A prospective study on 17 consecutive patients with primary or recurrent limb tumor (melanoma or sarcoma) subjected to ILP with escalating doses of TNF alpha (0.5-2.0mg) was carried out. Seventeen patients with primary or recurrent limb melanoma or sarcoma were subjected to ILP with escalating doses of TNF alpha. ILP was carried out with the standard techniques, blood being warmed at 42 degrees C for an hour. Serial serum TNF alpha determinations were performed before, during and after limb perfusion in nine patients. Systemic and pulmonary haemodynamics, by a radial and pulmonary artery catheter inserted before the induction of anesthesia, were monitored at 5 different times: before the induction of anesthesia (T0), and 6, 12, 24 and 48 hours after treatment (T1-4). Complete isolation of the limb was not always achieved, therefore leakage of TNF alpha occurred frequently during the perfusion in all patients with maximum systemic TNF alpha concentrations ranging from 431 to 111000 pg/ml. After perfusion only two patients showed detectable TNF alpha levels in peripheral blood which returned to baseline values within nine hours. These two patients had serious systemic toxicity: shock and respiratory failure secondary to pulmonary edema. Acute pulmonary edema was also observed in another patient. All three cases required supportive therapy provided by means of mechanical ventilation. In the remaining 14 patients a sepsis-like syndrome was observed. The most significant haemodynamic changes were due to the CO, which rose by 35%, and the SVR, which remained consistently low throughout. A reduction in Hb was observed in all patients (with an average decrease of 4 g/dl), while DO2 and VO2 levels rose, though not to statistically significant levels. Hypoxia occurred in all 14 patients. In three of the remaining 14 cases bilateral pulmonary leaks were noted, however the use of mechanical ventilation was not required. No perioperative death occurred and the aforementioned side effects were all reversible resulting in a patient's mean postoperative ICU permanence of 4 days (range 3 to 7 days). In conclusion, ILP with TNF alpha induces cardiovascular, respiratory and hematological toxicity with haemodynamic parameters being similar to those noted in SIRS probably due to leakage of TNF alpha in the systemic circulation during the perfusion. Nevertheless, this systemic toxicity was short-lived resulting in an acute reaction following a single application.

Adult↗

Up-regulation of P2X2, P2X4 receptor and ischemic cell death: prevention by P2 antagonists.

In the present work we examined the involvement of selected P2X receptors for extracellular ATP in the onset of neuronal cell death caused by glucose/oxygen deprivation. The in vitro studies of organotypic cultures from hippocampus evidenced that P2X2 and P2X4 were up-regulated by glucose/oxygen deprivation. Moreover, we showed that ischemic conditions induced specific neuronal loss not only in hippocampal, but also in cortical and striatal organotypic cultures and the P2 receptor antagonists basilen blue and suramin prevented these detrimental effects. In the in vivo experiments we confirmed the induction of P2X receptors in the hippocampus of gerbils subjected to bilateral common carotid occlusion. In particular, P2X2 and P2X4 proteins became significantly up-regulated, although to different extent and in different cellular phenotypes. The induction was confined to the pyramidal cell layer of the CA1 subfield and to the transition zone of the CA2 subfield and it was coincident with the area of neuronal damage. P2X2 was expressed in neuronal cell bodies and fibers in the CA1 pyramidal cell layer and in the strata oriens and radiatum. Intense P2X4 immunofluorescence was localized to microglia cells. Our results indicate a direct involvement of P2X receptors in the mechanisms sustaining cell death evoked by metabolism impairment and suggest the use of selected P2 antagonists as effective neuroprotecting agents.

Animals↗

Sitilo experience on peritoneal carcinomatosis from colorectal cancer: clinical prognostic features.

UNLABELLED: A multicentric prospective study has been carried on 69 patients affected by peritoneal carcinomatosis from colorectal cancer. Patients have been treated by cytoreductive surgery and intraoperative hyperthermic chemoperfusion. CC 0-1 has been achieved in 82%. Major morbidity and mortality was 21.7% and 2.9% respectively. Three-yrs overall survival was 26.7% for all series. Difference in survival evaluating CC 0-1 vs. CC 2 pts and PCI < or = 10 vs. >10 was statistically significant. Evaluating only patients CC 0-1 and PCI < or = 10 4-yrs overall survival rised up to 44.7%. A smaller subgroup of patients with a disease-free interval to peritoneal carcinomatosis > or = 2-yrs showed a 5-yrs disease-free survival of 50%. CONCLUSIONS: PCI < or = 10, complete or optimal cytoreduction feasibility have to be considered for the patients selection to the integrate treatment. Disease-free interval seems to be a powerful prognostic indicator and deserve to be better outlined in further studies.

