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Biomedical subjects

B H Pollock

Publications and source records attributed to B H Pollock.

At least 55 records · Page 3Linked to original sources

Meta-analyses of the effectiveness of intravenous immune globulin for prevention and treatment of neonatal sepsis.

OBJECTIVE: To determine the effectiveness of intravenous immune globulin (IVIG) in the prevention and treatment of neonatal sepsis. DESIGN: All published studies of IVIG for the prevention or treatment of neonatal sepsis were reviewed. Peer-reviewed, prospective, randomized trials with high merit were analyzed by two meta-analyses. The effect of prophylactic IVIG was evaluated by comparison of the numbers of cases of sepsis (bacteremia in the presence of systemic manifestations of sepsis), and of therapeutic IVIG by comparison of the numbers of deaths resulting from early-onset sepsis. RESULTS: Meta-analysis of 4933 evaluable newborns in 12 studies of IVIG prophylaxis showed a statistically significant negative association with the incidence of sepsis in premature low birth weight newborns given IVIG shortly after birth (P = .0193, two-sided). The heterogeneity across these studies precluded estimation of a common odds ratio. Meta-analysis of 110 evaluable cases of neonatal sepsis in three studies of IVIG treatment of neonatal sepsis showed a significant decrease in the mortality rate for neonates with sepsis given IVIG (P = .007, two-sided). The common odds ratio was .173 (95% confidence interval = .031 to .735). CONCLUSIONS: Using conservative and objective outcome rating criteria, the addition of IVIG to standard therapies is of minimal but demonstrable benefit in preventing sepsis when administered prophylactically to premature low birth weight newborns, and of unequivocal benefit in preventing death when administered therapeutically for early-onset neonatal sepsis. The likelihood of newborns with sepsis living past the neonatal period was improved nearly sixfold when IVIG was administered in addition to standard therapies.

Bacterial Infections↗

Benign and malignant smooth muscle tumors containing Epstein-Barr virus in children with AIDS.

Smooth muscle tumors (leiomyosarcomas) are the second most prevalent malignancy of children with the acquired immunodeficiency syndrome (AIDS). We have investigated the tumors, plasma, and peripheral white blood cells of eight children with AIDS with smooth muscle tumors for evidence of tumor association with human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV). Very low levels of HIV were found in the tumors of the AIDS patients, probably resulting from blood-borne carriage of virus. These smooth muscle tumors had very high quantities of EBV in all the tumor cells by in situ hybridization, with an average of 4.5 EBV genomes per cell by quantitative polymerase chain reaction amplification. Increased amounts of EBV were found in the peripheral blood cells of two AIDS patients before the time of tumor diagnosis. EBV clonality studies demonstrated different monoclonal EBV infection of two separate colonic tumors from one patient, and dual or mixed monoclonal EBV infection in another patient. The muscle cells of leiomyomas and leiomyosarcomas of patients with AIDS demonstrated prominent staining with antibodies to the EBV receptor. The uniform distribution and striking amount of EBV in the tumor cells demonstrates that EBV is capable of infecting smooth muscle cells and that these cells support EBV replication. Clonal EBV proliferation suggests that EBV infection occurs at an early stage of tumor development. These findings indicate that EBV has a causal role in the oncogenesis of leiomyosarcomas of patients with AIDS.

Acquired Immunodeficiency Syndrome↗

Childhood cancer in the United States. A geographical analysis of cases from the Pediatric Cooperative Clinical Trials groups.

