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Biomedical subjects

J A Wilimas

Publications and source records attributed to J A Wilimas.

At least 19 recordsLinked to original sources
PubMed1999

Factor V Leiden and other hypercoagulable state mutations are not associated with osteonecrosis during or after treatment for pediatric malignancy.

OBJECTIVE: Osteonecrosis (ON) is a debilitating complication of cancer treatment in children and is usually associated with systemic steroid therapy. Defects of coagulation may be important in the pathogenesis of ON. This study evaluated the prevalence of factor V Leiden (FVL, 1691G-->A), the most common inherited thrombophilic state, the prothrombin 20210G-->A polymorphism, and the thermolabile methylene tetrahydrofolate reductase (MTHFR, 677C-->T) variant in a group of children in whom ON developed during or after treatment for cancer. STUDY DESIGN: Children in whom ON developed during cancer treatment at St Jude Children's Research Hospital were studied (n = 24). Genomic DNA was isolated, and polymerase chain reaction was performed to identify the FVL, prothrombin 20210, and thermolabile MTHFR mutations. RESULTS: Sixteen of 24 patients had acute lymphoblastic leukemia. The mean age at ON diagnosis was 14.4 +/- 3. 7 years. The mean interval between cancer diagnosis and ON diagnosis was 27 +/- 21 months. Twenty-two patients had received steroids for a mean duration of 24 +/- 15 weeks before having development of ON. No patient had a history of thrombosis. Five (21%) patients had a family history of thrombosis. Genetic analysis revealed 0 (0%) of 24 FVL, 1 (4.5%) of 22 prothrombin 20210, and 3 (13.6%) of 22 thermolabile MTHFR. None of these mutation frequencies was significantly different from our control frequencies or published values. CONCLUSIONS: Although procoagulant abnormalities in general and FVL in particular have been detected in a significant number of patients with ON of the jaw and Legg-Perthes disease, we did not identify an increased prevalence of FVL or other hypercoagulable state mutations in a cohort of children with ON that developed during or after treatment for a variety of cancers.

Adolescent↗
PubMed1998

Abnormalities of the central nervous system in very young children with sickle cell anemia.

OBJECTIVE: To determine whether abnormalities of the CNS are present in very young children with sickle cell anemia. STUDY DESIGN: Thirty-nine children with hemoglobin SS between the ages of 7 and 48 months were examined with magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). No child had a history of clinical stroke, although 3 had a history of seizures (2 neonatal). Twenty-one patients underwent developmental testing with the Bayley or McCarthy Scales. RESULTS: The overall prevalence of CNS abnormalities in asymptomatic children was 4 of 36 (11%, confidence interval 3, 26%). One patient had a silent infarct observed on MRI and a stenotic lesion on MRA; 3 other patients had stenotic lesions on MRA. The 3 patients who had a history of seizures all had lesions consistent with infarcts on MRI. Of the asymptomatic patients who had psychometric testing, 1 of 18 was developmentally delayed. One of 3 with a history of seizures had mild developmental delay. CONCLUSIONS: Very young children with sickle cell anemia (and no history of clinical stroke) have infarction in the brain and/or stenosis of major cerebral arteries, similar to those reported in older children. These findings indicate a need for larger studies to define the incidence of CNS lesions in this age group and to determine the need for early therapeutic intervention to prevent CNS sequelae of sickle cell disease.

Anemia, Sickle Cell↗
PubMed1998

Increased mortality after successful treatment for Hodgkin's disease.