Adult↗

An Italian Multicentric Phase II study on peritonectomy and intra peritoneal hyperthermic perfusion (IPHP) to treat patients with pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is a rare disease with a poor prognosis when not adequately treated. It is characterized by a complete redistribution of mucin within the peritoneal cavity. The aim of this multicentric study was to evaluate the survival, morbidity, toxicity and mortality of patients with PMP treated by cytoreductive surgery (CRS) with intraperitoneal hyperthermic perfusion (IPHP). Seventy patients with PMP (31 males and 39 females) were enrolled onto a Phase II clinical trial. One patient was operated on twice because of disease recurrence. CRS was performed with peritonectomy procedures. The closed, opened and semi-closed abdomen techniques were employed for IPHP using cisplatin plus mitomycin-C for 60 minutes under hyperthermic conditions (42.5 degrees C). Sixty two (87%) patients were optimally cytoreduced. Five-year overall survival, progression-free survival and locoregional progression-free survival were 91%, 54% and 69%, respectively. Thirteen Grade III complications occurred in 10 (14%) patients and the most frequent one was gastrointestinal fistula/perforation (11%). There was one case (1.4%) of treatment-related mortality 21 days after treatment. CRS associated with IPHP permitted complete tumour removal with an acceptable morbidity and mortality in patients with PMP. This study confirms the efficacy of the combined treatment on long-term survival and local disease control.

Adult↗

An Italian Multicentric Phase II study on peritonectomy and intra peritoneal hyperthermic perfusion (IPHP) to treat patients with peritoneal mesothelioma.

Peritoneal mesothelioma (PM) is a rare disease, with a poor prognosis. We decided to prospectively evaluate the prognostic impact and the morbimortality of cytoreductive surgery combined with intraperitoneal hyperthermic perfusion in the treatment of this clinical entity. Sixty one patients with PM (31 males and 30 females) were enrolled onto a Phase II multicentric clinical trial. The mean age was 51 years (range: 24-72). CRS was performed with peritonectomy procedures. The closed, opened and semi-closed abdomen techniques were employed for IPHP using cisplatin plus mitomycin-C or cisplatin and doxorubicin for 60/90 minutes under hyperthermic conditions (42.5 degrees C). One patient was operated on twice because of disease recurrence. Mean follow-up was 20 months (range: 0.1-76). Forty six (74%) patients were optimally cytoreduced. Five-year overall and 5 yr progression-free survivals were 54% and 37%, respectively. Completeness of cytoreduction was significantly associated with outcome. Twenty Grade III complications occurred in 14 (23%) patients and the most frequent one was digestive fistula/perforation (11%). No treatment-related mortality was recorded. CRS + IPHP was proven to be acceptable in terms of morbidity and mortality in patients with PM and suggest a positive impact on outcome. Further prospective controlled studies are warranted to confirm these results.

Adult↗

Doxorubicin in isolation limb perfusion in the treatment of advanced limb soft tissue sarcoma.

Hyperthermic antiblastic perfusion/HAP) has been proven to be an effective neoadjuvant treatment in the treatment of advanced soft tissue limb sarcoma. As a matter of fact high percentage of limb sparing surgery, local control and functional results have been obtained wide this technique. Many antineoplastic drugs have been associated to hyperthermia by isolation limb perfusion, the aim of this paper was to describe the results obtained with doxorubicin in association to hyperthermia with or without Tumor Necrosis Factor (TNF) alpha in order to identify the most effective regimen in the multidisciplinary treatment of soft tissue limb sarcoma. A total of 106 patients have been evaluated. Three different study were performed: the first was a phase I study carried out in order to assess the maximum tolerable dose (MTD) of doxorubicin during HAP; the second was a phase II study with doxorubicin, and the third was a phase I - II study aimed at evaluating the MTD and tumor response of TNF alpha in association to doxorubicin and hyperthermia. Grade IV limb toxicity was recorded in 11 patients ( 4 in trial A, 3 in trial B, and 4 in trial C). The grade of limb reaction was strictly related to TNF dosage (> 1 mg) and temperature level (> 41.5 degrees C), therefore the best regimen is represented by temperature level not exceeding 41.5 degrees C and 1 mg of TNFalpha. The trimodality association (TNF, doxorubicin and hyperthermia) was proven to be the best regimen able to obtain a 77% of objective response (complete response, 22%) and a 77% of limb sparing in patients candidate to amputation. The results above mentioned showed the HAP with doxorubicin and TNFalpha (1 mg) is a very effective neoadjuvant treatment in the multidisciplinary treatment of advanced soft tissue limb sarcoma.

