Parenteral treatment of an experimental respiratory syncytial virus (RSV) infection in a cotton rat model with a monoclonal antibody directed against the viral F protein resulted in the clearance of infectious virus within 24 h but had no effect on the pulmonary pathology at 24 h and only a small effect on the pulmonary pathology at 72 h. Treatment with parenteral triamcinolone acetonide dramatically reduced the pathologic lesions of viral bronchiolitis and pneumonia but resulted in the delayed clearance of the virus. The combination of the monoclonal antibody given in a single dose 72 h after infection, combined with 3 daily doses of the corticosteroid starting 72 h after infection, demonstrated both the loss of infectivity and the disappearance of lesions. No rebound of lesions or infectivity was noted. Combined antiviral and anti-inflammatory therapy for RSV disease appears promising.Respiratory syncytial virus (RSV), the leading cause of infectious pulmonary disease in infants and children worldwide (reviewed in [1]), is increasingly recognized as a cause of serious disease in adults, particularly the elderly [2] and in immunocompromised persons [3]. Vaccine development programs spanning 4 decades have yet to result in a safe and effective RSV vaccine [4]. A major breakthrough in RSV prophylaxis has been the development and licensure both of polyclonal and monoclonal immunoglobulin products for use in high-risk infants (RespiGam [RSVIg] and Synagis [palivizumab]; MedImmune, Gaithersburg, MD). Although highly effective and apparently cost-effective in the targeted population, these products have not been widely used in persons at normal risk owing to the cost. Since most hospital admissions for RSV are among normal-risk patients, there is a pressing need for an effective RSV therapeutic [5].More than a decade has elapsed since the licensure by the US Food and Drug Administration (FDA) of ribavirin (Virazole; ICN Pharmaceuticals, Costa Mesa, CA) as an RSV therapeutic. Initial enthusiasm for this drug, however, has gradually been replaced by increasing resistance to its use, as concerns over efficacy, cost, and ease of use have grown [6].The use of RSV immunoglobulin in a therapeutic setting was first suggested in studies in cotton rats. Immunoglobulin given to RSV-infected animals reduced pulmonary virus titers 100-fold within 6 h [7], a level of reduction far greater than that seen with ribavirin in the same animal model [8]. This observation led to a series of therapeutic clinical trials of RSV immunoglobulin formulations, including generic human IgG given parenterally [9] or via aerosol [10,11], RSVIg given parenterally [12,13], and palivizumab given parenterally [14]. Although these studies showed immunoglobulin therapy to be safe, thus overturning a long-standing dogma [15], and monitored virus titers showed a reduction in immunoglobulintreated patients, none resulted in a clinically beneficial outcome.Although the goal of the clinician in treating an infectious disease has long been the elimination of th...

Hypopituitarism is common after moderate and severe traumatic brain injury (TBI). Herein, we address the association between mild TBI (mTBI) and pituitary and metabolic function in retired football players. Retirees 30-65 years of age, with one or more years of National Football League (NFL) play and poor quality of life (QoL) based on Short Form 36 (SF-36) Mental Component Score (MCS) were prospectively enrolled. Pituitary hormonal and metabolic syndrome (MetS) testing was performed. Using a glucagon stimulation test, growth hormone deficiency (GHD) was defined with a standard cut point of 3 ng/mL and with a more stringent body mass index (BMI)-adjusted cut point. Subjects with and without hormonal deficiency (HD) were compared in terms of QoL, International Index of Erectile Function (IIEF) scores, metabolic parameters, and football career data. Of 74 subjects, 6 were excluded because of significant non-football-related TBIs. Of the remaining 68 subjects (mean age, 47.3 -10.2 years; median NFL years, 5; median NFL concussions, 3; mean BMI, 33.8 -6.0), 28 (41.2%) were GHD using a peak GH cutoff of < 3 ng/mL. However, with a BMI-adjusted definition of GHD, 13 of 68 (19.1%) were GHD. Using this BMI-adjusted definition, overall HD was found in 16 (23.5%) subjects: 10 (14.7%) with isolated GHD; 3 (4.4%) with isolated hypogonadism; and 3 (4.4%) with both GHD and hypogonadism. Subjects with HD had lower mean scores on the IIEF survey ( p = 0.016) and trended toward lower scores on the SF-36 MCS ( p = 0.113). MetS was present in 50% of subjects, including 5 of 6 (83%) with hypogonadism, and 29 of 62 (46.8%) without hypogonadism ( p = 0.087). Age, BMI, median years in NFL, games played, number of concussions, and acknowledged use of performance-enhancing steroids were similar between HD and non-HD groups. In summary, in this cohort of retired NFL players with poor QoL, 23.5% had HD, including 19% with GHD (using a BMI-adjusted definition), 9% with hypogonadism, and 50% had MetS. Although the cause of HD is unclear, these results suggest that GHD and hypogonadism may contribute to poor QoL, erectile dysfunction, and MetS in this population. Further study of pituitary function is warranted in athletes sustaining repetitive mTBI.

