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Biomedical subjects

P K Roberson

Publications and source records attributed to P K Roberson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Concordance for childhood cancer in twins.

The causes of most childhood cancer remain elusive; some children clearly have a genetic predisposition, but in the majority the relative contributions of environmental and host factors are not established. One approach to this question is through twin concordance studies, but only the most common malignancy, acute leukemia, has been studied to date, owing to the rarity of other forms of childhood cancer. The aim of the study was to determine the concordance rates for childhood cancer in twins, in order to clarify the importance of constitutional predisposition for a range of tumor types. Twins with cancer were ascertained through three cooperative clinical trials groups, a cancer-twin registry, and a large pediatric hospital. Subjects were sent a postal questionnaire requesting information on cancer concordance and zygosity. Data were obtained on 556 twins with cancer. Three twin pairs, out of 197 twin pairs (76 monozygous, MZ, twin pairs), were concordant for leukemia, giving an MZ case-wise concordance rate (5%) that is substantially lower than previously reported. The case-wise concordance for non-retinoblastoma solid tumors was 2.2%: Two twin pairs were concordant for CNS tumors, one was concordant for neuroblastoma, and two twin pairs were concordant for cancer but not for the type of cancer. The results of the present study, together with previous data from population studies of siblings and offspring, suggest that there is not in general a strong constitutional genetic component for childhood cancers other than retinoblastoma.

Adolescent↗
PubMed1996

Reproductive toxicity and growth effects in rats exposed to lead at different periods during development.

The reproductive toxicity and growth effects of developmental lead exposure were assessed using a rat model in which 0.6% (w/v) lead acetate was administered in the drinking water ad libitum. Three series of experiments were conducted in which lead exposure was initiated beginning in utero, prepubertally, or postpubertally. Lead effects were measured on reproductive physiology and endocrinology, sexually dimorphic hepatic testosterone hydroxylation, and growth rates in both male and female animals. In male animals secondary sex organ weights were significantly decreased only in animals exposed prepubertally. In addition, serum testosterone levels were significantly suppressed, most severely in animals exposed from in utero (in the in utero group). Little effect was observed in adult female rats. However, in female animals exposed prepubertally, delayed vaginal opening and disrupted estrus cycling was observed. More severe reproductive disruption was accompanied by suppression of circulating estradiol in the in utero group. Effects on circulating sex steroids were accompanied by variable effects on circulating luteinizing hormone (LH) levels, pituitary LH, and pituitary LH beta mRNA, suggesting a dual site of lead action: (a) at the level of the hypothalamic pituitary unit, and (b) directly at the level of gonadal steroid biosynthesis. Prepubertal growth in both sexes was suppressed 25% in the in utero group. However, pubertal growth rates were significantly suppressed only in male animals and postpubertal growth was not significantly different from controls in any of the experiments, despite continued exposure to high lead levels in the drinking water. In addition, at age 85 days, male-specific hepatic hydroxylation of testosterone at positions 2 alpha and 16 alpha, which is catalyzed by a cytochrome P450 isozyme CYP 2C11, itself regulated by sexually dimorphic growth hormone secretion, was unaffected. This suggests that the growth effects of lead are possibly due to a delay in the development of sex-specific pituitary growth hormone secretion patterns rather than a persistent developmental defect. Thus, the reproductive and growth effects of lead are complex and sex-dependent, and appear to involve multiple sites on the hypothalamic-pituitary-gonadal axis.

Animals↗
PubMed1995

Safe administration of the measles vaccine to children allergic to eggs.

