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Biomedical subjects

J Blatt

Publications and source records attributed to J Blatt.

At least 19 recordsLinked to original sources
PubMed2001

Parental occupational exposures to chemicals and incidence of neuroblastoma in offspring.

To evaluate the effects of parental occupational chemical exposures on incidence of neuroblastoma in offspring, the authors conducted a multicenter case-control study, using detailed exposure information that allowed examination of specific chemicals. Cases were 538 children aged 19 years who were newly diagnosed with confirmed neuroblastoma in 1992-1994 and were registered at any of 139 participating hospitals in the United States and Canada. One age-matched control for each of 504 cases was selected through random digit dialing. Self-reported exposures were reviewed by an industrial hygienist, and improbable exposures were reclassified. Effect estimates were calculated using unconditional logistic regression, adjusting for child's age and maternal demographic factors. Maternal exposures to most chemicals were not associated with neuroblastoma. Paternal exposures to hydrocarbons such as diesel fuel (odds ratio (OR) = 1.5; 95% confidence interval (CI): 0.8, 2.6), lacquer thinner (OR = 3.5; 95% CI: 1.6, 7.8), and turpentine (OR = 10.4; 95% CI: 2.4, 44.8) were associated with an increased incidence of neuroblastoma, as were exposures to wood dust (OR = 1.5; 95% CI: 0.8, 2.8) and solders (OR = 2.6; 95% CI: 0.9, 7.1). The detailed exposure information available in this study has provided additional clues about the role of parental occupation as a risk factor for neuroblastoma.

Adolescent↗
PubMed2001

Comparison of assessment methods for pesticide exposure in a case-control interview study.

In epidemiologic studies, much of the variation in disease risk estimates associated with occupational pesticide exposure may be due to variation in exposure classification. The authors compared five different methods of using interview information to assess occupational pesticide exposure in a US-Canada case-control study of neuroblastoma (1992-1994). For each method, exposure assignment was compared with that of a reference method, and neuroblastoma effect estimates were calculated. Compared with the reference method, which included a complete review of occupation, industry, job tasks, and exposure-specific activities, the use of occupation-industry groups alone or in combination with general job task information diluted the exposed group by including individuals who were unlikely to have been truly exposed. The effect estimates representing associations between each exposure method and neuroblastoma were different enough to influence the study's conclusions, especially when the exposure was rare (for maternal occupational pesticide exposure, the odds ratio was 0.7 using the reference exposure assessment method and 3.2 using the occupation-industry group exposure assessment method). Exposure-specific questions about work activities can help investigators distinguish truly exposed individuals from those who report exposure but are unlikely to have been exposed above background levels and from those who have not been exposed but are misclassified as exposed because of their employment in an occupation-industry group determined a priori to be exposed.

Adult↗
PubMed2001

Hematologic abnormalities in children and young adults receiving tacrolimus-based immunosuppression following cardiothoracic transplantation.

To define the incidence, course, and etiology of hematologic abnormalities in children on tacrolimus-based immunosuppression, we reviewed records of 106 transplant patients (70 heart, 16 heart and lung, 20 double lung), 0-21 yr of age, who were transplanted at the Children's Hospital of Pittsburgh from 1989 to 1997. Fifty-four of the 106 patients (51%) developed 65 abnormal hematologic episodes (32 anemia, nine neutropenia, nine thrombocytopenia, 15 simultaneous anemia and neutropenia with or without thrombocytopenia). Common etiologies included: infections, post-transplant lymphoproliferative disease, and medications. Eleven episodes (seven anemia, one neutropenia, and three simultaneous anemia and neutropenia) had unclear etiologies and process of elimination suggested an association with tacrolimus. Interventions included filgrastim (effective in 15 of 15 patients, with resolution of neutropenia in a median of 5 days) and epoetin alfa (effective in five of 16 patients, including four of four patients with anemia possibly related to tacrolimus). Five patients (two with neutropenia and three with simultaneous neutropenia and anemia) were switched to cyclosporin A (CsA); rapid resolution occurred in four of the five patients, suggesting a possible association of the hematologic abnormalities with tacrolimus. In summary, hematologic abnormalities are common in children on tacrolimus-based immunosuppression. Most of these hematologic abnormalities are caused by common etiologies; however, a sub-population exists where tacrolimus may be the etiologic agent. Anemia and neutropenia respond to treatment with epoetin alfa and filgrastim. After thorough investigation, a trial switch to CsA may be warranted.

Adolescent↗
PubMed2001

Off-label use of recombinant factor VIIa in patients following bone marrow transplantation.