Adolescent↗

Hyperthermic antiblastic perfusion in the treatment of locoregional spreading limb melanoma.

On the basis of personal experience and a review of the literature, the authors have evaluated the results obtained with hyperthermic antiblastic perfusion (HAP) for the treatment of stage II, III and IIIAB limb melanoma. The evaluation showed that today HAP may be considered a safe and effective treatment, with a major complication rate ranging between 1% and 4%. In terms of tumor response, locoregional control and survival, this treatment has provided better results than other regional chemotherapeutic modalities and undoubtedly better results than those obtained with conventional, even radical, surgery. The multivariate analysis showed that, of the treatment-related prognostic factors, the minimum tumor temperature influenced the percentage of complete response (CR) to the greatest extent (P<0.03), with a positive trend also with regard to the dosage of the antiblastic drug employed (P<0.08). In turn, the complete response rate was a determinant as far as locoregional control (50%; P<0.0009) and disease-free (51.4%; P=0.0009) and overall survival (63%; P<0.009) rates were concerned. Of the tumor-related prognostic factors, the number of lesions (P<0.0014), sex (P<0.04), and the number of disease recurrences (P<0.01) appear to influence overall survival.

Antineoplastic Agents, Alkylating↗

Hyperthermic antiblastic perfusion with TNFalpha and melphalan in stage III limb melanoma patients: A phase I - II SITILO study.

Hyperthermic antiblastic perfusion (HAP) has been proven to be an effective treatment of loco-regional spreading limb melanoma. The mean complete response (CR) rate obtained is 54%, with an objective responses (OR) rate ranging between 70% and 100%. Recently, Tumor Necrosis Factor (TNFalpha) has been employed at high dosages (3-4 mg) in association to Melphalan and hyperthermia. This trimodality combination increased the percentage of CR (70%-90%), but systemic toxicity was also reported due to high TNF doses. A phase I - II study was undertaken in order to assess the MTD of TNFalpha in association to true hyperthermia (41.5 degrees C) and Melphalan. Twenty patients affected with stages IIIA (9 patients), IIIAB (10 patients), and IV (1 patient) were enrolled in this study. The trimodality treatment did not increase the local and systemic toxicity. CR was observed in 70% of the patients, PR in 20% with on OR rate of 90%. These figures are overlapping those obtained with high TNF dosages. No correlation was observed between tumor responses and TNF doses. Taking into account that 70% of our patients have been treated with TNF dosages between 0.5 mg on 1.6 mg, we conclude that 1 mg is the best dosage to be applied during HAP. Patients with bulky tumor are the best candidate to TNF perfusion, because no differences have been observed in terms of CR in patients with low tumor burden treated with TNF-Melphalan-hyperthermia or Melphalan-hyperthermia.

Adult↗

Effects of acid-base abnormalities on blood capacity of transporting CO(2): adverse effect of metabolic acidosis.

OBJECTIVE: To investigate the effects of some acid-base abnormalities on blood capacity of transporting CO(2). DESIGN: Prospective study. SETTING: General and Cardiosurgical ICUs of a University hospital. PATIENTS: Six groups of ten patients characterized by: metabolic alkalosis; respiratory alkalosis; absence of acid-base abnormalities; metabolic acidosis; uncompensated respiratory acidosis; and compensated respiratory acidosis. MEASUREMENTS AND RESULTS: The CO(2) dissociation curve, Haldane effect, and the ratio Ra-v between Ca-vCO(2) and Pa-vCO(2) were calculated from arterial and mixed-venous blood gas analyses. The CO(2) dissociation curve was shifted upwards by metabolic alkalosis and compensated respiratory acidosis and downwards by metabolic acidosis. The slope of the curve was unaffected, but CO(2) transport not due to Haldane effect was significantly lower in respiratory acidosis since the slope was less steep at higher PCO(2) values. In comparison with controls, patients affected by metabolic acidosis showed lower Haldane effect values (0.18+/-0.15 vs 0.59+/-0.26 ml of CO(2) per ml of arterial-mixed venous O(2) content difference; P <.05) and Ra-v values (0.43+/-0.10 vs 0.84+/-0.17 ml of CO(2) transported by 100 ml of blood per Torr of arterial-mixed venous PCO(2) gradient; P <.05). CONCLUSIONS: Our findings suggest that acid-base abnormalities, particularly metabolic acidosis, markedly affect blood capacity of transporting CO(2) and may worsen tissue hypercarbia associated with hypoperfusion. However, because of possible errors due to small measurements and the assumptions of the method, in the future definitive clarification will require the construction of original CO(2) dissociation curves for each acid-base abnormality.

Acidosis↗