Rhabdoid tumor of kidney. A report of 111 cases from the National Wilms' Tumor Study Pathology Center.

We review 111 cases of rhabdoid tumor of kidney (RTK), including 79 entered on the National Wilms' Tumor Study (NWTS). Median age at diagnosis was 11 months, with a range from 0 to 106 months. The male:female ratio was 1.5:1. Gross features included a characteristic involvement of perihilar renal parenchyma. A wide histological spectrum was encountered, including nine major morphological patterns (classical, epithelioid, sclerosing, lymphomatoid, histiocytoid, etc.). These appearances invite confusion with other renal neoplasms. Ultrastructural studies were performed in 20 cases; immunocytochemical studies were performed in 11. Vimentin was demonstrated in all tumors; epithelial membrane antigen was seen in 7. Nonspecific decoration of cytoplasmic inclusions by a variety of immunostains was found in several cases. Several findings suggested that RTK might arise from primitive cells involved in formation of the renal medulla. There was no evidence of a histogenetic relationship to Wilms' tumor, although RTK may overlap with mesoblastic nephroma and clear cell sarcoma. Of the 70 NWTS patients with adequate follow-up, 56 (80%) have died. Every patient presenting with distant metastases died, whereas 10 of 20 with negative nodes survived. Survival rates were higher for girls (56.3% versus 11.1%). None of the histological variables had independent prognostic significance.

Theoretical cost effectiveness of management options for children with persisting middle ear effusions.

OBJECTIVE: The purpose of this theoretical study is to assess the cost effectiveness of options involving observation, antibiotics alone, corticosteroids alone, corticosteroids plus antibiotics, and surgery to clear persisting middle ear effusions during three visits. METHODOLOGY: In a hypothetical case the expected average per patient expenditures are calculated using the efficacy rates determined by the meta-analysis of randomized controlled clinical trials involving corticosteroids plus an antibiotic (six trials), corticosteroids alone (three trials), and antibiotic alone (four trials). In this analysis, all children whose bilateral middle ear effusions persist for 12 weeks despite medical management are referred for ventilating tubes. RESULTS: The most cost-effective intervention combination is corticosteroid plus an antibiotic at visit 1 (6 weeks after diagnosis of acute otitis media) followed by a second antibiotic in nonresponders at visit 2 (9 weeks after diagnosis of acute otitis media) and referral for ventilating tubes in nonresponders at visit 3 (12 weeks after diagnosis of acute otitis media). The expected average expenditures per case to clear the bilateral middle ear effusions is $600.91 based on reimbursement of private practice charges and $350.27 based on Medicaid reimbursement (all payments to providers are based on 1992 data from Colorado). The difference in the expected average total expenditures per case between this most cost-effective approach versus the use of sequential courses of antibiotics followed by surgery is $372.81 ($973.72-$600.91) with full reimbursement of private practice charges and $202.57 ($552.84-$350.27) with Medicaid reimbursement. In clearing the middle ear effusion, the average estimated travel expenses per case is $21.46, and lost parental wages per case are $45.12. When the expenditures associated with an additional 6-month follow-up period are included, the expected average per case expenditures is $1088.54 with reimbursement of private practice charges and @659.00 with Medicaid reimbursement. The difference in the expected average per case expenditures to clear the effusions and follow-up for 6 months between the most cost-effective approach using corticosteroids plus antibiotics at the 6- and 9-week visits followed by surgery in nonresponders at 12 weeks versus sequential courses of antibiotics is $405.30 ($1493.84-$1088.54) with reimbursement of private practice charges and $217.32 ($876.32-$659.00) with Medicaid reimbursement. RECOMMENDATIONS: Although the analysis does not consider risks, side effects, and parental or provider preferences, the findings suggest that the implementation of cost-effective clinical guidelines can potentially reduce national expenditures for managing persistent middle ear effusions.

Developmental and neurologic sequelae of neonatal hyperviscosity syndrome.