Recombinant factor VIIa (rFVIIa, NovoSeven) is FDA-approved for the treatment of bleeding in patients with hemophilia A/B with inhibitors. A growing literature suggests that there may be expanded indications for the use of NovoSeven in patients with significant bleeding who do not have a known factor deficiency. Severe bleeding refractory to standard hematologic or hemostatic support is common in patients undergoing bone marrow transplantation (BMT). We review our experience with rFVIIa in three patients (8 years 8 months to 19 years, median 13 years) treated for pulmonary hemorrhage (n = 1), hemorrhagic cystitis (n = 3), and gastrointestinal bleeding (n = 2). Boluses of 90-270 microg/kg rVIIa with subsequent doses of 90 microg/kg every 4-24 h for 3-14 days were given, concurrent with maintaining platelet counts >50,000/mm(3). Transient clinical responses in gross hematuria (two patients) and in pulmonary hemorrhage were noted within several days of starting rFVIIa, but bleeding in a new site in two patients and renewed bleeding of the initial site in the third resulted in discontinuation of the drug. No toxicity or adverse events were observed while the patients were on rFVIIa treatment. Because of the substantial cost of this product, the lack of adequate monitoring methodology, and the variability of current dose and dosing intervals, large randomized studies are needed before definitive off-label use in the setting of BMT can be recommended.

Acute Disease↗
PubMed2001

Residential pesticide exposure and neuroblastoma.

Neuroblastoma is the most common neoplasm in children under 1 year of age. We examined the relation between residential exposure to pesticides and neuroblastoma, using data from a case-control study of risk factors for neuroblastoma. Incident cases of neuroblastoma (N = 538) were identified through the Pediatric Oncology Group and the Children's Cancer Group. One age-matched control was identified for each case by random digit dialing. Telephone interviews with each parent collected information on residential exposure to pesticides. Pesticide use in both the home and garden were modestly associated with neuroblastoma [odds ratio (OR) = 1.6 (95% confidence interval [95% CI] = 1.0-2.3, and OR = 1.7 (95% CI = 0.9-2.1), respectively]. Compared with infants [OR = 1.0 (95% CI = 0.6-2.0)], stronger associations were found for garden pesticides in children diagnosed after 1 year of age [OR = 2.2 (95% CI = 1.3-3.6)], which suggests that pesticides may act through a mechanism more common for neuroblastomas in older children. There was no evidence of differential pesticide effects in subgroups of neuroblastoma defined by MYCN oncogene amplification or tumor stage.

Canada↗
PubMed2001

Prospective randomized trial between two doses of granulocyte colony-stimulating factor after ifosfamide, carboplatin, and etoposide in children with recurrent or refractory solid tumors: a children's cancer group report.

PURPOSE: The objectives of this study were: 1) to compare the time to hematologic recovery (absolute neutrophil count [ANC] > or = 1,000/mm3 and platelet count > or = 100,000/mm3) in a randomized prospective study of two doses of granulocyte colony-stimulating factor (G-CSF) (5.0 vs. 10.0 microg/kg per day) after ifosfamide, carboplatin, and etoposide (ICE) chemotherapy; and 2) to determine the response rate (complete response [CR] + partial response [PR]) of ICE in children with refractory or recurrent solid tumors. PATIENTS AND METHODS: From June 1992 until November 1994, 123 patients with recurrent or refractory pediatric solid tumors were treated with ifosfamide (1,800 mg/m2 per day x 5), carboplatin (400 mg/m2 per day x 2), and etoposide (100 mg/m2 per day x 5) and randomized to receive either 5.0 microg/kg per day or 10.0 microg/kg per day of G-CSF subcutaneously until recovery of ANC to > or = 1,000/mm3. RESULTS: The incidence of grade 4 neutropenia during the first course was 88%. Median time from the start of chemotherapy to ANC > or = 1,000/mm(-3) for all patients during courses 1 and 2 was 21 and 19 days, respectively. The incidence of developing platelet count < or = 20,000/mm3 during course 1 was 82%. The median time from the start of the course of chemotherapy to platelet recovery > or =100,000/mm3 for all patients during courses 1 and 2 was 27 days. There was no significant difference in the median time of ANC recovery, platelet recovery, or incidence of grade 4 neutropenia; and in the median days of fever and the incidence of infections requiring hospitalization and intravenous antibiotics during courses 1 and 2, there was no significant difference between the two doses of G-CSF. One hundred eighteen patients were evaluated for response to ICE. The overall response rate (CR + PR) in this study was 51% (90% confidence interval, 43%-59%). The CR rate for all diagnostic categories was 27%. The Kaplan-Meier estimates of 1-year and 2-year survival probabilities for all patients were 52% and 30%, respectively. CONCLUSION: In summary, this combination of chemotherapy (ICE) was associated with a high CR rate (27%) in children with recurrent or refractory solid tumors, but also with a high incidence of grade 4 neutropenia and thrombocytopenia. Doubling the dose of G-CSF from 5.0 to 10.0 microg/kg per day after ICE chemotherapy did not result in an enhancement of neutrophil or platelet recovery or the incidence of grade 4 neutropenia developing.