BACKGROUND: After injuries, cancer is the leading cause of death in children younger than 15 years in the United States. Despite dramatic increases in 5-year survival rates, more than 100,000 person-years of life are lost to childhood cancer each year. The exact proportion of pediatric cancer patients who receive care at centers that utilize up-to-date therapeutic protocols [such as those affiliated with the Childrens Cancer Group (CCG) or the Pediatric Oncology Group (POG)] remains unknown. The purpose of this study was to estimate the proportion and geographic distribution of childhood cancer patients in the United States who are seen at participating centers of the CCG and the POG. METHODS: Patients included 21,026 incident pediatric cancer cases diagnosed from January 1, 1989 through December 31, 1991. Observed numbers of pediatric cancer cases were compared with expected numbers of cases calculated from incidence rates obtained from the Surveillance, Epidemiology, and End Results (SEER) Program and population counts obtained from the 1990 U.S. Census Bureau. RESULTS: Approximately 94% of children younger than 15 years diagnosed with cancer are seen at an institution that is a member of either POG or CCG. Comparisons of the observed-to-expected numbers of incident cases in the age groups (birth-4 years, 5-9 years, 10-14 years, and 15-19 years) demonstrated ascertainment rates of 100, 93, 84, and 21%, respectively. In some regions within the United States the observed number of cases was significantly less than that expected number, including areas of Idaho, Oklahoma, and Virginia. In addition, there were areas in which the observed number of childhood cancer cases was substantially greater than that expected, including areas in California and Florida. CONCLUSIONS: The membership of the cooperative clinical trials groups (the POG and CCG) ascertain and provide access to state-of-the-art treatment protocols for the vast majority of pediatric cancer patients in the country. For the younger age groups, the CCG and POG may represent a mechanism of case ascertainment that approximates a population-based series for the continental United States. Those areas that have large enough discrepancies in observed-to-expected numbers may warrant further investigation.

Adolescent↗

Quality-of-life research in the Pediatric Oncology Group: 1991-1995.

Quality-of-life end points for cancer clinical trials have received much attention in the adult literature. However, within pediatric cancer clinical trials, the inclusion of these alternate end points has only recently been considered. We review the Pediatric Oncology Group's approach to research in this area and describe our guidelines and protocols that incorporate quality-of-life end points and several of the methodologic barriers that must be addressed.

Child↗

Association of Epstein-Barr virus with leiomyosarcomas in young people with AIDS.

BACKGROUND: Children with the acquired immunodeficiency syndrome (AIDS) have an unusually high incidence of smooth-muscle tumors (leiomyomas and leiomyosarcomas) in addition to malignant lymphomas. We tested the hypothesis that the smooth-muscle tumors in these children are associated with the Epstein-Barr virus (EBV). METHODS: Tissue specimens of five leiomyosarcomas and two leiomyomas from six children with AIDS were studied for evidence of the human immunodeficiency virus (HIV) and EBV by in situ hybridization and quantitative polymerase chain reaction (PCR). Comparison specimens included samples of leiomyosarcoma and leiomyoma from HIV-negative children. EBV clonality of leiomyosarcomas was determined by Southern blot analysis with oligonucleotide probes for EBV terminal-repeat fragments. Tumor specimens were tested by immunoperoxidase staining for infiltration by B lymphocytes and expression of the EBV receptor. Serologic testing for EBV was performed. RESULTS: In situ hybridization showed EBV genomes in all muscle cells of the five leiomyosarcomas and the two leiomyomas from the six HIV-infected children. Quantitative PCR demonstrated strikingly high levels of EBV in tumor tissue, with as many as 4.3 genome copies per cell. Two colonic leiomyosarcomas obtained from different sites at different times from one patient contained different episomal EBV clones, signifying the presence of distinct monoclonal EBV-related tumors. We found biclonal EBV infection in the leiomyosarcoma of another patient. No EBV was detected in normal muscle or tumor specimens from HIV-negative patients. Immunostaining for the EBV receptor was strongly positive in six of the seven leiomyomas and leiomyosarcomas from the patients with AIDS. CONCLUSIONS: EBV can infect smooth-muscle cells, at least in patients with AIDS, and it may contribute to the pathogenesis of leiomyomas and leiomyosarcomas in children with AIDS. EBV seems to play no part in smooth-muscle tumors in HIV-negative children.

AIDS-Related Opportunistic Infections↗

Pediatric residents' continuity clinics: how are we really doing?

