Perspectives in transplantation immunology 1991

Summary The clinical success of organ transplantation depends to a large degree on the immunological acceptance of the grafted organ. This paper summarizes from an immunological point of view the recent progress that has been made to improve graft acceptance, and discusses some future aspects in the field. Over the last few years, major emphasis has been put on the development of new immunosuppressive drugs, including FK 506, rapamycin, and Deoxyspergualin. Together with monoclonal antibodies against defined T-cell surface antigens, there are now new and effective means available to prevent or treat rejection episodes. Progress has also been made in the field of HLA typing, where the introduction of molecular biology-based methods significantly increased the accuracy of HLA class II typing. The ultimate goal of transplantation immunology is the induction of (donor-) specific tolerance. While some protocols are effective in inducing peripheral tolerance in experimental animals, these regimens are at present not yet applicable in the clinical situation. To overcome the shortage of donor organs, alternative strategies are currently being considered. Among these, xenotransplantation may eventually prove successful, despite the massive immunological problems such as, e.g., the presence of preformed xenoreactive antibodies.Abbreviations CTL cytolytic T lymphocyte - HLA human leukocyte antigen - MHC major histocompatibility complex - PCR polymerase chain reaction - mAB monoclonal antibody - RFLP restriction fragment length polymorphism - TCR T-cell receptor Preprint of a lecture to be read at the 22nd Congress of the Gesellschaft für Nephrologie, Heidelberg, September 15–18, 1991 (Editor: Prof. Dr. E. Ritz, Heidelberg)     

Bilateral pneumothorax with pneumomediastinum under anaesthesia in a healthy female

A case of bilateral pneumothorax and Pneumomediastinum developing under general anaesthesia without apparent cause is reported. Possible aetiologic factors and mechanisms of the condition are outlined. Clinical signs and the immediate management of pneumothorax and Pneumomediastinum are discussed.     

Traumatic diaphragmatic rupture: associated injuries and outcome

A retrospective case note analysis was performed on all patients treated for traumatic diaphragmatic rupture (TDR) at a major teaching hospital between January 1990 and August 1998. Patients were identified from the prospectively maintained UK Trauma and Research Network Database. Of the 480 cases of torso trauma admitted during the study period, 16 (3.3%) had TDR. Blunt trauma accounted for 13 (81%) of the injuries. A radiological pre-operative diagnosis was made in 10 (62.5%) patients. Seven of these were made on initial chest radiography, two on ultrasound scan and one on computed tomography. All patients underwent a midline laparotomy and TDR was subsequently diagnosed at operation in 6 patients. The left hemidiaphragm was ruptured in 14 (87.5%) patients and there was visceral herniation in 8 (50%). Twelve patients with blunt trauma had associated abdominal and extra-abdominal injuries, but only one of the three patients with penetrating trauma had other injuries. The median Injury Severity Score (range) was 21 (9-50). The median time (range) spent on the intensive care unit was 2 days (0-35 days). Pulmonary complications occurred in 7 (44%) patients. Two (12.5%) patients died from associated head injuries. TDR results from blunt and penetrating torso trauma, is uncommon, rarely occurs in isolation and is associated with a high morbidity and mortality. A high index of suspicion makes early diagnosis more likely as initial physical and radiological signs may be lacking.     

Magnetic resonance imaging of a temporal lobe cerebral amyloidoma

Amyloidomas are focal solitary amyloid masses without systemic involvement that have been observed to occur in various body locations. When presenting intracranially, they pose a challenging diagnostic and therapeutic course given their location and rarity. We report a case of a 62-year-old man with a 4-year history of seizure and headaches. Magnetic resonance imaging was initially inconclusive but revealed an ill-defined right temporal lobe lesion. Biopsy later confirmed a cerebral amyloidoma. We also review the current literature on the pathogenesis, imaging findings, prognosis, and treatment of cerebral amyloidomas.     

Efficacy of a spatial repellent for control of Aedes-borne virus transmission: A cluster-randomized trial in Iquitos,Peru

