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Biomedical subjects

E Lynch

Publications and source records attributed to E Lynch.

At least 19 recordsLinked to original sources
PubMed1992

The gene for an inherited form of deafness maps to chromosome 5q31.

Primary--i.e., nonsyndromal-postlingual deafness is inherited as an autosomal dominant phenotype in a large kindred in Costa Rica. Genetically susceptible individuals begin to lose hearing at low frequencies at about age 10 years, after language and speaking are learned. Deafness inevitably progresses by age 30 years to bilateral hearing loss of all frequencies. Intelligence, fertility, and life expectancy are normal. The family traces its ancestry to an affected founder born in Costa Rica in 1754. We have mapped the gene for deafness in this kindred to chromosome 5q31, between the markers IL9 and GRL, by linkage analysis involving 99 informative relatives.

Base Sequence↗
PubMed1992

Varying intensity of postremission therapy in acute myeloid leukemia.

The Eastern Cooperative Oncology Group (ECOG) conducted a randomized trial in patients less than or equal to 65 years old (median, 44 years) to determine whether increasing the intensity of postremission therapy in acute myeloid leukemia (AML) would improve the outcome. After uniform induction therapy, patients in complete remission (CR) who were less than 41 years old and who had a histocompatible sibling underwent allogeneic bone marrow transplantation (alloBMT) (54 patients). The remainder of patients in CR were randomized to receive either 2 years of continuous outpatient maintenance therapy with cytarabine and 6-thioguanine (83 patients) or a single course of inpatient consolidation therapy consisting of 6 days of high-dose cytarabine plus 3 days of amsacrine (87 patients). The median duration of follow-up is now 4 years, and patients are included in the analyses of outcome regardless of whether they relapsed before starting the intended treatment. Four-year event-free survival (EFS) was 27% +/- 10% for consolidation therapy versus 16% +/- 8% for maintenance therapy (P = .068) and 28% +/- 11% versus 15% +/- 9% (P = .047) in patients less than 60 years old. The outcome for patients receiving alloBMT was compared with the subset of patients less than 41 years old who received consolidation therapy (N = 29) or maintenance therapy (N = 21). Four-year EFS was 42% +/- 13% for alloBMT, 30% +/- 17% for consolidation therapy, and 14% +/- 15% for maintenance therapy. AlloBMT had a significantly better EFS (P = .013) than maintenance therapy, but was not different from consolidation therapy. In patients less than 41 years old, 4-year survival after alloBMT (42% +/- 14%) did not differ from consolidation therapy (43% +/- 18%), but both were significantly better than maintenance therapy (19% +/- 17%), P = .047 and .043, respectively. The mortality rate for maintenance therapy was 0%, consolidation therapy, 21%; and alloBMT, 36%. Consolidation therapy caused an especially high mortality rate in the patients greater than or equal to 60 years old (8 of 14 or 57%). The toxicity of combined high-dose cytarabine and amsacrine is unacceptable, especially in older patients, and alternative approaches to consolidation therapy such as high-dose cytarabine alone need to be tested. In AML, a single course of consolidation therapy or alloBMT after initial CR produces better results than lengthy maintenance therapy. Although EFS and survival of alloBMT and consolidation therapy do not differ significantly, a larger number of patients need to be studied before concluding that they are equivalent.

Acute Disease↗
PubMed1992

Microleakage.

A critical review of techniques used in the assessment of microleakage in dental restorations is presented. These techniques include the use of air pressure, bacteria, radioisotopes, electrochemistry, chemical tracers and dye penetration. Wide variations in methodologies are revealed.

Dental Leakage↗
PubMed1991

Selective depletion of bone marrow T lymphocytes with anti-CD5 monoclonal antibodies: effective prophylaxis for graft-versus-host disease in patients with hematologic malignancies.

Seventy-one patients with hematologic malignancies received bone marrow from a histocompatible sibling (n = 48) or a partially matched relative (n = 23) that had been depleted of CD5+ T cells with either an anti-CD5 mooclonal antibody (MoAb) plus complement (anti-Leu1 + C) or an anti-CD5 MoAb conjugated to ricin A chain (ST1 immunotoxin [ST1-IT]). These patients received intensive chemoradiotherapy consisting of cytosine arabinoside, cyclophosphamide, and fractionated total body irradiation. Both anti-Leu1 + C and ST1-IT ex vivo treatments effectively depleted bone marrow of T cells (97% and 95%, respectively). Overall, primary and late graft failure each occurred in 4% of evaluable patients. The diagnosis of myelodysplasia was a significant risk factor for graft failure (P less than .001), and if myelodysplastic patients were excluded, there were no graft failures in major histocompatibility complex (MHC)-matched patients and 2 of 23 (8.7%) in MHC-mismatched patients. The actuarial risk of grade 2 to 4 acute graft-versus-host disease (GVHD) was 23% in MHC-matched patients and 50% in MHC-mismatched patients. In MHC-matched patients, acute GVHD tended to be mild and treatable with corticosteroids. Chronic GVHD was observed in 6 of 36 (17%) MHC-matched patients and none of 11 MHC-mismatched patients. There were no deaths attributable to GVHD in the MHC-matched group. Epstein-Barr virus-associated lymphoproliferative disorders were observed in 3 of 23 MHC-mismatched patients. The actuarial event-free survival was 38% in the MHC-matched patients versus 21% in the MHC-mismatched patients. However, if outcome is analyzed by risk of relapse, low-risk patients had a 62% actuarial survival compared with 11% in high-risk patients. These data indicate that the use of anti-CD5 MoAbs can effectively control GVHD in histocompatible patients, and that additional strategies are required in MHC-mismatched and high-risk patients.

