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The cardiovascular disease of atherosclerosis (myocardial ischemia and cerebrovascular disease) is the principal cause of death globally. Remote organ ischemic events or remote organ underlying disturbances and pathology may either injure the heart acutely or contribute to cardiovascular disease chronically. The most typical remote organ system that may provoke such effects to the heart is the intestine, either due to (a) thrombotic disease of its vasculature, producing acutely intestinal ischemia, or (b) gut-originated disturbance, deteriorating atherosclerosis. In the first case, at reperfusion, the heart acutely becomes a victim, causing circulatory shock due to myocardial ischemic changes. In the second case, when the intestinal microbial community has altered from symbiotic to dysbiotic, metabolites are composed in the intestine, resulting to chronic advance of atherosclerosis and CVD worsening. Specifically, food phosphatidylcholine is metabolized to TMA (trimethylamine) in the intestine, which is transformed in the liver to TMAO (TMA-N-oxide). Interest about TMAO is rapidly growing. This substance is being studied thoroughly, in an effort to understand and explain its adverse cardiovascular effects, the so-called cardio-intestinal axis. It appears that there exist many sites for possible therapeutic interventions to limit its effect.

We investigated whether hypoxemic resuscitation from hemorrhagic shock prevents lung injury and explored the mechanisms involved. We subjected rabbits to hemorrhagic shock for 60 min by exsanguination to a mean arterial pressure of 40 mm Hg. By modifying the fraction of the inspired oxygen, we performed resuscitation under normoxemia (group NormoxRes, PaO2 = 95–105 mm Hg) or hypoxemia (group HypoxRes, PaO2 = 35–40 mm Hg). Animals not subjected to shock constituted the sham group (PaO2 = 95–105 mm Hg). We performed bronchoalveolar lavage (BAL) fluid, lung wet-to-dry weight ratio, and morphological studies. U937 monocyte-like cells were incubated with BAL fluid from each group. Cell peroxides, malondialdehyde, proteins, and cytokines in the BAL fluid were lower in sham than in shocked animals and in HypoxRes than in NormoxRes animals. The inverse was true for ascorbic acid and reduced glutathione. Lung edema, lung neutrophil infiltration, myeloperoxidase, and interleukin (IL)-8 gene expression were reduced in lungs of HypoxRes compared with NormoxRes animals. A colocalized higher expression of IL-8 and nitrotyrosine was found in lungs of NormoxRes animals compared to HypoxRes animals. The BAL fluid of NormoxRes animals compared with HypoxRes animals exerted a greater stimulation of U937 monocyte-like cells for proinflammatory cytokine release, particularly for IL-8. In the presence of p38-MAPK and Syk inhibitors and monosodium urate crystals, IL-8 release was reduced. We conclude that hypoxemic resuscitation from hemorrhagic shock ameliorates lung injury and reduces oxygen radical generation and lung IL-8 expression.

This study explores the role of procalcitonin (PCT) in predicting the outcome of sepsis. In a prospective multicentre observational investigation, blood was sampled within 24 h of onset of sepsis in 1156 hospitalised patients; 234 were in the intensive care unit (ICU) at the point of presentation of sepsis while 922 were not. PCT was estimated in serum by the ultrasensitive Kryptor assay in a double-blinded fashion. Among patients outside the ICU, mortality was 8% in those with PCT ≤0.12 ng/mL but 19.9% in those with PCT0.12 ng/mL [P0.0001, odds ratio (OR) for death: 2.606; 95% confidence interval (CI): 1.553-4.371]. Among patients whose sepsis presented in ICU, mortality was 25.6% in those with PCT ≤0.85 ng/mL but 45.3% in those with PCT0.85 ng/mL (P=0.002; OR for death: 2.404; 95% CI: 1.385-4.171). It is concluded that PCT cut-off concentrations can contribute to predicting the outcome of sepsis and might be of particular value in identifying patients who would benefit from ICU admission.

