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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.

Produced free radicals exert their physiological function and thereafter become neutralized by antioxidants. In contrast, if they are produced in abundance, e.g., during ischemia/reperfusion (I/R), after they exhaust antioxidant reserves, they exert their harmful effect on cellular structures. The major significant reactive oxygen species (ROS) are the anion of superoxide (O2•-), the hydrogen peroxide (H2O2), and the hydroxyl radical (OH•). The collective term reactive nitrogen species (RNS) mainly includes the radical of nitric oxide (NO•), the peroxynitrite potent oxidant (ONOO−), the radical nitrogen dioxide (NO2•), and other nitrogen oxides. During ischemia, the tissue cells begin to suffer, when the oxygen delivery (DO2) to tissues decreases beyond the critical DO2 (cDO2) level, namely, when the metabolism becomes anaerobic. The cell suffering maximizes, when beta-oxidation of fatty acids is the last fuel that still feeds oxidative phosphorylation. Further drop of DO2 leads to severe ischemia with intracellular conversion of xanthine dehydrogenase to xanthine oxidase and increased concentration of xanthine and hypoxanthine. Upon reperfusion and abundant O2 reentry, free radical burst follows, with membrane destruction and massive cellular damage, mainly coming from the peroxidation of lipid bilayer arrangement. Suggested methods of I/R injury prophylaxis are the use of antioxidants, scavengers, and preconditioning techniques. The new approaches that seem to be promising focus on the progressive reentry of O2 to the thirsty for O2 ischemic tissues: initially in low concentrations of O2 to meet the low potentials of biochemical pathways to use O2 and thereafter in gradually increasing concentrations toward normal. Large, open, double blind, multicenter trials are still lacking.

The aim of the study was to calculate the in vitro inspiratory resistance (RETT) of adult endotracheal tubes (ETT), via the end-inspiratory occlusion method, and to apply this method in vivo in order to estimate RETT value in real time. By plotting RETT over inspiratory flow (V) and calculating Rohrer's coefficients of linear and nonlinear resistance, K1 and K2 respectively, we determined the resistive behaviour of each ETT. Peak and plateau pressures were recorded at both proximal and distal sites of the ETT after applying a three-second occlusion under constant flow. Distal pressure was obtained via an intraluminal catheter. RETT was calculated as (Ppeak – Pplateau)/(V;), at both sites. RETT value resulted from the difference Rproximal - Rdistal. Graph RETT over (V;) was plotted and Rohrer's constants were calculated by the method of least squares. For ETTs with inner diameter 9.0, 8.5, 8.0, 7.5, 7.0 and 6.5 mm, K2 was 2.42, 3.05, 4.65, 6.01, 9.17 and 12.80 cmH2O/l/s, respectively. The intraluminal catheter increased RETT No.7.0 by an average of 49%. Finally, ten patients with partially obstructed ETTs were tested and K2 in vivo constants found to be higher than their corresponding in vitro values (P value 0.00012). Therefore, knowing the performing size of an ETT may help the clinicians identify ETT obstruction and deal with weaning problems.

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.

Ischemic colitis is the most common type of intestinal ischemia, and it represents the consequences of acute or, more commonly, chronic blockage of blood flow through arteries that supply the large intestine. Ischemic colitis is manifested through a continuum of injury and considered as an illness of the elderly. The incidence of ischemic colitis has been underestimated, because many mild cases may go unreported. Patients experience abdominal pain, usually, localized to the left side of the abdomen, along with tenderness and bloody diarrhea. Severe ischemia may lead to bowel necrosis and perforation, which results in an acute abdomen and shock, frequently, being accompanied by lactic acidosis. Although computed tomography may have indicative findings, colonoscopy is the golden standard of diagnosis. Supportive care with intravenous fluids, optimization of hemodynamic status, avoidance of vasoconstrictive drugs, bowel rest, and empiric antibiotics will produce clinical improvement within 1 to 2 days in most patients. The condition resolves completely with conservative treatment, in most cases, but late diagnosis or severe ischemia can be associated with high rates of complications and death. However, when the interruption to the blood supply is more severe or more prolonged, the affected portion of the large intestine may have to be surgically removed. The present paper aims at bringing ischemic colitis up to date, by reviewing the current medical literature and extracting the contemporary data, about its presentation, diagnosis and treatment, which is of benefit to the readership, who may encounter this potentially fatal entity.