Adolescent↗
PubMed1991

The change in patterns of relapse in medulloblastoma.

The authors reviewed 89 patients treated for cerebellar medulloblastoma between 1970 and 1989 to determine the impact of changing treatment (high-dose posterior fossa radiation therapy and chemotherapy) on the pattern of failure in medulloblastoma. Between 1970 and 1983, 50 patients (median follow-up, 110 months) were treated with surgery and postoperative craniospinal irradiation (CSI). Nineteen of the 50 (38%) recurred in the central nervous system (CNS). Isolated systemic (bone) metastases occurred in six. The median time to the development of bone metastases was 12 months. Since 1984, 39 patients (median follow-up, 27 months) were treated with preradiation chemotherapy consisting of cisplatin and vincristine for 9 weeks before initiation of CSI. Nine of the 39 (23%) patients recurred in the CNS. There were no systemic failures in this cohort. The actuarial 5-year disease-free survival was 55 +/- 7% for the earlier cohort and 72 +/- 8% for the later cohort (P equals 0.3). Posterior fossa recurrence was associated with radiation therapy to this area. The cumulative incidence of posterior fossa relapse was 50 +/- 13% in patients who received less than 5300 cGy and 18 +/- 7% in those who received 5300 cGy or more (P equals 0.005). All six bone relapses were in patients treated with CSI alone and 5300 cGy or more to the posterior fossa for a 5-year cumulative incidence of bone metastases of 18 +/- 7% compared with 0% for patients treated with 5300 cGy or more and chemotherapy (P equals 0.03). The authors concluded that high-dose radiation therapy has altered the pattern of relapse with an increase in systemic recurrence after radiation therapy alone that is now equivalent to the risk of recurrence in the posterior fossa. Chemotherapy may be indicated in an attempt to decrease this high risk of systemic metastases.

Adolescent↗
PubMed1991

HiC-COM: a 2-month intensive chemotherapy regimen for children with stage III and IV Burkitt's lymphoma and B-cell acute lymphoblastic leukemia.

We designed a protocol that included 2 months of intensive Cytoxan (cyclophosphamide; Bristol-Myers Co, Evansville, IN), high-dose methotrexate (MTX), high-dose cytarabine (ara-C), and vincristine (HiC-COM) to improve event-free survival (EFS) for patients with advanced-stage Burkitt's lymphoma and B-cell acute lymphoblastic leukemia (ALL). We also wished to test the feasibility of rapidly cycling Cytoxan and high-dose ara-C based on signs of early marrow recovery. Twenty patients including 12 with stage III Burkitt's lymphoma and eight with stage IV Burkitt's lymphoma or B-cell ALL were entered onto this pilot study. The rate of complete remission was 95%. Four patients have relapsed. The 2-year actuarial EFS was 75% (median follow-up, 37 months). Two of the initial five patients developed transverse myelitis, which we believe may have been secondary to the concomitant administration of intrathecal (IT) and high-dose systemic ara-C. We conclude that this short but intensive regimen is highly effective for patients with advanced Burkitt's lymphoma and B-cell ALL. EFS has improved over previous less intensive regimens, and is comparable to regimens of longer duration.

Adolescent↗
PubMed1990

Prognostic correlation of HLA-DR expression in large cell lymphoma as determined by LN3 antibody staining. An Eastern Cooperative Oncology Group (ECOG) study.

Several previous studies employing surface-marker techniques suggest that HLA-DR antigen expression may correlate with prognosis in diffuse large cell lymphoma. Control studies in the authors' laboratory indicated that LN3 positivity in paraffin-embedded tissue correlates well with HLA-DR antigen expression. Accordingly they examined 212 cases of diffuse large cell lymphoma from one of Eastern Cooperative Oncology Group's (ECOG) high-grade malignant lymphoma treatment protocols. All patients studied had careful clinical follow-up of between 5 and 11 1/2 years from diagnosis and initiation of therapy. There was no correlation of strongly positive, positive, weakly positive, equivocal, or negative staining with survival. Cases that were LN3 negative had a median survival of 18.8 months versus a median survival of 39.4 months for all LN3-positive cases. However this difference was not statistically significant when using a log-rank test. The authors were unable to confirm that HLA-DR antigen expression, as defined by LN3, is prognostically valuable in diffuse large cell lymphoma in a multi-institutional study.