Objective: Study the effect of human protein C (PC) concentrate administration on organ damage and survival in septic rats. Design: Animal study. Setting: University laboratory. Subjects: Male Wistar rats. Interventions: Cecal ligation and puncture (CLP) was performed in 210 rats. Rats were randomly assigned to receive either human protein C (PC) IV 1, 7, and 13 hrs after CLP (CLP+PC) or placebo (CLP). Septic animals were again randomized in a survival group (CLP: n = 50 and CLP+PC: n = 40) that was monitored for 60 hrs and time groups (CLP: n = 60 and CLP+PC: n = 60) that were killed at 6, 12, 24, 36, 48, and 60 hrs after CLP. Brain, heart, lung, liver, kidney, gastric, and colon tissue were removed and postfixed in paraffin sections. Measurements and Main Results: PC infusion increased PC serum levels in early sepsis (median 7.25) compared with late sepsis (median 2, p = .001). Activated protein C/a1-antitrypsin complex levels in the CLP+PC group were significantly increased in late sepsis (60 hrs after CLP) compared with early sepsis (6, 12, and 24 hrs after CLP, p = .009, p = .004, and p = .008, respectively) and to late septic CLP and normal rats (p = .005 and p = .007, respectively). Their IL-6 and tumor necrosis factor a plasma levels were decreased (by 27% and 25%, respectively) at 6 hrs compared with placebo (p = .008 and p = .016). Their serum PC levels were also decreased in CLP+PC survivors compared with nonsurvivors of the same group (median = 1.5 vs. median = 7, p = .001). Apoptosis was reduced in brain (10% vs. 77.8%, p < .001), stomach (66.7% vs. 100%, p < .002) and intestine (33.3% vs. 85.2%, p < .001) compared with placebo. Finally, the survival of septic rats treated with human PC was significantly increased compared with placebo (75% vs. 54%, p = .033). Conclusions: Human Protein C administration increased survival in septic rats, decreased plasma inflammatory cytokines levels and tissue injury in vital organs.

Exogenous advanced glycation endproducts (AGEs, known atherogenic molecules) abundant in everyday precooked, rich in fat, overheated meals can possibly contribute to the increased risk for diabetes and cardiovascular disease in women with polycystic ovary syndrome (PCOS). The aim of the present study was to investigate the effect of a lipase inhibitor on absorbed food glycotoxins in healthy women and those with PCOS. A 2-day protocol was followed. In the first day, a meal rich in AGE was provided, which on the second day was followed by two 120-mg capsules of lipase inhibitor, orlistat. Serum AGE levels were evaluated at baseline (0 hours), and at 3 and 5 hours postmeal during the study. Thirty-six women were studied, 15 controls (mean age, 28.80 +/- 5.47 years; body mass index, 25.85 +/- 6.73 kg/m(2)) and 21 with PCOS (mean age, 25.29 +/- 5.06 years; body mass index, 30.40 +/- 7.51 kg/m(2)) (University Hospital, Athens, Greece, institutional practice). Serum AGE levels, on day 1, were significantly increased both in the control group and in the PCOS group as compared with basal values (control group, 14.1%; PCOS group, 6.0%; P < .001). The corresponding rise was significantly lower on day 2 when the same meal was combined with orlistat (control group, 4.1%; PCOS group, 2.0%; P < .01). A limitation of the study is that it is a nonplacebo, nonrandomized therapeutic trial where each subject is considered as its own control. In conclusion, this study demonstrated the beneficial effect of orlistat on the absorption of food glycotoxins.

Adenoid cystic carcinoma (ACC) is a rare epithelial tumor with a distinct natural history characterized by an indolent but persistent growth, late onset of distant metastases and eventual death of patients. Between 1991 and 2003, 23 patients with ACC were treated in our Department. Surgery with a curative intent followed by radiotherapy (RT) was applied in 22 patients. Complete resection was achieved in 72.73% of patients. Local recurrence occurred in 26% of patients. Positive margins emerged as the only statistically significant parameter (p < 0.0001) influencing the development of local recurrence. Distant metastasis (DM) occurred in 47.8% of patients. In 54.5% of the patients developing DM, this occurred between 5 and 10 years after the initial treatment. DM was influenced by perineural invasion (p = 0.04) and was disassociated from local control of the tumor. The mean overall survival of our patients was 70.58 months and the mean disease free survival 61.85 months. Perineural invasion (p = 0.048) and DM (p = 0.001) had a statistically significant impact on final patients' outcome. The most important factor influencing survival was DM. Its late onset, irrespectively of local control, supports the hypothesis that ACC has a potential to develop DM in the very early phases of tumor growth.

