Effect of extended preservation and reduced-size grafting on organ availability in pediatric liver transplantation.
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Adenosine↗
Biomedical subjects
L Williams
Publications and source records attributed to L Williams.
4-demethoxydaunorubicin (idarubicin) in combination with 1-beta-D-arabinofuranosylcytosine in the treatment of relapsed or refractory acute leukemia.
We conducted a Phase I-II trial of 4-demethoxydaunorubicin (idarubicin, IDR) in combination with 1-beta-D-arabinofuranosylcytosine (ara-C) in 51 patients with relapsed or refractory acute nonlymphocytic leukemia, acute lymphocytic leukemia, or chronic myelogenous leukemia in blast crisis. Only 1 of 12 patients treated at the first dose level (idarubicin, 10 mg/m2/day for 3 days and ara-C, 25 mg/m2 i.v. bolus followed by 200 mg/m2 continuous infusion daily for 5 days) achieved aplasia and complete remission. The dose of idarubicin was subsequently increased to 10 mg/m2/day for 4 days with the ara-C dose held constant. Complete remission incidence for this dose schedule was: 7 of 31 patients with acute nonlymphocytic leukemia, 0 of 5 patients with acute lymphocytic leukemia, 0 of 1 patient with chronic myelogenous leukemia in blast crisis, and 1 of 2 patients with biphenotypic leukemia. Nonhematological toxicity included nausea, vomiting, mucositis, and abnormal liver function tests. Detailed pharmacological studies were performed to determine whether ara-C altered IDR metabolism or that of its main metabolite, 13-hydroxyidarubicinol or IDR clearance. A high degree of variability among patients was apparent and no consistent effect could be demonstrated. In summary, 9 of 37 patients (24%) with relapsed or refractory ANLL, including 1 patient with biphenotypic leukemia, achieved remission. We conclude that idarubicin in combination with ara-C is an active combination in patients with relapsed or refractory leukemia.
Adolescent↗
Intraoral application of microcolpohysteroscopy. A new technique for clinical examination of oral tissues at high magnification.
Colposcopy is an established technique for diagnosis in gynecology. A recently developed optical instrument is the contact microcolpohysteroscope for macroscopic examination of the cervical mucosa. This article evaluates the application of the contact microcolpohysteroscope for examination and recording of the surface topography of the hard and soft tissues of the oral cavity. This is a promising, noninvasive method of observation of tissue surfaces at high magnification. Modifications of the method for oral use are described, and potential applications for diagnosis and research in dentistry are proposed.
Colposcopes↗
Renal vasodilators. The role of the 4-substituent in isoquinolin-3-ol cardiovascular agents: 4-ureido derivatives of isoquinolin-3-ol with selective renal vasodilator properties.
The synthesis and cardiovascular evaluation of a series of isoquinolin-3-ol derivatives bearing a variety of nitrogen substituents (amino, acylamino, carbamate, and ureido) at C-4 are described. Certain of these compounds have a selective renal vasodilating profile and have minimal effects on arterial blood pressure or heart rate when administered intravenously in the instrumented anesthetized dog. The most potent renal vasodilator in the series is 4-(allylureido)-6,7-dimethoxyisoquinolin-3-ol (38), which at a dose of 1.2 mg/kg iv produces a 97% maximal increase in renal blood flow without significant hypotensive or chronotropic effects. Structure-activity observations on the nature of the 4-substituent and the alkoxy substitution pattern in the aromatic ring of the isoquinolinol nucleus are discussed.
Animals↗
Vancomycin-induced red cell aggregation.
Vancomycin, an antibiotic similar in structure to ristocetin, is used to treat staphylococcal infections. However, vancomycin-induced hemagglutination complicated red cell (RBC) serologic testing in the blood bank. At concentrations greater than 3.0 mg per ml, vancomycin caused spontaneous macroscopic red cell (RBC) aggregation; concentrations of 2.0 and 2.5 mg per ml were associated with weakly positive aggregation with anti-IgG and polyspecific antiglobulin reagents negative with anti-complement; and concentrations less than 1.5 mg per ml had no apparent effect. Ficin-treated RBCs demonstrated negative reactions with the antiglobulin reagents. Vancomycin-induced aggregation was reversed partially with 0.2 M trisodium citrate, and supernatant transfer studies showed that normal RBCs retained a significantly (p less than 0.025) greater percentage of vancomycin than did ficin-treated RBCs. Vancomycin causes the aggregation of RBCs, which can be a source of confusion in the blood bank. The mechanism(s) through which vancomycin enhances aggregation may be related to its polycationic properties and to its direct protein binding to the RBC membrane, although other nonimmunologic mechanisms may be operative.