Antibodies, Monoclonal↗
PubMed1990

Rare McArdle disease locus polymorphic site on 11q13 contains CpG sequence.

When probes throughout the McArdle disease (myophosphorylase) gene region were used to search for DNA polymorphisms, only an MspI polymorphism was found in 94 enzyme-probe combinations. Along with an insertion/deletion polymorphism more 3' to the gene locus, these polymorphisms will be informative in 75% of at-risk patients. These results contrast strikingly to the six polymorphic sites detected in 15 enzyme-probe combinations in the homologous Her's disease (liver phosphorylase) gene region. This single MspI polymorphic site includes a CpG sequence of known increased mutability suggesting that DNA regions with rare polymorphisms will have most polymorphic sites at sequences with enhanced mutability. Fluorescence in situ hybridization sublocalized this gene to proximal band 11q13, establishing a point of cross-reference between the physical and genetic maps.

Base Sequence↗
PubMed1990

Effect of a new conditioning agent on dentin.

The effect of varying the duration of application of the conditioner for light-cured Zionomer was studied. The conditioner is a solution of oxalic acid and aluminum nitrate in a weak mineral acid and has a pH of 2.06. Recently extracted non-carious human premolars were sectioned horizontally 300 microns below the amelodentinal junction and then lightly ground with a high-speed diamond bur under copious water-spray to produce a smear layer. Each was then sectioned vertically into three and all the specimens were either treated with the Zionomer Conditioner for 5, 10, 20 or 30 seconds, or with distilled water as a control. All the specimens were examined in a scanning electron microscope at x1000 and photomicrographs taken which were then assessed, independently, by the authors. The results revealed that application of Zionomer Conditioner for as little as 5 seconds was sufficient to remove most of the smear layer. There was complete removal of the surface smear layer in specimens treated for 10 seconds or more. Either a 20 second or a 30 second application removed the smear layer completely and could also widen the exposed tubule orifices.

Acid Etching, Dental↗
PubMed1990

Glass-ionomer cements--clinical usage and experience: 2.

Glass-ionomer cements have unique and varied properties: they are tough, translucent, biologically inert, resistant to degradation in the mouth, adhesive to tooth structure and they inhibit caries. In a number of ways they are probably the one substance available today that most approaches the ideal restorative material. In Part 1 of this two-part article the authors reviewed the physical and clinical properties of glass-ionomer cements, here they go on to describe their use in practical and sometimes novel restorative procedures.

Child↗
PubMed1989

Prognostic implications of cytogenetic studies in an intensively treated group of children with acute lymphoblastic leukemia.

We assessed the prognostic significance of leukemia cell cytogenetics by analyzing bone marrow aspirates obtained at time of diagnosis in 165 children on a single protocol for acute lymphoblastic leukemia (ALL). These children were assigned to six mutually exclusive cytogenetic categories as follows: (1) hyperdiploid, with 50 or more chromosomes (n = 35); (2) hyperdiploid, with 47 to 49 chromosomes (n = 11); (3) diploid (n = 42); (4) pseudodiploid (n = 34); (5) hypodiploid (n = 9); and (6) insufficient data (n = 34). At a median follow-up of 5 years, there were no statistically significant differences between any of these cytogenetic categories in either event-free or overall survival. Those children with chromosomal translocations (n = 26) appeared to fare the same as those lacking translocations (n = 105). The absence of karyotypic prognostic significance was observed not only within the overall group, but also when the results were stratified by standard-risk and high-risk status. Of the specific structural chromosome changes that we studied, only the Philadelphia chromosome (Ph) appeared to confer a poor prognosis, although there were too few such cases to achieve statistical significance. Although we did not detect the event-free survival differences that have been described previously in hyperdiploid, hypodiploid, and pseudodiploid childhood ALL, our findings must be viewed as preliminary given the small number of children in some of the cytogenetic categories. We think that the prognostic implications of these cytogenetic features might have been nullified by improvements in therapy.

Adolescent↗
PubMed1989

The effect of reinforcing fibres in denture acrylics.

Since the early 1970's, various fibre reinforcement systems have been used to enhance the mechanical properties of denture base acrylics. The research conducted to date on fibre reinforcement systems for use with Poly(methylmethacrylate) (PMM) denture base material is reviewed and evaluated.

Acrylic Resins↗