PubMed Health⌕ Search

Biomedical subjects

D Ridgway

Publications and source records attributed to D Ridgway.

At least 19 recordsLinked to original sources
PubMed2000

The logic of causation and the risk of paralytic poliomyelitis for an American child.

Beginning in January 1997, American immunization policy allowed parents and physicians to elect one of three approved infant vaccination strategies for preventing poliomyelitis. Although the three strategies likely have different outcomes with respect to prevention of paralytic poliomyelitis, the extreme rarity of the disease in the USA prevents any controlled comparison. In this paper, a formal inferential logic, originally described by Donald Rubin, is applied to the vaccination problem. Assumptions and indirect evidence are used to overcome the inability to observe the same subjects under varying conditions to allow the inference of causality from non-randomized observations. Using available epidemiologic information and explicit assumptions, it is possible to project the risk of paralytic polio for infants immunized with oral polio vaccine (1.3 cases per million vaccinees), inactivated polio vaccine (0.54 cases per million vaccinees), or a sequential schedule (0.54-0.92 cases per million vaccinees).

Adult↗
PubMed1999

No-fault vaccine insurance: lessons from the National Vaccine Injury Compensation Program.

During the first eight years of the National Vaccine Injury Compensation Program (NVICP), 786 contested claims were resolved through published judicial opinions. The likelihood of compensation dependent in part on the closeness of the match between the described injury and a specified list of acknowledged untoward vaccine side effects. In addition, the chances of applicant success were influenced by the applicant's choice of attorney and expert witnesses, by the assignment of the Special Master to decide the case, and increasingly over time, by the applicant's ability to comply with procedural requirements. The majority of contested claims arose from pertussis immunizations. For pertussis claims, the goal of insulating manufacturers from product liability suits has been achieved by granting compensation to applicants whose injuries are not scientifically recognized effects of the vaccine. In spite of (or because of) this jarring contradiction between the legal and medical understanding of causation, vaccine availability and childhood immunization rates improved during the early years of the plan. The apparent success of the program may encourage the substitution of no-fault compensation plans for tort-based consumer protection for other products, both medical and nonmedical.

Adolescent↗
PubMed1998

Disputed claims for pertussis vaccine injuries under the National Vaccine Injury Compensation Program.

BACKGROUND: The National Vaccine Injury Compensation Program (NVICP) provides no-fault compensation to victims of serious untoward vaccine reactions under the supervision of the Department of Health and Human Services (HHS). Special Masters of the Court of Federal Claims settle compensation disputes that arise between applicants and program administrators. The majority of published NVICP claim decisions concern disputes over the cause of neurologic illness or unexpected infant death following pertussis vaccination. METHODS: Information was collected from the published decisions to determine the medical characteristics of cases in which injuries were legally attributed to pertussis vaccination. Because of practical and statutory restrictions on the application process and the evolving nature of HHS claim denials, vaccinees in the disputed cases are not representative of all vaccine casualties, or of all NVICP applicants. RESULTS: Injuries were blamed on pertussis vaccine in 542 claims disputed by HHS. Claims asserted that pertussis vaccine caused seizure disorders (333 claims, 189 were awarded compensation), anaphylaxis (7 claims, 6 awards), hypotonic/hyporesponsive episodes or other injuries leading to early death (107 claims, 73 awards), and long-term neurologic disease (51 claims, 18 awards). CONCLUSIONS: Assertions that pertussis vaccine caused unexpected infant death (other than anaphylaxis), seizure disorders, and long-term neurologic damage are inconsistent with epidemiological research. Findings of legal causation may contribute to popular perceptions that pertussis vaccine is a dangerous biological product. By providing compensation for these claimants, however, the NVICP may reduce the number of successful civil suits and thus protect the nation's vaccine supply.

Anaphylaxis↗
PubMed1995

Effects of growth hormone antagonists on 3T3-F442A preadipocyte differentiation.

We have previously shown that a bovine (b) GH antagonist, bGH-M8, which possesses three amino acid substitutions in its third alpha-helix, inhibits mouse 3T3-F442A preadipocyte differentiation. In the current studies, we used the bGH and human (h) GH analogs with single amino acid substitution, bGH-G119R and hGH-G120R, for determining their biological activity using the preadipocyte differentiation assay. Short-term and long-term GH-inducible events were studied during adipose differentiation, including late marker gene expression (adipocyte protein 2), immediate early gene induction (c-fos), and tyrosine phosphorylation of intracellular proteins. The results demonstrated that these GH analogs not only failed to induce these three events, but also antagonized GH induction of c-fos expression and phosphorylation of proteins of apparent molecular mass of 95 kDa. Our present study agrees with the notion that GH must bind to the GH receptor via site one and with a second GH receptor molecule (or with some yet unidentified 'second target') through GH binding site two. This interaction is important for subsequent GH-dependent biological events.

Adipocytes↗
PubMed1993

Active immunization of children with leukemia and other malignancies.