Adolescent↗
PubMed2001

Haemolymph sugar levels in foraging honeybees (Apis mellifera carnica): dependence on metabolic rate and in vivo measurement of maximal rates of trehalose synthesis.

Previous investigations of haemolymph sugar levels in honeybees have reported very different results, probably because different experimental conditions affected the activity levels of the animals. The present study investigated the dependence of haemolymph sugar levels in foraging honeybees on metabolic rate and whether the haemolymph sugar level is regulated. Free-flying foraging bees were trained to collect controlled amounts of sucrose solution of different concentrations (15%, 30% or 50% sucrose w/w). Immediately after feeding, metabolic rate was measured over a given time depending on the sucrose concentration, then crop-emptying rate and haemolymph sugar levels were measured. Bees exhibiting a wide range of metabolic rates were compared to establish whether the observed differences in haemolymph sugar levels were due to limits in the supply of sugars from the crop or in the rate of trehalose synthesis in the fat bodies. Independent of the concentration of the sucrose solution supplied, haemolymph trehalose, glucose and fructose levels were constant for metabolic rates from 0 to 4.5 ml CO(2)h(-1). At higher metabolic rates, trehalose concentration decreased while that of glucose and fructose increased, with the exception of bees fed 15% sucrose solution. As the supply of sugar from the crop via the proventriculus was sufficient to support even the highest metabolic rates, the observed pattern must result from an upper limit in the capacity of the fat body to synthesise trehalose. The maximal rate of conversion of glucose to trehalose in the fat body was therefore calculated to average 92.4 microg glucosemin(-1). However, for bees fed 15% sucrose solution both the rate of conversion of glucose to trehalose and the rate of sugar transport from the crop to the ventricle were limited, together resulting in a decrease in total haemolymph sugar levels for metabolic rates higher than 5 ml CO(2)h(-1).

Animals↗
PubMed2000

Sex steroid receptors in Hodgkin's disease.

A case report of a dramatic therapeutic response of Hodgkin's disease (HD) to diethylstilbestrol (DES) in a man who was being treated for concurrent prostate cancer suggested that there also may be a role for sex steroids in the pathogenesis of HD (1). High levels of estrogen receptors (ER) comparable to those seen in breast carcinoma cells were detected in that patient's Hodgkin's biopsy specimen. In order to determine whether this patient was unique or whether sex steroid receptors commonly are present in HD specimens, we examined expression of ER and progesterone receptors (PR) in diagnostic tissue from pediatric (n = 14) and adult (n = 41) patients with HD using immunohistochemistry. None of the 55 samples expressed PR. 16/55 (29%) demonstrated weak nuclear ER positivity, which was confined to germinal center and occasional mantle zone lymphocytes and was comparable to that seen in non-malignant control lymph nodes. (4/5)5 (7.3%) samples exhibited moderate positivity in Reed Sternberg cells, which in one case was nuclear. ER commonly are expressed weakly in some HD tumors unrelated to clinical stage or patient sex but are generally limited to germinal center and mantle zone lymphocytes. A rare patient displays moderate cytoplasmic or nuclear ER in Reed-Sternberg cells.

Adolescent↗
PubMed1999

Pregnancy outcome in long-term survivors of childhood cancer.

BACKGROUND: By the year 2010, 1/250 young adults will be long-term survivors of childhood cancer. One of the major concerns is whether they will be able to have healthy children. PROCEDURE: The literature was reviewed to determine 1) the extent of intrapartum and perinatal complications experienced by survivors or their spouses and 2) the risk of congenital malformations or cancer in their children. RESULTS AND CONCLUSIONS: Series have reported on pregnancy complications among approximately 400 female survivors and 300 partners of male survivors. An increased incidence of spontaneous abortions, low-birth-weight babies, and neonatal deaths has been described for women with Wilms tumor who had received at least 20 Gy abdominal radiation. Hodgkin disease survivors who had received both radiation and chemotherapy (but not either alone) also appear to be at increased risk of spontaneous abortions. Based on several thousand survivor offspring, there is no overall increased risk of either congenital malformations or childhood cancer. Further studies will define the outcome of offspring of cancer survivors treated in the modern era.