We have recently shown that hypoxaemic reperfusion, after an ischaemic brain insult, improves neurological outcome and decreases lipid peroxidation. In the present study, we investigated the effect of hypoxaemic reperfusion on brain histopathological changes.Sixteen pigs subjected to a 10-min global cerebral ischaemia were either hypoxaemically (PaO2 = 35 mmHg, hypoxaemic reperfusion (HR) group, n = 8) or hyperoxaemically (PaO2300 mmHg, control (C) group, n = 8) reperfused. The brains were removed 24 h after reperfusion and six neuropathological abnormalities were evaluated blindly and scored semi-quantitatively (0: normal to 3: severe injury) on eight representative regions of the brain. The overall cumulative score of the abnormalities and their regional prevalence, as well as the neurological outcome, were compared between the two groups.The neuronal degeneration, assessed in terms of cumulative score (P = 0.002) and regional prevalence (P = 0.025 to P = 0.041), was lower in the HR group than in the C group. Spongy degeneration attained statistically significant difference only in cerebellum (P = 0.002) and inflammation only in hippocampus (P = 0.046) but the difference in the cumulative score of these abnormalities was not statistically significant. The difference of the three neurological assessments over time was statistically significant between the two groups, i.e. after resuscitation (P = 0.001), at 8 h (P = 0.006) and at 24 h (P = 0.001) after reperfusion.Hypoxaemic reperfusion during resuscitation from a severe global ischaemic cerebral insult is associated with statistically significantly fewer histopathological changes of the brain than in controls. This is associated with a superior neurological outcome.

To investigate the activity of intravenous immunoglobulin (IVIG) as a prophylactic agent against infection in trauma victims.Prospective, randomized, double-blind, placebo-controlled study.A 20-bed university intensive care unit.Thirty-nine trauma patients with injury severity scores (ISSs) of 16-50.Penicillin was given at the time of admission and continued at least until day 4. Twenty-one patients received IVIG and 18 patients received human albumin at 1 g/kg in four divided doses (days 1, 2, 3, and 6). The two groups had similarities in age, gender, Acute Physiology and Chronic Health Evaluation II score, risk of death, and Glasgow Coma Scale score, but differing ISSs (p = .02), at the time of admission. Blood was collected on days 1, 4, and 7.Clinical variables related to infection were recorded. The complement components C3c, C4 and CH50, IgG, and the fractions of IgG were measured. The serum bactericidal activity (SBA) was assessed at 37 degrees C (98.6 degrees F) and 40 degrees C (104.0 degrees F) at the time of admission and during the course of IVIG administration. Controlling for ISS, IVIG-treated patients had fewer pneumonias (p = .003) and total non-catheter-related infections (p = .04). Catheter-related infections (p = .76), length of stay in the intensive care unit, antibiotic days, and infection-related mortality did not differ between the two groups. A significantly increased trend in IgG and its subclasses was shown on days 4 and 7 in the IVIG group but not in the control group (p.000001). No important differences were noted in complement fractions. The SBA of the groups was similar on day 1, but significantly higher on days 4 and 7 (p.000001) in the IVIG group, remaining so controlling for complement and ISS. SBA was higher at 40 degrees C (104.0 degrees F) compared with 37 degrees C (98.6 degrees F) (p.0001) under all three conditions. In both groups, low SBA (on days 1, 4, and 7) was associated with increased risk of pneumonia (p.01) and non-catheter-related infections (p = .06 for day 1; p.01 for days 4 and 7).Trauma patients receiving high doses of IVIG exhibit a reduction of septic complications and an improvement of SBA. Early SBA measurement may represent an index of susceptibility to infection.