Increased levels of cytokines or reactive oxygen species (ROS) in the bronchoalveolar lavage (BAL) fluid are associated with acute lung injury after ischemia/reperfusion. We investigated the correlation of these markers with the degree of lung injury in a rabbit model of hemorrhagic shock. Rabbits, maintained by mechanical ventilation, were left untreated (control) or subjected to hemorrhagic shock by withdrawing blood (n = 12 for each group). Shock animals were re-infused their shed blood for resuscitation. At the end of the experiment, BAL fluid was recovered, in which parameters of oxidative stress and cytokines were measured. Macrophages and malondialdehyde levels were increased (p = 0.043 and p = 0.003, respectively), and total antioxidant capacity (TAC) was decreased in the shock animals compared with control (p = 0.009). Production of ROS was significantly enhanced in shock animals compared with controls (p < 0.001). BAL fluid levels of tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6 were higher in shock rabbits by more than twofold (p < 0.001 for each). Shock animals also showed higher histopathological scores that represent severe tissue damage than controls (p = 0.022). Numbers of macrophages and levels of ROS and TAC were correlated with the degree of lung injury (p = 0.006, p = 0.02, and p = 0.04, respectively), but not cytokines. Therefore, resuscitation from hemorrhagic shock results in acute lung injury, with enhanced pulmonary oxidative and inflammatory responses. In conclusion, ROS in the BAL fluid are good markers that predict lung injury following hemorrhagic shock and resuscitation.

Based on former animal studies showing the effect of clarithromycin in experimental sepsis by multidrug-resistant Pseudomonas aeruginosa following administration of single doses, the significance of its administration for three consecutive days was evaluated. Acute pyelonephritis was induced in 20 rabbits after inoculation of the test isolate in the renal pelvis. Therapy was administered upon signs of sepsis in group B; A served as control. Survival was recorded; monocytes were isolated for determination of ex vivo TNFalpha secretion. Quantitative cultures of organs were performed after death. Mean survival of groups A and B was 2.65 and 7.95 days respectively. At 24 hours, serum malondialdehyde of group B, which is an index of the oxidant status in serum, was lower than A. Ex vivo release of TNFalpha by the isolated monocytes of group B was lower than A at 3.5 and 48 hours. Tissue bacterial load was similar in two groups after animal death. It is concluded that clarithromycin possessed considerable immunomodulatory effects restraining release of TNFalpha from blood monocytes.

We investigated whether hypoxemic resuscitation from hemorrhagic shock prevents the late circulatory instability and attenuates the oxidative and inflammatory responses associated with the standard strategy.Prospective, randomized, controlled animal study in an experimental laboratory of a university intensive care unit.Thirty-one New Zealand white rabbits weighting 3.1-3.4 kgAnesthetized animals were subjected to hemorrhagic shock by exsanguinations to a mean arterial pressure of 40 mmHg for 60 min. Resuscitation was performed by reinfusing the shed blood for 30 min under normoxemia (PaO(2) 95-105 mmHg, control group, n=10) or hypoxemia (PaO(2) 35-40 mmHg, hypox-res group, n=10); Ringer's lactate was given from 30 to 60 min to restore arterial pressure within baseline values. A sham group was assigned (n=11). Animals were recorded for 120 min postresuscitation and for further 360 min to assess the early mortality rate.Hypoxemic resuscitation compared with normoxemic resuscitation from hemorrhagic shock was associated with (a) a better hemodynamic condition assessed by the gradual restoration of blood pressure, higher urinary output associated with less fluid infusion; (b) lower reactive oxygen species production assessed by the reduced blood geometric mean fluorescence intensity, lower malondialdehyde, and higher ratio of reduced to total glutathione levels; (c) attenuation in the plasma concentrations of IL-1beta, TNF-alpha, and IL-6; and (d) no difference in mortality rate.Hypoxemic resuscitation from hemorrhagic shock is more efficient than normoxemic in restoring the blood pressure and in attenuating the excessive oxidative and inflammatory responses observed during normoxemic resuscitation.

