[High plasmatic concentration of vitamin B12: an indicator of hepatic diseases or tumors]. / Concentration plasmatique élevée de la vitamine B12 : un indicateur des maladies hépatiques ou tumorales.

PURPOSE: To identify the diseases that are associated with a high plasma concentration of vitamin B12 and to measure the strength of this association. PATIENTS AND METHODS: Retrospective study including all admissions between 1st May, 2005 and 30th April, 2008 in the UMAG pole departments (emergency, internal medicine, acute geriatrics and medical intensive care) with a test for plasma vitamin B12. The association between each of medical information system codes (solid tumors, malignant hematologic process, and renal disease) and a high or low vitamin B12 concentration was measured by odds ratios (OR) from logistic models taking into account repeated admissions, with adjustment for age and the weighted Charlson index. RESULTS: Among 3702 admissions, 12% had a B12 more than 820pg/ml, 10.4% a B12 less than 180pg/ml and 77.6% a normal B12 concentration. After adjustment for age and the weighted Charlson index, high concentration of vitamin B12 was associated with interstitial renal diseases (OR 2.7; 95% CI: [1.7-4.2]), and cirrhosis or hepatitis (OR 4.3; [2.9-6.4]). After additional adjustment for these parameters, it was still associated with tumors (OR 1.8; [1.2-2.6]), malignant hematologic diseases (OR 2.1; [1.3-3.5]), metastasis (OR 2.9; [1.5-5.9]), liver metastasis (OR 6.2; [2.7-14.5]), liver carcinoma (LC) (OR 3.3; [1.1-10.4]), liver tumors other than LC (OR 4.7; [1.2-17.9]) and lymphoma (OR 3.2; [1.6-6.4]) but not with myeloma (OR 1.9; [0.6-1.4]). Low concentration of B12 was associated with myeloma (OR 2.9; [1.3-6.6]). CONCLUSION: Finding a high plasma concentration of vitamin B12 should lead to a systematic search for a hepatic disease or a tumor, and particularly for a hepatic localization of a tumor.

Outcome of spontaneous and iatrogenic pneumothoraces managed with small-bore chest tubes.

BACKGROUND: Little is known about the efficacy of management of iatrogenic pneumothoraces with small-bore chest tubes. The aim of this study was to assess the outcome of iatrogenic pneumothoraces requiring drainage managed with a small-bore chest tube and to compare the results to spontaneous pneumothoraces treated in the same unit with the same device. The primary outcome was requirement of video-assisted thoracoscopic surgery for drainage failure; secondary outcomes were length of drainage and number of inserted chest tubes. METHODS: Patients with pneumothorax admitted between 1997 and 2007 were retrospectively identified. Traumatic pneumothoraces and those occurring under mechanical ventilation were excluded. All pneumothoraces were drained using the same small-bore chest tube (8 French) according to our local protocol. RESULTS: Five hundred sixty-one pneumothoraces were analysed, 431 (76.8%) were spontaneous pneumothoraces and 130 (23.2%) were iatrogenic. Iatrogenic pneumothoraces were associated with less requirement of video-assisted thoracoscopic surgery for drainage failure [adjusted odds ratio= 0.24 (0.04, 0.86)]. Length of drainage of iatrogenic pneumothoraces was longer than for primary spontaneous pneumothoraces (3.8 ± 3.1 vs. 2.7 ± 1.8 days, P < 0.001) and shorter than for secondary spontaneous pneumothoraces (4.6 ± 2.3 days, P = 0.004). Number of inserted chest tubes per patient was not significantly different according to pneumothoraces' aetiology. CONCLUSION: Small-bore chest tubes are feasible for treatment of iatrogenic pneumothoraces and have a better rate of success and slightly longer drainage duration than when used for spontaneous pneumothoraces.

[Field 3. Structural and managerial skills for improvement in safety practice. French-speaking Society of Intensive Care. French Society of Anesthesia and Resuscitation]. / Champ 3. Les procédures de sécurisation structurelles et managériales. SRLF. SFAR.