In order to explore whether an organ-specific pattern in cytokine and lactate concentrations exists in patients with multiple organ failure (MOF), we measured the cytokines interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha), and lactate in blood taken from the hepatic vein, pulmonary capillaries, and peripheral veins of 10 patients with MOF with hepatic involvement (MOF-HI), eight patients with MOF and adult respiratory distress syndrome (MOF-ARDS), and five head-injured patients (controls). Ten additional patients participated in a study of arteriovenous pulmonary concentration gradients of these substances. For statistical analysis, nonparametric tests and analysis of variance (ANOVA) were used. The regional concentrations of these substances exhibited a different pattern in the two MOF groups. In the MOF-HI group, mean +/- SD cytokines IL-1beta and IL-6 (pg/ml) were respectively 216 +/- 100 and 461 +/- 343 in the hepatic sinusoidal blood; 149 +/- 52 and 293 +/- 204 in pulmonary capillary blood; and 148 +/- 105 and 234 +/- 162 in peripheral venous blood. In the MOF-ARDS group the corresponding levels were 180 +/- 103 and 235 +/- 124; 235 +/- 94 and 280 +/- 108; and 130 +/- 77 and 194 +/- 127. The TNF-alpha levels also exhibited the same pattern. The mean +/- SD corresponding levels (mmol/L) for lactate in the MOF-HI group were 3.1 +/- 1.8, 1.5 +/- 0.3, and 1.2 +/- 0.6, and in the MOF-ARDS group were 1.1 +/- 0.9, 1.8 +/- 1.1, and 1.0 +/- 0.2, respectively. The differences in the levels of all substances between the liver and lungs in the two MOF groups were statistically significant (p0.003). In the study of transpulmonary gradients it was shown that the levels of cytokine and lactate were lower in arterial blood than in mixed venous blood in MOF-HI patients, whereas the opposite was true in MOF-ARDS patients. In this study, we found that in MOF, cytokines and lactate are secreted from the most severely affected organs.

Background A previous randomized study showed that clarithromycin decreases the risk of death due to ventilator-associated pneumonia and shortens the time until infection resolution. The efficacy of clarithromycin was tested in a larger population with sepsis. Methods Six hundred patients with systemic inflammatory response syndrome due to acute pyelonephritis, acute intra-abdominal infections or primary Gram-negative bacteraemia were enrolled in a double-blind, randomized, multicentre trial. Clarithromycin (1 g) was administered intravenously once daily for 4 days consecutively in 302 patients; another 298 patients were treated with placebo. Mortality was the primary outcome; resolution of infection and hospitalization costs were the secondary outcomes. Results The groups were well matched for demographics, disease severity, microbiology and appropriateness of the administered antimicrobials. Overall 28 day mortality was 17.1% (51 deaths) in the placebo arm and 18.5% (56 deaths) in the clarithromycin arm (P = 0.671). Nineteen out of 26 placebo-treated patients with septic shock and multiple organ dysfunctions died (73.1%) compared with 15 out of 28 clarithromycin-treated patients (53.6%, P = 0.020). The median time until resolution of infection was 5 days in both arms. In the subgroup with severe sepsis/shock, this was 10 days in the placebo arm and 6 days in the clarithromycin arm (P = 0.037). The cost of hospitalization was lower after treatment with clarithromycin (P = 0.044). Serious adverse events were observed in 1.3% and 0.7% of placebo- and clarithromycin-treated patients, respectively (P = 0.502). Conclusions Intravenous clarithromycin did not affect overall mortality; however, administration shortened the time to resolution of infection and decreased the hospitalization costs.

Systemic infection with Aspergillus fumigatus is an opportunistic disease that affects mainly immunocompromised hosts and is associated with a high mortality rate. We report a case of A. fumigatus endocarditis after an episode of thrombotic thrombocytopenic purpura. Diagnosis was established after sudden rupture of posterior papillary muscle of the normal native mitral valve. Soon after mitral valve replacement, Aspergillus endocarditis recurred, associated with multiple peripheral emboli, which necessitated a second operation.