Summary Apoptosis of blood monocytes was studied in experimental sepsis by multi-drug-resistant Pseudomonas aeruginosa. Thirty-six rabbits were used, divided into the following groups: A (n = 6), sham; B (n = 6), administered anaesthetics; and C (n = 24), acute pyelonephritis induced after inoculation of the test isolate in the renal pelvis. Blood was sampled at standard time intervals for estimation of tumour necrosis factor (TNF)-α and isolation of monocytes. Half the monocytes were incubated and the other half was lysed for estimation of the cytoplasmic activity of caspase-3 by a kinetic chromogenic assay. No animal in groups A and B died; those in group C were divided into two subgroups, CI (n = 8) with present activity of caspase-3 of blood monocytes at 3·5 h and CII (n = 16) with absent activity. Their median survival was 2·0 and 3·5 days, respectively (P = 0·0089). Ex vivo secretion of TNF-α from monocytes was higher by monocytes of subgroup CII than subgroup CI at 3·5 h (P = 0·039) and of group A than CII at 48 h (P = 0·010). Median change of caspase-3 activity between 3·5 and 24 h of sampling was 56·1 and −5·8 pmol/min per 104 cells for subgroups CI and CII (P = 0·040), respectively. Respective changes between 3·5 and 48 h were 28 981·0 and 0 pmol/min per 104 cells (P = 0·036). Early induction of apoptosis in blood monocytes is of prime importance for the survival of the septic host and might be connected to changes of monocyte potential for the secretion of TNF-α.

BACKGROUND Resuscitation of hemorrhagic shock is associated with tissue injury. The effect of hypoxemia during resuscitation was investigated. METHODS Shock was induced by withdrawing blood to mean arterial pressure (MAP) 40 mm Hg and maintained for 60 minutes in 25 Wistar rats. Animals were randomly divided to receive either normoxemic (controls, FiO2 = 21%, n = 14) or hypoxemic (HypRes, FiO2 = 12%, n = 11) resuscitation by re-infusing their shed blood. Outcome was assessed through hemodynamic and inflammatory parameters. Another nine rats served to correlate different FiO2 to the corresponding PaO2. RESULTS At 60 minutes of resuscitation HypRes had higher MAP than control animals (p = 0.008). The respective median (range) malondialdehyde and TNF-alpha levels was 1.7 (1-2.1) versus 3.1 (2.4-4.3) micromol/L, (p = 0.02) and 0 versus 5.8 (0-5.8) pg/mL, (p = 0.025). Glutathione, endotoxin, interferon-gamma, and nitric oxide values were similar between groups. FiO2 of 12% induced only a mild hypoxemia (PaO2 approximately 80 mm Hg). CONCLUSIONS Even mild hypoxemia during resuscitation of shock leads to effective hemodynamic stabilization.

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.

OBJECTIVE: The circulatory shock following intestinal ischemia-reperfusion injury has been attributed to hypovolemia. The purpose of the current study is to clarify the pathophysiology of this type of shock and to test the hypothesis that hypoxemic compared with normoxemic reperfusion improves hemodynamics. DESIGN: Randomized animal study. SETTING: Medical school laboratory. SUBJECTS: Twenty-one pigs. INTERVENTIONS: Pigs were subjected to 120 mins of intestinal ischemia by clamping the superior mesenteric artery. Upon declamping, the animals were randomized into two groups: a group that received hypoxemic reperfusion (HR group, n = 8) with a PaO2 = 30-35 and a control group reperfused with PaO2 = 100 mm Hg (control group, n = 13). MEASUREMENTS AND MAIN RESULTS: Measurements included mean arterial pressure, cardiac index, pulmonary artery occlusion pressure, and requirements for fluids and epinephrine. Biopsies from the terminal ileal mucosa were taken for malondialdehyde measurements at baseline, at 120 mins of ischemia, and at 30 and 60 mins of reperfusion. A piece of left ventricle was obtained after 120 mins of reperfusion for histologic studies. Five of 13 animals of the control group died in intractable shock; no animal of the HR group died (p =.11). The decrease in the mean arterial pressure during reperfusion was more pronounced in the control group (p