PURPOSE: To determine the impact of treatment toxicity on long-term survival in pediatric Hodgkin's disease. PATIENTS AND METHODS: We studied late events in 387 patients treated for pediatric Hodgkin's disease on four consecutive clinical trials at St Jude Children's Research Hospital from 1968 to 1990. Relative risks, actuarial risks, and absolute excess risks for cause-specific deaths were calculated. RESULTS: As of April 1997, 316 (82%) of patients were alive, with a median follow-up of 15.1 (range, 2.9 to 28.6) years. In this cohort, which represented 5,623 person-years of follow-up, 71 fatal events resulted from Hodgkin's disease (n=36), second malignancies (n=14), infections (n=7), accidents (n=7), cardiac disease (n=6), and asphyxiation (n=1). The 5-year estimated event-free survival (EFS) for the entire cohort was 79.6%+/-2.1 %, which declined to 63.1%+/-4.4% by 20 years. Cumulative incidences of cause-specific deaths at 25 years were 9.8%+/-1.6% for Hodgkin's disease, 8.1%+/-2.6% for second malignancy, 4.0%+/-1.8% for cardiac disease, 3.9%+/-1.5% for infection, and 2.1%+/-0.8% for accidents. Standardized incidence ratios showed excess risk for all second malignancies (12; 95% confidence interval [CI], 8 to 17), acute myeloid leukemia (81; 95% CI, 16 to 237), solid tumors (11; 95% CI, 7 to 16), and breast cancer (33; 95% CI, 12 to 72). Standardized mortality ratios also showed excess mortality from cardiac disease (22; 95% CI, 8 to 48) and infection (18; 95% CI, 7 to 38). CONCLUSION: Compared with age- and sex-matched control populations, survivors of pediatric Hodgkin's disease who were treated before 1990 face an increased risk of early mortality related to second cancers, cardiac disease, and infection.

Adolescent↗
PubMed1998

Late vascular occlusion of central lines in pediatric malignancies.

OBJECTIVE: To determine whether thrombi or vascular occlusion represent a late complication persisting several years after removal of central venous lines (CVLs) in children and adolescents treated for childhood cancer. METHODS: Children whose treatment for malignancy included placement of a CVL that had been removed at least 2 months previously were studied during scheduled follow-up that included contrast-enhanced computed tomography. Spiral volume acquisition was used to obtain 3-mm images from the chest apices through the right hilum, and three-dimensional reconstruction of angiograms was performed. Thrombosis/occlusion was defined as narrowing, obstruction, or filling defect of the deep venous system, with or without the formation of collateral veins. Charts were reviewed to document patient characteristics, previous CVL complications, administration of hyperalimentation, use of urokinase, and family history of venous thrombosis. RESULTS: Twenty-three patients treated for solid tumors and 2 treated for B-cell acute lymphocytic leukemia or lymphoma were studied. Lines had been in place from 0.2 to 36 months (median, 7.4) and were removed at 2.3 to 121.8 months (median, 32.5) before study. Nine patients received hyperalimentation for periods ranging from 2 to 38 weeks (median, 12). Four patients had required urokinase instillations, and one developed superior vena cava syndrome; 4 had a CVL-related infection (two superficial and two Candida line infections). Occlusion was seen on computed tomography angiograms in 3 of the 25 patients (12%; 95% confidence interval: 4.5-31%). One of the patients with occlusion had superior vena cava syndrome; none had a family history of thrombosis, use of a double lumen CVL, or multiple instillations of urokinase. CONCLUSIONS: Persistent asymptomatic vascular occlusion does occur as a late complication of CVL placement for treatment of childhood malignancies, although the frequency appears low among patients treated primarily for solid tumors. Prospective studies of large numbers of patients with a broader spectrum of diagnoses are necessary to define the incidence of and risk factors for this complication and to assess the need for prevention with anticoagulation or other therapy. Pediatricians caring for patients with a history of cancer and CVLs should be aware that these patients may have persistent vascular occlusion that could predispose them to recurrent thrombosis or postphlebitic syndrome.

Adolescent↗
PubMed1997

Recurrent Streptococcus pneumoniae sepsis in children with sickle cell disease.

Streptococcus pneumoniae sepsis is the most common invasive infection among patients with sickle cell disease. The risk of a recurrent episode of sepsis and subsequent death in those patients who have had a previous septic event is much higher. Patients with sickle disease who have had pneumococcal sepsis should continue penicillin prophylaxis indefinitely and should not be candidates for out-patient management of febrile episodes.

Anemia, Sickle Cell↗
PubMed1997

Use of chest computed tomography in the staging of pediatric Wilms' tumor: interobserver variability and prognostic significance.