One hundred eleven consecutive infants with neonatal hyperviscosity were identified by screening all newborns for polycythemia in an 18-month period. These polycythemic infants were matched with non-polycythemic newborns for birth weight, gestational age, Apgar scores, and sex. Maternal, intrapartum, and neonatal data were analyzed for associated morbidity. Maternal preeclampsia was more common among the hyperviscous patients than among control subjects. Hypoglycemia was also significantly increased among the hyperviscous patients. Follow-up studies at 1 to 3 years of age revealed a significantly higher incidence (38% vs 11%) of motor and neurologic abnormalities in the infants with neonatal hyperviscosity. The data suggested that concurrent hypoglycemia increased the risk of a poor outcome in hyperviscous infants inasmuch as 55% of infants with both characteristics were abnormal at follow-up. This, however, was not significantly different from the outcome of infants with hyperviscosity alone (P greater than .05 but less than .1). Further studies will be needed to confirm or deny this relationship.

A controlled study of longitudinal IQ changes in females and males with fragile X syndrome.

The aim is this study is to compare the longitudinal changes in IQ scores of females and males with fragile X syndrome and controls and to assess the impact on IQ of molecular variations of the FMR-1 gene in males. Medical records from the child development unit at a university-affiliated children's hospital were retrospectively reviewed. Chart review yielded 35 males with fragile X (19 with a fully methylated full mutation, 9 with a mosaic pattern, and 7 with a partially unmethylated full mutation) 16 females with fragile X and a full mutation, 9 female controls, and 9 male controls who had repeated standardized IQ testing separated by 7 months to 13 years. The differences between the first and last IQ scores from the same IQ test were compared by t tests and subsequently by analysis of variance. Overall, a significant IQ decline was seen in 10/35 (28%) of fragile X males, 0/9 (0%) of control males, 6/16 (36%) of fragile X females, and 1/9 (11%) of control females. The initial t tests and analysis of variance showed a significant difference in IQ (p = 0.02) between fragile X males and control males but did not show a significant difference between males and females with fragile X syndrome or between fragile X and control females. When an analysis of covariance was carried out with the initial IQ as a covariable, a significant difference persisted between fragile X and control males, with a greater IQ decline in fragile X males. There were limitations in using the same IQ test. A comparison among the molecular subgroups of males yielded a significant IQ decline in 3/9 (33%) of mosaic males, 6/19 (32%) of fully methylated full mutation males, and 1/7 (14%) of partially methylated full mutation males. An analysis of covariance using the initial IQ and the intertest interval as covariables demonstrated significant differences between the fragile X molecular subgroups and the controls. Our findings show that a substantial percentage of both male and female fragile X patients and female control patients demonstrated significant IQ decline. There was a significant difference in the IQ change between fragile X and control males. There were no significant differences between fragile X and female controls. There were also significant differences in IQ decline among males with different molecular patterns compared with controls. Males with a mosaic pattern versus control males had the most significant decline of the molecular subtypes. Although the numbers were limited, there was no significant IQ decline in males with less than 50% methylation of the full mutation. This suggests that a small amount of FMR-1 protein production, which is often seen in males with less than 50% methylation, protects against significant IQ decline.

Anaplasia in unilateral Wilms' tumor: a report from the National Wilms' Tumor Study Pathology Center.

Fifty-eight unilateral anaplastic Wilms' tumors entered on the Third National Wilms' Tumor Study (NWTS-3) were reviewed. The favorable outcome of stage I anaplastic tumors was confirmed. In stage II-IV tumors, the extent and severity of anaplasia were not of prognostic importance. However, two histologic features were correlated with extremely poor outcome; anaplasia in extrarenal tumor sites (P = .016) and predominantly blastemal tumor pattern (P = .020). The importance of these features in predicting relapse and death for children with anaplastic Wilms' tumor was supported by the study of 47 additional anaplastic Wilms' tumor cases from NWTS-2. These results emphasize the importance of examining sites of extrarenal spread in anaplastic Wilms' tumors. Cytologic criteria for anaplasia and clues to its recognition are reviewed, and the potential clinical and biological implications of our findings are discussed.

Diphtheria-tetanus toxoids-pertussis vaccination does not increase the risk of hospitalization with an infectious illness.

The purpose of this study was to determine whether children hospitalized with a primary diagnosis of infection were more likely than matched controls to have had a diphtheria-tetanus toxoids-pertussis immunization in the 30 days before hospitalization of the case. Cases were less likely than controls to have received an immunization (P = 0.003). They were also less likely to have been breast-fed (P < 0.001) and to have had a well-child care clinic visit (P = 0.01). Cases were significantly more likely to be preterm (< 38 weeks gestation), low birth weight (< 2500 g) and attending day care than their matched nonhospitalized controls (P = 0.003, 0.03 and 0.002, respectively). This study demonstrates no association between receipt of diphtheria-tetanus toxoids-pertussis immunization and subsequent hospitalization for an infectious illness.