ICU activity has to be authorized by regional hospital agencies. The structural aspects of ICU have been defined in official text in 2002. Thus, quality related to structural issues should be settled in the next future. The challenge is now focused on team building and managerial skills that should be developed in ICU in order to improve quality and security. Every effort should be developed to improve motivation and self-accomplishment of personnel working in ICU (period of integration for new nurses, basic and continuous education, clear tasks identification, formal interviews). It is important to follow alert indicators (absenteeism, important turn over) in order to detect burn out and take preventive measures. It is necessary to develop a new culture, team-oriented, with common goals. This new quality-security oriented policy must be supported by the institution. The volume-outcome relationship has been demonstrated across a wide range of medical and surgical procedures. On average, higher volume is associated with higher quality and better outcome.

Case volume and mortality in haematological patients with acute respiratory failure.

High case volume is associated with improved survival in medical and surgical conditions. The present study sought to determine whether intensive care unit (ICU) case volume was associated with survival of critically ill patients with haematological malignancies and acute respiratory failure (ARF). A regional database containing data from 1,753 haematological patients with ARF admitted to 28 medical ICUs from 1997 to 2004 was used. Multivariate analysis using mixed models was performed to adjust for severity of illness and other confounding factors, including a propensity score that incorporates differences between ICUs with different case volumes. The three case volume tertiles were: low volume (<12 admissions per year), intermediate volume (12-30 admissions per year), and high volume (>30 admissions per year). In univariate analyses, ICU case volume was not associated with ICU mortality. After adjusting for prognostic factors for ICU mortality and the propensity score, patients in high-volume ICUs had lower mortality than other patients. A case volume increase of one admission per year led to a significant mortality reduction with an odds ratio of 0.98 (95% confidence limits 0.97-0.99). Mortality was independently associated with severity of organ dysfunction. In intensive care units admitting larger numbers of critically ill haematological patients with acute respiratory failure, mortality was lower than in other intensive care units. The mechanisms of the relationship between volume and outcome among haematological patients with acute respiratory deserve additional studies.

Circulating endotoxin during initial antibiotic treatment of severe gram-negative bacteremic infections.

The impact of antibiotics on total endotoxemia and circulating tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 in 18 patients with severe bacteremic sepsis or septic shock due to gram-negative species was investigated. Endotoxemia, TNF-alpha, IL-6, and IL-8 were assayed before (H0) and 1 h (H1) and 4 h (H4) after the first antibiotic infusion. Endotoxemia decreased from H0 (median, 0.4 EU/mL; interquartile interval, 0.09-1.23) to H1 (median, 0.19 EU/mL; interquartile interval, 0.07-0.75; P = .03) and remained stable between H1 and H4 (median, 0.12 EU/mL; interquartile interval, 0.09-0.30; P = .4). IL-6 levels fell between H0 and H4 (P = .01) and between H1 and H4 (P = .03). IL-8 was higher at H0 than at H1 (P = .04) and at H4 (P = .01). These results suggest that endotoxemia is not increased by antibiotherapy of severe gram-negative bacteremia.

High doses of hydroxyethyl starch and human albumin have similar effects on monocyte function and oncotic pressure.

The accumulation of hydroxyethyl starches (HES) in monocytes/macrophages has raised concern over their potential detrimental effects on host defences. We assessed prospectively the function of circulating monocytes isolated from patients treated with plasma exchange (PE) using HES. The study was carried out in the medical intensive care unit of a university hospital. Eight patients underwent PE for neurological disorders. Each patient underwent three PEs, 48 h apart. The total exchange volume was 4 L per PE. Only 4% human albumin was used for the first PE. In the second and third PEs, the plasma substitute was 2 L of HES (200,000/6%/0.62) and 2 L of albumin. Mononuclear cells were collected before and immediately after each PE and 48 h after the last PE. They were placed in suspension culture and incubated with lipopolysaccharide (LPS). Monocyte function was assessed in terms of procoagulant activity (PCA) and tumour necrosis factor alpha (TNF-alpha) production. LPS-stimulated PCA increased after the first PE (P < 0.05). Stimulated TNF-alpha production increased, but not significantly so. Similar effects were observed after the second and third PE (P < 0.05 for stimulated TNF-alpha). Values 48 h after the last PE were similar to those obtained before the second PE, suggesting that repeated infusions of HES had no detrimental effect on monocyte function. Furthermore, plasma oncotic pressure was preserved after PE with HES. These results support the partial replacement of costly human albumin with HES during repetitive PE, and suggest that HES might be a safe plasma expander in septic patients.

