Parainfluenza Virus Infection in Adult Lung Transplant Recipients: An Emergent Clinical Syndrome with Implications on Allograft Function

Parainfluenza virus is a common cause of seasonal upper respiratory tract infections in children and adults. Studies indicate that parainfluenza virus may play an important role in the etiology of respiratory tract infections in lung transplant recipients with an estimated incidence of 5.3 per 100 patients. Parainfluenza virus type 3 is the most frequent serotype in lung transplant patients. The rate of lower respiratory tract infections with parainfluenza virus among lung transplant recipients is between 10 and 66% of cases. In addition, trans-bronchial biopsy at the time of parainfluenza infection shows signs of acute allograft rejection. Subsequently, 32% of patients have been found to have active bronchiolitis obliterans at a median time of 6 months (range 1-14) postviral infection. These findings indicate that parainfluenza virus infections may have long-term implications for lung transplant recipients. Further studies are required to identify the mechanisms of immunomodulation of parainfluenza virus among these patients. In addition, controlled studies are needed to evaluate the efficacy of aerosolized ribavarin in the treatment of parainfluenza virus infection and to determine whether vaccines may be effective in these high-risk patients.     

Can the gracilis replace the anterior cruciate ligament in the knee? A biomechanical study

Purpose

The purpose of this study was to determine whether a four-strand gracilis-only construct possesses the biomechanical properties needed to act as an anterior cruciate ligament (ACL) reconstruction graft.

Methods

This was a pilot study with 32 cadaver specimens. The biomechanical properties of three types of grafts were determined using validated tensile testing methods: patellar tendon (BTB), both hamstring tendons together (GST4) and gracilis alone (G4).

Results

The maximum load at failure of the G4 was 416.4 N (±187.7). The GST4 and BTB had a maximum load at failure of 473.5 N (±176.9) and 413.3 N (±120.4), respectively. The three groups had similar mean maximum load and stiffness values. The patellar tendon had significantly less elongation at failure than the other two graft types.

Conclusions

The biomechanical properties of a four-strand gracilis construct are comparable to the ones of standard grafts. This type of graft would be useful in the reconstruction of the anteromedial bundle in patients with partial ACL ruptures.

     

SV40 in human brain cancers and non-Hodgkin's lymphoma

Simian virus 40 (SV40) is a potent DNA tumor virus that is known to induce primary brain cancers and lymphomas in laboratory animals. SV40 oncogenesis is mediated by the viral large tumor antigen (T-ag), which inactivates the tumor-suppressor proteins p53 and pRb family members. During the last decade, independent studies using different molecular biology techniques have shown the presence of SV40 DNA, T-ag, or other viral markers in primary human brain cancers, and a systematic assessment of the data indicates that the virus is significantly associated with this group of human tumors. In addition, recent large independent studies showed that SV40 T-ag DNA is significantly associated with human non-Hodgkin's lymphoma (NHL). Although the prevalence of SV40 infections in humans is not known, numerous observations suggest that SV40 is a pathogen in the human population today. This review examines the molecular biology, pathology, and clinical data implicating SV40 in the pathogenesis of primary human brain cancers and NHL and discusses future research directions needed to define a possible etiologic role for SV40 in these malignancies.     

Outcome of aplastic anemia in adolescence: a survey of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation

We analyzed the outcome of 537 adolescents (age 12–18 years) with idiopathic aplastic anemia included in the database of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation comparing: i) matched family donor hematopoietic stem cell transplantation performed as first-line treatment with ii) front-line immunosuppressive therapy not followed by subsequent transplant given for failure and with iii) hematopoietic stem cell transplantation performed after failed front-line immunosuppressive therapy. Overall survival was 86% in the matched family donor hematopoietic stem cell transplantation group, 90% in patients given front-line immunosuppressive alone (those who did not fail this treatment and who did not receive subsequent rescue with hematopoietic stem cell transplantation) and 78% in subjects who underwent hematopoietic stem cell transplantation post failed front-line immunosuppressive therapy (P=0.14). Event-free survival in the same groups was respectively 83%, 64% and 71% (P=0.04). Cumulative incidence of rejection was 8% in matched family donor hematopoietic stem cell transplantation and 9% in transplants post failed front-line immunosuppression (P=0.62). Cumulative incidence of acute graft-versus-host disease was 12% in matched family donor transplants and 18% in transplants post failed immunosuppression (P=0.18). Chronic graft-versus-host disease was higher in matched family donor hematopoietic stem cell transplantation (8%) than in transplants post failed immunosuppressive therapy (20%) (P=0.0009). Cumulative incidence of post-therapy malignancies was 0.7% in matched family donor transplantations, 7% in transplantations post failed immunosuppression and 21% after front-line immunosuppression (P=0.0017). In the whole cohort, under multivariate analysis, the diagnosis to treatment interval of two months or under positively affected overall survival whereas up-front immunosuppression alone (with no subsequent rescue transplants) negatively affected event-free survival. In transplanted patients an interval from diagnosis to treatment of 2 months or under, bone marrow as source of cells and first-line matched family donor transplants provided a significant advantage in overall and event-free survival. Aplastic anemia in adolescents has a very good outcome. If a matched family donor is available, hematopoietic stem cell transplantation using bone marrow cells is the first choice treatment. If such a donor is not available, immunosuppressive treatment may still be an acceptable second choice, also because, in case of failure, hematopoietic stem cell transplantation is a very good rescue option.     

Traumatic brain injury: differences among pedestrians and motor vehicle occupants]

OBJECTIVE: The purpose of this study was to discover the differences among victims who had traumatic brain injury due to traffic accidents. METHODS: Medical record of the head injury patients were analyzed according to their classification as traffic accident victims (pedestrian, motorcyclist or passenger and other motor vehicle deriver or passenger), age, gender, admission type (admitted from scene of the injury or from another hospital), duration of hospitalization, type of head injury, types of lesions present in other body segments and mortality. Patient's injury severity was measured by Injury Severity Score and head injury severity was analyzed using the ranking on the Glasgow Coma Scale, recorded by neurosurgeons during their first neuro assessment. All head injured patients admitted to a trauma center in S. Paulo city over a four-month period from March through June 1993, were included in the study. The sample was of 156 victims, with subsets of 80 pedestrians, 26 occupants of motorcycles and 50 occupants of other motor vehicles. RESULTS AND CONCLUSION: The results of this study showed that the mortality rate was higher in the pedestrian subset (25.0%) than among other victims and higher for motorcycle occupants (19.2%) than for motor vehicle victims (8.0%). Statistical differences between the subsets were established when the head injury severity variable was analyzed using the Glasgow Coma Scale. On the other hand, the differences between the three subsets was not statistically significant when the measurement used was the Injury Severity Score. Analyses of other variables showed important differences among subset distributions.     

Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: A double‐blind,randomized, placebo‐controlled study

Depression is one of the most common psychiatric disturbances in Parkinson's disease (PD). Recent reviews have highlighted the lack of controlled trials and the ensuing difficulty in formulating recommendations for antidepressant use in PD. We sought to establish whether antidepressants provide real benefits and whether tricyclic and selective serotonin reuptake inhibitor (SSRI) antidepressants differ in their short‐term efficacy, because the time to onset of therapeutic benefit remains an important criterion in depression. The short‐term efficacy (after 14 and 30 days) of two antidepressants (desipramine, a predominantly noradrenergic reuptake inhibitor tricyclic and citalopram, a SSRI) was assessed in a double‐blind, randomized, placebo‐ controlled study of 48 nondemented PD patients suffering from major depression. After 14 days, desipramine prompted an improvement in the Montgomery Asberg Depression Rating Scale (MADRS) score, compared with citalopram and placebo. Both antidepressants produced significant improvements in the MADRS score after 30 days. Mild adverse events were twice as frequent in the desipramine group as in the other groups. A predominantly noradrenergic tricyclic antidepressant induced a more intense short‐term effect on parkinsonian depression than did an SSRI. However, desipramine's lower tolerability may outweigh its slight short‐term clinical advantage. © 2008 Movement Disorder Society     