Intrauterine resuscitation with tocolysis. An alternate month clinical trial.

Fifty patients were compared for the purpose of investigating the usefulness of intrauterine resuscitation with tocolysis (IURT). Terbutaline was given, as an intravenous bolus, to 31 women in labor in whom fetal distress was diagnosed and urgent delivery by cesarean section was indicated. In alternate months, a control group of 19 women with similar diagnoses was urgently delivered after standard interventions such as maternal positioning, oxygen administration, hydration, and discontinuation of oxytocin. Improvement in perinatal outcome was shown in infants after IURT. Apgar scores were less than 7 in 42% of the study group and in 71% of the control group at 1 minute (P = .04). Five-minute Apgar scores less than 7 occurred in 7% of the study group and 24% of the control group. A low venous pH was seen in 55% of the control group compared with 29% of the infants resuscitated with terbutaline. Estimated maternal blood loss and hematocrit change was not different in the two groups. Maternal blood pressure and pulse changes following IURT were modest and of doubtful significance. We conclude that intravenous terbutaline administered as a bolus injection at the time of fetal distress in labor improves infant outcome as evidenced by more vigorous Apgar scores and less acidemia without significant adverse physiologic effects on the mother.

Prediction of the need for transfusion during anemia of prematurity.

We reviewed erythrocyte transfusions, given after 2 weeks of age to premature infants, to derive patient selection criteria for trials of administration of recombinant human erythropoietin to maintain hematocrit during the anemia of prematurity. We first studied 122 infants, less than 36 weeks of gestational age, who remained in a level 3 nursery longer than 4 weeks. Multiple logistic regression analysis was used to select those variables associated with more than two transfusions after the second week; these included gestational age, 5-minute Apgar score, transfusion during the first week, and patent ductus ligation. The best predictor, alone or combined, was gestational age less than 30 weeks. This predictor was applied to a second population of 44 premature infants from a level 2 nursery, and we found a 94% probability of excluding those infants who did not receive a transfusion. This information will allow selection of premature infants who are candidates for administration of recombinant human erythropoietin.

Three immunoassay methods evaluated for quantifying prealbumin (transthyretin) in serum.

We developed an immunoturbidimetric assay for prealbumin on the Cobas Bio centrifugal analyzer and compared results from this assay with those from a rate nephelometric assay (Beckman Instruments Inc.) and a radial immunodiffusion kit (Behring Diagnostics). All three assays were evaluated for precision, linearity, and correlation to each other for analysis of sera from pediatric patients. All assays gave similar results for patients' samples. Values were higher by the radial immunodiffusion assay than by the other two methods, which gave similar results for the same specimens. We conclude that the immunoturbidimetric and rate nephelometric assay for prealbumin are acceptable alternatives for quantifying prealbumin in serum and also have a faster turnaround time than radial immunodiffusion.

Relapse-associated variables in stage I favorable histology Wilms' tumor. A report of the National Wilms' Tumor Study.

All 24 cases of confirmed and evaluable Stage I favorable histology (FH) Wilms' tumor (WT) relapsing to date on the Third National Wilms' Tumor Study (NWTS-3) were compared with 48 matched control subjects who had not relapsed for at least 2 years after diagnosis. Fifteen of the clinical and pathological variables studied, including patient age and tumor size, had no significant relationship to the outcome of this study. Four histologic features, all related to the degree of tumor extension within the "tumor-kidney unit" proved to be significantly associated with relapse. These were (1) invasion of the tumor capsule, (2) presence of an "inflammatory pseudocapsule," (3) renal sinus invasion, and (4) tumor in intrarenal vessels. One or more of these features was present in 100% of relapsed cases (excluding one for which two variables were unevaluable), but occurred in only 46% of controls (P less than 0.0002). Therefore, no relapses occurred in the NWTS-3 when all four variables were negative. This result was confirmed by a review of all Stage I cases in the NWTS-1 who had relapsed and who were treated by single-agent chemotherapy. Again, no relapses occurred when all four factors were negative. These results demonstrate the feasibility of "microsubstaging" and could serve as a basis for future refinements of therapy for Stage I favorable histology Wilms' tumor.