AIM: To investigate factors predicting failure of percutaneous endoscopic gastrostomy (PEG) to eliminate gastroesophageal reflux (GER). METHODS: Twenty-nine consecutive mechanically ventilated patients were investigated. Patients were evaluated for GER by pH-metry pre-PEG and on the 7th post-PEG day. Endoscopic and histologic evidence of reflux esophagitis was also carried out. A beneficial response to PEG was considered when pH-metry on the 7th post-PEG day showed that GER was below 4%. RESULTS: Seventeen patients responded (RESP group) and 12 did not respond (N-RESP) to PEG. The mean age, sex, weight and APACHE Ⅱ score were similar in both groups. GER (%) values were similar in both groups at baseline, but were significantly reduced in the RESP group compared with the N-RESP group on the 7th post-PEG day [2.5 (0.6-3.8) vs 8.1 (7.4-9.2, P < 0.001)]. Reflux esophagitis and the gastroesopha geal flap valve (GEFV) grading differed significantly between the two groups (P = 0.031 and P = 0.020, respectively). Histology revealed no significant differ ences between the two groups. CONCLUSION: Endoscopic grading of GEFV and the presence of severe reflux esophagitis are predisposing factors for failure of PEG to reduce GER in mechanically ventilated patients.

Ampicillin-sulbactam has a wide range of antibacterial activity that includes Gram-positive and Gram-negative aerobic and anaerobic bacteria. However, the drug is not active against Pseudomonas aeruginosa and pathogens producing extended-spectrum beta-lactamases. The combination could be considered particularly active against Acinetobacter baumannii infections due to the intrinsic activity of sulbactam. The drug is indicated as empirical therapy for a broad range of community acquired infections supervened in adults or children and is effective in either parenteral (ampicillin-sulbactam) or oral (as a mutual prodrug sultamicillin) form. In clinical trials, sultamicillin has proved clinically and bacteriologically effective in adults and children against a variety of frequently encountered infections, including mild upper and lower respiratory tract infections, urinary tract infections, diabetic foot and skin and soft tissue infections. Furthermore, adverse effects rarely occur with the diarrhoea to represent the most commonly reported. The parenteral ampicillin-sulbactam is indicated for community infections of mild-to-moderate severity acquired infections such as intra-abdominal or gynecological. Moreover, it seems to represent the alternative of choice for the treatment of A. baumannii infections for carbapenem-resistant strains in the nosocomial setting. Thus, ampicillin-sulbactam remains a valuable agent in the physician's armamentarium in the management of adult and pediatric infections.

To describe the concentrations of sTREM-1 in patients with sepsis and to explore the effects of their serum on the expression of TREM-1 on U937 monocytes.Blood was sampled at regular time intervals in 56 patients with sepsis. Concentrations of tumour necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1alpha), IL-6, IL-8, IL-10 and IL-12p70 and sTREM-1 were measured. U937 monocytes were incubated in the presence of serum at sepsis onset.Median sTREM-1 concentration on day 1 for patients with septic shock was 915 pg/ml and 228.5 pg/ml for those without shock (p = 0.002). TNFalpha, IL-1alpha, IL-6, IL-8 and IL-10 did not differ between them. A positive correlation was found between changes of sTREM-1 and SOFA scores from day 1 to 7. Sera of patients with septic shock evoked a significant increase of the expression of TREM-1. The concentrations of TNFalpha and IL-8 in supernatants increased only after stimulating with sera of patients without shock, but not after stimulating with sera of patients with shock.Levels of sTREM-1 correlated with sepsis severity. sTREM-1 is considerably higher in patients with shock compared to patients without shock. The serum of shocked patients could stimulate the expression of TREM-1 on U937 monocytes.

