An exploratory study of long-term neurocognitive outcomes following recovery from opportunistic brain infections in HIV+ adults

Central nervous system opportunistic infections (CNS-OI) are a significant cause of morbidity and mortality in AIDS. While current interventions are increasingly successful in treating CNS-OI, little information exists regarding long-term behavioral outcomes among survivors. In this exploratory study we examined neurocognitive data among three groups of adults with different AIDS-related CNS-OI: 15 with past cryptococcal meningitis (CM), 8 with toxoplasmosis encephalitis (TE), and 8 with progressive multifocal leukoencephalopathy (PML). A group of 61 individuals with AIDS, but without CNS-OI, was used as a comparison group. A battery of standardized neuropsychological tests assessing a variety of cognitive domains was administered upon entry. Results indicate that individuals with a history of CNS-OI were most impaired on measures of cognitive and psychomotor speed relative to the HIV+ comparison group. Among the CNS-OI groups, individuals with history of TE had the most severe and varied deficits. The results are discussed in relation to what is known about the neuropathological consequences of the various CNS-OIs. While this is the first systematic group study of residual CNS-OI effects on neurocognitive function, future studies employing more participants, perhaps focusing on specific CNS-OIs, will further characterize the long-term outcomes in AIDS-related CNS-OI.     

Value of measuring plasmatic levels of neurosin in the diagnosis of Alzheimer's disease

The search for molecular biomarkers for diagnosing and classifying dementias is becoming a high priority need. Neurosin (Kallikrein 6, hk6) is one molecule with promising preliminary results since its levels in brain tissue, cerebrospinal fluid and blood have been found to be abnormal in Alzheimer's disease (AD). In this study, we measured plasmatic levels of neurosin in healthy individuals and patients with cognitive symptoms independently of what the final diagnosis was. We collected plasma samples from 228 controls and 447 patients finally diagnosed with either AD, Mild Cognitive Impairment, Dementia with Lewy Bodies or Parkinson-Dementia, Frontotemporal Dementia, Huntington's disease, Primary Progressive Aphasia, Corticobasal degeneration, Creutzfeldt-Jakob's disease or Pseudodementia. We found that plasmatic levels of neurosin increase with age in healthy individuals and decrease in patients with AD. Plasmatic levels of neurosin differ significantly between AD and Vascular Dementia, Pseudodementia and the control group. Analyses comparing any other form of neurodegenerative dementia to the AD group did not show significant differences. In conclusion, measurement of plasmatic levels of neurosin is useful to distinguish AD patients from subjects without neurodegenerative dementia (either Pseudodementia, Vascular Dementia or controls) although it is not useful to distinguish among neurodegenerative dementias.     

Strapping the spinal cord: an innovative experimental model of CNS injury in rats

Experimental models of spinal cord (SC) lesion are essential for understanding a few of the primary and secondary mechanisms of injury and functional recovery of the central nervous system (CNS). We have developed an experimental model of SC injury in adult rats (n=32), that involves the use of a device (SC-STRAPPER) that straps the SC and promotes gradual and controlled SC injury similar to clinical compressive SC injuries. SC strapping is a less-invasive procedure in comparison to other SC injury models, and it performs compression with smaller infection risk and undetectable paravertebral or vertebral lesions. The survival of the rats was 100%, minimizing the suffering of the animals. We have analyzed the histopathological changes that occur during experimental SC compression, as well as the immunohistochemical labeling for glial fibrillary acidic protein (GFAP). Animals survived for 21 days being thereafter anesthetized and perfused with aldehydes. SC lesions were associated with motor deficits and local increase in GFAP immunolabeling proportionate to the severity of the compression. This experimental model represents a potential contribution for neuroscientific research, providing a low-cost and rather simple system of controllable and reproducible SC experimental damage.     

Incidence and management of anemia in renal transplantation: an observational-French study