Adult↗
PubMed1999

Haemolymph sugars and the control of the proventriculus in the honey bee Apis mellifera.

Crop emptying and rectal filling rates were investigated in bees trained to collect defined amounts of sucrose solution. Crop emptying rates strongly depended on the sucrose concentration of the collected solution. There was a close match between the energy expenditure of the bees and the amount of sucrose transported through the proventriculus, irrespective of the fluid dilution. Results indicated that the controlling variable was the amount of sucrose flowing through the proventriculus rather than the volume flow. In order to distinguish between haemolymph osmolality and haemolymph carbohydrate levels as factors controlling the activity of the proventriculus, bees were injected with either metabolizable or non-metabolizable carbohydrates. Only the injection of metabolizable carbohydrates modulated the activity of the proventriculus, indicating that the titers of metabolizable carbohydrates are involved in the feedback loop controlling crop emptying, and that haemolymph osmolality alone does not influence the activity of the proventriculus.

Journal Article↗
PubMed1998

Neurodevelopmental anomalies in children with neuroblastoma.

BACKGROUND: Case reports have associated neuroblastoma, a cancer derived from the embryonal neural crest, with aganglionosis coli and neurofibromatosis type I. The aim of the current study was to test the hypothesis that neuroblastoma is part of a global defect in neurodevelopment. METHODS: Neuropathologic findings from autopsies of children who died of neuroblastoma during the period 1980-1995 at the Children's Hospital of Pittsburgh were reviewed for macroscopic and microscopic abnormalities. As controls, autopsies of children who had died of other primary extracranial cancers over the same time period also were studied. Medical records of neuroblastoma patients for whom autopsies were available were reviewed for clinical evidence of preexisting nonmalignant neurologic disease. RESULTS: Of 145 children diagnosed with neuroblastoma, 49 had died, and autopsies not restricting examination of the brain had been performed on 13. Macroscopic anatomic abnormalities (a small cerebellum and the absence of the corpus callosum) were noted in one patient who was known to have been mentally retarded without having a defined syndrome. Microscopic abnormalities of cytoarchitecture were noted in that patient as well as 3 of the 12 other patients (focal cortical dysplasia [fcd], n = 3; leptomeningeal heterotopia, n = 1; abortive sulcation or flattened gyri, n = 2). None of 3 patients with only microscopic abnormalities had clinical evidence of problems with neurodevelopment. Of the 26 children with nonneuroblastoma cancers for whom complete autopsies were available, 1 infant had major macroscopic structural abnormalities of the brain. None of these patients had microscopic abnormalities (P < 0.01). CONCLUSIONS: Children with neuroblastoma have an increased incidence of abnormalities of brain cytoarchitecture, particularly fcd. These abnormalities are generally asymptomatic and are diagnosed by histologic examination. Such abnormalities cannot be attributed to chemotherapy and are not observed in other children with non-central nervous system tumors. These findings are consistent with the concept that neuroblastoma may occur in the setting of a more global defect in neurodevelopment. A blinded review of larger numbers of cases will be needed to verify these data.

Adolescent↗
PubMed1998

Residence location of drivers involved in fatal crashes.

Traffic safety researchers have long known that the majority of fatal crashes occur on rural roads, but it is not clear whether these crashes involve people who live in rural areas or residents of urban areas traveling on rural roads. 'Geodemographic' market-research tools allow determination of the urbanization of drivers' residence locations from their postal 'zip code.' Using data from the 1988-1992 files of the Fatal Accident Reporting System (FARS) maintained by the National Highway Traffic Safety Administration (NHTSA), this study determined the residence location of several subgroups of drivers involved in fatal crashes. Not only did the majority of fatal crashes occur in rural areas, but the majority of fatal crashes involved rural and small-town residents and the majority of the rural and small-town residents involved in fatal crashes were traveling on rural roads.

Accidents, Traffic↗
PubMed1998

Partial splenic embolization for treatment of disseminated intravascular coagulation in lymphangiomatosis.

A 1-year-old boy presented with pericardial effusion, pulmonary infiltrates, and disseminated intravascular coagulation; lung biopsy indicated pulmonary lymphangiomatosis. He did not respond to medical therapy and was a poor surgical candidate; therefore, he underwent partial splenic embolization. The procedure resulted in a complete disappearance of the DIC and marked improvement in his cardiorespiratory status. He continues to thrive and is transfusion-independent 2 years after the procedure.

