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Biomedical subjects

P Bruzzone

Publications and source records attributed to P Bruzzone.

At least 19 recordsLinked to original sources

Early enteral immunonutrition vs. parenteral nutrition in critically ill patients without severe sepsis: a randomized clinical trial.

OBJECTIVES: We compared early parenteral nutrition (PN) and early enteral immunonutrition (iEN) in critically ill patients, distinguishing those with and without severe sepsis or septic shock (SS) on admission to intensive care units (ICUs). DESIGN AND SETTING: Multicenter, randomized, unblinded clinical trial in 33 Italian general ICUs. PATIENTS AND PARTICIPANTS: The study included 326 patients, 287 of whom did not have SS on ICU admission. Eligibility criteria excluded the two tails in the spectrum of critical conditions, i.e., patients either too well or too ill. Of the patients recruited 160 were randomized to iEN (142 without SS) and 166 to PN (145 without SS). INTERVENTIONS: Patients were randomized to two arms: early iEN or early PN. MEASUREMENTS AND RESULTS: Primary endpoint was 28-day mortality for all patients and the occurrence of SS during ICU stay for patients admitted without such condition. While 28-day mortality did not differ between iEN and PN (15.6% vs. 15.1%), patients without SS who received iEN had fewer episodes of severe sepsis or septic shock (4.9% vs. 13.1%). ICU length of stay was 4 days shorter in patients given iEN. CONCLUSIONS: Compared to parenteral nutrition iEN appears to be beneficial in critical patients without severe sepsis or septic shock. Parenteral nutrition in these patients should be abandoned, at least when enteral nutrition can be administered, even at an initial low caloric content.

Critical Illness↗

Historical aspects of hepatocyte transplantation.

Hepatocyte transplantation has been used for temporary metabolic support of patients in end-stage liver failure awaiting whole organ transplantation as a method to support liver function and facilitate regeneration of the native liver in cases of fulminant hepatic failure and as a "cellular therapy" for patients with genetic defects in vital liver functions. The aim of this paper was to discuss the basic research that led to clinical hepatocyte transplantation, the published clinical experience with this experimental technique, and some possible future uses of hepatocyte transplantation.

Animals↗

Survival in kidney transplantation from living donors: a single-center experience.

BACKGROUND: Transplantation from living donors, in Italy, is still not accepted, in particular those from unrelated donors. The aim of this paper was to present the experience of one transplant center. MATERIALS AND METHODS: Since 1982, 608 transplants were performed from living donors using cyclosporine as the main component of immunosuppressive therapy. Among those, 402 transplants were from related living donors (338 one haplotype pairs and 25 zero haplotypes pairs) and 206 from unrelated living donors (171 spouses and 35 emotionally related subjects). RESULTS: Graft survival at 1, 5, and 10 years showed no statistically meaningful difference between the two groups. A group of 19 transplants performed in predialytic phase patients was compared with a contemporaneous group of 167 transplants performed in patients who were already receiving dialysis. These two groups did not show any statistically meaningful difference in graft survival at 1, 5, or 10 years. DISCUSSION AND CONCLUSIONS: We think that transplants from living donors, whether related or unrelated, must always be proposed as a therapeutic option for end-stage renal disease patients, since they show an higher graft survival than that from cadaveric donors, independent of the compatibility between donor and recipient and independent of the degree of relationship of the pair. Transplantation from living donors definitely is a complementary, not substitutive, program to that from cadaveric donors, which should always be encouraged with awareness campaigns among the population and targeted programs for healthy personnel.

Actuarial Analysis↗

[The fluid balance in the critically ill patient].

AIM: In the critically ill patient the hemodynamic management is essential. Usually the hemodynamic status is estimated by the measurement of the intravascular pressure or volume and by computing the fluid balance, while the change in body weight estimates the total body water. The fluid balance is computed by subtracting the fluid output to the input. Although the input (fluids, drugs, infusion.) are well known, the output are difficult to correctly compute, because they depend on several factors such as the body-room temperature, amount of humidity and may change with time. Aim of this study was to prospectively evaluate the accuracy of the fluid balance compared to the body weight measured by a dedicated mattress (Hill-Rom). METHODS: Fifteen critically ill patients were enrolled (mean age of 63.2+/-19.7 years, body mass index of 24.9+/-3.5 kg/m2) and the measurements were computed every 8 hours. The data were analyzed by the Bland-Altman test. RESULTS: Four-hundred and seventy-two measurements for a mean intensive care stay of 12.3.+/-7.3 days were computed. The Bland-Altamn showed a great inaccuracy, because the agreement (the difference between the 2 methods) was poor with a standard deviation of 1 840 L. CONCLUSION: Although the fluid balance was not accurate, the only body weight without any intravascular measurement is not helpful for a correct clinical hemodynamic management of the patient.

Adult↗

Oxygen delivery and oxygen tension in cerebral tissue during global cerebral ischaemia: a swine model.