Citrates↗
A comparative analysis of the sequence of the thymidine kinase gene of a gammaherpesvirus, herpesvirus saimiri.
We present the nucleotide sequence of a region from the genome of the A + T-rich gammaherpesvirus, herpesvirus saimiri (HVS), which includes the coding sequences for the viral thymidine kinase (TK) gene. The organization of genes in this region resembles the homologous region of the Epstein-Barr virus (EBV) genome and is very compact, using overlapping coding sequences and with nucleotides shared by initiation and termination codons of neighbouring reading frames. The HVS TK is predicted to contain a 527 residue polypeptide with the first part of the presumptive nucleotide-binding site [(L, I, V)(F, Y)(I, L)(D, E)(G)(X)(X)(G)(L, I, V, M)(G)(K)(T, S)(T, S)] located at residues 212 to 224. This motif is close to the amino terminus of the TK polypeptides of alphaherpesviruses and the polypeptides of the cellular and poxvirus-encoded enzymes. The corresponding reading frame of the human gammaherpesvirus (EBV) also has a long amino-terminal extension but significant amino acid sequence similarities between the HVS and EBV sequences are not observed until the region of the nucleotide-binding site. Comparisons of these homologous carboxy-terminal sequences of the HVS- and EBV-encoded proteins with those from six alphaherpes viruses and proteins encoded by Marek's disease virus (MDV) and the herpesvirus of turkeys (HVT) confirm that the HVS and EBV sequences are products of a distinct lineage. The sequences of alphaherpesvirus enzymes than to those of HVS and EBV. Comparison of these 10 highly divergent TK sequences extends and refines the identification of essential features of this family of herpesvirus enzymes and defines 19 positions at which all sequences have identical residues.
Amino Acid Sequence↗
Interaction of concanavalin A and a divalent derivative with lymphocytes and reconstituted lymphocyte membrane glycoproteins.
Both concanavalin A (con A) and its divalent derivative, succinyl-concanavalin A (S-con A) are mitogenic for porcine lymph node lymphocytes. We have compared the binding of these two lectins to intact porcine lymphocytes and phospholipid vesicles containing reconstituted lymphocyte membrane glycoproteins. Both con A and S-con A showed high- and low-affinity binding to intact cells, as indicated by LIGAND analysis of Scatchard plots of binding data. Despite the apparently identical saccharide specificities of the two lectins, high-affinity binding sites for S-con A were only one-third as numerous as high-affinity sites for the parent lectin. Large numbers of low-affinity binding sites existed for con A, while many fewer were present for S-con A. It is suggested that these sites result from hydrophobic association. Con A bound to lymphocytes in a positively cooperative fashion, while S-con A showed noncooperative behavior. Lectin binding to large unilamellar phospholipid vesicles containing reconstituted lymphocyte membrane glycoproteins was measured using a rapid filtration assay, and was linear with the glycoprotein content of the vesicles. Almost all of the outward-facing glycoprotein was functional in terms of lectin binding. Reconstituted glycoproteins showed only a single class of high-affinity binding sites for both con A and S-con A, with association constants similar to those measured for intact cells. Con A, but not S-con A, showed positively cooperative binding to reconstituted vesicles. Cooperativity was observed in both gel phase and liquid crystalline phase lipid, and was thus not dependent on long-range lateral rearrangement of glycoprotein receptors. Results suggested that con A induces a microredistribution of receptors on the lymphocyte membrane surface, leading to the exposure of glycoproteins that were previously inaccessible to the lectin. S-Con A does not cause glycoprotein redistribution, and a large fraction of the receptors remain cryptic.
Animals↗
Physical abuse, sexual victimization, and illicit drug use: replication of a structural analysis among a new sample of high-risk youths.
Mounting evidence of serious adverse consequences of childhood physical and sexual abuse has important implications for public health officials and care providers. Given the potential impact on social policy of this area of inquiry, programmatic research is needed for the validation of theoretical models across populations and over time. This study, based on a sample of high-risk youths, replicates a structural model that specified the influence of child physical and sexual abuse on self-derogation and drug use. Results suggest that for male and female youths, physical abuse and sexual victimization had a direct effect on self-derogation and illicit drug use, and an indirect effect on drug use that was mediated by self-derogation. Moreover, structural coefficients for the model were found to be identical across gender. Subsequent analyses demonstrated the equivalence of the structural model of child physical and sexual abuse on drug use across two study cohorts. Implications for the identification and treatment of youths in high-risk groups are discussed.