Summary:Respiratory syncytial virus (RSV) is widely recognized as a leading cause of pneumonia, with substantial mortality, in bone marrow transplant recipients. We tested the efficacy of a systemic monoclonal antibody (MAB) preparation possessing a high titer of anti-RSV neutralizing antibody, palivizumab (Synagis) for prophylaxis and therapy of RSV infection in cytoxan (CY) immunosuppressed cotton rats, a model in which the efficacy of a polyclonal anti-RSV product (Respigam) has been demonstrated. Both prophylaxis and therapy with this MAB were highly effective in reducing pulmonary viral replication. However, multiple sequential therapeutic doses of MAB were necessary to control rebound viral replication in continually suppressed animals. Bone Marrow Transplantation (2002) 29, 117-120. DOI: 10.1038/sj/bmt/1703326 Keywords: RSV; BMT; immunotherapy; palivizumab; Synagis; cotton rat Respiratory syncytial virus (RSV) is widely recognized as one of the major causes of pneumonia in immunocompromised cancer patients. 1 The most striking impact of this pathogen to be identified over the last decade has been its propensity to lead to severe pneumonia during the early period post stem cell transplantation, with a high morbidity and mortality. 1-3 A recent case review reported three deaths among seven patients who developed RSV infections in the post-engraftment period, suggesting a continued significant impact of this pathogen. 4 Those authors also reported an association between RSV infection and both primary and secondary graft failure in four patients. The opinions or assertions contained herein are those of the author(s) and are not to be construed as official or reflecting the views of the Department of Defense, the United States Air Force, or the Uniformed Services University.The cotton rat model has been a useful tool in the study of RSV pathogenesis and therapy for over 30 years. 5 We recently reported a modification of the use of that model where, by prolonged high-dose cytoxan immunosuppression, we replicated the persistent RSV pneumonia seen in stem cell transplant recipients. 6 In that paper, we demonstrated the ability of a human commercial polyclonal high anti-RSV activity IgG preparation (RSVIG or Respigam) to control RSV replication when given either prophylactically or therapeutically. We return to that model to test the use of the next generation of the product, the humanized anti-RSV monoclonal antibody (MAB) palivizumab (Synagis). Materials and methods AnimalsWeanling inbred cotton rats (Sigmodon hispidus) were obtained from Virion Systems Incorporated. Animals were housed in large polycarbonate cages in small groups, and were provided water and rat chow ad libitum. ImmunosuppressionAnimals were treated with intraperitoneal (i.p.) injections of cyclophosphamide (CY) at a dose of 50 mg/kg three times weekly for at least 21 days prior to viral challenge. Immunosuppressive therapy was continued until the end of each experiment. Prior and current use of this regimen has consistently led to the develo...

After undergoing simultaneous bilateral TKA, patients demonstrate functional gains when admitted to inpatient rehabilitation facilities based on FIM gains and FIM efficiency scores; 8.5% of patients in this cohort required transfer to an acute care facility as a result of complications during inpatient rehabilitation, and 93.6% of patients were discharged home.