COMPARISON OF THE IMMUNE RESPONSIVENESS OF NZB AND NZB x NZW F1 HYBRID MICE WITH THAT OF OTHER STRAINS OF MICE

The immune responsiveness of (NZB x NZW) F₁ hybrid mice (NZB/W) has been compared with that of three other strains of mice, A/J, BALB/c, and CBA/J. The antigens used included sheep red blood cells (SRBC), keyhole limpet hemocyanin (KLH), bovine serum albumin (BSA), and human γ-globulin (HGG). It was found that important strain differences existed in the amount of antibody produced, but the relative immune responsiveness depended very much upon the nature of antigen. By comparison with the other strains tested, NZB/W mice had a higher antibody production to some antigens (SRBC and BSA) but were low responders to others (KLH). Induction of unresponsiveness to HGG by treatment with ultracentrifuged HGG was studied in the strains cited above. NZB/W mice became tolerant after injection of HGG ultracentrifuged at 100,000 g for 2 hr. Similar experiments carried out with another preparation of HGG (centrifuged at 20,000 g for 30 min) failed to reveal any abnormal behavior of NZB/W mice as compared to BALB/c or A/J mice. These results do not support the concept that NZB/W mice possess a general immune hyperreactivity or a relative inability to be made tolerant to protein antigens. However, they do not rule out the possibility that these mice have a genetically determined hyperresponsiveness to some antigens, in particular to nuclear antigens.     

Agitation and aggressiveness among the elderly population living in nursing or retirement homes in France

The aim of this study was to describe the epidemiological features of agitation and aggressiveness in elderly individuals living in French nursing and retirement homes in the year 2000. Data were collected on the type, time of onset, and duration of symptoms, medical evaluation and treatment, and medical and psychiatric comorbidities of the elderly patients. The most frequently reported behavior was verbal aggressiveness and the least reported behavior was physical aggressiveness. A triggering factor initiating the symptoms of agitation or aggressiveness was reported in 61% of the cases. In 61% of the study population, there were several morbidities reported as caused by the agitated or aggressive behavior (anorexia, weight loss, dehydration). A specialist was consulted for nearly half of the agitated or aggressive patients. For 55% of the patients, a new medication regimen was started or the administration of previous medications was modified, the most frequently prescribed drugs being antipsychotics. The results of our study and others show that agitation and aggression have a substantial impact on the lives of the elderly population, as well as on the lives of their family members and caretakers.     

Generation of adult-like antibody avidity profiles after early-life immunization with protein vaccines

The capacity to induce high-avidity antibodies following early-life immunization has long been questioned, and the possibility of inducing such antibodies soon after birth is a recognized goal for a number of vaccination strategies. Therefore, we assessed the capacity to develop high-avidity antibodies to peptidic vaccines in 1-week-old BALB/c mice. The dynamics of the generation of antibody molecules of increasing avidity were analyzed on circulating serum antibodies and, where feasible, at the single-cell level on spleen and bone marrow antibody-secreting cells. Two alum-adsorbed protein-based human vaccines, tetanus toxoid (TT) and pertussis toxin, induced neonatal antibody responses with adult-like avidity profiles. This was confirmed at the level of spleen and bone marrow ASC. In contrast, immunization with TT-P30, a 21-mer synthetic peptide containing a TT-immunodominant epitope, trinitrophenyl hapten (TNP) conjugated to ovalbumin or TNP conjugated to Ficoll, induced a much lower avidity profile in early life than in adults. These observations indicate that in murine models the avidity maturation of T cell-dependent antibody responses induced by structurally complex protein vaccines can be fully elicited after early life immunization, as opposed to the maturation of responses induced with short peptides or hapten-based vaccines.     

Acute asthma attack in children presenting to the emergency department. Survey of 96 cases

Throughout a 2-year period, children who presented at H?tel-Dieu de France emergency department (ED) with acute asthma were analyzed prospectively and data on their environment, family and personal history as well as treatment were recorded. Treatment delivered at the ED, response and further outcome were analyzed. Out of 2024 children aged less than 15 years, 96 (5%) had acute asthma attack. Their median age was 4 years and M/F ratio was 2:1. Median age at onset of asthma was 2 years. Only 66 patients were recognized as asthmatics and 20% were given regular inhaled daily treatment. Current attack was mild in 45%, moderate in 45% and severe in 10% of cases. Home treatment before ED admission was often inadequate. Nine patients required hospital admission after failure of treatment at the ED. Within a median follow-up of 12 months, half of the patients experienced further attacks sometimes requiring ED care (27%) or hospital admission (8%). These data highlight the fact that asthma in our country is still largely under recognized and inadequately treated.     

