Consensus on a core curriculum in American training programs in pediatric hematology-oncology: a report from the ASPHO Training Committee.

The Training Committee (TC) of the American Society of Pediatric Hematology/Oncology created a foundation of common goals and objectives that could provide a structure for fellowship programs. The TC conducted a survey of program directors for input into the structure of their programs and training methods and the results are presented here. Additionally, a suggested core program is outlined, taking into account the new common requirements as stipulated by the ACGME and ABP, and additional suggestions from the program directors. This paper highlights the suggested training objectives and educational opportunities that should be afforded all fellows in this sub-specialty. The goal of this consensus statement is to provide a model curriculum to improve quality and consistency of training and achieve compliance with new requirements while simultaneously recognizing the importance of alternative approaches that emphasize each program's unique strengths and character.

Recombinant urate oxidase for the prophylaxis or treatment of hyperuricemia in patients With leukemia or lymphoma.

PURPOSE: To improve the control of hyperuricemia in patients with leukemia or lymphoma, we tested a newly developed uricolytic agent, recombinant urate oxidase (SR29142; Rasburicase; Sanofi-Synthelabo, Inc, Paris, France), which catalyzes the oxidation of uric acid to allantoin, a highly water-soluble metabolite readily excreted by the kidneys. PATIENTS AND METHODS: We administered Rasburicase intravenously, at 0.15 or 0.20 mg/kg, for 5 to 7 consecutive days to 131 children, adolescents, and young adults with newly diagnosed leukemia or lymphoma, who either presented with abnormally high plasma uric acid concentrations or had large tumor cell burdens. Blood levels of uric acid, creatinine, phosphorus, and potassium were measured daily. The pharmacokinetics of Rasburicase, the urinary excretion rate of allantoin, and antibodies to Rasburicase were also studied. RESULTS: At either dosage, the recombinant enzyme produced a rapid and sharp decrease in plasma uric acid concentrations in all patients. The median level decreased by 4 hours after treatment, from 9.7 to 1 mg/dL (P =.0001), in the 65 patients who presented with hyperuricemia, and from 4.3 to 0.5 mg/dL (P =.0001) in the remaining 66 patients. Despite cytoreductive chemotherapy, plasma uric acid concentrations remained low throughout the treatment (daily median level, 0.5 mg/dL). The urinary excretion rate of allantoin increased during Rasburicase treatment, peaking on day 3. Serum phosphorus concentrations did not change significantly during the first 3 days of treatment, decreased significantly by day 4 in patients presenting with hyperuricemia (P =.0003), and fell within the normal range in all patients by 48 hours after treatment. Serum creatinine levels decreased significantly after 1 day of treatment in patients with or without hyperuricemia at diagnosis (P =.0003 and P =.02, respectively) and returned to normal range in all patients by day 6 of treatment. Toxicity was negligible, and none of the patients required dialysis. The mean plasma half-lives of the agent were 16.0 +/- 6.3 (SD) hours and 21.1 +/- 12.0 hours, respectively, in patients treated at dosages of 0.15 or 0.20 mg/kg. Seventeen of the 121 assessable patients developed antibodies to the enzyme. CONCLUSION: Rasburicase is safe and highly effective for the prophylaxis or treatment of hyperuricemia in patients with leukemia or lymphoma.

Stachybotrys chartarum alters surfactant-related phospholipid synthesis and CTP:cholinephosphate cytidylyltransferase activity in isolated fetal rat type II cells.

Stachybotry chartarum, a fungal contaminant of water-damaged buildings commonly grows on damp cellulose-containing materials. It produces a complex array of mycotoxins. Their mechanisms of action on the pulmonary system are not entirely clear. Previous studies suggest spore products may depress formation of disaturated phosphatidylcholine (DSPC), the major surface-active component of pulmonary surfactant (PS). If S. chartarum can indeed affect formation of this phospholipid, then mold exposure may be a significant issue for pulmonary function in both mature lung and developing fetal lung. To address this possibility, fetal rat type II cells, the principal source of DSPC, were used to assess effects of S. chartarum extract on formation of DSPC. Isolated fetal rat lung type II cells prelabeled with 3H-choline and incubated with spore extract showed decreased incorporation of 3H-choline into DSPC. The activity of CTP:cholinephosphate cytidylyltransferase (CPCT), the rate-limiting enzyme in phosphatidylcholine synthesis was reduced by approximately 50% by a 1:10 dilution of spore extract. Two different S. chartarum extracts (isolates from S. chartarum (Cleveland) and S. chartarum (Hawaiian)) were used to compare activity of CPCT in the presence of phosphatidylglycerol (PG), a known activator. PG produced an approximate two-fold increase in CPCT activity. The spore isolate from Hawaii did not alter enzyme activity. S. chartarum (Cleveland) eliminated the PG-induced activation of CPCT. These results support previous observations that mold products alter PS metabolism and may pose a risk in developing lung, inhibiting surfactant synthesis. Different isolates of the same species of fungus are not equivalent in terms of potential exposure risks.

