y Both authors contributed equally.Belatacept is a novel immunosuppressive agent that may be used as an alternative to calcineurin inhibitors (CNI) in immunosuppression (IS) regimens. We report two cases of pancreas transplant that were switched from tacrolimus (TAC) to belatacept. Case 1: 38-yearold female with pancreas transplant alone maintained on TAC-based IS regimen whose serum creatinine (SCr) slowly deteriorated from 0.6 mg/dL at baseline to 2.2 mg/dL, 16 months posttransplant. A native kidney biopsy performed showed CNI toxicity. The patient was started on belatacept and TAC was eliminated. Case 2: 49-year-old female with simultaneous pancreas-kidney transplant, maintained on TAC-based regimen where the SCr worsened over an initial 3-month period from a baseline of 1.0 to 3.0 mg/dL. Belatacept was started and TAC was lowered. Due to persistent graft dysfunction and kidney transplant biopsy still showing changes consistent with CNI toxicity, the TAC was then discontinued. At >1 year postbelatacept and off TAC follow-up, kidney function as measured by SCr remains stable at 1.0 AE 0.2 mg/dL in both recipients. Neither patient developed rejection following the switch, and pancreas allograft function remains stable in both recipients.
There is anecdotal evidence that bone strains may increase to the point that bone becomes susceptible to rapid failure when muscles become fatigued. To determine whether neuromuscular response could be a factor in accelerating bone failure, we tested the hypothesis that muscle fatigue causes a significant increase in peak principal and shear strains in bone. Ten adult foxhounds were subjected to rigorous exercise that caused muscular fatigue while myoelectrical activity of the quadriceps and hamstrings and strain on the distal tibia were monitored simultaneously. Ground reaction forces on the dog hindlimbs were measured before and after strain gauges had been applied to the tibia. The data show a significant shift to lower median myoelectrical frequencies in the quadriceps, indicating muscular fatigue, following the 20 min exercise period. In conjunction with this shift, peak principal and shear strains increased on both compressive and tensile cortices of the tibia and shear strain on the tensile cortex increased significantly (P = 0.02). The largest changes were along the anterior and anterolateral surfaces of the tibia, where peak principal strain increased by an average of 26-35% following muscular fatigue. The cross-sectional strain distribution was calculated at the gauge site at peak strain at the beginning of the exercise period and at peak strain after 20 min of exercise. These data show a change in strain distribution when muscle becomes fatigued. Strains on the posterior cortex of the bone showed the greatest change. Correlation analysis demonstrated a significant inverse association between median myoelectrical frequency and bone strain after 20 min of exercise (Spearman r2 = 1.00; P = 0.05). These data show that muscle fatigue may be associated with increased bone strain.
We examined the molecular basis of adenine phosphoribosyltransferase (APRT) deficiency in homozygous-deficient, identical twin brothers who were born to non-consanguineous German parents. DNA was isolated from blood, and the APRT gene was amplified by PCR, subcloned into M13, and sequenced completely. A single T insertion between bases 1831-1832 or 1832-1833 was identified. This alters the consensus sequence at the exon 4 - intron 4 spice donor site and leads to aberrant splicing. The same mutation has been described previously in two affected brothers from Belgium, and the Indianapolis group has also identified it in two other, unrelated Caucasian patients. Thus, this mutation may be a common cause of APRT deficiency in the Caucasian population.
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