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Biomedical subjects

S O'Brien

Publications and source records attributed to S O'Brien.

At least 343 records · Page 19Linked to original sources
PubMed1989

High dose chemotherapy with autologous hematopoietic stem cell support in the treatment of refractory stage IV breast carcinoma.

Fourteen patients with refractory metastatic breast cancer were treated with high dose chemotherapy and autologous hematopoietic stem cell rescue. All patients received cyclophosphamide (7.5 g/m2 over 3 days) and thiotepa (150-225 mg/m2 over 3 days), three patients in addition received melphalan (4.5 mg/kg), and seven patients received carmustine (150-562 mg/m2). Toxicities included pancytopenia, infection, hemorrhagic cystitis, skin rash, nausea, vomiting, diarrhea, and mucositis. There was one toxic death secondary to sepsis and ventricular tachycardia. The overall response rate was 77% including a 15% complete response rate. The overall median survival for all patients was 6.0 months (range 2-22 months). The median survival for nonresponders was 3.5 months. The median duration of response was 89 days (range 40-262). In our experience high dose chemotherapy with autologous stem cell reinfusion produces a high response rate in refractory breast cancer. However, because of the short duration of response and overall survival, we feel this type of therapy should be utilized earlier in the course of disease.

Adult↗
PubMed1989

A special challenge.

Explore the source record for details and available documents.

Dental Care for Persons with Disabilities↗
PubMed1988

Fetal heart rate monitoring by telephone. II. Clinical experience in four centres with a commercially produced system.

A commercially produced domiciliary fetal monitoring (DFM) system was assessed in four centres in the UK (Bristol, Glasgow, London and Nottingham) chosen to allow for comprehensive assessment in various settings in many different women. Overall, 825 recordings were made from 368 women (2.24 per woman). There were 56 unsuccessful attempts at transmission (6.8%), most were due to problems with telephone equipment. The system worked most efficiently when a dedicated direct line was used. The data transmission time varied between 40 and 60 s. The median telephone time (including data transmission and conversation) with a dedicated direct line was 7 min. Mean acceptance times from the four centres were between 70 and 80%. All recordings with acceptance times of 40% or more were interpretable. Ten recordings were abnormal. The women and mid-wives were equally proficient at using the DFM system. The DFM system represents an important addition to current methods of fetal assessment. Specific guidelines are outlined.

England↗
PubMed1988

Tumor necrosis factor and human hematopoiesis: II. Inhibition and mode of action on normal and chronic myelogenous leukemia-derived granulocyte-macrophage progenitor cells.

Recombinant technology-produced tumor necrosis factor alpha (rTNF-alpha) inhibits clonogenic growth of normal granulocyte-macrophage colony-forming cells (GM-CFC) when it is continuously present in the culture medium. In our studies, day 7 and day 14 GM-CFC were inhibited and showed similar response. A decrease in the number of large colonies accounted for most of the inhibition, whereas growth of small clusters was inhibited to a lesser extent. Comparable inhibition was observed when bone marrow cells were cloned at low (2.5 x 10(4)/ml) or high (10 x 10(4)/ml) cell densities. A similar degree of inhibition by rTNF-alpha was found when conditioned medium from the human placenta or a bladder carcinoma cell line was used as the source of the colony-stimulating factors (CSF). The dose-response curve of GM-CFC to rTNF-alpha was sigmoidal, the maximum inhibition (90%) occurring at approximately 100 ng/ml of rTNF-alpha. Short-term treatment of bone marrow in suspension culture for 2 hr did not affect the subsequent colony formation, suggesting that TNF had an antiproliferative rather than a direct toxic effect on normal GM-CFC. GM-CFC derived from previously untreated patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) showed an in vitro dose response to rTNF-alpha similar to that of normal GM-CFC. Inhibition of colony formation by CML-derived GM-CFC was more pronounced than GM-CFC from normal marrows, especially at low concentrations of rTNF-alpha. An increase in the concentration of rTNF-alpha above 250 ng/ml had no further effect on colony formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Cells↗
PubMed1988

Lack of breakpoint cluster region rearrangement in marrow fibroblasts of patients with Philadelphia chromosome-positive chronic myelogenous leukemia.