UNLABELLED: Interest in tissue oxygen (PtiO2) monitoring is increasing. However the exact interactions between ptiO2, systemic and cerebral variables are a matter of debate. Particularly, the relationship between ptiO2, cerebral oxygen supply and consumption needs to be clarified. We designed a model to achieve progressive Cerebral Blood Flow (CBF) reduction through 3 steps: 1. baseline, 2. CBF between 50-60% of the baseline, 3. CBF < 30% of the baseline. In 7 pigs, under general anaesthesia, Cerebral Perfusion Pressure (CPP) and CBF were reduced through the infusion of saline in a lateral ventricle. PtiO2 and CBF were monitored respectively through a Clark electrode (Licox, GMS) and laser doppler (Peri-Flux). Blood from superior sagittal sinus and from an arterial line was simultaneously drawn to calculate the artero-venous difference of oxygen (AVDO2). Brain oxygen supply was calculated by multiplying relative CBF change and arterial oxygen content. PtiO2 reflected CBF reductions, as it was 27.95 (+/- 10.15) mmHg during the first stage of intact CBF, declined to 14.77 (+/- 3.58) mmHg during the first CBF reduction, declined to 3.45 (+/- 2.89) mmHg during the second CBF reduction and finally fell to 0 mmHg when CBF was completely abolished. CBF changes were also followed by a decline in O2 supply and a parallel increase in AVDO2. CONCLUSION: This model allows stable and reproducible steps of progressive CBF reduction in which ptiO2 changes can be studied together with oxygen supply and consumption.

Animals↗

An in vivo model of hyperacute rejection: characterization and evaluation of the effect of transgenic human complement inhibitors.

Hyperacute rejection (HAR) occurring after transplantation within phylogenetically distant species is a severe reaction triggered by preexisting xenoreactive antibodies and complement activation, leading to the destruction of the donor organ. Expression of human complement inhibitors in transgenic pig organs prolongs the survival of xenograft in experimental models. Moreover, the extent of protection from hyperacute rejection is dependent on the level and site of expression of the transgenic molecules and, probably, on the combination of different molecules. In this regard a small animal model to test the efficacy of expression vectors and different human molecules could be very advantageous. A murine model developed in our laboratory was characterized by measurement of several parameters characteristic of HAR in the livers of control and transgenic mice expressing transgenic human DAF (CD55) or MCP (CD46) at the end of 2 h of perfusion with human plasma and after I day. The parameters studied were heamatological values of hepatic functions (GOT and GPT), induction of pro-inflammatory molecules and histopathological evaluation. Cytokines (IL-1alpha, IL-1beta, IL-6) induction and exposure of P-selectin on the endothelial cell surface, was only observed in control animals after 2 h of perfusion, as an early event. GOT and GPT values increase dramatically after 2 h perfusion and 1 day after the treatment according to the histopathological observation of liver damage. On the contrary, the livers of hDAF or hMCP transgenic mice, under the same treatment were significantly protected although the extent of this protection is dependent on the level of expression of transgenic human molecules.

Alanine Transaminase↗

[Cerebral tissue oxygen monitoring: a useful thing?].

Monitoring cerebral oxygenation has been one of the main fields of interest in neurointensive care during the past few years. In fact it is strongly believed that restoring adequate cerebral oxygenation is the premise to maintaining the viability and restoring the function of the damaged CNS. Global monitoring provides an indirect estimation of adequacy of substrates supply to the brain. Local measurement of brain oxygen tension (ptiO2) is possible through a Clark electrode implanted into the cerebral parenchyma. The paper describes the physical basis of the monitoring, the pathophysiology of ptiO2 and its clinical use.

Brain Chemistry↗

Effects of cerebral perfusion pressure on brain tissue PO2 in patients with severe head injury.

Ischemia causes secondary brain damage after severe head injury (SHI). Cerebral perfusion is commonly estimated by monitoring CPP, but the adequacy of cerebral oxygenation requires further measurements, such as jugular oxygen saturation or, more recently, PtiO2 monitoring. In 7 patients with severe head injury, ICP, MAP, CPP, SjO2 and PtiO2 were monitored for a mean time of 9.0 +/- 2.2 days. Most of the data were in a "normal" range. Focusing on values under the thresholds of 60 mm Hg for CPP and 20 mm Hg for PtiO2, we found a relationship between CPP and PtiO2. Looking at the PtiO2 time-course, we observed a quite constant increasing trend during the first 48 hours of monitoring, then the values remained relatively constant within a normal range. Our data show that decreases of PtiO2 are not uncommon after severe head injury and therefore it seems that monitoring of PtiO2 in SHI may be useful in order to minimize secondary insults.

Adolescent↗

Kidney transplantation from living unrelated donors.