PURPOSE: To determine the specificity and prognostic significance of computed tomography (CT) of the chest in pediatric Wilms' tumor. PATIENTS AND METHODS: Patients treated for newly diagnosed Wilms' tumor at St Jude Children's Research Hospital between December 1978 and July 1995 were included in the study if an initial chest radiograph and CT were available and if pulmonary involvement (determined by chest radiographs) was absent. For the 202 patients studied, radiographs and CT scans were reviewed blindly and independently by three experienced radiologists for the presence of pulmonary nodules. Outcome variables consisted of intraobserver variability (in a subsample of 40 cases) and concordance between ratings on radiographs and CT scans (both by McNemar's test), interrater variability (by logistic regression), and the cumulative incidence of pulmonary relapse for patients with and without positive CT scans, by reviewer. RESULTS: As expected, ratings of pulmonary involvement on radiographs were discordant with CT ratings. There was marked variability among reviewers in CT ratings (P = .0001). Of 202 CT scans, 78 were read as positive by at least one reviewer, 41 were rated positive by only one reviewer, 18 by two reviewers, and 19 by all three. Intrarater variability on repeat reviews was not significant. Patients with nodules identified on CT had a significantly higher pulmonary relapse rate when analyzed separately by reviewer. However, for the 14 patients who had pulmonary relapse, CT scans were rated positive by all three reviewers in only five cases and as negative by all three in another five cases. CONCLUSION: The variability in interpretation of chest CT scans in patients with Wilms' tumor limits the predictive utility of these studies. Optimal, standardized techniques and central review are essential if chest CT is to be used for staging in cooperative studies.

Adolescent↗
PubMed1997

Nasopharyngeal carriage of penicillin-resistant Streptococcus pneumoniae in children with sickle cell disease.

OBJECTIVE: We studied the prevalence of nasopharyngeal (NP) carriage, antimicrobial susceptibilities, and serotypes of Streptococcus pneumoniae (SP) in children with sickle cell disease (SCD) in the Mid-South. In addition, we examined risk factors for NP carriage of penicillin-resistant SP (PRSP). STUDY DESIGN: Between July 1994 and December 1995, we obtained NP cultures from 312 children with SCD followed at the Mid-South Sickle Cell Center, 208 (67%) of whom were receiving penicillin prophylaxis. RESULTS: Among the 312 patients, colonization with SP occurred in 42 (13%), 30 (71%) of whom were receiving penicillin prophylaxis. Twenty-three of the 42 SP isolates (55%) were resistant to penicillin; 5 of the 23 (22%) were highly resistant. PRSP organisms were also resistant to cefotaxime (43%), trimethoprim-sulfamethoxazole (57%), and erythromycin (22%). Serotypes 6A, 6B, 14, 19A, and 23F accounted for 19 (90%) of 21 resistant strains. Children who were treated with antibiotics during the preceding month were more likely to carry PRSP than children who were not treated. CONCLUSIONS: There is a high prevalence of NP carriage of PRSP in children with SCD in the Mid-South, which raises concerns regarding the continued effectiveness of penicillin prophylaxis in these children. Further studies on the antimicrobial susceptibilities of resistant organisms and the relationship between NP carriage of SP and invasive disease are needed before developing new recommendations for prophylaxis and treatment.

Adolescent↗
PubMed1996

Antibiotic-resistant pneumococcal infection in children with sickle cell disease in the United States.

OBJECTIVE: The purpose of this report is to examine the increasing problem of antibiotic-resistant pneumococcal infection in children with sickle cell disease in the United States. PATIENTS AND METHODS: In this retrospective review, 16 children with sickle cell disease and penicillin-resistant pneumococcal invasive infection were identified. They had a median age of 2 years (range 1-15) and were treated in Memphis, Dallas, Los Angeles, and five other cities between 1987 and early 1995. RESULTS: At presentation, patients frequently had high fever (> or 40.0 degrees C in 75%) and a toxic appearance (44%). Meningitis was present initially in two and diagnosed on days 4 and 5 in two. All were treated with an intravenous cephalosporin and nine received vancomycin. The clinical course was variable: two died within 36 h of presentation. In 20-86% of cases the organisms were resistant to cephalosporins, chloramphenicol, trimethoprim/sulfamethoxazole, erythromycin, and clindamycin; none were resistant to vancomycin. CONCLUSIONS: (a) The increasing prevalence of antibiotic-resistant Streptococcus pneumoniae infection in the United States poses special problems for patients with sickle cell disease. (b) Prompt antibiotic susceptibility testing of pneumococcal isolates should be performed. (c) Initial antibiotic management for patients suspected of sepsis/meningitis should include intravenous cephalosporin and vancomycin. (d) No alternative to penicillin prophylaxis is currently available. (e) An effective conjugated pneumococcal vaccine is needed.