Chronic ethanol modulates delta and mu-opioid receptor expression in rat CNS: immunohistochemical analysis with quantitiative confocal microscopy.

Ethanol consumption affects levels of endogenous opioids as well as opioid receptors in both animals and humans. We studied the expression of delta (delta) and mu (mu) opioid receptors (ORs) in brain sections of adult male Sprague-Dawley rats after 2 weeks of consuming ethanol in a liquid diet, with comparisons to sections from pair-fed control animals. Immunohistochemical staining for the ORs, using selective antibodies, and quantitation of confocal images, revealed increased expression of delta-ORs in hippocampal CA1 of the chronic ethanol-treated rats. In contrast, mu-ORs decreased in their expression after ethanol treatment in multiple brain areas, including cortex, hippocampus, midbrain colliculi, striatum and nucleus accumbens. The alterations in immunoreactive OR expression may be related to reduced functional coupling of the ORs to G-proteins, as found in prior studies in several brain regions, using the same chronic ethanol diet protocol. Changes in OR expression and functional coupling in the CNS may be factors in ongoing ethanol consumption and tolerance.

Double-elevating osteotomy for late-presenting infantile Blount's disease: the importance of concomitant lateral epiphysiodesis.

We reviewed 34 knees in 24 children after a double-elevating osteotomy for late-presenting infantile Blount's disease. The mean age of patients was 9.1 years (7 to 13.5). All knees were in Langenskiöld stages IV to VI. The operative technique corrected the depression of the medial joint line by an elevating osteotomy, and the remaining tibial varus and internal torsion by an osteotomy just below the apophysis. In the more recent patients (19 knees), a proximal lateral tibial epiphysiodesis was performed at the same time. The mean pre-operative angle of depression of the medial tibial plateau of 49 degrees (40 degrees to 60 degrees ) was corrected to a mean of 26 degrees (20 degrees to 30 degrees ), which was maintained at follow-up. The femoral deformity was too small to warrant femoral osteotomy in any of our patients. The mean pre-operative mechanical varus of 30.6 degrees (14 degrees to 66 degrees ) was corrected to 0 degrees to 5 degrees of mechanical valgus in 29 knees. In five knees, there was an undercorrection of 2 degrees to 5 degrees of mechanical varus. At follow-up a further eight knees, in which lateral epiphysiodesis was delayed beyond five months, developed recurrent tibial varus associated with fusion of the medial proximal tibial physis.

Cofactor dependency of soluble 3 alpha-hydroxysteroid oxidoreductases in rat testis, prostate, and epididymis.

The present paper demonstrates the presence of at least two 3-hydroxysteroid oxidoreductases (3-HSO) in rat testis, prostate, and epididymis cytosol preparations. The enzymes were either NADH or NDAPH dependent. Further investigation by Sephadex G-200 chromatogrphy revealed the presence of enzyme activities in the void volume (peak 1) and also eluting close to the methyl-carbonic anhydrase standard (mol wt, 34,000; peak 2). Enzyme activity in peak 1 was predominantly stimulated by NADH and that in peak 2 was stimulated mainly by NADPH. Both 3 alpha- and 3 beta-HSO activities were observed in testicular eluates from 1; 3 beta-Adiol accounted for up to 50% of the 5 alpha-androstanediols formed. In peak 2,3 alpha-HSO constituted more than 90% of the enzyme activity. In contrast, the prostatic and epididymal eluates revealed only 3 alpha-HSO activity; 3 beta-Adiol constituted less than 5% of the 5 alpha-androstanediols formed in either peak 1 or 2. The apparent Km values for enzyme activation reveal differences in sensitivity to cofactors for enzymes in peaks 1 and 2 and also among testis, epididymis, and prostate. NADH caused a very similar activation of enzyme activity in peak 1 or the prostate and epididymis (Km 50-100 micro M), whereas the enzyme in the testis was activated by much lower cofactor concentration (Km approximately 5 microM). It is possible that this enzyme activity may represent microsomal contamination. The enzyme activity in peak 2 revealed very similar sensitivity to NADPH in all three organs (Km, 0.6-1.7 microM), confirming previous studies from our laboratory that the soluble. NADPH-dependent enzymes in all three tissues are very similar, if not identical.