The Accreditation Council for Graduate Medical Education (ACGME) established guidelines in 1989 requiring pediatric residents to attend a continuity clinic (CC) one half-day per week. OBJECTIVE. To assess pediatric residents' CCs, with an emphasis on those factors potentially affecting house staff education and patient care. DESIGN AND PARTICIPANTS. A multi-item questionnaire designed to assess the educational, administrative, and clinical components of CCs was distributed to all US CC directors. RESULTS. Responses were received from 164 programs (74.9%), which represented more than 90% of all house staff in accredited US pediatric programs. Fifty-five percent of programs acknowledged non-ACGME-approved exemptions from attendance, and 64% changed CC schedules dependent on in-patient rotation assignment. Less than half of the programs had core curricula or didactic conferences. Most programs (76%) were located in hospital clinics. Clinic resources and equipment were often limited; faculty preceptors and nursing and clerical support staff were frequently insufficient in number. On average, PL1s saw four patients per session, whereas PL2s and PL3s saw five. Continuity of care for the patient for phone calls, acute and after-hours visits, and hospitalization was limited. Directors' perceived support for CCs' educational programs ranged from a high of 87% by generalists to a low of 33% by intensivists. CONCLUSIONS. Despite the ACGME directives, many residency programs have not provided the required priority, protected time, or adequate resources for CCs. The recent emphasis on health care reform and primary care medical education highlights the prominent role the CC should play as an important site in our teaching of longitudinal and ambulatory medicine. Departmental support and committed resources necessary to enhance the experience and to meet the educational challenge successfully will be required.

Ambulatory Care↗

Bone marrow transplants from HLA-identical siblings as compared with chemotherapy for children with acute lymphoblastic leukemia in a second remission.

BACKGROUND: It is unclear how best to treat children with acute lymphoblastic leukemia who are in a second remission after a bone marrow relapse. For those with HLA-identical siblings, the question of whether to perform a bone marrow transplantation or to continue chemotherapy has not been answered. METHODS: We compared the results of treatment with marrow transplants from HLA-identical siblings in 376 children, as reported to the International Bone Marrow Transplant Registry, with the results of chemotherapy in 540 children treated by the Pediatric Oncology Group. A preliminary analysis identified variables associated with treatment failure in both groups. We selected cohorts by matching these variables. A possible bias associated with differences in the interval between remission and treatment was controlled for by choosing matched pairs in which the duration of the second remission in the chemotherapy recipient was at least as long as the time between the second remission and transplantation in the transplant recipient. A total of 255 matched pairs were studied. RESULTS: The mean (+/- SE) probability of a relapse at five years was significantly lower among the transplant recipients than among the chemotherapy recipients (45 +/- 4 percent vs. 80 +/- 3 percent, P < 0.001). At five years the probability of leukemia-free survival was higher after transplantation than after chemotherapy (40 +/- 3 percent vs. 17 +/- 3 percent, P < 0.001). The relative benefit of transplantation as compared with chemotherapy was similar in children with prognostic factors indicating a high or low risk of relapse (the duration of the first remission, age, leukocyte count at the time of the diagnosis, and phenotype of the leukemic cells). CONCLUSIONS: For children with acute lymphoblastic leukemia in a second remission, bone marrow transplants from HLA-identical siblings result in fewer relapses and longer leukemia-free survival than does chemotherapy.

Adolescent↗

Quality assurance for interventions in clinical trials. Multicenter data monitoring, data management, and analysis.

Quality assurance for the management of multicenter clinical trials requires timely patient and data accrual and consistency with design parameters. Data from central pathology review, treatment modality, and follow-up as well as trial end points direct the selection of appropriate compliance measures. To integrate these data to monitor group performance on a specific protocol, to monitor discipline performance, or to monitor an institution's performance is a formidable task. This is especially true for a group such as the Pediatric Oncology Group, where there are a large number of protocols, many diseases, and widely differing protocol requirements. Quality assurance methods for the Pediatric Oncology Group are discussed.

Clinical Trials as Topic↗

Recombinant alpha-2B interferon treatment for childhood T--lymphoblastic disease in relapse. A Pediatric Oncology Group Phase II study.

BACKGROUND: Children with chemotherapy refractory T-cell lymphoblastic leukemia/lymphoma were given alpha-interferon (alpha-IFN) to evaluate the efficacy and toxicity of this biologic response modifier. METHODS: Twenty children with T-cell acute lymphoblastic leukemia (T-cell ALL) in marrow relapse and one patient with mediastinal recurrence of T-cell non-Hodgkin's lymphoma (T-cell NHL) were enrolled. All patients had failed at least two previous multiagent drug trials. Recombinant alpha-IFN was given at 30 million U/M2/dose intravenously or subcutaneously for 10 doses over 14 days, followed by 3 doses per week until disease progression occurred. RESULTS: One child had a complete response (< 5% blasts) and three patients a partial response (5-25% blasts) in their bone marrow. All patients eventually showed signs of progressive disease. Significant toxicities included cardiac hypofunction in two patients and profound lethargy in two patients. CONCLUSIONS: alpha-IFN is tolerated in children with T-cell ALL and T-cell NHL and has activity against chemotherapy resistant disease.