Active immunization against measles, Haemophilus influenza B, tetanus, diphtheria, hepatitis B, influenza, poliomyelitis, and, when indicated varicella and pneumococcus induces long-lasting immunologic protection in most healthy pediatric vaccine recipients. Among children receiving immunosuppressive therapy for cancer, possible early loss of specific immunity acquired from prior vaccination or disease, and likely diminished responsiveness to initial or booster vaccination must be considered. In addition, the safety of vaccine administration requires separate study in this population. Published evidence demonstrates preservation of vaccine-induced antibody titers against tetanus, diphtheria, poliomyelitis and (in children treated for lymphoma) pneumococcus. In contrast, prior immunity to varicella, influenza, and hepatitis B (when naturally acquired), and measles (acquired by vaccination) is compromised during and/or after antineoplastic therapy. Studies of immunologic protection acquired by prior vaccination against hepatitis B, varicella, and H influenza have not been published. The safety of administering toxoids and inactivated vaccines in this population is well documented. In contrast, morbidity must be expected if live attenuated vaccines (oral polio vaccine, attenuated measles vaccine or attenuated varicella vaccine) are administered to children receiving anti-cancer therapy. The risks of using live vaccines should be measured against demonstrable benefits in any vaccine program. The response to initial or booster immunizations against tetanus and diphtheria are similar to those in healthy children. For all other immunizations reviewed, responsiveness is diminished during periods of chemotherapy, more strikingly in children treated for leukemia than for solid tumors. Antibody responses to these vaccines range from slightly blunted (in the case of H influenza B) to marginal (influenza) or completely useless (pneumococcus and hepatitis B in children treated for leukemia).

Chickenpox↗
PubMed1992

Cloning and characterization of a phospholipase gene from Erwinia chrysanthemi EC16.

A single gene (plcA) was cloned from a cosmid library of Erwinia chrysanthemi EC16 DNA that encoded an extracellular phospholipase. The gene was subcloned and DNA sequence data showed the presence of a single open reading frame encoding a protein with a predicted size of 39 kDa. The coding region was G+C-rich and the protein had a predicted basic isoelectric point. The protein showed no significant homology with others in the PIR library, including other phospholipases. When overexpressed in Escherichia coli cells, the plcA gene directed production of a c. 39 kDa protein that was largely localized in the periplasm, but its N-terminal amino acid sequence was that of the native protein predicted from DNA sequence data. Unlike the wild-type bacterium, an E. chrysanthemi EC16 marker exchange mutant of the plcA gene did not secrete extracellular phospholipase activity in the medium. However, no detectable change was observed in terms of the virulence of the mutant strain on potato tubers or chrysanthemum stems.

Amino Acid Sequence↗
PubMed1992

Defective production of granulocyte-macrophage colony-stimulating factor and interleukin-1 by mononuclear cells from children treated for acute lymphoblastic leukemia.

The production of colony-stimulating activity (CSA) by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) from patients receiving maintenance chemotherapy for acute lymphoblastic leukemia (ALL) was examined. Supernatants from only 14 of 22 patient PBMC cultures (64%), but all supernatants from normal PBMC cultures, supported myeloid colony growth. When present, colony-stimulating activity always included granulocyte-macrophage colony-stimulating factor (GM-CSF). In addition, in nine of ten patient studies and in all control studies, stimulated PBMC produced interleukin-1 (IL-1). These results show that the chemotherapy administered to children with ALL can damage the cytokine production mechanisms in PBMC; the diminished ability to produce GM-CSF and IL-1 may contribute to the increased risk of overwhelming infection in these patients.

Adolescent↗
PubMed1991

Childhood cancer among the Polynesian population.

From June 1981 through June 1989, 95 Polynesian children were seen for initial care of malignancy at the Princess Mary Hospital for Children (PMHC). The incidence of malignancy in the Polynesian populations served, the histology of the malignancies, and the outcome of therapy were reviewed and compared with 185 non-Polynesian (non-P) patients seen during the same period. Incidence figures for Polynesians and non-P were similar, but histologic patterns differed, showing an increased occurrence of leukemia, particularly nonlymphoblastic leukemia, an increased occurrence of bone tumors, and a decreased incidence of central nervous system tumors for Polynesians. Survival for Polynesian children with acute lymphoblastic leukemia was worse than for non-P. Survival in all other disease categories was similar.

Child↗
PubMed1991

Immunization response varies with intensity of acute lymphoblastic leukemia therapy.

Twenty-four children receiving maintenance chemotherapy for acute lymphoblastic leukemia were given booster doses of tetanus-diphtheria combined toxoids. One month later, 19 of the 24 children were given Haemophilus influenzae B oligosaccharide-cross-reacting material conjugate vaccine. Following immunization, all patients had protective antibody titers against tetanus, 92% had protective antidiphtheria titers, and 84% had protective titers against H influenzae. Preimmunization titers, postimmunization titers, and response to immunization varied according to the intensity of therapy. There was no correlation with duration of therapy or quantitative hematologic values in the peripheral blood. These observations support the recommendation that children treated for acute lymphoblastic leukemia should be immunized against H influenzae B.

Antibodies, Bacterial↗
PubMed1991

Indomethacin-sensitive monocyte killing defect in a child with disseminated atypical mycobacterial disease.