To compare the safety and efficacy of ampicillin/sulbactam (Amp/Sulb) and colistin (COL) in the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP).A prospective cohort study in adult critically ill patients with VAP. Patients were randomly assigned to receive Amp/Sulb (9 g every 8h) or COL (3 MIU every 8h) intravenously. Dosage was adjusted according to creatinine clearance.A total of 28 patients were enrolled (15 COL, 13 Amp/Sulb). Resolution of symptoms and signs occurred in 60% (9/15) of the COL group and 61.5% (9/13) of the Amp/Sulb group, improvement in 13.3% (2/15) vs. 15.3% (1/13) and failure in 26.6% (4/15) vs. 23% (3/13), respectively. The difference was not statistically significant. Bacteriologic success was achieved in 66.6% (10/15) vs. 61.5% (8/13) in the COL and Amp/Sulb groups, respectively (p0.2). Mortality rates (14 days and 28 days) were 15.3% and 30% for the Amp/Sulb and 20% and 33% for the COL group, respectively. Adverse events were 39.6% (including 33% nephrotoxicity) for the COL group and 30.7% (15.3% nephrotoxicity) for the Amp/Sulb group (p=NS).Colistin and high-dose ampicillin/sulbactam were comparably safe and effective treatments for critically ill patients with MDR A. baumannii VAP.

Renal dysfunction is common in liver diseases, either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. The presence of renal impairment in both groups is a poor prognostic indicator. Renal failure is often multifactorial and can present as pre-renal or intrinsic renal dysfunction. Obstructive or post renal dysfunction only rarely complicates liver disease. Hepatorenal syndrome (HRS) is a unique form of renal failure associated with advanced liver disease or cirrhosis, and is characterized by functional renal impairment without significant changes in renal histology. Irrespective of the type of renal failure, renal hypoperfusion is the central pathogenetic mechanism, due either to reduced perfusion pressure or increased renal vascular resistance. Volume expansion, avoidance of precipitating factors and treatment of underlying liver disease constitute the mainstay of therapy to prevent and reverse renal impairment. Splanchnic vasoconstrictor agents, such as terlipressin, along with volume expansion, and early placement of transjugular intrahepatic portosystemic shunt (TIPS) may be effective in improving renal function in HRS. Continuous renal replacement therapy (CRRT) and molecular absorbent recirculating system (MARS) in selected patients may be life saving while awaiting liver transplantation.

To investigate the effect of percutaneous endoscopic gastrostomy (PEG) on gastroesophageal reflux (GER) in mechanically-ventilated patients.In a prospective, randomized, controlled study 36 patients with recurrent or persistent ventilator-associated pneumonia (VAP) and GER6% were divided into PEG group (n = 16) or non-PEG group (n = 20). Another 11 ventilated patients without reflux (GER3%) served as control group. Esophageal pH-metry was performed by the "pull through" method at baseline, 2 and 7 d after PEG. Patients were strictly followed up for semi-recumbent position and control of gastric nutrient residue.A significant decrease of median (range) reflux was observed in PEG group from 7.8 (6.2 - 15.6) at baseline to 2.7 (0 - 10.4) on d 7 post-gastrostomy (P0.01), while the reflux increased from 9 (6.2 - 22) to 10.8 (6.3 - 36.6) (P0.01) in non-PEG group. A significant correlation between GER (%) and the stay of nasogastric tube was detected (r = 0.56, P0.01).Gastrostomy when combined with semi-recumbent position and absence of nutrient gastric residue reduces the gastroesophageal reflux in ventilated patients.