Data mining of spectroscopic data for biomarker discovery.

The goals of precise diagnosis, prevention and treatment of disease can be realized through the discovery of biological markers. Spectroscopic tools can simultaneously detect and quantify multiple small molecule and macromolecular components of biological samples, and are therefore ideal methods for the discovery of previously uncharacterized markers. However, the identification of meaningful spectral features is complicated by the lack of foreknowledge of the molecular nature of a disease, spectral noise and biological variability that is uncorrelated with the disease state. Pattern recognition techniques, both statistical and machine-learning, have been increasingly used in recent years with spectroscopic data to identify markers and classify patients into disease subsets. This review summarizes recent developments, limitations and future prospects in the use of data mining techniques with magnetic resonance spectroscopy, mass spectrometry and optical spectroscopy for the discovery of biomarkers.

Health status and disease activity in systemic lupus erythematosus.

The physical manifestations of disease activity and health status of patients with systematic lupus erythematosus (SLE) were measured in this study. Forty-nine patients completed the Arthritis Impact Measurement Scale (AIMS) and consented to examination for physical features of SLE documented by a Clinical Activity Index (CAI). Results showed a mean score of 22 on the AIMS and 6.6 on the CAI. The total scores for each measure were significantly correlated (r = 0.55, p less than 0.001), indicating a relationship between health status and clinical disease activity. The total score for CAI was significantly correlated with the physical activity, pain, and depression subscales of health status. The total score for health status was significantly correlated with mucocutaneous, musculoskeletal, and general features of CAI. Within scale correlations were also found. Mucocutaneous aspects of disease activity were significantly correlated with pain and depression. Musculoskeletal features were significantly correlated with physical activity and pain. General aspects of SLE, including fatigue, were significantly correlated with physical activity. The study concludes that there is a relationship between certain physical features of SLE and key components of health status.

Analysis of pulmonary surfactant by Fourier-transform infrared spectroscopy following exposure to Stachybotrys chartarum (atra) spores.

Lung cells are among the first tissues of the body to be exposed to air-borne environmental contaminants. Consequently the function of these cells may be altered before other cells are affected. As gas exchange takes place in the lungs, changes in cellular function may have serious implications for the processes of oxygen uptake and carbon dioxide elimination. In order for these processes to occur, the lung must maintain a high degree of expandability. This latter function is accomplished in part by the pulmonary surfactant which is synthesized and released by alveolar type II cells. Earlier studies have shown that exposure to gas phase materials such as smoke or organic solvents can alter the composition and function of the surfactant. The present study examines the ability of highly toxigenic mold spores to alter surfactant composition. Stachybotrys chartarum spores suspended in saline were instilled into mouse trachea as described earlier. After 24 h, the lungs were lavaged and the different processing stages of surfactant isolated by repeated centrifugation. Intracellular surfactant was isolated from the homogenized lung tissue by centrifugation on a discontinuous sucrose gradient. Samples were extracted into chloroform-methanol, dried and analyzed by Fourier-Transform infrared spectroscopy (FTIR). Exposure to S. chartarum induced an overall reduction of phospholipid among the three surfactant subfractions. The intermediate and spent surfactant fractions in particular were reduced to about half of the values observed in the saline-treated group. The relative distribution of phospholipid was also altered by spore exposure. Within the intracellular surfactant pool, higher levels of phospholipid were detected after spore exposure. In addition, changes were observed in the nature of the phospholipids. In particular strong intramolecular hydrogen bonding, together with other changes, suggested that spore exposure was associated with absence of an acyl chain esterified on the glycerol backbone, resulting in elevated levels of lysophospholipid in the samples. This study shows that mold spores and their products induce changes in regulation of both secretion and synthesis of surfactant, as well as alterations in the pattern of phospholipid targeting to the pulmonary surfactant pools.

