Biomedical subjects
Publications and source records attributed to J Piscitelli.
Cruzain is an essential cysteine protease of Trypanosoma cruzi and a therapeutic target for Chagas' disease. Eight dogs were infected with T. cruzi; three were treated with an inhibitor of cruzain, K777, for 14 days. Treatment with K777 abrogated myocardial damage by T. cruzi, as documented by histopathological lesion scores and serum troponin I levels.
AIMS: To evaluate the effects of vitamin E supplementation on haemoglobin concentration and the requirement for transfusion in premature infants treated with erythropoietin and iron. METHODS: Randomised, double blind, placebo controlled trial. Thirty infants </=32 weeks gestation and </=1250 g birth weight, who were defined as stable based on minimal requirements for respiratory support and phlebotomy, and absence of major congenital anomalies were enrolled. All were treated with erythropoietin and iron, and were randomised to receive, in addition, either vitamin E 50 IU/day or placebo for eight weeks or until discharge, whichever came first. RESULTS: Despite higher vitamin E (alpha-tocopherol) levels in the experimental group in weeks 3 (49.0 v 28.1 micro mol/l) and 8 (66.2 v 38.5 micro mol/l), there were no differences in haemoglobin, reticulocyte count, iron concentration, or transfusion requirement. CONCLUSIONS: Oral vitamin E supplementation at 50 IU/day does not increase the response of preterm infants to erythropoietin and iron. Vitamin E obtained through standard nutrition may have been sufficient or higher doses may be required.
Amyloidosis is a complication of long-term hemodialysis treatment. The major histological feature of hemodialysis-associated amyloidosis (HAA) is the deposition of amyloid fibrils in the affected lesions, due, in part, to elevated serum beta2-microglobulin (beta2M) levels. In vitro studies reveal that serum immunoglobulin light and heavy chains co-deposit with beta2M in tissues affected by HAA. Only one study of HAA has been performed in young dialysis patients. We therefore assessed risk factors for HAA in a group (n=30) of young (18.7+/-0.9 years) patients receiving chronic, uninterrupted hemodialysis using cellulose acetate membranes. All patients initiated dialysis before reaching 18 years of age. The pre-dialysis serum beta2M level was 49.7+/-3.9 mg/l (normal 0-2.4 mg/l). Since serum albumin was normal (4.3+/-0.1 mg/dl) and serum protein/albumin was elevated (1.7+/-0.0, normal 1.2-1.5), indicating increased circulating protein, we assayed immunoglobulins in the same patients. The serum immunoglobulin levels (expressed as a percentage of the total level of serum proteins) were elevated (21.3+/-0.9%, normal 11.1%-21.0%). The Kt/v was 1.37+/-0.03, suggesting that the high levels of serum beta2M and immunoglobulins were not due to inadequate dialysis in these patients. Patients with residual renal function (Kr) did display significantly lower serum levels of beta2M (33.2+/-2.3, P=0.03). Furthermore, improved clearance of beta2M correlated with higher values of Kr (r=0.914). In contrast, serum levels of immunoglobulin (22.6+/-3.7, P=0.5) were unaffected by Kr. In addition, there was no correlation between older age at onset of dialysis and serum levels of either beta2M (r=0.107) or immunoglobulins (r=0.321). Finally, the length of time on dialysis had no effect on serum levels of either beta2M (r=0.105) or immunoglobulins (r=0.092). Taken together, these results indicate that young hemodialysis patients may be at risk for HAA.
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Polyclonal antisera to human recombinant interleukin-1 beta have been developed in rabbits and mice. When measured by indirect enzyme-linked immunoassays, the antisera bound rIL-1 beta in a dose-dependent manner but did not bind to rIL-1 alpha or murine rIL-1. Both antisera specifically neutralized thymocyte activation induced by rIL-1 beta or normal monocyte IL-1 and growth inhibition induced by rIL-1 beta. The antiserum specificities led us to examine a double antibody ELISA for quantitating IL-1 beta. The linear portion of the standard curve from an ELISA against rIL-1 beta ranged from 0.5 to 10.0 half-maximal units of [3H]thymidine incorporation in mouse thymocyte cultures. A similar correlation was observed using monocyte derived IL-1 from two sources. The major result of this work was the observation that polyclonal antibodies made against a recombinant molecule also recognized natural IL-1. We suggest that these antisera recognize epitopes unique to IL-1 beta which reside at or near regions of the molecule responsible for biological activity.
A review of 185 obstetrical patients, having a family history of diabetes mellitus without medical history of glucose intolerance in the non-pregnant state was conducted. A 3-hour 100-g oral glucose tolerance test was performed on all patients between 20 and 34 weeks of gestation. According to O'Sullivan's criteria for glucose tolerance testing, normal glucose tolerance occurred in 89.7%, while Class A diabetes was identified in 10.3% of patients tested. 3.8% of the study population fulfilled the O'Sullivan criteria for abnormal glucose intolerance and required insulin treatment during pregnancy. The Division of Perinatal Medicine at Duke University has traditionally defined the abnormal glucose tolerance test at glucose values lower than O'Sullivan's internationally accepted criteria. An intermediate group, having abnormal glucose values according to the Duke criteria, was classified as "Carbohydrate Intolerance", comprised 32.4% of the patients tested and were managed identically to O'Sullivan Class A Diabetes. Analysis or perinatal outcome, including macrosomia, birth trauma and neonatal morbidity, revealed that Carbohydrate Intolerance patients fulfilling O'Sullivan criteria, being similar to patients with 'normal' GTT test results. Patients having a family history of diabetes mellitus, appeared as a group to be at increased risk for macrosomia, fetal distress and cesarean delivery, compared with the general population.
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Serum levels of parathyroid hormone (PTH), alkaline phosphatase (AP), and calcium (Ca2+) have been used to evaluate renal osteodystrophy (RO) in adult patients undergoing dialysis. Osteocalcin (BGP) is a bone protein which also serves as a marker for bone turnover. Serum BGP levels correlate positively with rates of bone turnover and serum concentrations of PTH, AP, and Ca2+ in various studies of adult end-stage renal disease (ESRD) patients, whereas other studies reveal BGP to be a poor indicator of bone turnover in ESRD. RO is a significant problem in pediatric ESRD patients; however, there have been few studies evaluating the correlation of markers for RO in children with ESRD. We measured serum PTH, AP, Ca2+, and BGP levels in a group (n=23) of pediatric patients with ESRD and assessed the correlation among the markers. There was a positive correlation between serum PTH and AP (r=0.658, p<0.001). In contrast, there was no correlation between either serum Ca2+ or BGP, and either PTH or AP. The correlation between Ca2+, BGP and either PTH or AP was unaffected by growth in our patient population. Finally, neither age nor pubertal stage improved the correlation between either Ca2+ or BGP, and either PTH or AP. We conclude that serum PTH and AP are useful markers for RO, whereas calcium and BGP levels should not be used to evaluate RO in pediatric ESRD patients.