Adolescent↗
PubMed1996

Outpatient therapy with ceftriaxone and oral cefixime for selected febrile children with sickle cell disease.

PURPOSE: Children with sickle cell disease are at increased risk for bacterial sepsis and, when febrile, are usually hospitalized for intravenous antibiotic therapy pending results of blood cultures. In this study, we prospectively identified a group of febrile patients with sickle cell disease who were at low risk for sepsis and treated them with outpatient therapy. PATIENTS AND METHODS: Children identified as low risk for sepsis were treated with an initial dose of intravenous ceftriaxone, followed by outpatient therapy with oral cefixime, and were monitored for 14 days after the initial visit. Compliance was assessed by phone calls to parents and by analysis of urine samples. RESULTS: In 107 eligible febrile episodes (80 patients) over a 21-month period, no patient developed sepsis. One child developed bacteremia 3 days after completing the course of cefixime, and one had splenic sequestration on the fourth study day. Both patients did well. Side effects of cefixime were modest, and overall compliance was excellent (approximately 95%), although urine samples were returned by only 56% of parents. CONCLUSION: We conclude that outpatient therapy is safe and effective in febrile patients with sickle cell disease who meet the criteria for a low risk of sepsis.

Administration, Oral↗
PubMed1996

Transdermal fentanyl administration in children and adolescents with sickle cell pain crisis.

PURPOSE: The purpose of this study was to determine the dose-concentration relationship and clinical effect of transdermal fentanyl (TF) in patients with sickle cell pain crisis (SCPC). PATIENTS AND METHODS: Ten patients aged 9-16 years were studied. Patients initially received a TF dose of 25 (n = 7) or 50 (n = 3) micrograms/h if morphine use was > 2.5 mg/h. Supplemental morphine usage via patient-controlled analgesia (PCA), sedation status, pain status, respiratory rate, pulse rate, oxygen saturation, and blood pressure were monitored. RESULTS: The average TF dose was 0.77 +/- 0.37 micrograms/kg/h on day 1 and 1.17 +/- 0.46 micrograms/kg/h on day 2. Fentanyl concentrations measured at 24 and 48 h were 0.60 +/- 0.31 and 1.18 +/- 0.44 ng/ml, respectively. A significant relationship existed between TF dose and fentanyl concentration (r2 = 0.56, p < 0.01). There was no difference in any of the clinical monitoring parameters between day 1 and day 2. However, 7 of 10 patients reported subjective improvement in pain control over that achieved with PCA alone. No adverse effects were noted. CONCLUSIONS: Improved understanding of the dose-effect relationship for TF in children and adolescents is necessary before adequate pain control can be achieved with this delivery system.

Administration, Cutaneous↗
PubMed1995

Serial pulmonary function studies in children treated for newly diagnosed Hodgkin's disease with mantle radiotherapy plus cycles of cyclophosphamide, vincristine, and procarbazine alternating with cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine.