Androgen metabolism by rat epididymis. Metabolic conversion of 3H 5alpha-androstane-3alpha,17beta-diol, in vitro.

The epididymis of adult rats metabolizes 3H 5alpha-androstane-3alpah,17beta-diol (3alpha-diol) by experiments in vitro. After incubation of tissue slices at 37 degrees C for 2 hours, 2% of the radioactivity was found in the water-soluble fraction whereas 98% was found to be ether soluble (free steroids). Further investigation of the free steroids showed the following to be present: 3alpha-diol 39.9%, DHT (17beta-hydroxy-5alpha-androstan-3-one) 33.7%, androsterone (3alpha-hydroxy-5alpha-androstan-17-one) 9.2%, 3beta-diol (5alpha-androstane-3beta,17beta-diol) 2.6%, 5alpha-A-dione (5alpha-androstan-3,17-dione) 1.1%, delta 16-3alpha-ol (5alpha-androst-16-en-3alpha-ol) 1.0%, delta16-3beta-ol (5alpha-androst-16-en-3beta-ol) 2.6%, delta 16-3-one (5alpha-androst-16-en-3-one) 2.9%, and polar compounds 3.3%. When segments of the epididymis (caput and cauda) were incubated in the same way, qualitatively similar metabolites were formed but a greater amount of 3alpha-diol was metabolized by the cauda epididymis. This increase was mainly accounted for by an increased formation of delta 16 compounds (14.3% in cauda, 4.3% in caput). This is most probably due to the presence of larger numbers of mature spermatozoa, which, as we have previously shown, form delta16 steroids from 3alpha-diol and DHT (5).

Androgen metabolism by rat epididymis. 5. Metabolic conversion and nuclear binding after injection of 5alpha-androstane-3alpha, 17beta-diol, in vivo.

The pattern of androgenic metabolites in blood, muscle, caput and cauda epididymidis has been investigated in functionally hepatectomized 24 hours castrated rats, 3 hours after the intra-muscular injection of 200 muCi of 3H-3H-3alpha-diol. Identification of the radioactive metabolites showed only negligible differences between the epididymal regions. In both caput and cauda the main metabolite was DHT (17beta-hydroxy-5alpha-androstane-3-one); 3alpha- and 3beta-diol, androsterone (3alpha-hydroxy-5alpha-androstane-17-one), 5-A-dione (5alpha-androsterone-3, 17-dione), delta16-3alpha-01 (kalpha-androst-16-en-3alpha-01), delta16-3beta-01 (5alpha-androst-16-en-3alpha-01) and delta16-3-one (5alpha-androst-16-en-3-one) were also present. Androsterone and 3alpha-diol were the predominant metabolites in blood and muscle. No delta16 compounds could be detected and in constrast to epididymis, more than 50% of the radioactivity was associated with polar compounds. From determination of total radioactivity, it was seen that retention by epididymis varied from two to four times that of muscle. Purification and identification of the radioactivity associated with the nuclear fraction demonstrated that DHT was the only nuclear bound androgen. It is suggested from these results that at least one effect of 3alpha-diol on the rat epididymis is exerted through its conversion to DHT.

Uptake and metabolism of androgens by bovine spermatozoa.

Spermatozoa from bovine ejaculates and cauda epiditymidis were incubated with either tritiated 17 beta-hydroxy-5 alpha-androstane-3-one (DHT) or 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol). Examination of the medium incubations demonstrated metabolic conversion of both DHT and 3 alpha-diol when these steriods were incubated with ejaculated sperm. In addition to this interconversion, the following metabolities were identified: 5 alpha-androstane-3 beta, 17 beta-diol, (3 beta-diol), androsterone and 5 alpha-androstane-3, 17-dione (5 alpha-A-dione). Incubations with cauda spermatozoa showed similar metabolic patterns. Androgen binding was exhibited by both sperm types. Examination of the washed cauda sperm pellet, following incubations with 3 alpha-diol showed that the incubated steroid was the most abundantly bound. DHT and 5 alpha-androst-16-en-3 alpha-ol (delta 16-3 alpha-ol1 were also detected. The major part of the radioactivity bound in the sperm pellet was identified as DHT when this steroid was used as the substrate; the remaining radioactivity consisted of 3 alpha-diol and delta 16-3 alpha-ol. Investigations of ejaculated sperm pellets gave similar results apart from the additional identification of 5 alpha-androst-16-en-3 one (delta 16-3-one) and 5 alpha-androst-16-en-3 beta-ol (delta 16-3 beta-ol (delta 16-3 beta-ol).

