Induction of CD40 expression and enhancement of monoclonal antibody production on murine B cell hybridomas by cross-linking of IgG receptors.

The 55-6 murine B cell hybridoma line not constitutively expressing CD40 was treated with increasing amounts of intact anti-mouse surface immunoglobulin G antibody (anti-mIgG) either not preincubated or preincubated for 48 h with lipopolysaccharide (LPS). In vitro, cross-linking of surface immunoglobulin G (sIgG) with the whole molecule of anti-IgG antibodies induced the expression of CD69, CD40, and CD19 surface antigens on 55-6 cells. The effect of sIgG ligation was dose-dependent, and preincubation with LPS enhanced their responsiveness to anti-mIgG stimulation. The expression of these surface molecules reached the maximum value during the first part of the cell cycle, corresponding to the position of the G1 peak of the DNA distribution. Stimulation of cells with anti-mIgG did not induce changes either in the number of viable cells or in the fraction of cells undergoing proliferation (mitosis). However, preincubation of 55-6 cells with LPS for 48 h before stimulation with anti-mIgG increased both the maximum specific growth rate (micromax) and the percentage of cells in the G2/M phase, in comparison with non-preincubated cells. Moreover, on cells preincubated with LPS prior to anti-mIgG treatment, specific IgG2a production rate was enhanced significantly compared to that obtained in control cultures. The correlation between the antibody production rate and the amount of IgG that is detectable on the cell surface was analyzed by flow cytometry. A good correlation between secreted and surface IgG was observed, and the results of cell cycle analyses demonstrated that the 55-6 hybridoma cell line has a substantially higher sIgG content in G1 phase.

Pleurodesis using autologous blood: a new concept in the management of persistent air leak in acute respiratory distress syndrome.

OBJECTIVE: Pneumothorax is present as a frequent complication in acute respiratory distress syndrome (ARDS). Persistent air leak (PAL) prolongs pneumothorax in 2% of cases of ARDS, increasing the rate of mortality by 26%. Pleurodesis using autologous blood (PAB) is an effective method in cases of oncological pulmonary surgery. The goal of this study was to compare PAB with the conventional drain and water seal in the management of PAL in patients with ARDS and pneumothorax. DESIGN: The study was a case-control, prospective, nonrandomized one comparing 2 groups subjected to artificial pairing (1:1). SETTING: The study took place at the Torrecardenas Hospital (Andalusian Health Service, Almería, Spain). PATIENTS: Participants were 2 groups of 27 patients, all with ARDS, pneumothorax, and PAL. INTERVENTIONS: One group received conventional treatment whereas the other received PAB. MAIN RESULTS: The severity of the conditions of both groups is homogeneous, shown by sex; age; Murray, Marshall, and Acute Physiology and Chronic Health Evaluation II scores; and etiology of ARDS. The patients in the PAB group had a shorter stay in the ICU, shorter weaning time (WT), and lower death rate. The average differences between the groups were 11 days less WT (adjusted odds ratio [OR] = 0.1) and 9 days less on average time spent in the ICU (adjusted OR = 0.24). The death rates in the PAB group and the control group were 3.7% and 29.6%, respectively (adjusted OR = 0.6). CONCLUSIONS: The use of PAB makes possible a decrease in ventilator WT and a shorter stay in the ICU, with a resulting increase in functional recuperation and decrease in patient mortality.

Reversible myocardial dysfunction after cardiopulmonary resuscitation.