Our center activated our living-related donor (LRD) kidney transplantation program in 1967 and the living-unrelated donor (LURD) kidney transplantation program in 1968. We performed 62 kidney transplants (of which 6 were LURD) under conventional immunosuppression therapy of the period. During the cyclosporine era, our group performed the first living-donor kidney transplant in 1982 and the first LURD transplant in Europe in 1983. Since then 184 LURD transplants (1/3 of all living kidney transplants) took place in our center under cyclosporine therapy. LURD remains a controversial procedure as a consequence of problems related both to the donor's risk, which can be reduced by careful medical evaluation and selection, and to the recipient's outcome, including the importance of HLA compatibility, as well as concerns about the danger of commercialism. According to international evidence, as well as our own experience, LURD kidney transplantation is a safe and effective approach to increase the donor pool. Living donor mortality is extremely low, while long-term graft survival is the same as that observed after LRD transplantation and is superior to that for cadaver donor transplantation. We do not recommend DST because the long-term survival benefits do not justify the risks of sensitization and infections. At least for primary transplants, there is not an increased risk of transplantation from a husband to his wife with previous pregnancies. The pretransplant screening of taboo HLA mismatches could be useful to increase long-term graft survival. It is our opinion that LURD transplantation should be considered at least as good a clinical option as cadaver donor transplantation for patients with end-stage renal failure. A selective advantage of this procedure is that dialysis could be avoided before transplantation, with significant socio-economic benefits and improved recipient quality of life.

Adult↗

Kidneys derived from mice transgenic for human complement blockers are protected in an in vivo model of hyperacute rejection.

PURPOSE: The major obstacle to successful discordant kidney xenotransplantation is hyperacute rejection (HAR). Complement plays a key role in the induction of HRA, defined by endothelial cell activation, loss of vascular integrity, hemorrhage and thrombosis. The activation of complement is tightly controlled by a number of species-specific regulatory proteins which inhibit, at different points, the cascade of events leading to the formation of the membrane attack complex (MAC). We have tested the hypothesis that kidneys derived from transgenic mice expressing two human complement inhibitors, Decay Accelerating Factor (hDAF) and Membrane Cofactor Protein (MCP), could be protected from human complement-mediated damage. MATERIALS AND METHODS: Control and transgenic mice were perfused with human plasma by cannulation of the right jugular vein, at a perfusion rate of 10 microL./min. for two hours. Complement C3 deposition was detected on kidney sections by immunohistochemistry using specific FITC antibody. Complement-induced tissue damage was evaluated by histopathological examination. RESULTS: Heavy deposition of complement C3 was observed on kidneys derived from perfused control mice. This was associated with a characteristic HAR pathology of severe interstitial hemorrhage, inflammatory reaction, loss of glomerula and tubuli structure. Kidneys derived from mice transgenic for hDAF or hMCP were partially protected from both complement C3 deposition and tissue damage. The expression of both hDAF and hMCP in double transgenic mice significantly increases the protection from human complement-mediated damage. CONCLUSION: A novel model of in vivo perfusion with human plasma has been adopted to recreate the initial event of HAR. Our data show that this murine model could be very valuable to determine the effect of transgenic human molecules in protecting vascularized organs from human complement attack.

Acute Disease↗

The use of indomethacin to treat acute rises of intracranial pressure and improve global cerebral perfusion in a child with head trauma.

BACKGROUND: The use of vasoconstrictors (e.g. dihydroergotamine, indomethacin) for the treatment of increased intracranial pressure (ICP) secondary to brain trauma is controversial. In particular, it has been suggested that vasoconstrictors be employed only for intracranial hypertension secondary to hyperemia, when venous jugular bulb saturation (SjO2) is > 75%. METHOD: We administered indomethacin as a bolus i.v. (5-10 mg) on 18 occasions to a multiple-injured 3-year-old child with acute rises of ICP secondary to severe brain trauma (GCS score 7) determining a large hypodensity area in and swelling of the right hemisphere. RESULTS: Before indomethacin administration the average of mean ICP was 68.1 +/- 10.8 (SD) mm Hg (range 47-84) and the cerebral perfusion pressure (CCP) was 38.4 +/- 10.4 mm Hg (range 30-65). In response to indomethacin, ICP dropped in a few seconds to 22.7 +/- 5.6 and CCP increased to 82.4 +/- 6.1 mm Hg (P < 0.001), while the mean arterial pressure remained unchanged. On 6 occasions SjO2 was also evaluated immediately before and 5 and 10 min after indomethacin administration. Before indomethacin administration, SjO2 values were within the normal range on 2 occasions and abnormally low on four. SjO2 increased from the mean value of 45.6 +/- 15.7 to 59.8 +/- 8.9 (after 5 min) and 60.6 +/- 12.4% (after 10 min) (P < 0.01 versus pre-indomethacin). At the same time the cerebral venous pH increased from 7.43 +/- 0.01 to 7.45 +/- 0.01 (P = 0.01). These findinge suggest that the global cerebral perfusion was improved. Eighteen days after injury the child was awake and was discharged from the ICU. CONCLUSION: To our knowledge, increase of SjO2 in response to indomethacin has not been previously reported. Although great caution is necessary in the use of indomethacin for the treatment of ICP, these findings suggest that indomethacin can be useful for the treatment of acute rises of ICP compromising severely the CCP, even if SjO2 is normal or abnormally low. Under these circumstances, indomethacin can improve the global cerebral perfusion.

Cerebrovascular Circulation↗