BACKGROUND: The safety of administering the combined measles-mumps-rubella (MMR) vaccine to patients who are allergic to eggs has been debated for decades because of concern about potential anaphylaxis, since the live attenuated virus used in the vaccine is grown in cultured chick-embryo fibroblasts. METHODS: We recruited 54 children (mean age, 18.5 months) who had not previously been vaccinated and were allergic to eggs. The children's histories of allergy were confirmed with skin tests and double-blind, placebo-controlled food-challenge tests; some children also underwent skin testing with the MMR vaccine. We then routinely administered the vaccine to the children in one subcutaneous (0.5-ml) dose. RESULTS: All 54 children had positive results on skin testing with egg. Allergy to eggs was confirmed in 26 of the children by convincing histories of anaphylaxis after the ingestion of eggs, in 22 children by food-challenge tests, and in 6 patients by convincing histories of recent allergic reactions occurring after the ingestion of eggs. Of the 17 children who underwent skin testing with the MMR vaccine, 3 had positive results. All 54 children received the MMR vaccine as a single subcutaneous injection; none had an immediate or delayed adverse reaction. CONCLUSIONS: The MMR vaccine can be safely administered in a single dose to children with allergy to eggs, even those with severe hypersensitivity.

Anaphylaxis↗
PubMed1995

Comparative virulence of Staphylococcus epidermidis isolates in a murine catheter model.

Among coagulase-negative staphylococci, Staphylococcus epidermidis is the species most commonly implicated in catheter-related infections. Whether some staphylococcal organisms are inherently more virulent than others, or whether their ability to infect relates more to the sheer numbers of organisms at the catheter site, remains unclear. We therefore compared eight S. epidermidis isolates and two other coagulase-negative staphylococci using a murine model that allowed us to quantify catheter colonization and abscess formation in the same animal. The organisms were isolated from different clinically relevant settings and were classified according to their slime phenotype. The ability to evoke abscesses or colonize catheters in half of the animals (ID50) was assessed. ID50 inoculum titers (log10 data +/- SD) ranged widely, from 8.5 +/- 0.3 to 10.2 +/- 0.2 for abscess formation (p < 0.005) and from 7.5 +/- 0.5 to 10.3 +/- 1.0 for catheter colonization (p < 0.005). ID50 values by statistical criteria suggested variability among organisms in the ability to induce abscess formation. High slime production correlated with both parameters, but not with the clinical source of the isolate. Our findings demonstrate impressive heterogeneity in the ability of a representative group of S. epidermidis isolates to colonize catheters and to evoke abscess formation and implicate slime productivity as a major virulence factor. The murine model used permitted simultaneous analysis of multiple factors involved in pathogenesis and should be useful in establishing the basis of S. epidermidis pathogenicity.

Abscess↗
PubMed1994

Correlation of pathologic features with clinical outcome in pediatric adrenocortical neoplasia. A study of a Brazilian population. Brazilian Group for Treatment of Childhood Adrenocortical Tumors.

Although the relationship between pathologic features and clinical outcome is well established in adult adrenocortical neoplasms, the prognostic value of these features in pediatric adrenocortical neoplasms (PACN) is unclear. In a series of PACNs from 54 Brazilian children, the authors retrospectively investigated the prognostic value of histologic classification, ploidy, proliferative index, and size (as tumor weight or greater diameter). Histologic classification was most predictive of clinical behavior: there were no failures in 11 adenomas, 5 failures in 27 low-grade carcinomas, and 9 failures in 16 high-grade carcinomas (P = .0003). Tumor weight was predictive of failure in tumors weighing > or = 100 versus < 100 g (P = .04), and a trend was found toward failure among tumors measuring > or = 5 cm, as opposed to those < 5 cm (P = .07). Proliferative index was marginally related to failure (P = .05 at < 11% vs. > or = 11% and .07 at < 10% vs. > or = 10%), and ploidy was not significantly predictive of outcome (P = .25). Histologic type and tumor weight were the most reliable predictors of outcome in PACN.

Adrenal Cortex Neoplasms↗
PubMed1994

Decreased counts of blood neutrophils, monocytes, and platelets in human immunodeficiency virus-infected children and young adults treated with diethyldithiocarbamate.

Nineteen young human immunodeficiency virus-infected patients were randomized to receive 400 mg of oral diethyldithiocarbamate (DTC) per m2 or placebo weekly for 12 weeks. Changes in blood CD4+ lymphocytes were not significantly different between groups. However, neutrophil, monocyte, and platelet counts consistently decreased during DTC treatment, suggesting DTC-mediated myelosuppression.