Only Multiple Autoantibodies to Islet Cells (ICA), Insulin, GAD65, IA-2 and IA-2β Predict Immune-Mediated (Type 1) Diabetes in Relatives

We report here our prospective study of 15,224 non-diabetic, first-degree relatives of probands with immune-mediated (type 1) diabetes (IMD), of which 135 were found to eventually develop diabetes. We determined islet cell, insulin, GAD65, insulinoma-associated antigen-2 and 2βautoantibodies (ICA, IAA, GAD65A, IA-2A and IA-2βA), on the first available serum samples. The latter three autoantibodies were however assayed on subsets of the relatives with and without ICA, IAA and/or GAD65A, plus most of the relatives who developed diabetes. Of the relatives who progressed to diabetes, 94% had at least one of these autoantibodies on the first screening, while ICA proved to be the most sensitive single marker (sensitivity 74%). Risk of diabetes was however negligible when ICA was found in the absence of the others (5-year RISK=5.3%), but increased dramatically whenever two or more autoantibodies were present (5-year RISK=28.2% and 66.2%, respectively). The most predictive combination of markers was ICA plus IA-2A and/or IA-2β A. Loss of first phase insulin release to IVGTT also occurred only in those ICA-positive relatives who had one or more of the other autoantibodies. The data suggests that significant β-cell damage is seen only when the underlying autoimmunity has spread to multiple antigenic islet cell determinants. Combinations of the autoantibodies occurred most often in relatives with the highest risk HLA-DR/DQ phenotypes. These data document that only relatives positive for at least two or more of these five autoantibodies are at significant risk of diabetes themselves. Intervention trials for the prevention of type 1 diabetes could be designed based on testing for these autoantibodies alone, without the need for HLA typing and IVGTT testing.     

Métodos para cuantificar la testosterona sérica en pacientes con cáncer de próstata sometidos a castración: una revisión sistemática

Background

The clinical practice guidelines recommend measuring serum testosterone in patients with prostate cancer (PC) who undergo castration. The serum testosterone concentration should be <50 ng/dL, a level established by using a radioimmunoassay method. The use of chemiluminescent immunoassays (IA) has become widespread, although their metrological characteristics do not seem appropriate for quantifying low testosterone concentrations. The objective of this review is to analyse the methods for quantifying testosterone and to establish whether there is scientific evidence that justifies measuring it in patients with PC who undergo castration, through liquid chromatography attached to a mass spectrometry in tandem (LC-MSMS).

Six-year follow-up of a preformed spacer for the management of chronically infected total hip arthroplasty

Antibiotic-loaded cement spacers are currently used in two-stage revision of septic total hip arthroplasty as temporary devices. Prolonged spacer implantation in infected shoulder has been described occasionally in poor candidates for reconstruction surgery (medically compromised and/or low-physical demand patients, deficient bone stock). Few papers previously reported the use of spacers in infected hip prosthesis as a permanent solution, but limited information is available on the medium-term behaviour. We detail medium-term clinical and radiographic follow-up of a preformed spacer in the management of a chronically infected hip arthroplasty in a 50-year-old female patient who did not undergo a second-stage surgery. Normalization of inflammatory markers was detected 3 weeks after surgery and persisted over time. Six years after surgery, the patient recovered a good range of motion and was able to walk pain free with assisted weightbearing. Remarkable radiological changes of the bone stock around the spacer stem have been assessed. New bone formation developed rapidly in the femur, leading to the consolidation of transfemoral osteotomy 6 months postoperatively. Two years after implantation, spontaneous and asymptomatic fatigue fracture in the mid-part of the stem occurred. Radiographs at 6 years showed a sufficient preservation of bone stock, though a slowly progressive resorption of the cortical femur around the stem was evident in the last year. In conclusion, prolonged spacer implantation seems to be not appropriate in septic hip arthroplasty as a permanent solution. In patients not undergoing a second-stage surgery, a careful and periodic monitoring is required to rule out possible and severe complications.