BACKGROUND: The pulmonary toxicity of bleomycin-containing chemotherapy combined with mantle radiotherapy in children treated for Hodgkin's disease was longitudinally assessed. METHODS: The results of serial pulmonary function studies in 37 children, newly diagnosed and treated at St. Jude Children's Research Hospital between September 23, 1983, and June 30, 1988, with cyclophosphamide, vincristine, and procarbazine (COP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus low dose mantle radiotherapy are analyzed. All patients had pulmonary function studies at least before the first bleomycin dose, after completion of radiotherapy, and serially upon discontinuation of therapy. Bleomycin therapy was withheld whenever measured carbon monoxide diffusing capacity was less than 50% of the predicted value. RESULTS: Vital capacity, diffusing capacity, and diffusing capacity per unit of alveolar volume declined during the first 6 months of therapy but improved there after. At 2 years postdiagnosis, diffusing capacity per unit of alveolar volume remained significantly reduced. Only one patient was symptomatic at the 2-year point. The survival rate of these patients was 95% at a median follow up of 93 months. CONCLUSION: If bleomycin is with held when diffusing capacity is diminished to 50% predicted, clinical compromise of pulmonary function appears to be minimal in pediatric patients receiving alternating cycles of COP/ ABVD in combination with low-dose mantle radiotherapy. Survival was excellent, even with reduction of the total bleomycin dose.

Adolescent↗
PubMed1995

Penicillin- and cephalosporin-resistant strains of Streptococcus pneumoniae causing sepsis and meningitis in children with sickle cell disease.

OBJECTIVE: We investigated the possibility that antimicrobial-resistant pneumococci were causing invasive disease in children with sickle-cell disease (SCD). STUDY DESIGN: Records of all children with SCD observed at the Mid-South Sickle Cell Center (MSSCC) at LeBonheur Children's Medical Center were reviewed from January 1990 to June 1994. Children with SCD and pneumococcal sepsis were identified. The Streptococcus pneumoniae isolates from these children were examined for serotype and antimicrobial susceptibilities. Two additional children not observed in the MSSCC had pneumococcal sepsis caused by penicillin-resistant isolates and were also included. RESULTS: Antimicrobial susceptibility testing of the six penicillin-resistant isolates revealed that four were resistant to trimethoprim-sulfamethoxazole, two to erythromycin, and one to clindamycin. The two isolates that were resistant to ceftriaxone also were multiply resistant. From the MSSCC, 26 children had pneumococcal sepsis during the 4 1/2-year period studied. Five of these children (19%) died. Four (15%), including one who died, were infected with penicillin-resistant strains. CONCLUSION: Pneumococcal sepsis, meningitis, and infections of other foci in children with SCD may be caused by S. pneumoniae that is resistant to one or more antimicrobial agents, including penicillin. The addition of vancomycin to the antibiotics currently used for initial management should be considered in areas where the antibiotic resistance of S. pneumoniae is prevalent.

Anemia, Sickle Cell↗
PubMed1995

Higher activity of polymorphic thiopurine S-methyltransferase in erythrocytes from neonates compared to adults.

Thiopurine S-methyltransferase (TPMT) catalyses the S-methylation of aromatic and heterocyclic sulfhydryl compounds, including thiopurine antimetabolites (i.e. mercaptopurine and thioguanine). The activity of TPMT in erythrocytes and other tissues exhibits genetic polymorphism, which is inherited as an autosomal codominant trait. Although inheritance is the principal determinant of TPMT activity, other factors (e.g. renal function, race and thiopurine therapy) have been shown to influence erythrocyte TPMT activity. Because the TPMT polymorphism has not been established in early erythrocyte populations, and the activity of many enzymes differs in neonates, we determined the activity of TPMT in erythrocytes obtained from 60 full-term newborns. Median peripheral blood TPMT activity was 25.3 U per ml pRBC (range 9-52.8 U per ml pRBC), which was > 50% higher than race matched healthy adults (p < 0.001). Western blot analysis demonstrated higher TPMT protein content in erythrocytes from newborns compared to adults, and revealed a significant correlation between TPMT protein and TPMT activity in erythrocytes (rs = 0.63, p = 0.03). Although erythrocyte TPMT activity was significantly higher in newborns, the distribution of activity in newborns was consistent with the genetic polymorphism previously observed in adults.

Adult↗
PubMed1995

A longitudinal study of granulocyte colony-stimulating factor levels and neutrophil counts in newborn infants.