Self-concept differentiation across the adult life span.

This study used 2 measures to examine 158 adults' (80 men, 78 women; ages 20 to 88 years) self-concept differentiation (SCD) across 5 role-specific self-representations. Findings revealed that the 2 measures did not assess SCD in similar ways and that they showed different associations with age. Specifically, the 1st measure was not significantly related to age, whereas the 2nd measure showed a curvilinear, U-shaped association with age. The 2nd SCD index also showed significant associations with several measures of emotional adjustment and 6 dimensions of psychological well-being. Additional analyses showed that age moderated the associations between SCD and positive and negative psychological well-being. A high level of SCD was associated with lower positive and higher negative psychological well-being for both young and older adults. However, this effect was significantly more pronounced in older adults.

The effects of ethylene oxide sterilization on the in vitro cytotoxicity of a bone replacement material.

The effect of degassing on the cytotoxicity of an ethylene oxide (EtO)-sterilized copolymer constituent of a bone replacement material, was determined using the (51)Cr release assay. An initial experiment used mouse L929 cells and a copolymer with an ambient pressure and temperature (APT) degassing time of 24 hr. Both copolymer and nylon control discs caused a significantly (P

Classification issues in ambulatory care nursing.

Classification issues in ambulatory care nursing present an exciting area for future research and development that is only beginning to be tackled. It will be important to validate both the conceptual basis of the nursing workload model and the tools and methods used to measure workload. Comparative studies are needed in a variety of settings to reach consensus about the variables affecting workload in ambulatory nursing, and ways to measure them. Timed observation and validation studies are needed as new reporting and evaluation instruments are developed. At NIH a validation study looking at a modification of the taxonomy of ambulatory nursing practice (Verran, 1981) is underway, using a national sample of nursing administrators (Hastings, 1984). Studies to establish interrater reliability and to refine criteria for classifying patients and nursing activities are also needed.

Repair of calvarial nonunions by osteogenin, a bone-inductive protein.

Efforts were taken to determine the dose of bovine osteogenin (OG) that would induce more bone than that induced by 20 mg of rat particulate demineralized bone matrix (DBM), the amount allowed by the confines of an 8-mm rat craniotomy defect. Dose-response studies were performed for demineralized bone matrix alone and osteogenin, partially purified from bovine demineralized bone matrix, plus rat insoluble collagenous bone matrix (M). Demineralized bone matrix alone (2.5, 5.0, 10, 20, or 40 mg) or osteogenin (0.0625, 0.125, 0.250, 0.50, or 1.0 mg) plus 25 mg insoluble collagenous bone matrix was implanted into the pectoralis muscle for 3, 5, and 7 weeks. Both materials induced time- and dose-dependent formation of bone. The three highest dosages of osteogenin (plus insoluble collagenous bone matrix) induced more bone than 20 mg demineralized bone matrix and seemed to accelerate bone repair. However, when implanted into the 8-mm rat craniotomy defect for 4 weeks, 20 mg demineralized bone matrix and 0.5 mg osteogenin (plus insoluble collagenous bone matrix) induced comparable amounts of bone. These results suggest different mechanisms for bone formation in heterotopic and orthotopic sites.

Validation of a taxonomy of ambulatory nursing practice.

Ambulatory care is a complex and challenging nursing specialty. This survey of 33 ambulatory nursing administrators addressed the roles and responsibilities of nurses in ambulatory care settings.

Nursing leaders predict top trends for 2000.

Nursing Management's Editorial Advisory Board predicts the top 10 trends that will impact nurse leaders in 2000. Use them to lead in the new millennium.