Encouraging results have recently been reported in patients (pts) with locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN) when induction chemotherapy (IC) is used and followed by radiotherapy (RT). The present study assessed the therapeutic response of an aggressive regimen consisting of docetaxel (TXT), cisplatin (CDDP) and 5-fluorouracil (5-Fu) as IC and concurrent with RT in pts with locally advanced (stages III and IV) SCCHN. 42 pts (35 male and 7 female) with a mean age of 58 years suffering from stages III and IV (Mo) SCCHN were included to this organ preservation phase II clinical trial. The site of the primary tumors was the anterior mouth in 9 pts, base of tongue and oropharynx in 12, middle third of the face in 8 and larynx in 13. The performance status of the pts was 0-1 according to WHO and above 80% according to Karnofsky classification. IC consisted of TXT (40 mg/m2), CDDP (40 mg/m2) and 5-Fu (350 mg/m2) every two weeks (wks) for a total of four courses and repeated, coupled with RT (66-68 cGys total dose fractionated at 200 Gy per day, 5 days a week), for up to seven wks. In total, pts received eight courses of chemotherapy (CT) at the end of RT treatment. Pts were evaluated at the end of IC, after RT and every six wks thereafter. 41 pts were eligible for evaluation after IC (one died from myocardial infarction) and 39 after completion of treatment (two died during RT). Statistical multivariate analysis was performed using SPSS (11) package. Complications from IC and RT were evaluated according to WHO criteria and included mucositis Grade (Gr) IV in 10% of the pts, Gr III in 50%, Gr II in 20%. Anemia presented in 40% of the pts with Gr II, 40% with Gr I, neutropenia 17% with Gr IV, 20% with Gr III, 30% with Gr II, thrombocytopenia 3% with Gr III, 10% with Gr I and xerostomia up to Gr II in 70% of the pts. The response rate (RR) after IC was complete response (CR) for 10 pts (24.4%), partial response (PR) for 22 (53.7%) and no response (NR) for 9 (21.9%). At the end of the treatment the RR in the intention-to-treat population were CR for 25 pts (64.1%), and PR for 14 (35.9%). Follow up ranges from 18 to 56 months (mts). 14 pts died during follow-up time. The mean survival time is 41 mts and the median 40. 2 pts with CR developed local recurrence and two distant metastases, whereas all pts with PR developed progressive disease (PD) and all but two are dead from disease. It is evident from this phase II study that TXT-CDDP-5Fu based IC followed by the same regimen coupled with RT improves local control. Pts that showed CR after IC continued to maintain disease status during RT (P-value=0.0181). In pts with SD concurrent RT did not alter dramatically disease outcome. Patients who showed complete response after both IC and RT presented a four-year survival rate of 74% compared to a 30% to partial responders (P-value=0.0001). Results are encouraging and further study of the toxicity and follow-up is needed to validate treatment effectiveness.

A recent randomized trial of our group showed that blind treatment with clarithromycin decreased mortality from septic shock and multiple organ dysfunction, shortened time until resolution of infection in patients with severe sepsis/shock and decreased hospitalization costs [1]. The efficacy of clarithromycin in relation with the type of failing organs is analyzed.

To investigate the morphological changes in the liver in patients with organ failure and hyperbilirubinemia and to correlate them to the outcome.A case series prospective study.Intensive care units of two general hospitals.Twelve patients in organ failure with predominant hepatic involvement, aged 16 to 69 years (mean 56 years).Liver biopsy was performed on all patients 3-15 days after organ failure. A second biopsy was also performed on all four surviving patients, as well as on 3 patients just before death at a mean time of 16 days (6-32) and 31 days (14-55), respectively, after the first biopsy. The samples were studied by electron microscopy and findings were assessed according to Rappaport's designation.In the first biopsy it was shown that in zone III there was complete degeneration of bile canaliculi and hepatocytes in contrast to zone I. The grade of histological severity for zone III is positively correlated to the bilirubin concentration (p = 0.001). In the specimens from the second biopsy, it was shown that numerous, newly formed secondary bile canaliculi per 20 consecutive hepatocytes had developed in zone III in the surviving patients, whereas there was a complete absence of such canaliculi in the patients who died (mean +/- SD: 9.6 +/- 3.2 vs 0).It appears that the destruction of primary bile canaliculi is a striking anatomical defect in patients with organ failure and impaired bilirubin excretion. The restoration of liver function coincides with adequate formation of new secondary bile canaliculi in zone III, giving credence to the hypothesis that this formation is an important structural change responsible for the improvement in liver function.