Adolescent↗

Evaluation of the interrupter technique for the use of assessing airway obstruction in children.

The purpose of this study was to determine if the interrupter technique, a noninvasive method for measuring airflow resistance, could be used to assess airway obstruction in children. In 107 children (74 with asthma, 12 with cystic fibrosis, and 21 without lung disease) conductance (mostly of airways) measured with the interrupter technique (Gint) was correlated with both forced expiratory volume in 1 second (FEV1) and the forced expired flow rate between 25% and 75% of vital capacity (FEF25-75). In addition, 17 children with significant airway obstruction due to asthma also had airway resistance measured by body plethysmography (R(aw)) before and after treatment. Resistance and conductance measurements made with the interrupter technique were subdivided into inspiratory (Rint-insp, Gint-insp) and expiratory (Rint-exp, Gint-exp) values. In the 107 children, a high degree of linear correlation was found between Gint and FEV1; for Gint-exp, r = 0.77 (P < 0.001), and for Gint-insp, r = 0.76 (P < 0.001). There was also good linear correlation between Gint and FEF25-75; for Gint-exp, r = 0.70 (P < 0.001), and for Gint-insp, r = 0.67 (P < 0.001). In the 17 asthmatic children who were tested before and after treatment of their airway obstruction, Rint correlated highly with R(aw); for Rint-exp, r = 0.91 (P < 0.001), and for Rint-insp, r = 0.83 (P < 0.001). The pre- to post-treatment changes in Rint and R(aw) were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Obstruction↗

Phase I trial of continuous infusion carboplatin and etoposide in children with refractory acute leukemia: a Pediatric Oncology Group study.

PURPOSE: The purpose of this phase I study was to determine the toxicities and response to continuous infusion carboplatin in combination with a fixed dose of etoposide (VP-16) in children with refractory acute leukemia. PATIENTS AND METHODS: From January 1989 to February 1992, 20 patients received 28 courses of treatment. Each course of treatment consisted of a 1-hour intravenous (IV) infusion of VP-16 100 mg/m2/d for 5 days, followed by a 23-hour IV infusion of carboplatin each day. The initial, total 5-day dose of carboplatin (1,000 mg/m2) was escalated by 250- to 375-mg increments to a final, total dose of 1,875 mg/m2 over 5 days. RESULTS: Significant marrow suppression was observed in all patients, with prolonged marrow aplasia at the 1,875-mg/m2 dose level. Grade III diarrhea occurred in three patients; 10 patients experienced life-threatening infection and three had severe thrombocytopenic bleeding. Major marrow responses (two complete remissions and two partial remissions) occurred in four patients (20%). CONCLUSION: In view of the apparent antileukemic efficacy and minimal extramedullary toxicity, carboplatin deserves further study in a phase II trial.

Acute Disease↗

Oral rehydration therapy. North Florida physicians' attitudes.

This study assessed primary care physicians' familiarity and attitudes toward oral rehydration therapy in the management of mild, moderate or severe diarrheal dehydration in children. An anonymous questionnaire was distributed to a cross-sectional representation of pediatricians, family practitioners and pediatric residents in North Central Florida. All were familiar with this type of therapy. Fewer were familiar with the Florida Oral Rehydration Therapy Program. Pediatricians reported significantly higher self-assessment scores than family practitioners or residents, and more of them were familiar with the American Academy of Pediatrics' recommendations for treatment of dehydration. Pediatric residents used intravenous therapy more frequently than pediatricians or family practitioners. The major obstacles to oral rehydration therapy use were identified as parental acceptance, compliance, and lack of a specific treatment area. The findings of this study suggest that pediatricians are more confident in their assessment, management and use of this type of therapy in children. Efforts to increase its use should focus on educational programs for physicians and parents. Dissemination of information to parents and pediatric providers may promote early treatment which should prevent more severe degrees of dehydration, decrease hospitalization and possibly prevent unnecessary deaths.

Adult↗

Using a population-based registry to identify patterns of care in childhood cancer in Florida.