A child with disseminated disease due to Mycobacterium avium had progressive disease in spite of 4.5 years of therapy with multiple antimicrobial agents selected on the basis of in vitro sensitivity testing of her organism. A defect in monocyte bactericidal activity was detected which was corrected in vitro by exposure of the patient's monocytes to indomethacin and normal serum. Indomethacin therapy resulted in normalization of monocyte bactericidal activity and striking, albeit temporary, clinical improvement.

Blood Bactericidal Activity↗
PubMed1991

Restriction fragment length polymorphisms associated with the factor VIII and factor IX genes in Polynesians.

New Zealand Maoris (72 X chromosomes) have been compared with Pacific Island Polynesians (121 X chromosomes) and Caucasian New Zealanders (51 X chromosomes) as a control group to determine the allelic frequency of six RFLPs associated with the genes for two X linked diseases (haemophilia A and haemophilia B). RFLPs examined were BclI, XbaI, and BglI within the factor VIII gene, the factor VIII extragenic TaqI system, and the factor IX intragenic TaqI and XmnI sites. The information obtained facilitates the design of strategies for both carrier detection and prenatal diagnosis of haemophilia A within these groups. Strong linkage disequilibrium was observed between the factor VIII BclI and XbaI sites in Polynesians. Genetic counselling for Polynesians with haemophilia B continues, however, to rely on phenotypic diagnosis. The RFLP data from the two separate loci on the X chromosome in Polynesians show similarities with Chinese and Japanese populations, reinforcing theories of an early Polynesian ancestry originating in east Asia.

Alleles↗
PubMed1990

Transient myeloproliferative disorder of the Down type in the normal newborn.

Two infants with congenital nonlymphoblastic leukemia were discovered to have mosaicism for trisomy 21. Both infants achieved durable spontaneous remissions. Trisomy was apparently restricted to the leukemic clone and could be detected in neither phytohemagglutinin-stimulated peripheral blood cells or bone marrow in either patient nor in myeloid progenitor cells from the second patient after resolution of the transient myeloproliferative disorder. We conclude that spontaneous remission of congenital leukemia is not confined to infants with partial or complete systemic trisomy 21 but can occur in genetically normal newborns whose leukemic cells contain a third chromosome 21.

Down Syndrome↗
PubMed1990

Differential effect of continuous versus cyclic maintenance chemotherapy on cytokine-induced myeloid colony growth.

Myeloid colony growth by bone marrow cells obtained from pediatric cancer patients was stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or interleukin 1 (IL-1). Although patients recovering from cyclic high-dose chemotherapy showed normal colony growth in response to GM-CSF, patients with acute lymphoblastic leukemia (ALL) receiving continuous maintenance chemotherapy at moderate dose had variable but often severe decreases in myeloid colony growth compared with controls. Marrow from all patients and controls demonstrated enhanced colony growth in GM-CSF-stimulated cultures which also contained IL-1. For patients on continuous daily maintenance therapy for ALL, enhancement of myeloid colony growth in response to IL-1 was proportional to the decrease in colony growth in response to GM-CSF. These observations support a possible clinical role for GM-CSF or other direct stimulators of myeloid growth in the patients receiving episodic high doses of chemotherapy, but suggest that alternative strategies may be more effective for those patients receiving chronic moderate-dose chemotherapy.

Adolescent↗
PubMed1989

Prolonged defects of interleukin-2 production, responsiveness, and receptor expression in patients with acute lymphoblastic leukemia.

The proliferative responsiveness to, production of, and the expression of cell-surface receptors for interleukin-2 (IL-2) were examined in 14 children with acute lymphoblastic leukemia (ALL) in remission and receiving maintenance chemotherapy for 6 to 35 months; in 19 children with ALL in remission and off all therapy for 2 to 138 months; and 15 control subjects. Short-term concanavalin A (Con A)-activated, purified T lymphocytes from patients on, as well as patients off, therapy had a significantly decreased proliferative responsiveness to a saturating amount of exogenous, recombinant IL-2 as compared to control subjects (P less than 0.005 and less than 0.05, respectively). Phytohemagglutinin (PHA)-stimulated IL-2 production by peripheral blood mononuclear cells (PBMC) was also substantially decreased in both patient groups with the median values of IL-2 produced being 2.2, 2.1, and 8.1 U/mL in the on therapy, off therapy, and control groups, respectively. In addition, PHA-induced expression of cell-surface receptors for IL-2 on PBMC was significantly decreased in both patient groups as compared to control subjects (P less than 0.01). Lymphocyte proliferation to mitogens (PHA, Con A, and pokeweed mitogen) was similar in all three groups studied. These results demonstrate that substantial quantitative and qualitative abnormalities of the IL-2-T lymphocyte system are present in the majority of treated patients with ALL, not only during maintenance therapy, but also for a prolonged period after the cessation of all chemotherapy. These long-lasting defects of the IL-2 system are most likely a late effect of chemotherapy and may result in increased complications in some long-term survivors of ALL.

Adolescent↗