Hip flexion contracture in cerebral palsy. The association between clinical and radiologic measurement methods.

Hip flexion contracture was examined in 51 spastic cerebral palsy patients by three clinical methods and two radiologic methods. An extremely low association was found between the clinical and radiologic methods with no particular method, clinical or radiologic, showing a higher association. The method of clinical examination should be chosen by convenience. Radiologic measurements by the methods used did not add useful information.

Coagulopathy in pediatric abusive head trauma.

OBJECTIVES: Coagulopathy is a potential complication of head trauma that may be attributable to parenchymal brain damage. The objectives of this study were to assess the frequency of coagulation defects in pediatric abusive head trauma and to analyze their relationship to parenchymal brain damage. METHODS: We reviewed the records of 265 pediatric patients hospitalized for head trauma. One hundred forty-seven patients met study inclusion criteria: (1) radiologic evidence of head trauma, (2) multidisciplinary validation that head trauma had been inflicted, and (3) coagulation screening performed within 2 days of presentation. Using nonparametric analysis, initial coagulation test results were compared between study patients without parenchymal brain damage and those with parenchymal brain damage. RESULTS: Mild prothrombin time (PT) prolongations (median 13.1) occurred in 54% of study patients with parenchymal brain damage and only 20% of study patients without parenchymal brain damage. Among pediatric abusive head trauma patients with parenchymal brain damage who died, 94% displayed PT prolongations (median 16.3) and 63% manifested evidence of activated coagulation. CONCLUSIONS: PT prolongation and activated coagulation are common complications of pediatric abusive head trauma. In the presence of parenchymal brain damage, it is highly unlikely that these coagulation abnormalities reflect a preexisting hemorrhagic diathesis. These conclusions have diagnostic, prognostic, and legal significance.

Saturation by pulse oximetry: comparison of the results obtained by instruments of different brands.

We noticed that arterial oxygen saturation by pulse oximetry (SpO2) was generally lower when determined by the Ohmeda Biox 3700 pulse oximeter than when determined by the Nellcor N-100 pulse oximeter, and we investigated whether this finding was consistent and the reason for the discrepancy. We placed both oximeters simultaneously on 30 infants with indwelling arterial catheters and measured arterial partial pressure of oxygen (PaO2), percentage of fetal hemoglobin, and complete cooximetry, including arterial oxygen saturation (SaO2) with a Radiometer OSM-3 cooximeter, with and without correction for fetal hemoglobin levels, in four samples of blood from each infant during a 12-hour period for a total of 120 samples. The Nellcor SpO2 was consistently higher than the Ohmeda SpO2 by a mean (+/- SD) of 1.61% +/- 2.69% (p < 0.001). The Nellcor SpO2 correlated best with functional SaO2 (oxyhemoglobin (HbO2)/(HbO2 + reduced hemoglobin)) x 100); Ohmeda SpO2 correlated best with fractional SaO2 (HbO2/(HbO2 + reduced hemoglobin + carboxyhemoglobin + methemoglobin)) x 100), reflecting a fundamental difference in the calibration algorithms used in the two instruments. A desired PaO2 of 50 to 100 mm Hg, is maintained when the range of SpO2 is 90% to 96% for Ohmeda SpO2 and 92% to 98% for Nellcor SpO2 in the neonate, giving a positive predictive value in this study of 94% to 95%. We conclude that SpO2 determined by pulse oximeters of different brands is not interchangeable, and this may be of clinical importance in predicting PaO2 on the basis of SpO2.

The effect of preoperative therapy on the histologic features of Wilms' tumor. An analysis of cases from the Third National Wilms' Tumor Study.