Adolescent↗
PubMed1993

Continuous infusion of interleukin-2 in children with refractory malignancies.

BACKGROUND: The toxicity of interleukin-2 (IL-2) administered by continuous infusion has not been investigated in children. METHODS: This study enrolled 10 boys and 7 girls with refractory malignancy. Recombinant IL-2 was infused continuously for cycles of 120 hours at doses escalating from 3 to 30 x 10(6) IU/m2 per day. RESULTS: A total of 45 cycles was administered. The most common toxicities included fever, anemia, hypotension (usually responsive to fluid bolus), hyponatremia, oliguria, hypoalbuminemia, nausea, thrombocytopenia, vomiting, and weight gain. Most side effects were correlated significantly with a dosage of 18 x 10(6) IU/m2 or more per day. Respiratory distress was infrequent. Two cycles were interrupted due to severe toxicity (hypotension in one case and confusion in another), but there were no fatalities. During infusion, there was a significant nondose-related increase in serum IL-2 receptor levels. Despite this evidence of immunomodulation, no objective tumor response was noted. CONCLUSIONS: Continuous infusion of IL-2 at doses up to 30 x 10(6) IU/m2 per day can be administered safely to children by this method.

Adolescent↗
PubMed1993

A phase II trial of ifosfamide in previously untreated children and adolescents with unresectable rhabdomyosarcoma.

BACKGROUND: Children and adolescents with unresectable rhabdomyosarcoma fare poorly when treated with contemporary chemotherapeutic regimens. Evaluation of newly developed agents in these patients is important to improve their outcome. Based on a preclinical rhabdomyosarcoma xenograft model that accurately predicted the activity of new agents, the safety and efficacy of ifosfamide was evaluated as part of a Phase II clinical trial in previously untreated children with unresectable rhabdomyosarcoma. METHODS: Twenty-two children and adolescents (median age, 9 years) with newly diagnosed unresectable rhabdomyosarcoma (Intergroup Rhabdomyosarcoma Study Group III [n = 15] or IV [n = 7]) received two courses of ifosfamide at a dose of 1.6 g/m2 intravenously for 5 days over a 6-week period. Then the patients were evaluated for response, and additional treatment with surgery, radiation therapy, and multiagent chemotherapy (vincristine, cyclophosphamide, dactinomycin, and doxorubicin) was administered. RESULTS: Nineteen of 22 patients (86%) had a partial response to ifosfamide given as a single agent. No complete responses to this agent alone were observed. After administration of additional chemotherapy and local control measures (radiation therapy and surgery), the estimated proportion of patients surviving progression-free at 2 years was 63% (95% confidence interval, 37-80%). Ifosfamide was tolerated well; the most frequent toxicity was nondose-limiting myelosuppression. Transient mild renal toxicity infrequently was observed, and no central nervous system toxicity occurred in this group of patients. CONCLUSIONS: Ifosfamide appears to have significant clinical activity in untreated patients with unresectable rhabdomyosarcomas. These findings provide an accurate estimate of the response rate to single-agent ifosfamide in this group of previously untreated patients and thus provide a foundation for its rational incorporation into multiagent clinical trials. In addition, the potential benefits of this type of new drug development were demonstrated.

Adolescent↗
PubMed1993

MACOP-B treatment in children and adolescents with advanced diffuse large-cell non-Hodgkin's lymphoma.

From 1986 through 1990, 13 previously untreated pediatric patients with advanced diffuse large-cell non-Hodgkin's lymphoma (LC-NHL) were treated with a 12-week MACOP-B regimen at St Jude Children's Research Hospital. Although 12 patients (92%) achieved a complete response, and one had a partial response, the 2-year event-free survival was only 54 +/- 15% (SE). Seven patients remain in continuous complete remission at a median of 40 months after therapy (range 23-57 months). Relapses occurred at sites of initial involvement in five patients at a median of 3.0 months after remission (range 1.2-8.5 months). Salvage therapy with radiation, and high-dose chemotherapy and bone marrow transplantation produced four durable second remissions. The 2-year overall survival for the entire group is 84 +/- 10% (SE). The 12-week MACOP-B regimen proved feasible in an ambulatory clinic setting with only minimal toxicity. We found that MACOP-B is an effective and tolerable treatment for pediatric patients with LC-NHL but did not provide improved survival over that of a similar group of children treated in previous trials at this institution.