Complications after Laparoscopic Adjustable Gastric Banding for Morbid Obesity: Experience with 1,000 Patients over 7 Years

Background: Laparoscopic adjustable gastric banding (LAGB) is considered the least invasive surgical option for morbid obesity. It is less efficient than gastric bypass in weight loss, but has the advantage of being potentially reversible and can improve the quality of life if mortality and morbidity are low. Methods: Between 1996 and 2003, 1,000 patients underwent LAGB. There were 896 women and 104 men with mean age 40.4 years (16.3-66.3). Preoperative mean BMI was 44.3 kg/m². Results: There were no deaths. Cumulative rate of complications was 192 (19.2%). 12 were life-threatening (1.2%): gastric perforation (n=4), acute respiratory distress (n=2), pulmonary embolism (n=2), migration (n=3), and gastric necrosis (n=1). 111 patients required an abdominal reoperation (11.1%) for perforation (n=2), slippage (n=78), migration (n=3), necrosis (n=1), esophageal dilatation (n=2), incisional hernias (n=4) and port problems (n=21). Before October 2000, we used the perigastric technique, and the slippage rate was 24% (91 / 378 ).Then, we changed to the pars flaccida approach and the slippage rate fell to 2% (13 / 622). The pars flaccida approach demonstrated safety in relation to both risks of perforation and slippage. Conclusion: The cumulative complication rate increased to 3-4 years, and then decreased with experience and technical improvement. Concerns of long-term follow-up should be migration and esophageal dilatation, which seem to be rare at 3 years.     

Human immune associated nucleotide 1: a member of a new guanosine triphosphatase family expressed in resting T and B cells

TAL-1 is a basic helix-loop-helix oncoprotein that is expressed in up to 30% of T-cell acute lymphoblastic leukemias but not in the T lineage. We have cloned a complementary DNA, called Human Immune Associated Nucleotide 1 (hIAN1), whose messenger RNA (mRNA) level expression is inversely correlated to the TAL-1 mRNA level in human leukemic T-cell lines. The hIAN1 encodes a 38-kd protein that belongs to a novel family of proteins conserved from plants to humans and characterized by motifs related to, but highly divergent from, the consensus motifs found in guanosine triphosphate (GTP)-binding proteins. Despite these divergent amino acids at positions involved in GTP/guanosine diphosphate (GDP) binding and guanosine triphosphatase (GTPase) activities, we found that hIAN1 specifically binds GDP (K(d) = 0.47 microM) and GTP (K(d) = 6 microM) and exhibits intrinsic GTPase activity. Among mature hematopoietic cells, hIAN1 is specifically expressed in resting T and B lymphocytes, and its expression level tremendously decreased at the protein but not the mRNA level during B- or T-lymphocyte activation, suggesting a specific role for this new type of GTPase during the immune response.     

Decreased Heat-Labile Opsonic Activity and Complement Levels Associated with Evidence of C3 Breakdown Products in Infected Pleural Effusions

Heat-labile opsonic activity was measured simultaneously in serum and pleural fluid of patients with transudates, infectious exudates (with positive or negative bacterial culture) and neoplastic exudates, using two different complement-dependent phagocytic tests: the killing of Staphylococcus aureus Wood 46 variant strain (K50 opsonic titers) and the assessment of ingestion rate of endotoxin-coated paraffin particles (Oil Red 0 uptake test). K50 opsonic titers were lower in culture-positive pleural effusions as compared to culture-negative (P < 0.002) or neoplastic effusions (P < 0.002). These results were corroborated by the Oil Red 0 uptake test. The data obtained with the two assays showed a significant correlation (P < 0.001).The hemolytic activity of complement (CH50) as well as the levels of C3 breakdown product, C3d, were measured in the same sera and pleural fluid samples and in an additional group of patients with pleural effusions of the same etiology. Effusions with positive cultures showed lower CH50 values (P < 0.01) and higher C3d values (P < 0.05) when compared to culture-negative pleural fluids. Finally, evidence for immune complexes in pleural effusions and sera was looked for by determination of Clq binding activity. Levels were higher in culture-positive effusions when compared to culture-negative fluids (P = 0.005).K50 opsonic titers showed a positive correlation with CH50 values (P < 0.001) for all fluids tested. Similarly Clq binding activity correlated with C3d levels in effusions of infectious origin (P = 0.05). Recovery experiments using the various bacterial species isolated from culture-positive pleural effusions showed evidence of complement inactivation upon incubation with pooled sera at concentrations of 10(7)-10(8) microorganisms/ml.These results indicate that one important reason for bacterial persistence in empyema may be decreased opsonization secondary to local consumption of complement.     

Role of intraoperative enteroscopy in the management of obscure gastointestinal bleeding at the time of video-capsule endoscopy

Background

This study aimed at evaluating the role of intraoperative enteroscopy (IOE) for the management of obscure gastrointestinal (GI) bleeding in patients who had been preoperatively explored by video-capsule endoscopy (VCE).

Methods

Eighteen patients who underwent IOE for obscure GI bleeding were prospectively recorded between November 2000 and January 2007. The bleeding site was preoperatively localized by VCE in the small bowel in 15 patients, but the origin of bleeding remained unknown in 3 patients.

Results

In the 3 patients with negative VCE, IOE was normal, but intraoperative conventional endoscopy identified gastric (n = 1) and colonic (n = 2) lesions. Among the 15 patients with VCE positive for small-bowel lesions, laparotomy and IOE yielded localization and treatment (surgical n = 11 and endoscopic n = 2) guidance for 13 of 15 (87%) lesions. At median 19-month follow-up, 3 bleeding recurrences (3 of 15 [20%]) were recorded, resulting in a 73% therapeutic efficacy of IOE.

Conclusions

IOE remains useful for the management of obscure GI bleeding when preoperative VCE is positive for small-bowel lesions that are not reachable by nonoperative enteroscopy. When VCE is negative, new conventional endoscopy should be proposed instead of IOE.