OBJECTIVE: Myocardial stunning frequently has been described in patients with an acute coronary syndrome. Recently, it has also been described in critically ill patients without ischaemic heart disease. It is possible that the most severe form of any syndrome, leading to cardio-respiratory arrest, may cause myocardial stunning. Myocardial stunning appears to have been demonstrated in experimental studies, though this phenomenon has not been sufficiently studied in human models. The aim of the present work has been to study and describe the possible development of myocardial dysfunction in patients resuscitated after cardio-respiratory arrest, in the absence of acute or previous coronary artery disease. DESIGN: Descriptive study of a case series. SETTING: The intensive care unit (ICU) of a provincial hospital. PATIENTS AND PARTICIPANTS: The study period was from April 1999 to June 2001. All patients admitted to the ICU with critical, non-coronary artery pathology, with no past history of cardiac disease, and those who were resuscitated after cardio-respiratory arrest, were included in the study. MEASUREMENTS AND RESULTS: Transthoracic and transoesophageal echocardiography was used to assess left ventricular ejection fraction (LVEF) and disturbances of segmental contractility. This study was carried out within the first 24h after admission, during the first week, during the second or third week, after 1 month, and between 3 and 6 months. Twenty-nine patients with a median age of 65 years (range 24--76) were included in the study. Twelve patients died. Twenty patients developed myocardial dysfunction; the initial LVEF in these patients was 0.28 (0.12--0.51), showing improvement over time in the patients who survived. All of these patients presented disturbances of segmental contractility which also became normal over time. CONCLUSIONS: After successful CPR, reversible myocardial dysfunction, consisting of systolic myocardial dysfunction and disturbances of segmental contractility, may occur.

Post-thrombolysis intracerebral hemorrhage: data from the Spanish Register ARIAM.

OBJECTIVE: Our objective was to investigate the predisposing factors in patients with acute myocardial infarction (AMI) treated with thrombolysis and complicated by intracranial hemorrhage (ICH), as well as the factors associated with death for patients whose conditions were complicated by ICH. DESIGN: A retrospective study. SETTING: An intensive care/critical care unit. PATIENTS: All patients with AMI listed in the Spanish ARIAM register. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study period was from June 1996 to December 2003. The follow-up period was limited to the time spent in the intensive care unit/coronary care unit. Associations with the development of ICH were studied by univariate analysis. Another univariate analysis was used to evaluate the differences between patients affected by AMI complicated by ICH who died and those who survived. Two multivariate analyses were also used: one to evaluate the factors related to the development of ICH and the other to evaluate the factors associated with the death of patients with ICH. A total of 17,111 patients with AMI were included in the study. ICH occurred in 151 (0.9%) of these patients during their stay in the intensive care unit/coronary care unit. The multivariate analysis showed that the variables associated with ICH development were smoking (odds ratio [OR], 0.684; 95% confidence interval [CI], 0.478-0.979); oral b-blockers (OR, 0.488; CI, 0.337-0.706); angiotensin-converting enzyme (ACE) inhibitors (OR, 0.480; CI, 0.340-0.678); arterial hypertension (OR, 4.900; CI, 2.758-8.705); age of 55-64 yrs (OR, 2.253; CI, 1.117-4.546); age of 65-74 yrs (OR, 4.240; CI, 2.276-7.901); age of 75-84 yrs (OR, 4.450; CI, 2.319-8.539); and age of >84 yrs (OR, 2.997; CI, 1.039-8.647). The mortality rate among patients with ICH was 48.3%, vs. 8.3% among patients without ICH. The multivariate study showed that the mortality rate among patients with ICH was associated with age (OR, 1.086; CI, 1.033-1.143), arterial hypertension cardiovascular risk factor (OR, 2.773; CI, 1.216-6.324), and the need for mechanical ventilation (OR, 4.324; CI, 1.665-11.230) or cardiopulmonary resuscitation (OR, 12.258; CI, 1.268-118.523). However, the administration of b-blockers (OR, 0.369; CI, 0.136-0.997) or ACE inhibitors (OR, 0.367; CI, 0.149-0.902) was associated with a reduction in the mortality rate. CONCLUSIONS: Factors associated with the development of ICH in our population were age and arterial hypertension, whereas smoking and the administration of b-blockers or ACE inhibitors were associated with a reduction in incidence. Among patients with AMI complicated by ICH, mortality was associated with age, arterial hypertension, cardiopulmonary resuscitation, and the use of mechanical ventilation, whereas the administration of oral b-blockers and ACE inhibitors could be associated with a reduction in mortality.