Summary Aim Little is known about the significance of angiogenesis in the bone marrow of HIV-positive patients with myelodys-plastic features (MDF). However, this process has been associated with the pathogenesis of primary myelodysplastic syndromes (MDS). The aim of the study was to investigate angiogenesis in the bone marrow of HIV-positive patients. Methods Bone marrow biopsies from 28 HIV-positive patients were immunostained for factor VIII and the micro-vessel density (MVD) was quantitatively evaluated and compared with that of 32 biopsies from patients with primary MDS and to 18 control bone marrows from patients with no evidence of bone marrow disease. Results Bone marrow MVD in HIV-positive patients was similar to that of MDS. However, both groups revealed significantly higher MVD counts compared to those of control bone marrows (MDF vs controls P = 0.022, MDS vs controls P = 0.001). Conclusions Bone marrow from HIV-positive patients with MDF reveals similar microvessel counts compared to those with primary MDS, although both differ significantly from that of control bone marrow. Elucidation of the mechanisms underlying bone marrow angiogenesis in HIV-positive patients, may provide further insights into the pathobiology of AIDS and might be of value for the development of new therapeutic strategies for this disease.

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.

Background and purpose: Reactive oxygen species contribute to membrane lipid peroxidation and neuronal death and have been implicated in anoxic encephalopathy. We tested whether hypoxemic reperfusion (HR) after global cerebral ischemia would improve neurological recovery. Methods: Two groups of pigs (n=11 in each group) were subjected to a model of a 10-min global cerebral and systemic ischemia to compare the effect of hypoxemic reperfusion (group HR) with the classical hyperoxemic control (group C). A third group not subjected to ischemia served as control to the control group (n=6, group CC), but received hyperoxygenation at the respective period of reperfusion. The outcome was evaluated by means of neurological assessment and the extent of lipid peroxidation measuring the plasma malonaldehyde (MDA) together with hydroxyalkenals (HALK). Results: Animals of group HR exhibited a significantly superior neurological outcome compared with those of group C at all three consecutive assessments after reperfusion (post-resuscitation P=0.006, at 8 h P=0.003, and at 24 h P=0.007). The levels of MDA and HALK are lower in the HR group than in group C (P=0.029). Additionally, in the CC group these molecules increased significantly early at hyperoxygenation (P=0.02). A faster lactate metabolism in the HR group was observed during reperfusion, though non-significant. Conclusions: Hypoxemic reperfusion during resuscitation from a severe global ischemic cerebral insult improves the neurological outcome compared with classic hyperoxemic reperfusion. This is additionally confirmed by the decreased production of the molecules of lipid peroxidation. In the absence of preceding ischemia, these molecules may increase by simple over-oxygenation.

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.

We present a case of severe Pneumocystis jirovecii pneumonia and coexisting cytomegalovirus infection in a glucose-6-phosphate dehydrogenase (G6PD) enzyme deficient woman with anaplastic astrocytoma on temozolomide and corticosteroid therapy. She was successfully treated with oral atovaquone and ganciclovir. Atovaquone represents a safe alternative in severe Pneumocystis infection when trimethoprim-sulfamethoxazole (co-trimoxazole) is contraindicated.

Background: To investigate whether angiopoietin-2 (Ang2) and vascular endothelial growth factor (VEGF) are implicated in the hypoxemic resuscitation from hemorrhagic shock. Methods: Twenty rabbits were subjected to hemorrhagic shock after blood exsanguination; resuscitation was performed by infusion of the shed blood in ten rabbits under normoxemic conditions (NormoxRes) and in 10 under hypoxemic conditions (HypoxRes); four rabbits were subjected to sham operation. Serum was drawn at serial time intervals; serum was applied for stimulation of U937 monocytes. Results: Serum concentrations of Ang2 were higher in the NormoxRes group compared to the HypoxRes group at 90 min ( p : 0.049) and at 120 min ( p : 0.028). Serum concentrations of VEGF did not differ between groups. Concentrations of VEGF in the supernatants of U937 stimulated with sera of all groups were below detection limit. The wet to dry lung ratio of the HypoxRes group was significantly lower than the NormoxRes group ( p Conclusions: Hypoxemic resuscitation from hemorrhagic shock is a process accompanied by reduced serum levels of Ang2. These findings add significantly to our understanding of that experimental treatment strategy of resuscitation.