Preoperative chemotherapy is being used with increasing frequency in the US for the management of selected children with Wilms' tumor, despite relatively limited knowledge as to the effects of such therapy on tumor histologic features. The authors reviewed pathologic material from all preoperatively treated unilateral Wilms' tumors registered on the third National Wilms' Tumor Study. Preoperative therapy was associated with increased ambiguity of tumor stage. The prevalence of anaplasia in the 83 evaluable specimens was similar to, although slightly increased over, that in comparable high-stage untreated Wilms' tumors (11% versus 5% to 8%), and it appeared to retain its adverse connotations. These data also suggest that alterations of tumor character and distribution by therapy provide useful prognostic information. All 17 children whose residual viable tumor was limited to intrarenal sites at the time of resection were alive and disease-free at last follow-up. Extensive (greater than 90%) tumor necrosis, low mitotic activity, and high degrees of differentiation of residual tumor were also associated with favorable outcomes. Although careful utilization of preoperative chemotherapy can be of value in children with otherwise difficult-to-manage Wilms' tumors, the potential benefits of preoperative tumor bulk reduction must be weighed against the risk of overtreatment or undertreatment as a result of increased ambiguity of tumor stage.

High frequency of Gag- and envelope-specific cytotoxic T lymphocyte precursors in children with vertically acquired human immunodeficiency virus type 1 infection.

Circulating human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocytes (CTL) are seen less frequently in unstimulated peripheral blood mononuclear cells (PBMC) from children with vertically acquired HIV infection than in PBMC from HIV-infected adults. HIV-1 Gag-, reverse transcriptase (RT)-, and envelope (Env)-specific cytotoxic activity was studied in PBMC from HIV-infected children. Only 9% of subjects had Gag- or RT-specific CTL in unstimulated PBMC. However, in PBMC studied after CD3 stimulation, Gag- and Env-specific CTL were found in PBMC from 91% and 78% of HIV-infected children, respectively. Limiting dilution analysis of precursor CTL (pCTL) frequencies in PBMC from children > 12 months old demonstrated Gag- and Env-specific pCTL frequencies from 0.5 to 6.3/10,000 PBMC and from 0.66 to 33.0/10,000 PBMC, respectively. Thus, children with vertically acquired HIV infection have high frequencies of HIV-specific pCTL.

Evaluation of the vomiting infant.

This 12-month prospective study was undertaken to evaluate the cost, risk, and benefit of ultrasound followed by upper gastrointestinal series for the evaluation of the infant who vomits. Results suggest minimal morbidity from the upper gastrointestinal series, only a 33% reduction in the number of upper gastrointestinal series performed, and a 95% increase in cost if this imaging sequence is used. We conclude that the use of ultrasound for the initial evaluation of vomiting in infants substantially increases the cost with no meaningful decrease in morbidity and mortality.

Long-term effects of home visitation on maternal life course and child abuse and neglect. Fifteen-year follow-up of a randomized trial.

CONTEXT: Home-visitation services have been promoted as a means of improving maternal and child health and functioning. However, long-term effects have not been examined. OBJECTIVE: To examine the long-term effects of a program of prenatal and early childhood home visitation by nurses on women's life course and child abuse and neglect. DESIGN: Randomized trial. SETTING: Semirural community in New York. PARTICIPANTS: Of 400 consecutive pregnant women with no previous live births enrolled, 324 participated in a follow-up study when their children were 15 years old. INTERVENTION: Families received a mean of 9 home visits during pregnancy and 23 home visits from the child's birth through the second birthday. DATA SOURCES AND MEASURES: Women's use of welfare and number of subsequent children were based on self-report; their arrests and convictions were based on self-report and archived data from New York State. Verified reports of child abuse and neglect were abstracted from state records. MAIN RESULTS: During the 15-year period after the birth of their first child, in contrast to women in the comparison group, women who were visited by nurses during pregnancy and infancy were identified as perpetrators of child abuse and neglect in 0.29 vs 0.54 verified reports (P<.001). Among women who were unmarried and from households of low socioeconomic status at initial enrollment, in contrast to those in the comparison group, nurse-visited women had 1.3 vs 1.6 subsequent births (P=.02), 65 vs 37 months between the birth of the first and a second child (P=.001), 60 vs 90 months' receiving Aid to Families With Dependent Children (P=.005), 0.41 vs 0.73 behavioral impairments due to use of alcohol and other drugs (P=.03), 0.18 vs 0.58 arrests by self-report (P<.001), and 0.16 vs 0.90 arrests disclosed by New York State records (P<.001). CONCLUSIONS: This program of prenatal and early childhood home visitation by nurses can reduce the number of subsequent pregnancies, the use of welfare, child abuse and neglect, and criminal behavior on the part of low-income, unmarried mothers for up to 15 years after the birth of the first child.