Over half the world’s population is at risk for viruses transmitted by Aedes mosquitoes, such as dengue and Zika. The primary vector, Aedes aegypti, thrives in urban environments. Despite decades of effort, cases and geographic range of Aedes-borne viruses (ABVs) continue to expand. Rigorously proven vector control interventions that measure protective efficacy against ABV diseases are limited to Wolbachia in a single trial in Indonesia and do not include any chemical intervention. Spatial repellents, a new option for efficient deployment, are designed to decrease human exposure to ABVs by releasing active ingredients into the air that disrupt mosquito–human contact. A parallel, cluster-randomized controlled trial was conducted in Iquitos, Peru, to quantify the impact of a transfluthrin-based spatial repellent on human ABV infection. From 2,907 households across 26 clusters (13 per arm), 1,578 participants were assessed for seroconversion (primary endpoint) by survival analysis. Incidence of acute disease was calculated among 16,683 participants (secondary endpoint). Adult mosquito collections were conducted to compare Ae. aegypti abundance, blood-fed rate, and parity status through mixed-effect difference-in-difference analyses. The spatial repellent significantly reduced ABV infection by 34.1% (one-sided 95% CI lower limit, 6.9%; one-sided P value = 0.0236, z = 1.98). Aedes aegypti abundance and blood-fed rates were significantly reduced by 28.6 (95% CI 24.1%, ∞); z = −9.11) and 12.4% (95% CI 4.2%, ∞); z = −2.43), respectively. Our trial provides conclusive statistical evidence from an appropriately powered, preplanned cluster-randomized controlled clinical trial of the impact of a chemical intervention, in this case a spatial repellent, to reduce the risk of ABV transmission compared to a placebo.

Aedes-borne viral diseases (ABVDs) [e.g., dengue (DENV), chikungunya, Zika (ZIKV), and yellow fever] are devastating, expanding global public health threats that disproportionally affect low- and middle-income countries. DENV, one of the most rapidly increasing vector-borne infectious diseases, results in ∼400 million infections each year (1, 2), with 4 billion people at risk for infection annually (3). Currently, the primary means for ABVD prevention is controlling the primary mosquito vector, Aedes aegypti. Existing vector control interventions, however, have failed to prevent ABV transmission and epidemics (4–6).There is an urgent need to develop evidence-based guidance for the use of new and existing ABV vector control tools. The evidence base for vector control against ABVs is weak, despite considerable government investments in World Health Organization (WHO)-recommended control of larval habitats (larviciding, container removal) and ultra-low-volume insecticide spraying (4, 5, 7–9). These strategies continue to be implemented despite the lack of rigorously generated data from controlled clinical trials demonstrating they reduce ABV infection or disease (6). The only ABV intervention with a proven epidemiological impact in a cluster-randomized control trial (cRCT) assessed community mobilization to reduce mosquito larval habitats (10). A recent test-negative trial with Wolbachia-infected mosquitoes reported a significant reduction of DENV illness in Indonesia (11).Spatial repellents (SRs) are devices that contain volatile active ingredients that disperse in air. The active ingredients can repel mosquitoes from entering a treated space, inhibit attraction to human host cues, or disrupt mosquito biting and blood-feeding behavior and, thus, interfere with mosquito–human contact (12–14). Any of these outcomes reduce the probability of pathogen transmission. Pyrethroid-based SRs have shown efficacy in reducing malaria infections in China (15) and Indonesia (16). There have, however, been no clinical trials evaluating the protective efficacy (PE) of SRs against ABV infection or disease.To generate evidence for public health consideration, we conducted a double-blinded, parallel cRCT to demonstrate and quantify the PE of a transfluthrin-based SR to reduce ABV infection incidence over 2 y in a human cohort in Iquitos, Peru.     

Significance of anti-lymphocyte antibodies in systemic lupus erythematosus

Sera from patients with SLE frequently contain IgM and IgG antibodies with multiple specificities for lymphocyte surface determinants, including autologous antigens. The IgM antibodies are of relatively low binding avidity and exhibit broad reactivity with B and T lymphocytes from most individuals. IgG antibodies are reactive selectively with PBL from different individuals and appear to be more specific for B cell and a minor proportion of T cells. The molecular nature of the surface determinants involved and their relationship with known antigens and receptors remain largely undefined. Interest in anti-lymphocyte antibodies in SLE relates in part to data suggesting a causal role in the abnormal immune system function in this disorder. In this regard, possible mechanisms that are supported by indirect data include: a) antibody-mediated lymphocyte depletion in vivo, perhaps involving functional subsets specifically; b) antibody blockade of surface receptors operant in cell-cell and in cell-soluble antigen interactions. Certain data have raised the possibility that anti-lymphocyte antibodies represent serum markers for infection with virus as etiologic in SLE, but this question is controversial. Nevertheless, further investigation may yet reveal viral or genetically determined “SLE-specific” lymphocyte surface antigens. Clinically, anti-lymphocyte antibodies may have potential for mediating tissue injury in SLE, either directly or indirectly as circulating complexes in association with “shed” lymphocyte surface antigen. Direct evidence in support of such a role in the natural history of this disorder has not been forthcoming.