Secretory non-pancreatic phopholipase A2 in severe sepsis: relation to endotoxin, cytokines and thromboxane B2.

Circulatory secretory non-pancreatic phospholipase A2 (snp-PLA2) was measured prospectively at the onset (day 0) of severe sepsis in 52 patients as well as on day 1 and 2 in 25 patients, in order to answer two questions: 1) does the snp-PLA2 plasma concentration differ according to the type and severity of infection? 2) what is the relation between snp-PLA2 and other mediators involved in severe sepsis, such as endotoxin, cytokines (TNF alpha, IL-1 beta, IL-6) and thromboxane B2 (the stable metabolite of thromboxane A2)? On day 0, the snp-PLA2 circulatory level was 78 +/- 17 nmol/min/ml in patients with severe sepsis as compared to 3.5 +/- 2 nmol/min/ml in 40 healthy volunteers. There was no statistical difference according to the outcome, the presence of shock, or the type of infection on day 0. However, snp-PLA2 remained elevated or even increased in patients who ultimately died, while it decreased in survivors (p = 0.01 by ANOVA). The cytokine profiles during the 2-day follow-up were similar to that of snp-PLA2, but the differences were not statistically significant between survivors and non-survivors. No correlation was found between snp-PLA2 and other mediators for either initial or peak values.

Generalized air cysts complicated by fatal bilateral pneumothoraces in a patient with AIDS-related Pneumocystis carinii pneumonia.

We describe a case of air cyst lesions in an AIDS patient suffering from Pneumocystis carinii pneumonia. This case is unique because these lesions were generalized to both lungs and initially well tolerated. Pathologic examination revealed extensive tissue invasion by P carinii. The prognosis was complicated by bilateral pneumothoraces. Surgical right pleurodesis allowed lung re-expansion but did not prevent recurrence of fatal contralateral pneumothorax.

[Cytokines and severe infections]. / Cytokines et états infectieux graves.

In severe infections two factors play a part: the infectious agent and the response of the host. The response of the host involves production of a large number of endogenous mediators including a number of cytokines that are currently the focus of many studies: tumor necrosis factor (TNF alpha), interleukins (IL-1 and IL-6), and interferon gamma (IGN gamma). These cytokines are part of the body's normal defense mechanisms but can have toxic effects when produced in excessive amounts. Although levels of these cytokines are often high in the blood of patients with sepsis, persistence of these elevations is the main indicator of severe infection. Experimentally, injections of TNF alpha and IL-1 reproduce the manifestations of severe sepsis. Mice that are genetically unable to produce TNF alpha are resistant to the injection of endotoxin. Severe sepsis can be prevented by pretreatment of animals with anticytokine agents (polyclonal and monoclonal antibodies and anti-receptor agents ...). Many issues remain unresolved: for instance, the experimental results obtained with an intravenous bolus of endotoxin or bacteria have not been confirmed in some animal models of subacute infection. These models may more closely resemble human infections. The interrelations between these cytokines are extremely complex. Synergistic effects do occur, but the effects of combinations of cytokines can be different from those of each cytokine given alone... It follows that therapeutic use in humans of anti-cytokine molecules is still an approach of uncertain outcome that will perhaps be clarified by ongoing multicenter clinical trials.

Gentamicin-induced mobilization of iron from renal cortical mitochondria.