Involvement of marrow fibroblasts in myeloproliferative disorders such as chronic myelogenous leukemia (CML) is controversial. We examined the blood leukocytes and bone marrow fibroblasts of four patients with Philadelphia chromosome- (Ph1) positive CML for evidence of rearrangement in the breakpoint cluster region (BCR). Fibroblasts were obtained by growing bone marrow in long-term culture, disposing of nonadherent cells, and passaging three times before final trypsinization and analysis. DNA from fibroblasts and peripheral leukocytes was digested with Bg1II, Bc1I, EcoRI, and HindIII restriction endonucleases and hybridized to both 3' and 5' BCR probes. Southern blot analysis of the DNA from the peripheral leukocytes in all four patients demonstrated rearrangement in the BCR. However, analysis of DNA from marrow fibroblasts showed only the normal BCR restriction fragments in all patients. This study demonstrates the absence of the Ph1 -associated molecular events in the fibroblasts of patients with CML. It is consistent with previous studies using G6PD isoenzymes to show polyclonality in CML fibroblasts and with most cytogenetic studies that did not show the Ph1 in these cells. In summary, we present further evidence that involvement of CML fibroblasts is a secondary event in the leukemogenic process.

Bone Marrow Cells↗
PubMed1988

Tumor necrosis factor and human hematopoiesis: I. Kinetics and diversity of human bone marrow cell response to recombinant tumor necrosis factor alpha in short-term suspension cultures in vitro.

The response of normal human bone marrow-derived granulocyte macrophage progenitor cells (GM-CFC) to human recombinant tumor necrosis factor alpha (TNF-alpha) was studied in short-term suspension cultures, in the presence or absence of human placenta-derived colony-stimulating factors (CSF). The effect of rTNF-alpha on GM-CFC was correlated with its influence on more mature progeny, as defined by standard morphological criteria, and was related to both dose of rTNF-alpha and length of exposure. After very short-term exposure (2 h), "inactivation" of a substantial number of GM-CFC was observed only in the presence of very high rTNF-alpha doses (1 x 10(4) ng/ml). When the exposure was prolonged to 16 h, a significant killing of both day 8 (GM-CFC8d) and day 14 (GM-CFC14d) progenitor cells was detected in the presence of 10 ng of rTNF-alpha/ml. Exposure for 5 days resulted in a further increase in the GM-CFC killing. Presence of yet unknown factor(s) in human placenta-conditioned medium sensitized GM-CFC to the action of rTNF-alpha. By morphological analysis of marrow cells, it was found that rTNF-alpha inhibited growth and/or recruitment of granulocytic precursor cells and caused inhibition of their differentiation. This effect was not dose dependent above 1 x 10(1) ng/ml. The presence of rTNF-alpha slightly promoted dose-dependent differentiation along the macrophage pathway. rTNF-alpha appeared to promote eosinophilic differentiation, also in a dose-dependent manner.

Colony-Stimulating Factors↗
PubMed1987

A new moderately repetitive DNA sequence family of novel organization.

In cloning adenovirus homologous sequences, from a human cosmid library, we identified a moderately repetitive DNA sequence family consisting of tandem arrays of 2.5 kb members. A member was sequenced and several non-adjacent, 15-20 bp G-C rich segments with homology to the left side of adenovirus were discovered. The copy number of 400 members is highly conserved among humans. Southern blots of partial digests of human DNA have verified the tandem array of the sequence family. The chromosomal location was defined by somatic cell genetics and in situ hybridization. Tandem arrays are found only on chromosomes 4 (4q31) and 19 (q13.1-q13.5). Homologous repetitive sequences are found in DNA of other primates but not in cat or mouse. Thus we have identified a new family of moderately repetitive DNA sequences, unique because of its organization in clustered tandem arrays, its length, its chromosomal location, and its lack of homology to other moderately repetitive sequence families.

Adenoviruses, Human↗
PubMed1987

Chromosomal localization of the met proto-oncogene in the mouse and cat genome.

The met proto-oncogene was mapped in the mouse and cat genomes with the use of mouse X hamster and cat X rodent somatic cell hybrid DNA panels. Based on these analyses we assigned the met gene to mouse chromosome 6 and to cat chromosome A2. We also assigned the cat raf-1 proto-oncogene to the A2 chromosome; met and raf-1 are the first cloned DNAs mapped to this linkage group. Using an interspecies backcross we further localized met on mouse chromosome 6 to a position proximal to the beta chain of the T-cell receptor. This places met near the obese locus in a region of mouse chromosome 6 that appears to be homologous with the long arm of human chromosome 7. The close linkage of met to the gene responsible for cystic fibrosis in humans suggests that further genetic analysis of mouse chromosome 6 may be useful in developing a mouse model for the disease.

Animals↗
PubMed1987

Successful medical management of neutropenic enterocolitis in adults with acute leukemia.