Disseminated Intravascular Coagulation↗
PubMed1998

Phase I trial and pharmacokinetic study of pyrazoloacridine in children and young adults with refractory cancers.

PURPOSE: To define the maximum-tolerated dose (MTD), quantitative and qualitative toxicities, recommended phase II dose, and pharmacokinetics of pyrazoloacridine (PZA) administered as a 1- or 24-hour infusion in children and young adults with refractory cancers. PATIENTS AND METHODS: Twenty-two patients received PZA as a 1-hour infusion at doses of 380 mg/m2 (n = 3), 495 mg/m2 (n = 6), 640 mg/m2 (n = 6), and 835 mg/m2 (n = 7). An additional four patients received PZA as a 24-hour infusion at the MTD (640 mg/m2) for the 1-hour infusion schedule. Plasma samples were obtained for pharmacokinetic analysis in 17 patients. PZA concentration in plasma was measured by reverse-phase high-performance liquid chromatography (HPLC). A two-compartment pharmacokinetic model was fit to the PZA plasma concentration data. RESULTS: On the 1-hour infusion schedule, dose-limiting myelosuppression (neutropenia more than thrombocytopenia) was observed in two of seven patients at the 835-mg/m2 dose level. Myelosuppression did not appear to be ameliorated by prolonging the infusion to 24 hours. Nonhematologic toxicities were minor. Significant neurotoxicity, which was dose-limiting in adults treated with a 1-hour infusion of PZA, was observed in one patient treated at 640 mg/m2, but was not dose-limiting. There was marked interpatient variability in plasma PZA concentrations at all dose levels. The pharmacokinetic profile of PZA was characterized by an initial rapid decline (alpha half-life [t(1/2)alpha], 0.5 hours) followed by a prolonged elimination phase (t(1/2)beta, 30 hours). The volume of distribution at steady-state (Vd(ss)) was 700 L/m2 and the clearance was 300 mL/min/m2. There was no evidence of dose-dependent clearance. The area under the PZA concentration-time curve (AUC) correlated poorly with dose and was more predictive of the degree of myelosuppression than was PZA dose. CONCLUSION: PZA administered as 1- or 24-hour infusion is well tolerated by children and young adults. The dose-limiting toxicity (DLT) is myelosuppression. Neurotoxicity is not prominent in this age group. There was marked interpatient variation in plasma concentrations of PZA. The recommended dose for phase II studies is 640 mg/m2.

Acridines↗
PubMed1997

Delayed resection in the management of non-orbital rhabdomyosarcoma of the head and neck in childhood.

This retrospective study was undertaken to evaluate the effect of delayed resection on outcome of head and neck rms in a single institution which has experience in cranial base surgery. Since 1988, patients with primary non-orbital rms of the head and neck following treatment at the Children's Hospital of Pittsburgh, were evaluated by the Department of Otolaryngology, Eye and Ear Hospital at the University of Pittsburgh Medical Center either at the time of presentation or when response to chemotherapy and/or radiation therapy was thought to have been optimized for the possibility of definitive surgery. Medical records of patients who did or did not have delayed surgery were reviewed and compared with respect to demographics, tumor stage, response to therapy, survival, and cosmetic results. Of 16 children diagnosed with non-orbital head and neck rms from 1988-1994 and treated with chemotherapy according to IRS II-IV, 3 had group I or II disease following extensive surgery at diagnosis. Thirteen had group III or IV disease. Of these, 6 patients had delayed resection and 7 did not. Delayed resection was undertaken 3-12 months (median, 4 months) from diagnosis in 4 children who had a partial response (PR) and 2 children who had stable disease (SD) with chemotherapy and/or radiation. Delayed resection converted all children to complete responses (CR), including one child with clinical SD and one with PR who were found to have no viable tumor at surgery. The overall percentages of CRs for patients with group III or IV disease (documented any time post-diagnosis) were at least as good for patients who had undergone delayed surgery as for those who had not (100% vs. 71%, p = .465). Median survivals for patients with advanced disease were 3 1/2 years and 2 years, respectively (p = .2801). Cosmetic and functional problems attributable to surgery were not severe but included facial asymmetry (n = 4), trismus (n = 1), cranial nerve deficits (n = 1), and abnormal dentition (n = 1). In locally extensive head and neck rms, cranial base surgery should be considered after initial cytoreductive therapy, since it may contribute to achievement of CR and to survival with acceptable morbidity.

Child↗