Low-dose Thymoglobulin vs Basiliximab Induction Therapy in Low-Risk Living Related Kidney Transplant Recipients: A Prospective Randomized Trial

ContextThymoglobulin is used effectively as induction agent in kidney transplantation but the optimal dose is not well established.ObjectiveDemonstrate that low-dose thymoglobulin (3 mg/kg) has similar efficacy and safety compared to basiliximab induction in low-risk kidney transplantation under standard maintenance immunosuppressionDesign, Setting, ParticipantsProspective randomized study in kidney transplant patients (12/2016-05/2018). Inclusion criteria: Recipients > 18 years, first living donor transplant. Exclusion criteria: Second and multiorgan transplant, ABO incompatibility, positive cross-match, panel reactive antibodies (PRA) > 30%, positive donor-specific antibody, human immunodeficiency virus, hepatitis B surface antigen, hepatitis C virus positive, white blood cells < 2000 cells/mm³, platelets < 75,000 cells/mm³ and malignancy.InterventionGroup A: basiliximab (20 mg D0 and D4). Group B: thymoglobulin (3 mg/kg total). Maintenance immunosuppression: tacrolimus, mycophenolate mofetil, and steroids.Main Outcome MeasuresBiopsy-proven acute rejection (BPAR), delayed graft function, slow graft function, leukopenia, infections, adverse events, graft loss, estimated glomerular filtration rate, and death within 12 months.Results100 patients (basiliximab, n = 53) (thymoglobulin, n = 47) were included. Donor and recipient characteristics were similar except for longer dialysis (basiliximab), PRA class I (1.2% basiliximab, 4.5% thymoglobulin), HLA match (basiliximab 2.8, thymoglobulin 2.2), and cytomegalovirus status. BPAR rate was basiliximab 3.8% and thymoglobulin 6.4% (P = ns). Delayed graft function (basiliximab 3.8%; thymoglobulin 4.3%), slow graft function, and 12-month leukopenia (basiliximab 11.3%, thymoglobulin 21.3%) were similar between groups (P = ns). There was no difference in infections and adverse events between groups. Patient and graft survival were as follows: basiliximab 98.1% and 92.5%, thymoglobulin 100% and 93.6% (P = ns).ConclusionLow-dose thymoglobulin induction (3 mg/kg) can be used effectively and safely in low-risk kidney transplantation with good results during the first year post-transplant.     

Characterization of the epitope recognized by a mAb that reacts differentially with murine suppressor T cells

Although reliable antibodies are available that distinguishhuman suppressor T (T_s) cells from CTL and other T cells, feware available for murine T_s cells. We have developed a mAb (984D4.6.5)that, in the presence of complement, depletes alloantigen-specificT_s cells but not CTL. This antibody recognizes activated TT_scells but not their precursors. In these studies, flow cytometricanalysis demonstrates that 984D4.6.5 reacts with several T_scell hybridomas, cloned T_h cell lines and WEHI-3 (a myelomonocytictumor cell line). Reactivity was not detected with BW5147, T_hcell hybridomas, cloned T_h cells, CTL lines and hybridomas,B cell lines, thymocytes, splenocytes, bone marrow cells nora variety of tumor cells. Among 984D4.6.5 positive lines, expressionis heterogeneous and the number of cells expressing high levelsof the epitope is increased when the hybridomas are maintainedat a relatively high cell density. Neuriminidase and pronasedeplete the epitope recognized by mAb 984D4.6.5. Protein synthesisand glycosylation inhibitors also reduce expression of thisepitope. These observations suggest that the epitope recognizedby 984D4.6.5 is a carbohydrate linked to a polypeptide. Thisantibody was tested by ELISA for binding to a large panel ofcarbohydrates and glycollpids coupled to BSA. The only one thatbound 984D4.6.5 was LS tetrasaccharide c (NeuNAc2-6Galpß1-4GIcNAcß1-3GaIß1-4Glc),an O-linked carbohydrate. Comparative analysis shows that boththe sequence and the linkage of these sugars are essential tothe reactivity with the 984D4.6.5 antibody. This epitope isexpressed by a glycoprotein of-200 kDa, as shown by Westernblots. The identity of this glycoprotein remains to be determined,but indirect evidence suggests that it is not CD45.     