Seven adults with acute leukemia had a clinical and radiologic diagnosis of neutropenic enterocolitis. Six of the seven patients had granulocyte counts less than 500/microliter. All seven patients responded to intensive medical therapy, including bowel rest, broad spectrum antibiotics, and white blood cell transfusions, and recovered from the neutropenic enterocolitis without surgical intervention. We discuss the clinical spectrum of neutropenic enterocolitis and the favorable results of medical therapy.

Adult↗
PubMed1987

Calcium, vitamin D and parathyroid hormone relationships in pregnant Caucasian and Asian women and their neonates.

Plasma calcium, serum 25 hydroxyvitamin D [25(OH)D], 1,25 dihydroxyvitamin D[1,25(OH)2D] and parathyroid hormone (PTH) have been measured in pregnant and newborn Caucasians and Asians. Calcium and 25(OH)D concentrations were lower in Caucasian than in Asian women at all four stages (three trimesters and during labour) of pregnancy. PTH concentrations were greater in Asian than in Caucasian women during the three trimesters, but not at labour, and increased in both groups through pregnancy, without a concomitant change in plasma calcium concentrations. There was a significant inverse correlation between calcium and PTH, as well as 25(OH)D and PTH, concentrations. These data demonstrate the presence of progressive 'hyperparathyroidism' during pregnancy in Caucasian and Asian women. The higher PTH concentrations in Asian women may reflect the necessity of maintaining adequate plasma calcium concentrations through PTH-induced osteolysis in the face of vitamin D deficiency. Relative hyperparathyroidism in Asians may contribute to net loss of calcium from the skeleton and osteopenia in Asian women. Calcium, 25(OH)D and 1,25(OH)2D concentrations were lower, and those of PTH higher, in Asian newborns compared with Caucasian newborns. Serum 1,25(OH)2D concentrations in the Asian newborn, though lower than respective maternal levels, were comparable with normal adult levels, indicating that 1,25(OH)2D biosynthesis is stimulated in the Asian newborn to compensate for the low serum 25(OH)D concentrations.

Alkaline Phosphatase↗
PubMed1987

The human myelin-basic-protein gene: chromosomal localization and RFLP analysis.

With a human myelin-basic-protein (MBP) cDNA used as a probe, the human MBP gene has been mapped to chromosome region 18q22-q23 by a combination of Southern hybridization to a panel of somatic-cell hybrid DNAs and in situ hybridization to metaphase chromosomes. Restriction-fragment-length polymorphisms (RFLPs) have also been identified with this probe in human DNA, by means of the restriction enzymes BamHI, PvuII, and PstI. In studies of informative families, the alleles of the BamHI and PvuII polymorphisms have been shown to segregate as Mendelian traits.

Alleles↗
PubMed1987

The effect of long-term marrow culture on the nonadherent Philadelphia chromosome-positive clone in chronic myelogenous leukemia: preliminary observations.

To evaluate the effect of long-term culture on the Philadelphia chromosome-positive nonadherent hemopoietic clone in chronic myelogenous leukemia, bone marrow aspirates from five patients were grown in culture for three to four weeks. In addition to control cultures, samples were incubated with recombinant alpha-interferon. Cytogenetic studies performed on the nonadherent hemopoietic cells demonstrated suppression of the Philadelphia chromosome-positive clones, and appearance of cells with normal diploid karyotype in two of the five patients studied; cells from the remaining three patients showed persistent Philadelphia chromosome-positive cells in 100% of the metaphases. Exposure to alpha-interferon did not enhance the suppression of the Philadelphia chromosome-positive clones. A good correlation was noted between in vitro results and in vivo cytogenetic response: the two patients whose in vitro studies showed diploid clones achieved complete hematologic remission and suppression of Philadelphia chromosome-positive metaphases with therapy. Our data suggest that long-term culture favors the growth of normal clones over Philadelphia chromosome-positive clones in the nonadherent hemopoietic cells of some patients with chronic myelogenous leukemia. The value of the procedure as an in vitro predictive test for residual normal stem cells and response to therapy and for autologous marrow in vitro purging needs further exploration.

Adult↗
PubMed1986

Varied citrus treatment of ruminant gagging in a teenager with Batten's disease.

Chronic ruminant gagging was substantially reduced in a severely retarded 13-year-old girl with Batten's disease through the use of contingent citrus juice in an ABAB design. Previous literature suggests that citrus juice may not be effective for treatment of rumination in older and/or handicapped children due to habituation. In this study, habituation may have been prevented by alternating lime juice and lemon juice when ruminative gagging reached a predetermined rate. The lemon/lime variation offers an effective, practical, and acceptable alternative to other response suppression procedures for rumination.

Adolescent↗