Iron, presumably by participating in generation of hydroxyl radical or other oxidant species or initiation of lipid peroxidation, has been shown to play an important role in several models of tissue injury, including acute renal failure induced by the antibiotic gentamicin. However, the sources of iron remain unknown. Rat renal mitochondria incubated at 37 degrees C with gentamicin resulted in a time- (15-60 min) and a dose-dependent (0.01-5 mM) iron release as measured by formation of iron-bathophenanthroline sulfonate complex FeII-(BPS)3 [at 60 min, control: 1.2 +/- 0.1 nmol/mg protein, n = 7; gentamicin (5 mM): 5.1 +/- 0.4 nmol/mg protein, n = 7]. No formation of FeII(BPS)3 complex was detected in the absence of mitochondria or when incubations were carried out at 0 degrees C. Similar results were obtained when 2,2'-dipyridyl, another iron chelator, was used for measurement of iron release. On the basis on our previous study that gentamicin enhances generation of hydrogen peroxide by renal cortical mitochondria, we examined whether effect of gentamicin on iron release is mediated by hydrogen peroxide. Catalase (which decomposes hydrogen peroxide), but not heat-inactivated catalase, as well as pyruvate, a potent scavenger of hydrogen peroxide, prevented gentamicin-induced iron mobilization. Superoxide dismutase, a scavenger of superoxide anion, or hydroxyl radical scavengers (dimethylthiourea or sodium benzoate) had no effect. Taken together, the data with scavengers indicate that gentamicin-induced iron mobilization from mitochondria is mediated by hydrogen peroxide.

Mechanical ventilation for Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. Is the prognosis really improved?

The mortality rate among patients with human immunodeficiency virus (HIV) requiring mechanical ventilation (MV) for acute respiratory failure (ARF) secondary to Pneumocystis carinii pneumonia (PCP) is still a matter of discussion. For some authors, it is in the 50 percent range, while for others the prognosis is grim, with virtually no survivors. The aim of this retrospective study conducted between January 1987 and January 1992 was to analyze the outcome of such patients. We studied 33 patients, 29 men and 4 women (38.6 +/- 9.9 years, 21 homosexuals, 8 intravenous drug users, 3 transfusion related, 1 heterosexual) infected by HIV for at least 19.7 +/- 21.6 months. It was the first PCP episode in all but 2 patients and the diagnosis was made by bronchoalveolar lavage (n = 32) or lung biopsy specimen (n = 1). Only three patients were receiving primary prophylaxis for PCP (trimethoprim-sulfamethoxazole [TMP-SMZ], n = 2; pentamidine, n = 1). Pneumocystis carinii pneumonia was the first manifestation of AIDS in nine patients. The duration of symptoms prior to treatment was 19.6 +/- 11.3 days. At the time of hospital admission, laboratory findings were as follows: PaO2 = 40.7 +/- 7.8 mm Hg on room air; serum LDH = 1,172 +/- 792 IU/L; T4 cell count = 60.2 +/- 67/mm3. Mechanical ventilation was always required for ARF, which was never induced by bronchoscopy. The interval between treatment and MV was 8.1 +/- 6.5 days and the duration of MV was 11.4 +/- 9.9 days. The patients were classified into 3 groups on the basis of the duration and type of treatment before MV, as follows: group 1, n = 10: TMP-SMZ (20-100 mg/kg) IV and methylprednisolone (MP) < 5 days before MV; group 2, n = 4: TMP-SMZ > or = 5 days and MP < 5 days; group 3, n = 19: TMP-SMZ and MP > or = 5 days before MV. (The MP dose was as follows: 240 mg/d once a day from day 1 to day 3; 120 mg/d from day 4 to day 6; and 60 mg/d from day 7 to day 9.) Despite MV, TMP-SMZ, and MP, death secondary to PCP-related ARF occurred in 81.9 percent of patients, 20 +/- 4.8 days after the beginning of treatment and 11.4 +/- 9.9 days after the beginning of MV. Six patients survived, five in group 1 and one in group 3.(ABSTRACT TRUNCATED AT 400 WORDS)

[Interleukins and TNF in septic shock]. / Interleukines et TNF dans le choc septique.

Tumor necrosis factor alpha (TNF alpha) and interleukins (IL) are the principal cytokines involved in the clinical and biological manifestations of septic shock. Their secretion are triggered mainly by endotoxin, but products of Gram positive cocci as well as of virus or of parasites are equally effective. Cytokines represent a normal protective defense against infection, but an excessive production have toxic effects. In experimental models of endotoxinemia, TNF alpha is the first cytokine produced, then IL-1 and IL-6. Other inflammatory mediators are secreted later. Thus it seems logical to try to modulate cytokine production or actions. However, several questions remains since experimental data are sometimes not applicable too human diseases, cytokines are organised in a network with several interaction. It is too early to propose routine anti-cytokines drugs in septic shock.