BACKGROUND: Unlike cancers occurring in adults, childhood cancers are distinguished by being primarily nonepithelial in origin and by their relative rarity. Even with the availability of registries such as the Surveillance, Epidemiology and End Results program of the National Cancer Institute or the Florida Cancer Data System for the State of Florida, there are potential biases that may affect the estimates of pediatric cancer incidence, studies related to elucidating patterns of care, and other epidemiologic studies. METHODS: To evaluate the magnitude of these potential biases and elucidate the settings (pediatric cancer center versus non-cancer center) in which childhood cancers are treated, the authors performed a retrospective study of childhood cancer in Florida. RESULTS: Approximately 19% of childhood cancer cases (in patients 0-19 years of age) in Florida diagnosed from 1981 to 1986 were treated outside of identified pediatric cancer centers in the state. Children with Hodgkin disease and brain tumors represented 43% of these cases. Among those cases treated in pediatric cancer centers, 23% were treated by physicians other than pediatric oncologists. Children with brain tumors represented 28% of these cases. Of those treated by pediatric oncologists, 65% were eligible for a cooperative group protocol and 55% of these were enrolled. CONCLUSIONS: Population-based registries are necessary for describing the full extent of childhood cancer, but they have limitations in demonstrating patterns of care. Consequently, generalization from the experience of pediatric cancer centers is questionable, and the opportunity to test and achieve advances in diagnosis and treatment may be subject to selection bias.

Adolescent↗

Pediatric cancer in the United States. A preliminary report of a collaborative study of the Childrens Cancer Group and the Pediatric Oncology Group.

BACKGROUND: Cancer is the second leading cause of death in children younger than 15 years. Although 5-year survival rates have increased dramatically for many childhood tumors, more than 100,000 person-years of life are lost to childhood cancer each year. The exact proportion of pediatric patients with cancer who receive care at centers that use up-to-date therapeutic protocols (such as those affiliated with the Childrens Cancer Group (CCG) or the Pediatric Oncology Group (POG) is unknown. METHODS: Based on residence at the time of diagnosis, observed numbers of pediatric cancer cases seen by member institutions of the CCG and the POG in 1989 and 1990 were compared with the expected number of cases. Expected values were calculated from incidence rates obtained from the Surveillance, Epidemiology and End Results Program and population counts obtained from the US Census Bureau. RESULTS: Results indicate that more than 90% of children younger than 15 years who have a diagnosis of malignant neoplasm are seen at an institution that is a member of either CCG or POG. The highest proportion seen occurs in the youngest (0-4 years) age group, and the proportion declines steadily with increasing age. CONCLUSIONS: There are specific regions within the United States where the observed number of cases was substantially less than the expected number, including areas of Texas, Idaho, and Virginia. Although the exact reasons for these potential deficits are unknown, additional study of these areas is recommended.

Adolescent↗

The temporal association between gamma delta T cells and the natural history of insulin-dependent diabetes.

We previously reported a significant increase in percentages of peripheral blood gamma delta+ T cells in islet cell antibody (ICA) positive relatives of patients with insulin-dependent diabetes (IDD). In the present study, we further characterized this T cell abnormality in a larger group of ICA+ subjects and report that (1) Percentages of gamma delta+ T lymphocytes were significantly increased only in subjects with high ICA titers (> or = 20 JDF units) (P = 0.005) and resulted from an increase in absolute numbers of gamma delta+ T lymphocytes. (2) In these subjects, the increase in gamma delta+ T lymphocytes was associated with an increase in the V gamma 9 V delta 2 subpopulation (r = 0.99). (3) In these same subjects, high percentages of gamma delta+ T lymphocytes were associated with normal beta cell function while low percentages were associated with diminished insulin response. Using 65 microU/ml as the threshold of abnormal intravenous glucose tolerance test (IVGTT) response, percentages of gamma delta+ T lymphocytes could significantly predict IVGTT status in these subjects (P < 0.01). A longitudinal follow-up further suggested that the development of an abnormal IVGTT response and progression to diabetes was associated with a decrease in percentages of gamma delta+ T lymphocytes while patients whose gamma delta+ T cell percentages remained high retained normal beta cell function. Our data therefore suggest that gamma delta+ T lymphocytes and more specifically V gamma 9 V delta 2 T cells are implicated in the autoimmune process leading to diabetes and may have a regulatory role. The monitoring of their percentages in the blood of patients at risk for diabetes may be useful as an additional predictor of diabetes development.

Adolescent↗