Introduction. An experimental epidural hematoma model was used to study the relation of ultrasound indices, namely, transcranial color-coded-Doppler (TCCD) derived pulsatility index (PI), optic nerve sheath diameter (ONSD), and pupil constriction velocity (V) which was derived from a consensual sonographic pupillary light reflex (PLR) test with invasive intracranial pressure (ICP) measurements.Material and Methods. Twenty rabbits participated in the study. An intraparenchymal ICP catheter and a 5F Swan-Ganz catheter (SG) for the hematoma reproduction were used. We successively introduced 0.1 mL increments of autologous blood into the SG until the Cushing reaction occurred. Synchronous ICP and ultrasound measurements were performed accordingly.Results. A constant increase of PI and ONSD and a decrease ofVvalues were observed with increased ICP values. The relationship between the ultrasound variables and ICP was exponential; thus curved prediction equations of ICP were used. PI, ONSD, andVwere significantly correlated with ICP (r2=0.84±0.076,r2=0.62±0.119, andr2=0.78±0.09, resp. (allP<0.001)).Conclusion. Although statistically significant prediction models of ICP were derived from ultrasound indices, the exponential relationship between the parameters underpins that results should be interpreted with caution and in the current experimental context.

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.

OBJECTIVES To investigate the relationship of thrombotic thrombocytopenic purpura to adult respiratory distress syndrome (ARDS) and study the responses of thrombotic thrombocytopenic purpura patients to early plasmapheresis. DESIGN Case series. SETTING ICU of a university hospital. PATIENTS Twenty-four consecutive patients with thrombotic thrombocytopenic purpura, with various periods of time (1 to 18 days) having elapsed since the onset of this condition. Patients ranged in age from 17 to 66 yrs. INTERVENTIONS Plasmapheresis, using intermittent flow separators, was instituted soon after the patients' ICU admission. The retinoscopic findings on admission and the relationship of Pao2 to platelet counts before and after plasmapheresis therapy were recorded. Antiplatelet agents were given to the survivors to prevent relapses. MEASUREMENTS AND MAIN RESULTS Eighteen patients survived and six died. Plasmapheresis was administered for a range of 1 to 5 days (mean 3) and 3 to 18 days (mean 9.8) in survivors and nonsurvivors, respectively (p less than .001). Four patients with confluent fundus hemorrhages died and seven without these fundoscopic findings had easily controlled disease. Increases in Pao2 paralleled increases in platelet counts after plasmapheresis (p less than .001) in this small series of patients. Three of 18 discharged survivors relapsed over a period of 3 to 56 months of follow-up. CONCLUSIONS Early introduction of plasmapheresis in thrombotic thrombocytopenic purpura seems to increase the survival rate and to halt the development of ARDS. Fundus findings may be a prognostic factor in thrombotic thrombocytopenic purpura. The antiplatelet agents seem to be efficacious in the prevention of relapses.

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.