Adolescent↗
Expanded assessment for discrimination learning with mentally retarded persons: a practical strategy for research and training.
Practical and reliable instruments to assess basic discriminations by severely and profoundly retarded persons are almost nonexistent. Research findings were reviewed on an assessment instrument, the AVC Discrimination Test, which can be administered in approximately 30 minutes to assess basic position, visual, and auditory discriminations. This test can be used with severely and profoundly mentally retarded persons and is reliable and predictive of client performance in classroom learning, language, and vocational tasks. The advantages of expanding current baseline assessment practices to include the AVC Discrimination Test in research and training programs for persons with mental retardation were discussed.
Adolescent↗
Plasma dilution during transdermal clonidine antihypertensive monotherapy.
In eight hypertensive patients treated with transdermal clonidine for one year, there was plasma dilution, as shown by a reduction in serum sodium, hemoglobin, and serum protein levels. Free water clearance did not change significantly. Plasma dilution was likely sustained by increased water intake due to "dry mouth", as frequently seen with central acting drugs such as clonidine.
Administration, Cutaneous↗
Phase I trial and clinical pharmacological evaluation of 10-ethyl-10-deazaaminopterin in adult patients with advanced cancer.
10-Ethyl-10-deazaaminopterin (10-EDAM) is an analogue of methotrexate with improved preclinical anticancer activity, more selective entry, and greater conversion to polyglutamate forms in neoplastic cells. In this Phase I trial, we have treated 62 adults with advanced solid tumors, giving 10-EDAM i.v. on either a weekly x 3 schedule (35 patients) or a weekly schedule (27 patients). The dosage levels ranged from 5 to 120 mg/m2. The toxicity observed with 10-EDAM was qualitatively similar to that of methotrexate. Oral mucositis was the dose-limiting toxicity; diarrhea, skin rash, leukopenia, thrombocytopenia, and mild elevations of serum glutamic-oxaloacetic transaminase, prothrombin, and partial thromboplastin times were also observed, but were not dose limiting. A weekly dosage of 80 mg/m2 with escalation or attenuation in accordance with patient tolerance, or 100 mg/m2 weekly for 3 weeks, followed by a 2-week "rest period" are recommended for Phase II assessment. 10-EDAM produced partial remissions in three patients with non-small cell lung cancer and one patient with breast cancer lasting 6, 40+, 26+, and 15 months, respectively. Pharmacokinetic studies carried out at the 5, 30, and 100 mg/m2 dosage levels demonstrated the drug to have a triphasic disappearance from plasma. Elimination was independent of dose over the range tested, with mean plasma half-lives of: alpha = 12.9 min, beta = 1.5 h, and gamma = 11.9 h. Cumulative urinary excretion of the drug ranged from 13 to 55% of the administered dose (mean = 33%); 88% of the urinary drug appeared within the first 4 h following drug administration. The pharmacokinetic behavior of the first and second weekly dosages were consistent within a given patient. The metabolites 7-hydroxy-10-EDAM, and 10-ethyl-10-deaza-2,4-diamino-pteroic acid were demonstrated in the plasma and urine of treated patients. In studies of tissue homogenates from two patients with skin metastases, more extensive retention of the drug and of its polyglutamates was observed in the breast cancer metastases than in the metastases from a kidney cancer or in normal skin.
Adult↗
Neurosurgical complications of pediatric orthotopic liver transplantation.
Liver transplantation is the only definitive treatment of end-stage liver disease. The University of Nebraska began its hepatic transplantation program in July 1985. Since that time, 43 children and 48 adults have undergone orthotopic liver transplantation (OLTx) with survival rates to date of 79.1% and 79.2%, respectively. Eight children developed complications of neurosurgical interest (18.6% incidence). Hemorrhagic complications were the most frequent. Neurosurgical salvage was achieved in five patients, but delayed complications of the transplant caused the death of two of these children. Two survivors are functioning well at home and in kindergarten, one child is doing well but is still hospitalized, and one child is vegetative. Aggressive management of life-threatening CNS problems is thus appropriate in this population. The authors review the pathophysiology of these complications, as well as potential pitfalls in their management.
Brain Abscess↗