[Severe immunoallergic hemolytic anemia caused by a glafenine metabolite]. / Anémie hémolytique immuno-allergique grave provoquée par un métabolite de la glafénine.

Three weeks after a surgical operation, a 74-year old woman was admitted to hospital for severe haemolytic anaemia. A strongly positive IgG type direct Coombs test pointed to a iatrogenic origin, but a search for anti-molecule antibodies directed against all medicines taken by the patient after surgery was negative. We extended our immunological investigations and were able to demonstrate the presence of IgG type antibodies directed against an ex vivo metabolite of glafenine.

[Acidoketosis in a chronic alcoholic woman]. / Acidocétose chez une alcoolique chronique.

A 37-year-old chronic alcoholic female was admitted with epigastric pain, complete anorexia, vomiting and diarrhoea. She was dehydrated, and had polypnoea. Laboratory investigations revealed severe metabolic acidosis (pH 7.14) with a major anion gap (37.4 mmol.l-1), and ketone bodies in blood and urine. Blood glucose concentration was 6.1 mmol.l-1, there was no glycosuria. Rehydration (2 l.day-1 of 5% glucose) together with sodium bicarbonate (500 ml of 1.4% sodium bicarbonate over the first four hours) normalized the pH (7.37). The ketone bodies disappeared on the following day. During the acute illness, were found high blood levels of glucagon and low levels of insulin. The diagnosis of alcoholic ketoacidosis, the pathogenesis of which remains unknown, is discussed.

Capillary leakage complicated by compartment syndrome necessitating surgery.

A single episode of systemic capillary leak syndrome is reported in a HIV-positive patient. The shock had necessitated the infusion of large amounts of fluid with concomitant diffuse swelling and weight gain leading to compartment syndrome of both legs. This required surgical relief. The initial high hematocrit (62%) and low serum protein concentration (48 g/l) with normal factor V (molecular weight above 300,000) concentrations are the hallmark of capillary leak when they are associated with hypovolemic shock. It must be emphasized that fluid resuscitation may worsen the muscle damage with ultimate compartment syndrome. Therefore, it appears reasonable to monitor muscular pressure during volume expansion in patients with capillary leak syndrome, severe shock and muscular swelling.

[Recurrence of atypical pulmonary pneumocystosis treated with pentamidine aerosol]. / Récidives de pneumocystoses pulmonaires atypiques sous aérosols de pentamidine.

Two cases are reported of atypical relapses of pneumocystosis in AIDS patients treated with aerosol pentamidine for 14 and 22 months. These pneumopathies are unusual because of their pitted aspect and recurrent spontaneous pneumothoraxes in spite of repeated drainage. They are difficult to diagnose because bronchoalveolar lavage fluid is negative for Pneumocystis carinii, despite their presence in lung biopsies. Histological lesions vary, being granulomatous, necrotizing and invasive, with involvement of the pleura and lymph nodes. Although a highly effective therapy against P. carinii pneumonia, aerosol pentamidine may play a role in these atypical episodes: either by causing bronchial obstructions beyond which the pneumocytotic lesions cannot be reached by lavage and become necrotic, or by favoring the extrapulmonary spread of P. carinii.

[Specificity and serum concentrations of tumor necrosis factor in septic shock]. / Spécificité et évolution du tumor necrosis factor (TNF) sérique dans le choc septique.

