Acute mucosal pathogenesis of feline immunodeficiency virus is independent of viral dose in vaginally infected cats

<p>Abstract</p> <p>Background</p> <p>The mucosal pathogenesis of HIV has been shown to be an important feature of infection and disease progression. HIV-1 infection causes depletion of intestinal lamina propria CD4+ T cells (LPL), therefore, intestinal CD4+ T cell preservation may be a useful correlate of protection in evaluating vaccine candidates. Vaccine studies employing the cat/FIV and macaque/SIV models frequently use high doses of parenterally administered challenge virus to ensure high plasma viremia in control animals. However, it is unclear if loss of mucosal T cells would occur regardless of initial viral inoculum dose. The objective of this study was to determine the acute effect of viral dose on mucosal leukocytes and associated innate and adaptive immune responses.</p> <p>Results</p> <p>Cats were vaginally inoculated with a high, middle or low dose of cell-associated and cell-free FIV. PBMC, serum and plasma were assessed every two weeks with tissues assessed eight weeks following infection. We found that irrespective of mucosally administered viral dose, FIV infection was induced in all cats. However, viremia was present in only half of the cats, and viral dose was unrelated to the development of viremia. Importantly, regardless of viral dose, all cats experienced significant losses of intestinal CD4+ LPL and CD8+ intraepithelial lymphocytes (IEL). Innate immune responses by CD56+CD3- NK cells correlated with aviremia and apparent occult infection but did not protect mucosal T cells. CD4+ and CD8+ T cells in viremic cats were more likely to produce cytokines in response to Gag stimulation, whereas aviremic cats T cells tended to produce cytokines in response to Env stimulation. However, while cell-mediated immune responses in aviremic cats may have helped reduce viral replication, they could not be correlated to the levels of viremia. Robust production of anti-FIV antibodies was positively correlated with the magnitude of viremia.</p> <p>Conclusions</p> <p>Our results indicate that mucosal immune pathogenesis could be used as a rapid indicator of vaccine success or failure when combined with a physiologically relevant low dose mucosal challenge. We also show that innate immune responses may play an important role in controlling viral replication following acute mucosal infection, which has not been previously identified.</p

Reasons, considerations, difficulties and documentation of end-of-life decisions in European intensive care units: the ETHICUS Study

OBJECTIVE: To evaluate physicians' reasoning, considerations and possible difficulties in end-of-life decision-making for patients in European intensive care units (ICUs). DESIGN: A prospective observational study. SETTING: Thirty-seven ICUs in 17 European countries. PATIENTS AND PARTICIPANTS: A total of 3,086 patients for whom an end-of-life decision was taken between January 1999 and June 2000. The dataset excludes patients who died after attempts at cardiopulmonary resuscitation and brain-dead patients. MEASUREMENTS AND RESULTS: Physicians indicated which of a pre-determined set of reasons for, considerations in, and difficulties with end-of-life decision-making was germane in each case as it arose. Overall, 2,134 (69%) of the decisions were documented in the medical record, with inter-regional differences in documentation practice. Primary reasons given by physicians for the decision mostly concerned the patient's medical condition (79%), especially unresponsive to therapy (46%), while chronic disease (12%), quality of life (4%), age (2%) and patient or family request (2%) were infrequent. Good medical practice (66%) and best interests (29%) were the commonest primary considerations reported, while resource allocation issues such as cost effectiveness (1%) and need for an ICU bed (0%) were uncommon. Living wills were considered in only 1% of cases. Physicians in central Europe reported no significant difficulty in 81% of cases, while in northern and southern regions there was no difficulty in 92-93% of cases. CONCLUSIONS: European ICU physicians do not experience difficulties with end-of-life decisions in most cases. Allocation of limited resources is a minor consideration and autonomous choices by patient or family remain unusual. Inter-regional differences were found

Complex elbow Instability: treatment and rehabilitation

Complex elbow instability represent a challenging injury even for expert elbow surgeons. Chronic instability, posttraumatic osteo-arthritis, stiffness and poor functional outcomes are frequent if these injuries are not adequately treated. A correct preoperative evaluation includes X-rays, CT scan with 2D and 3D reconstruction and stability tests under fluoroscopy in order to recognize all osseous and ligamentous lesions. The most common patterns of complex elbow instability includes: (1) radial head fractures associated with lateral and medial collateral ligaments lesions; (2) coronoid fractures and lateral collateral ligament lesion; (3) Terrible Triad; (4) fracture-dislocations of the proximal ulna and radius, also referred to as transolecranon fracture-dislocations and Monteggia-like lesions; and (5) humeral shear fractures associated with lateral and medial collateral ligament lesions. The main goals of the treatment are (1) to perform a stable osteosynthesis of all fractures, (2) to obtain concentric and stable reduction of the elbow throught the repair of soft tissue constraint lesions and (3) to allow early motion. All the patterns of complex elbow instability share the same therapeutic algorithm based on seven main principles: 1) the proximal ulna must be anatomically reduced and fixed; 2) the radial head or humeral shear fracture must be repaired or replaced, 3) bone length, alignment and rotation of ulnar and radial shaft fractures must be recovered; 4) the lateral collateral ligament complex must be repaired to obtain elbow stability; 5) the medial collateral ligament must be repaired if persistent instability is observed after lateral collateral ligament repair; 6) an hinged external fixator must be considered if the elbow remains unstable or the protection of the joint reconstruction is required; 7) re-evaluation of the surgical steps if congruent ulno-humeral and radio-humeral joints have not been achieved. Following the surgical treatment an adequate rehabilitation programme should be started promptly and continued for at least 6 months since a significant improvement of the range of motion occurs prevalently in this period, which should be considered the critical time period to obtain a functional elbow