A comparative proteome analysis of hippocampal tissue from schizophrenic and Alzheimer's disease individuals

The proteins expressed by a genome have been termed the proteome. Comparative proteome analysis of brain tissue offers a novel means to identify biologically significant gene products that underlie psychopathology. In this study we collected post mortem hippocampal tissue from the brains of seven schizophrenic, seven Alzheimer's disease (AD) and seven control individuals. Hippocampal proteomes were visualised by two-dimensional gel electrophoresis of homogenised tissue. A mean of 549 (s.d. 35) proteins were successfully matched between each disease group and the control group. In comparison with the control hippocampal proteome, eight proteins in the schizophrenic hippocampal proteome were found to be decreased and eight increased in concentration, whereas, in the AD hippocampal proteome, 35 proteins were decreased and 73 were increased in concentration (P<0.05). One protein, which was decreased in concentration in both diseases, was characterised as diazepam binding inhibitor (DBI) by N-terminal sequence analysis. DBI can regulate the action of the GABA(A) receptor. Protein changes involved 6% of the assessed AD hippocampal proteome, whereas, in schizophrenia protein changes involved less than 1% of the assessed hippocampal proteome. We conclude that schizophrenia has a subtle neuropathological presentation and comparative proteome analysis is a viable means by which to investigate diseases of the brain at the molecular level.     

A to Z: Vitamin A and zinc,the miracle duo

Dietary micronutrients such as vitamins and trace minerals are known modulators of host immune responses against common pathogens. In this respect, vitamin A and zinc have recently received increased attention. Severalin vivo andin vitro studies suggest that vitamin A may be a critical player in the mucosal immune responses in the respiratory and gastrointestinal tracts, particularly in undernourished children. The effect may be mediated primarily by stabilization of the membrane of mucosal epithelial cells, as well as enhanced leukocyte functions. The beneficial effect of vitamin A therapy in reducing measles-associated morbidity and mortality suggests its crucial role in defenses against viral pathogens. Zinc is also known affect leukocyte functions such as phagocytosis and T-lymphocyte-mediated immune responses. However, unlike vitamin A, zinc has been investigated primarily for its effects on bacterial infections. Dietary supplementation or therapeutic treatment with vitamin A and zinc may be a cheap yet effective means of preventing or treating infections in highly susceptible populations. Additional studies, however, are required to better define the types of pathogens and the specific human populations that may benefit from such therapy.     

Motion discrimination of single targets: comparison of preliminary findings in normal subjects and patients with glaucoma

Background: Luminance, global motion and flicker sensitivities are affected in patients with primary open-angle glaucoma. Although no theoretical model has been put forward to explain the observed reduction in sensitivity in this patient group, these findings have often been attributed to diffuse and selective loss of large optic nerve fibres. Methods: Movement processing was investigated using an optical projection system that generates smooth, continuous motion with control of speed, displacement and motion direction. Motion-displacement and direction-discrimination thresholds were measured in eight normal subjects and in three patients with diagnosed glaucoma. At each speed tested, targets were presented for a range of displacements and thresholds were extracted after probit analysis. The measurements were carried out both foveally and at 19° in the periphery and provided the data necessary to develop and optimise a model of motion perception based on multiple time delays for the correlation of signals that map progressively more distant parts of the visual field. Results: Our preliminary findings show that direction discrimination can be at chance level even for large displacements when motion is detected 80% of the time. Model simulations show that specific changes in the spatial sampling interval and the speed of transmission of the motion signals involved can cause the observed reduction in motion sensitivity and direction discrimination in patients with glaucoma. Conclusions: A model for motion detection and direction discrimination of single targets has been proposed to account for the measured functional relationship between motion displacement thresholds and target speed in normal subjects. Tested patients with glaucoma show reduced motion sensitivity and poor discrimination of motion direction. The type of degraded performance observed experimentally in glaucoma patients is also predicted by the model. Such predictions require specific changes in model parameters that may be indicative of changes in the retina caused by the disease.     

Cost Consequences of Surveillance, Medical Management or Surgery for Benign Prostatic Hyperplasia

Purpose

The cost consequences of alternative treatment modalities for benign prostatic hyperplasia (BPH) were investigated. The present lifetime costs of watchful waiting, medical management and surgery alone and in various combinations were estimated for a synthetic cohort of men comprised of 5 age groupings.

Materials and Methods

Synthetic cohort models were constructed to follow men at different ages “analytically” for specific intervals and to calculate the cumulative health care costs associated with alternative BPH treatment regimens during those periods. These models accounted explicitly for survival probabilities, the use of different types of health care services and products, price changes for those services and products, failure rates of some therapies and a discount factor needed to compute the present value of the cost streams. The models were implemented with hospital discharge and other data on BPH incident cases in the state of Florida in approximately 1989.

Results

The addition of medical management to the mix of therapies is likely to increase overall health care spending on BPH treatment, perhaps by a considerable amount. The cost-effectiveness of each type of BPH therapy differs by the age of the patient at which it is first initiated. All other parameters being equal, surgery appears to be more cost-effective at younger patient ages, while medical management has a cost advantage at older ages.

Conclusions

The cost implications of alternative BPH therapies are substantial, and warrant more detailed consideration by clinicians and health policy specialists.