Adolescent↗
PubMed1992

Hyperdiploid (47-50) acute lymphoblastic leukemia in children.

Among ploidy groups in childhood acute lymphoblastic leukemia (ALL), hyperdiploidy 47 to 50 is perhaps the least well known. From December 1979 to December 1990, we successfully studied banded karyotypes in 598 cases of newly diagnosed ALL, of which 86 (14.4%) had modal chromosome numbers of 47 to 50. In this group, the most frequently acquired numerical abnormalities were +21 (n = 34), +X (18), +8 (8), and +10 (7). The chromosomal regions most often affected by structural abnormalities were 1q (n = 13), 6q (12), 12p (18), and 19p (9). Analysis of event-free survival (EFS) for Studies X and XI among patients with hyperdiploid (47 to 50) ALL showed no significant differences in outcome according to the presence (n = 36) or absence (n = 35) of chromosomal translocations (P = .81) or the gain of specific chromosomes (P = .40). Patients with hyperdiploid (47 to 50) ALL treated in a contemporary program of multiagent chemotherapy had a significantly better outcome than did those in an earlier study using less intensive therapy (4-year EFS = 75% [95% confidence interval, 55% to 86%] v 41% [22% to 59%]; P = .006 by the logrank test). Our findings indicate that the adverse prognosis previously attributed to hyperdiploidy 47 to 50 improves significantly with more effective chemotherapy.

Adolescent↗
PubMed1992

Trisomy 21 as the sole acquired chromosomal abnormality in children with acute lymphoblastic leukemia.

Most studies of cytogenetic abnormalities in leukemia patients have focused on structural chromosomal rearrangements. Less attention has been paid to the role of single numerical abnormalities in the complex mechanisms of leukemia pathogenesis. We therefore studied 11 cases of acute lymphoblastic leukemia (ALL) with trisomy 21 as the sole chromosomal abnormality, representing 1.8% of 601 completely banded cases of ALL seen during a 10-year period. Bone marrow cells from all but one of these cases also had normal karyotypes, representing 8 to 77% of the completely analyzed metaphases. Each of the five cases tested lacked evidence of trisomy 21 mosaicism of constitutional origin in peripheral blood samples. The presenting features of these five girls and six boys were heterogeneous but tended to reflect lower-risk ALL: median age, 3.3 years (range 1-18 years), median leukocyte count, 11.6 x 10(9)/l (range 1.8-82 x 10(9)/l), white race, and a B-cell precursor immunophenotype. Complete remissions were readily induced in all 11 patients. With follow-up ranging from 1+ months to 6.4+ years, the only relapses have been extramedullary (testis and central nervous system) in two patients, both of whom have since achieved second remissions of greater than 76 and greater than 65 months. Trisomy 21 as the sole chromosomal abnormality in childhood ALL appears related to favorable presenting risk features and may represent a good prognosis subset within the group of patients with 47-50 chromosomes.

Adolescent↗
PubMed1991

Infrared, thermistor, and glass-mercury thermometry for measurement of body temperature in children with cancer.