Summary The present study was designed to investigate whether serum of animals subjected to hypoxaemic resuscitation from haemorrhagic shock may be a weak stimulant for monocytes or not. Twenty rabbits were subjected to haemorrhagic shock after blood exsanguination; resuscitation was performed by infusion of the shed blood in eight rabbits under normoxaemic conditions (NormoxRes) and in 12 under hypoxaemic conditions (HypoxRes); seven rabbits were subjected to sham operation. Malondialdehyde (MDA) and tumour necrosis factor (TNF)-α were estimated in serum at serial time intervals; the serum was applied for stimulation of U937 monocytes with or without the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. Expression of triggering receptor expressed on myeloid cells-1 (TREM-1) on U937 was also assessed by flow cytometric analysis. Death supervened in four animals of the NormoxRes (50%) and in one animal of the HypoxRes group (8·33%, P: 0·032). Serum levels of TNF-α and MDA were higher in NormoxRes compared to HypoxRes animals. Expression of TREM-1 on U937 monocytes was similar after stimulation with serum sampled from both groups. Concentrations of interleukin (IL)-1β, IL-6 and IL-8 of monocyte supernatants were higher after stimulation with serum of NormoxRes than HypoxRes rabbits. Production of cytokines after stimulation with serum was decreased significantly after addition of SB203580. It is concluded that stimulation of monocytes may contribute to the generation of the systemic inflammatory response during reperfusion after ischaemia. Lower stimulation of the p38 MAPK-mediated production of IL-1β, IL-6 and IL-8 by monocytes may be implicated as an explanation for the benefits shown for the host when resuscitation is performed under hypoxaemic conditions.

The present study compared two different systems of classification of patients with common variable immunodeficiency (CVID); one based on in vitro immunoglobulin biosynthesis; and another on CD4-naïve cell counts. Peripheral blood mononuclear cells (PBMCs) were isolated from 35 patients with CVID and 20 healthy controls. They were stimulated for the secretion of IgM and IgG after stimulation with Staphylococcus aureus Cowan I (SAC) upon supplementation of interleukin-2 (IL-2) or with pokeweed mitogen. T cell subsets were estimated by flow cytometry. By the first system, patients were classified into group A (n=18) with secretion of neither IgG nor IgM; into group B (n=12) with detectable IgM but no IgG secretion; and into group C (n=5) with IgM and IgG secretion similar to controls. By the second system, patients were classified into group I (n=12) with less than 109 CD4-naïve cells/mul; into group II (n=12) with CD4-naïve cells within 109-225microl(-1); and into group III (n=11) with more than 225 CD4-naïve cells/mul. All groups I-III were defective for in vitro release of IgG and IgM. The likelihood ratio for splenomegaly in patients with225 CD4-naïve cells/mul was 5.08 (p: 0.024). CD4-naïve cell counts of patients were positively correlated to serum levels of IgG and IgA of patients. The presented results revealed that the former system described adequately the function of B cells and the latter the clinical status of the patient. Our proposal is that both should be used for the characterization of patients with CVID.

The role of blood monocytes in the secretion of soluble triggering receptor expressed on myeloiod cells (sTREM-1) was studied in 90 patients with septic syndrome due to ventilator-associated pneumonia. Blood monocytes were isolated on 7 consecutive d after initiation of symptoms. Monocytes were incubated in the absence or presence of LPS and concentrations of sTREM-1 and TNFalpha in cell supernatants and serum were estimated by an enzyme-immunoassay. sTREM-1 and TNFalpha were consistently present at detectable levels in the cell supernatants. LPS induced increased levels of TNFalpha but not of sTREM-1. Supernatants recovered from monocytes on d 1 showed levels of sTREM-1 higher than those recovered on any of the following 6 d (p0.05); these levels were higher in non-survivors than in survivors. Supernatants recovered from monocytes on d 1 of patients with severe sepsis had elevated concentrations of sTREM-1 compared to patients with septic shock and similar to patients with sepsis. A negative correlation was found between levels of sTREM-1 in the cell supernatants and the percentage of apoptotic monocytes. In essence, the above results suggest that monocytes contribute to the production of sTREM-1 in the event of septic syndrome.

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.