The management of anemia after kidney transplantation remains poorly explored. The Management of Anemia in French Kidney Transplant Patients (MATRIX) study is an observational study conducted in 10 academic hospitals among kidney-transplant patients designed to evaluate the prevalence, associated factors and management of post-transplant anemia. Over two consecutive weeks, 418 recipients (males: 248; age: 50.8+/-12.7 years) were included, all were transplanted for more than six months. Mean serum creatinine (Scr) was 152+/-67 micromol/l and mean hemoglobin (Hb) was 12.4+/-1.8 g/dl (males: 12.8+/-1.9 g/dl; females 11.9+/-1.6 g/dl). Irrespective of the delay following transplantation, 23% of patients (n=95) were severely anemic (Hb < or = 11 g/dl). Eighteen percent of the patients received an antianemic treatment (10% oral iron, 7% erythropoiesis stimulating agents (ESA), 4% folic acid) and only 35% of the severely anemic patients were actually treated (n=33). A significantly-negative correlation was observed between eGFR and Hb levels (R= -0.347, p<0.02). Ninety-six percent of the 193 patients transplanted for more than six months and a Scr greater than 150 micromol/l (n=185) suffered at least one comorbidity (89% hypertension, 32% hypercholesterolemia, 13% diabetes); this group represent the second cohort. Seventy-four percent of them were treated with mycophenolate mofetil, 16% with azathioprine, and 62% with an ACEI or angiotensin II receptor antagonists. Since the transplantation, 127 patients (66%) have been anemic (Hb < or = 11 g/dl) and 58% (n=112) were treated (iron and/or ESA, respectively 81 and 55%). Among the patients not treated for anemia, 74% had an Hb level below 12g/dl. ESA-treated patients received a mean dose of 8500 UI+/-2800 per week. Anemia is under-diagnosed and under-treated in renal-transplant recipients, despite its high prevalence. As expected, a correlation between renal function and Hb levels was observed, as in CKD patients. Prospective studies are underway to assess the consequences of postkidney transplant anemia on quality of life, cardiovascular morbidity and chronic allograft nephropathy and to define the benefit of the treatment.     

Prognostic Value of Lymph Node Yield and Metastatic Lymph Node Ratio in Medullary Thyroid Carcinoma

Introduction  Lymphadenectomy and thyroidectomy is standard treatment for medullary thyroid carcinoma (MTC), but the prognostic importance of the number of lymph nodes removed (lymph node yield, LNY) and the proportion of metastatic lymph nodes resected (metastatic lymph node ratio, MLNR) is unknown. We hypothesized that MTC survival is influenced by LNY and MLNR. Methods  Patients (N = 534) who underwent thyroidectomy with lymphadenectomy for MTC between 1988 and 2004 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan–Meier method was used for univariate comparisons of survival for LNY and MLNR with a maximum follow-up of 12 years. Cox regression models adjusted for age, sex, extent of disease, tumor size, nodal status, LNY, and MLNR. Results  By univariate analysis, increasing LNY was associated with improved survival in all patients (P < 0.002) and node-positive patients (P < 0.001). In a multivariate analysis using LNY and MLNR as categorical variables, significant factors influencing survival included: age (P < 0.001), tumor size (P < 0.001), LNY (P = 0.007), and MLNR (P < 0.02); in node-negative patients: age (P = 0.002); in node-positive patients: age (P < 0.001), tumor size (P < 0.001), and LNY (P = 0.001). Using LNY and MLNR as continuous variables, significant factors influencing survival included: age (P < 0.001), tumor size (P < 0.001), and MLNR (P = 0.01); in node-negative patients: age (P < 0.001); in node-positive patients: age (P < 0.001) and tumor size (P < 0.001). Conclusion  In patients undergoing thyroidectomy and lymphadenectomy for MTC, LNY and MLNR predict poorer survival, but their impact on survival was limited to node-positive patients and was otherwise dominated by the effects of age and extent of disease. Supported by Grant Number KL2RR024144 from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Presented in part at the 3rd Annual Academic Surgical Congress, February 12–15, 2008, Huntington Beach, California.     

Endomorphin 1 and endomorphin 2 suppress in vitro antibody formation at ultra-low concentrations: anti-peptide antibodies but not opioid antagonists block the activity

Endomorphin 1 (EM-1) and endomorphin 2 (EM-2) were tested for their capacity to alter immune function. Addition of either of these peptides to murine spleen cells in vitro inhibited antibody formation to sheep red blood cells in a bi-phasic dose dependent manner. Maximal inhibition was achieved at doses in the range of 10⁻¹³ to 10⁻¹⁵ M. Neither naloxone (general opioid receptor antagonist) nor CTAP (selective mu opioid receptor antagonist) blocked the immunosuppressive effect. To show that there was specificity to the immunosuppressive activity of the peptides, affinity-purified rabbit antibodies were raised against each of the synthetic EM peptides haptenized to KLH and tested for capacity to inhibit immunosuppression. Antibody responses were monitored by a standard solid phase antibody capture ELISA, and antibodies were purified by immunochromatography using the synthetic peptides coupled to a Sepharose 6B resin. Verification of the specificity of affinity-purified antisera was performed by immunodot-blot and solid-phase RIA assays. The antisera specific for both EM-1 and EM-2 neutralized the immunosuppressive effects of their respective peptides in a dose-related manner. Control normal rabbit IgG had no blocking activity on either EM-1 or EM-2. These studies show that the endomorphins are immunomodulatory at ultra-low concentrations, but the data do not support a mechanism involving the mu-opioid receptor.