Body temperature is often the sole determinant of whether or not the neutropenic cancer patient is admitted to the hospital for empiric antibiotic therapy. Recently developed infrared tympanic thermometers offer rapid readings, but their accuracy has not been established. We studied two infrared thermometers (FirstTemp and Thermoscan) and a thermistor (IVAC) in children with cancer. Mean infrared measurements did not differ significantly between right and left ear canals, and the mean IVAC temperature did not differ significantly from the left to the right axilla (P greater than 0.05, paired t test). IVAC predictive mode mean temperature was 0.2 degrees C lower than monitor mode mean temperature in the axilla (P less than 0.0001), but 0.1 degree C higher than monitor mode orally (P less than 0.0001). Aiming the infrared instrument at the tympanic membrane using an ear tug resulted in a 0.2 degree C higher mean temperature than casual placement in the ear canal (P less than 0.0001). After compensation for the mean difference in reference oral glass-mercury versus test instrument temperatures, the FirstTemp, Thermoscan, and oral and axillary predictive mode IVAC measurements yielded sensitivities for the detection of fever of 84%, 84%, 82%, and 86%; specificities of 100%, 99%, 100%, and 100%; positive predictive values of 100%, 93%, 100%, and 100%; and negative predictive values of 95%, 98%, 98%, and 98%, respectively. We conclude that each of these instruments detects fever with comparable reliability. Infrared instruments are especially attractive alternatives due to their time efficiency.

Age Factors↗
PubMed1990

Risk of Haemophilus influenzae type b disease in children with cancer and response of immunocompromised leukemic children to a conjugate vaccine.

From 1969 to 1988, 8 cases of systemic Haemophilus influenzae type b (Hib) disease occurred among 5288 patients with cancer. For the first 4 years of life, systemic Hib disease was significantly greater in leukemic children than in the general population (606/100,000 vs. 90/100,000, respectively). Fifty children aged 2-6 years with acute leukemia were vaccinated with a Hib conjugate vaccine, ProHibit. The overall response rate was 50%; however, 75% of children receiving leukemic therapy for less than 12 months responded versus 18% of those treated longer. After vaccination, the geometric mean antibody concentration was 7.2 micrograms/ml, appreciably lower than for normal children of similar ages. After 12 months, the geometric mean antibody concentration had declined to 0.35 micrograms/ml, and 75% of subjects had antibody levels greater than or equal to 0.15 micrograms/ml. A booster dose for unsuccessfully vaccinated subjects was of minimal benefit. Children with acute leukemia in remission who were treated according to the leukemia therapy protocol of St. Jude Children's Research Hospital had a good likelihood of responding to the conjugate Hib vaccine if administered within a year of initiation of chemotherapy.

Adolescent↗
PubMed1990

Controlling for time-varying population distributions in disease clustering studies.

Both the Knox test and the Mantel test for the presence of disease clustering have previously been shown to be sensitive to changes that occur in the relative geographic population distribution during the time period of study. Although these procedures do not require knowledge of the underlying population density, they implicitly assume it is constant with time. If this is not the case, one may detect clustering which is completely independent of the disease process and simply reflects time-space clustering of the population. Modified procedures are presented which incorporate information from appropriately selected controls to adjust for the effect of a shifting population. Results of a computer simulation study demonstrating the stability of the modified tests in the face of an expanding population are reported.

Cluster Analysis↗
PubMed1990

Detoxification of plasma containing lipopolysaccharide by adsorption.

We compared the ability of 13 materials, all with known affinity for lipopolysaccharide (LPS), to remove LPS from water, pooled normal human plasma, and plasma from a patient with Gram-negative bacterial sepsis. Escherichia coli O111:B4 LPS was added to water and pooled normal human plasma to a concentration of 200 ng/ml and aliquots were adsorbed in parallel with each of the materials. Plasma containing 25 ng/ml of LPS was obtained by plasmapheresis from a patient with fatal Klebsiella pneumoniae sepsis and was similarly adsorbed. Ethanolamine bound to Sepharose 4B served as a control adsorbent. LPS was most readily removed from water and least readily removed from plasma obtained from the patient with sepsis. Nonetheless, some materials removed substantial quantities of LPS from the patient's plasma. Upon ip injection of control-adsorbed patient's plasma into LPS-sensitized mice, death occurred in 13 of 13 mice within 12 h. In contrast, when this plasma was first adsorbed with activated charcoal, Kaopectate, or polymyxin B bound to Sepharose 4B, death occurred 12 h after challenge in 0/13, 0/13, and 2/13 mice, respectively (p less than .0001 by actuarial life table analysis of survival distributions). Thus, plasma that contains bacterial toxins produced during Gram-negative bacterial sepsis can be detoxified by adsorption.

Adsorption↗