To investigate the influence of infliximab (Remicade) on experimental colitis produced by 2,4,6,trinitrobenzene sulfonic acid (TNBS) in rats.Thirty-six Wistar rats were allocated into four groups (three groups of six animals each and a fourth of 12 animals). Six more healthy animals served as normal controls (Group 5). Group 1: colitis was induced by intracolonic installation of 25 mg of TNBS dissolved in 0.25 mL of 50% ethanol and infliximab was subcutaneously administered at a dose of 5 mg/kg BW; Group 2: colitis was induced and infliximab was subcutaneously administered at a dose of 10 mg/kg BW; Group 3: colitis was induced and infliximab was subcutaneously administered at a dose of 15 mg/kg BW; Group 4: colitis was induced without treatment with infliximab. Infliximab was administered on d 2-6. On the 7(th) d, all animals were killed. The colon was fixed in 10% buffered formalin and examined by light microscopy for the presence and activity of colitis and the extent of tissue damage. Tumor necrosis factor-alpha (TNF-alpha) and malondialdehyde (MDA) were also measured.Significant differences concerning the presence of reparable lesions and the extent of bowel mucosa without active inflammation in all groups of animals treated with infliximab compared with controls were found. Significant reduction of the tissue levels of TNF-alpha in all groups of treated animals as compared with the untreated ones was found (0.47+/-0.44, 1.09+/-0.86, 0.43+/-0.31 vs 18.73+/-10.53 respectively). Significant reduction in the tissue levels of MDA was noticed in group 1 as compared to group 4, as well as between groups 2 and 4.Subcutaneous administration of infliximab reduces the inflammatory activity as well as tissue TNF-alpha and MDA levels in chemical colitis in rats. Infliximab at a dose of 5 mg/kg BW achieves better histological results and produces higher reduction of the levels of TNF-alpha than at a dose of 10 mg/kg BW. Infliximab at a dose of 5 mg/kg BW produces higher reduction of tissue MDA levels than at a dose of 15 mg/kg BW.

Ischemia and reperfusion (I/R) – induced injury has been described as one of the main factors that contribute to the observed morbidity and mortality in a variety of clinical entities, including myocardial infarction, ischemic stroke, cardiac arrest and trauma. An imbalance between oxygen demand and supply, within the organ beds during ischemia, results in profound tissue hypoxia. The subsequent abrupt oxygen re-entry upon reperfusion, may lead to a burst of oxidative aggression through production of reactive oxygen species by the primed cells. The predominant role of oxidative stress in the pathophysiology of I/R mediated injury, has been well established. A number of strategies that target the attenuation of the oxidative burst have been tested both in the experimental and the clinical setting. Despite these advances, I/R injury continues to be a major problem in everyday medical practice. The aim of this paper is to review the existing literature regarding an alternative approach, termed hypoxemic reperfusion, that has exhibited promising results in the attenuation of I/R injury, both in the experimental and the clinical setting. Further research to clarify its underlying mechanisms and to assess its efficacy in the clinical setting is warranted.

Aztreonam at doses of 1 or 2 g given intramuscularly or intravenously every 8 h for 7 to 42 days was given to 55 patients, most of them suffering from difficult-to-treat infections either because the isolated pathogens were multiresistant or because of the location of the infection. Infections included: urinary tract (23 cases), deep soft tissue phlegmon (12 cases), chronic osteomyelitis in exacerbation (7 cases), abscesses (7 cases), pneumonia (4 cases), and external otitis (2 cases). In culture specimens, Pseudomonas aeruginosa (24 isolates) and various Enterobacteriaceae species (37 isolates) were isolated with MICs ranging from 0.25 to 16 micrograms/ml. Clinically, at the completion of treatment and after a 6-week posttreatment follow-up, 45 (81.6%) patients were cured, 4 (7.2%) improved, 3 (5.6%) relapsed, and 3 (5.6%) failed to respond to therapy. Bacteriologically, at the end of treatment, the pathogen was eradicated in 50 patients (91%) and persisted in 5 (9%). After a 6-week follow-up, cultures remained sterile in 33 patients (60.0%), 16 (29.1%) relapsed, in 6 (10.9%) bacteria persisted, and superinfection was reported in 4 (7.3%) patients. No appreciable adverse effects or toxicity was observed. From the reported results, it is concluded that aztreonam is a valuable addition to the field of antimicrobial chemotherapy that can be used effectively and safely in the treatment of a variety of gram-negative infections.