Several lines of evidence implicate tumor necrosis factor (TNF), a cytokine produced by monocytes-macrophages, in the systemic manifestations of shock induced by Gram-negative bacteria. Whether the increase of circulating TNF levels is specific to septic shock as compared to sepsis without shock or to non-septic shock is still unclear. Since TNF values recorded at the time of admission to the hospital vary widely, statistical analysis has not been possible. Therefore, we postulated that the evolution of a patient's TNF serum level as compared to his initial value may better distinguish the survivor from the non-survivor than a single initial determination. Using a radioimmunoassay, we measured the TNF concentrations in the sera of 7 patients with severe infections without shock, 16 patients with septic shock and 8 patients with non-septic shock. Blood samples were drawn within the first 12 hours after the onset of shock. Patients with cancer, HIV infection, or under steroid therapy were excluded. Repeated measurements were made during the first 3 days of septic shock in 10 patients. The circulating TNF level, determined upon admission, appears to be neither specific nor predictive of the outcome of septic shock. In contrast, persistently high levels of circulating TNF seem to be well correlated with a poor prognosis, since 5 out of 6 patients with elevated TNF values died of septic shock.

[Acute respiratory distress caused by distal neoplastic pulmonary emboli]. / Détresse respiratorire aiguüe secondaire à des embols pulmonaires néoplasiques distaux.

In contrast to pulmonary parenchyma metastases or lymphangitic carcinomatosis, neoplastic emboli of small pulmonary arteries and capillaries frequently go unrecognized and are only discovered at autopsy. Five patients (48 +/- 12 years old) were admitted to 3 intensive care units for severe acute respiratory failure and died between the first and the tenth day following hospitalization. Each patient had a history of rapidly progressive dyspnea, and physical examination showed clinical evidence of right ventricular failure. The lungs were clear on chest X-rays and the ECG revealed sinus tachycardia with a right QRS axis. The mean partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) were, respectively, 50.8 +/- 9.1 mm Hg and 22.2 +/- 2.4 mm Hg. A swan-Ganz catheter, inserted into 4 patients, revealed pulmonary arterial hypertension (55, 43, 37, 28) with capillary wedge pressure within the normal limits and cardiac output normal or low (3.0, 3.8, 4.4, 5.0 l/min). Pulmonary angiograms from each patient showed decreased distal lung perfusion without any proximal defects suggestive of pulmonary embolism. The inferior vena cava always appeared clear. Malignant cells were found upon autopsy (4 cases) in the lumina of the pulmonary arterioles and the primary site of the cancer was determined in 3 patients (2 hepatomas and 1 pancreatic carcinoma). The last patient had a known breast cancer with bone marrow metastases and clinical, hemodynamic and angiographic evidence of neoplastic emboli. The clinical course of neoplastic emboli can suggest acute pulmonary embolism, but the diagnosis can only be advanced after pulmonary angiography, especially if the patient is to have a cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Polycythemia in chronic obstructive pulmonary disease. A study of serum and urine erythropoietin and medullary erythroid progenitors.

In order to investigate the mechanism of polycythemia in chronic obstructive pulmonary disease (COPD), serum and urinary levels of erythropoietin and medullary erythroid progenitors were studied in 21 patients; nine were nonpolycythemic (hematocrit, 39 +/- 4 percent; red blood cell [RBC] mass, 28 +/- 5 ml/kg; forced expiratory volume in one second [FEV1], 0.6 +/- 0.1 L), and 12 patients were polycythemic (hematocrit, 52 +/- 7 percent; RBC mass, 46 +/- 7 ml/kg; FEV1, 0.9 +/- 0.3 L). Hypoxia was severe in both groups, with mean arterial oxygen pressure of 47 mm Hg. The following parameters of tissue oxygenation were not significantly different between the two groups: arterial and mixed-venous oxygen saturations; cardiac output; oxygen utilization coefficient; 2, 3-diphosphoglycerate, and carboxyhemoglobin level. The level of erythropoietin was measured by bioassay in vitro. The level was increased in the serum of 85 percent (18) and in the urine of 38 percent (8) of the patients. There was no significant difference between the nonpolycythemic and polycythemic groups. Without exogenous erythropoietin, none of the subjects showed spontaneous colonies of erythroid progenitors. The addition of one unit of erythropoietin induced a similar normal proliferation of erythroid progenitors in both groups. The absence of adaptative polycythemia in the nonpolycythemic group with severe hypoxia was seemingly related neither to a quantitative deficit of erythropoietin nor to a lack of sensitivity of erythroid progenitors to its action.