Human CTLA4 knock-in mice unravel the quantitative link between tumor immunity and autoimmunity induced by anti-CTLA-4 antibodies

Although results from preclinical studies in animal models have proven the concept for use of anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies in cancer immunotherapy, 2 major obstacles have hindered their successful application for human cancer therapy. First, the lack of in vitro correlates of the antitumor effect of the antibodies makes it difficult to screen for the most efficacious antibody by in vitro analysis. Second, significant autoimmune side effects have been observed in a recent clinical trial. In order to address these 2 issues, we have generated human CTLA4 gene knock-in mice and used them to compare a panel of anti-human CTLA-4 antibodies for their ability to induce tumor rejection and autoimmunity. Surprisingly, while all antibodies induced protection against cancer and demonstrated some autoimmune side effects, the antibody that induced the strongest protection also induced the least autoimmune side effects. These results demonstrate that autoimmune disease does not quantitatively correlate with cancer immunity. Our approach may be generally applicable to the development of human therapeutic antibodies.     

Acromesomelic dysplasia associated with mild lumbar spine stenosis

A rare case of acromesomelic dysplasia is reported. The radiological findings were consistent with shortness of all tubular bones, especially those of the forearms. There was also evidence of mild lumbar spine stenosis. Received: 16 June 1997; Revision received: 13 January 1998; Accepted: 24 March 1998     

Effectiveness of a 30-min CPR self-instruction program for lay responders: a controlled randomized study

BACKGROUND: The length of current 4-h classes in cardiopulmonary resuscitation (CPR) is a barrier to widespread dissemination of CPR training. The effectiveness of video-based self-instruction (VSI) has been demonstrated in several studies; however, the effectiveness of this method with older adults is not certain. Although older adults are most likely to witness out-of-hospital cardiac arrests, these potential rescuers are underrepresented in traditional classes. We evaluated a VSI program that comprised a 22-min video, an inflatable training manikin, and an audio prompting device with individuals 40-70 years old. The hypotheses were that VSI results in performance of basic CPR skills superior to that of untrained learners and similar to that of learners in Heartsaver classes. METHODS: Two hundred and eighty-five adults between 40 and 70 years old who had had no CPR training within the past 5 years were assigned to an untrained control group, Heartsaver training, or one of three versions of VSI. Basic CPR skills were measured by instructor assessment and by a sensored manikin. RESULTS: The percentage of subjects who assessed unresponsiveness, called the emergency telephone number 911, provided adequate ventilation, proper hand placement, and adequate compression depth was significantly better (P<0.05) for the VSI groups than for untrained controls. VSI subjects tended to have better overall performance and better ventilation performance than did Heartsaver subjects. CONCLUSIONS: Older adults learned the fundamental skills of CPR with this training program in about half an hour. If properly distributed, this type of training could produce a significant increase in the number of lay responders who can perform CPR.     

Effects of smaller tidal volumes during basic life support ventilation in patients with respiratory arrest: good ventilation, less risk?

OBJECTIVE: When ventilating an unintubated patient in cardiac or respiratory arrest, smaller tidal volumes of 500 ml instead of 800-1200 ml may be beneficial to decrease peak airway pressure, and to minimise stomach inflation. The purpose was to determine the effects of small (approximately 500 ml) versus large (approximately 1000 ml) tidal volumes given with paediatric versus adult self-inflatable bags and approximately 50% oxygen on respiratory parameters in patients during simulated basic life support ventilation. METHODS: While undergoing induction of anaesthesia, patients were randomised to three minutes of ventilation with either an adult (n = 40) or paediatric (n = 40) self-inflatable bag. RESULTS: When compared with an adult self-inflatable bag, the paediatric bag resulted in significantly lower mean (+/- standard deviation) exhaled tidal volume (365 +/- 55 versus 779 +/- 122 ml; P < 0.0001), peak airway pressure (20 +/- 2 versus 25 +/- 5 cm H2O; P < 0.0001), but comparable oxygen saturation (97 +/- 1% versus 98 +/- 1%; NS (nonsignificant)). Stomach inflation occurred in five of 40 patients ventilated with an adult self-inflatable bag, but in no patients who were ventilated with a paediatric self-inflatable bag (P = 0.054). CONCLUSION: Administering smaller tidal volumes with a paediatric instead of an adult self-inflatable bag in unintubated adult patients with respiratory arrest maintains good oxygenation and carbon dioxide elimination while decreasing peak airway pressure, which makes stomach inflation less likely.     

Effects of a major earthquake on blood donor types and infectious diseases marker rates

This observational study attempted to identify the effect of a natural disaster on the safety of blood supply and donor types with the influx of donors after a severe earthquake. Blood donation rate, blood discard rate and safety of blood donations responding to the earthquake, as projected from the infectious disease marker rate, were evaluated in blood donated immediately before (1 July-17 August) and after 17 August 1999 (17 August-21 August). These were compared with the results from the corresponding periods in 1998 and 2000 for donations at a university medical centre and two regional blood centres. 8055 units of allogeneic blood were collected at two regional blood centres, and 450 units were collected at a university medical centre during 4 days. Viral marker rates were nearly the same at the former but were slightly lower at the latter. The blood discard rate was nearly twice the comparative periods at the former, but it remained unchanged at the latter. Voluntary donors replaced the replacement donors during 4 days. This analysis highlights the size of the pool of potential donors that are available as a national resource that can be motivated to give blood with the right motivation.     

Hemi-meningitis with hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare lymphoproliferative disorder. HLH may occur as a complication of Epstein-Barr virus (EBV), particularly in patients with immunodeficiencies. Herein, we describe a 16-year-old girl with neurological complications associated EBV-induced HLH. Her cerebral magnetic resonance imaging (MRI) showed contrast-enhanced axial T1-weighted images with enhancement of meningeal surface in the right hemisphere that was consistent with right hemi-meningitis. Hydrocephalus, dilated subdural spaces, delayed myelination, edema, diffuse parenchymal atrophy, calcifications, diffuse/patchy white matter abnormalities have all been previously described with HLH. To the best of our knowledge, this is the first case of hemi-meningitis associated with HLH. We suggest that clinicians should consider HLH with vascular disorders when they determine unilateral meningitis on a brain MRI.     

A SARS-CoV-2 targeted siRNA-nanoparticle therapy for COVID-19

1. Download : Download high-res image (156KB)
2. Download : Download full-size image