Malignant fibrous histiocytoma (MFH) is a high-grade and aggressive sarcoma. Since its description as a distinct clinicopathologic entity by O’Brien and Stout in 1964, it has been recognized as the most common soft tissue sarcoma of late adult life. The majority of tumors occur in one of the extremities (lower extremity, 49%; upper extremity, 19%) or in the retroperitoneum or abdominal cavity (16%), with the thigh being the most common site (30%). MFH rarely occurs in the head and neck region. It has been estimated that only approximately 3%–7% of these tumors present in the head and neck region. The sinonasal tract is the most common craniofacial location, accounting for 30% of cases. Other common head and neck sites include the facial skeleton (15%–25%), the larynx (10%–15%), the soft tissues of the neck (10%–15%), and the major salivary glands (10%–15%). Involvement of the mandible, maxilla, maxillary sinus, and perioral soft tissues has been reported. MFH occurs in oral soft tissues only occasionally, and knowledge about its clinical presentation in this specific anatomic location is based on a limited number of cases reported in the literature. Excluding cases of postradiation MFH and metastatic lesions of this neoplasm to the oral tissues from other primary locations, fewer than 45 cases of MFH arising in the hard or soft tissues of the oral cavity have been previously described. Five of these cases had the tongue as a primary site of MFH. The present study reviews the previously reported cases and describes an additional case.

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 (p0.0001) 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.

Summary Aim To investigate whether the frequency and distribution of mast cells (MCs) in pleomorphic adenomas (PAs) of major and minor salivary glands justifies the suggestion that there exists an association between MCs and mucoid stromal changes in PAs. Methods The material consisted of 22 cases of pleomorphic adenoma (eight arising in major and 14 in minor salivary glands) and a control group represented by five cases of monomorphic adenoma (MA). Representative 3-μm thick, paraffin-embedded sections were stained with H &E and Azur A. Computer-aided image analysis was performed in order to evaluate the relative surface area occupied by epithelial and connective tissue components, as well as the absolute number of MCs. Results According to our findings, PAs from minor salivary glands contain significantly greater numbers of mast cells compared with tumours from major glands. Additionally, the distribution of MCs within the stromal connective tissue appeared not to be random. Conclusion It is possible that differences in the pattern of connective tissue might influence the actual concentration of MCs and that these differences are responsible for the observed variations between major and minor gland PAs.

Objective To verify brain eigenfrequency shifting after the occurrence of a lesion producing mass effect into the cranial vault. Design Experimental animal study. Setting Laboratory of experimental surgery affiliated with a university critical care department. Subjects Six adult male New Zealand white rabbits. Interventions A Camino ICP monitor was placed in the parenchyma, and a 5-Fr balloon-tipped catheter and accelerometer were placed into the epidural space. Measurements Before and after the introduction of successive 0.1-mL increments of autologous blood into the balloon, intracranial pressure (ICP) was recorded along with the accelerometer signal obtained during free vibration of the skull triggered by a calibrated hammer. Fast Fourier transformation of the digitized signal provided the eigenfrequency spectrum. The eigenfrequency showing the sharpest decrease after the initial 0.1-mL volume addition was considered as the best frequency, and its variation in response to subsequent 0.1-mL increments represents the brain eigenfrequency shifting. Main Results Brain eigenfrequency shifting to lower values occurs for small blood volume increments (up to 0.2 mL). When volume addition becomes >or=to0.3 mL, brain eigenfrequency shifting to higher values is exhibited. The decrease in best frequency after the initial introduction of 0.1 mL is statistically significant (p = .003), in a range of volume in which no significant intracranial pressure difference appears. The respective variation of ICP is explained using a quadratic curve. For volumes of 0 to 0.1 mL, the change in ICP is not statistically significant (p = .08). Conclusions Changes of the brain's physical characteristics by mass addition in the cranial vault can be expressed by brain eigenfrequency shifting. The method seems advantageous because it reliably detects mass additions at low levels where no ICP change occurs. Additionally, it provides serial measurements, and it is less invasive than the currently used methods for intracranial compliance. (Crit Care Med 1999; 27:978-984)

Peritoneal lavage is one of the interventional approaches that have gained some attention in the early, toxaemic phase of acute pancreatitis. Additionally some kind of drainage is necessary for suppurative collections that characterize the late phase of the disease. In both the above situations tube plugging is a common problem and it is usually associated with a relapse of the patient’s septic state and newly formed collection(s) on abdominal CT. Two cases are presented, in early and in late phases respectively, in which drainage tube adoscopy (DTE) re-established tube patency and ensured drainage. DTE may represent an alternative to surgery or to CT-guided paracentesis and evacuation of newly formed intra-abdominal collections secondary to tube obstruction.

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.