PURPOSE: The goal of this study was to longitudinally measure endogenous granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels in newborn infants and to attempt to correlate these levels with neutrophil counts. PATIENTS AND METHODS: Samples for complete blood count, G-CSF, and GM-CSF were obtained from groups of healthy full-term infants at 0 (cord blood or nursery admission), 12, 24, 48, and 72 h. Samples were also obtained from premature infants at the above times and at 1 week. G-CSF and GM-CSF levels were measured using bioassays. RESULTS: Levels of G-CSF ranged from < 5 to 53,800 pg/ml. Levels were significantly higher (p < 0.001) in premature infants and decreased over time in all infants. White blood cell counts also decreased over the first week of life. All GM-CSF levels were below the detectable range. CONCLUSIONS: Levels of G-CSF at birth are higher than those seen in adults. These increased levels may partially explain the leukocytosis seen in the first week of life. This, as has been shown in preliminary studies, suggests that infants are capable of an increase in neutrophil count after administration of exogenous G-CSF.

Cell Cycle↗
PubMed1995

Subsequent malignancies in children and adolescents after treatment for Hodgkin's disease.

PURPOSE: We assessed the cumulative risk of malignancies following treatment for Hodgkin's disease in childhood and adolescence and investigated related patient and treatment characteristics. PATIENTS AND METHODS: Medical records of 499 Hodgkin's disease patients treated between 1962 and 1993 were reviewed. There were 385 adolescents (> or = 10 years of age at diagnosis) and 114 preadolescents (< 10 years). Most patients (n = 346) were treated with radiation plus multiagent chemotherapy, while 30 received only chemotherapy and 123 only radiation therapy. Radiation doses ranged from 20 to 42 Gy. RESULTS: At a median follow-up duration of 9 years (range, 0.1 to 27.4), 25 patients have had second malignancies: 19 solid tumors, four acute nonlymphoblastic leukemias (ANLLs), 1 non-Hodgkin's lymphoma (NHL), and one chronic myeloid leukemia (CML). Three patients have had a third malignancy. The estimated cumulative risk of second malignancies increased from 1.5% at 5 years to 7.7% at 15 years. All but two of the patients with second malignancies were > or = 10 years of age at initial diagnosis, which reflects the higher risk among patients treated for Hodgkin's disease as adolescents (P = .01). Second malignancies were more common among female patients (P = .0002), even when those breast cancer were excluded (P = .007), and in those treated for recurrent Hodgkin's disease (P = .02). Patients with ANLL/NHL were older at diagnosis of Hodgkin's disease than those with solid tumors, (median age, 18.3 v 13.8 years; P = .04). There was no difference between groups treated with radiation therapy alone, chemotherapy alone, or radiation plus multiagent chemotherapy. CONCLUSION: Adolescents treated for Hodgkin's disease are at greater at risk of second malignancies than younger patients. Overall, adolescent females treated for recurrent Hodgkin's disease appear to be at greatest risk, while preadolescents appear to be protected from this late complication.

Adolescent↗
PubMed1994

Bone metastases in Wilms' tumor--report of three cases and review of literature.

Bone metastases are extremely rare in patients with classical Wilms' tumor (WT). We describe the clinical and radiologic features, treatment and outcome of three patients with WT (one with favorable histology and two with anaplasia) in whom bone metastases were detected at diagnosis or relapse. Bone metastases were documented by skeletal radiographs, computed tomography and/or bone scintigraphy. The patient with favorable histology WT had no evidence of pulmonary metastases and is now free of disease following aggressive chemotherapy and radiotherapy.

Biopsy, Needle↗
PubMed1994

Laparoscopic splenectomy in childhood.

The authors describe their technique for laparoscopic splenectomy in childhood. Five ports, including one 12-mm port for an endoscopic stapler, are placed. With the patient in the supine position, the short gastric vessels are divided between clips. The patient is then placed in the lateral decubitus position for mobilization of the splenic flexure of the colon, division of the posterolateral ligamentous attachments, and en masse transection of the splenic hilum using the EndoGIA stapler. The freed spleen is placed in a nylon reinforced Lap Sac, which is exteriorized at the neck. The spleen is morcellated and the sac removed. Concomitant cholecystectomy is performed in patients with hereditary spherocytosis who have cholelithiasis or sludge. The procedure has been performed without complication in six patients who had hematologic disorders. For another patient, the procedure was converted to an open splenectomy to achieve better hemostasis.

Adolescent↗