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Biomedical subjects

G W Douglas

Publications and source records attributed to G W Douglas.

At least 19 recordsLinked to original sources
PubMed1990

Human umbilical cord blood: a clinically useful source of transplantable hematopoietic stem/progenitor cells.

This is a review and discussion of studies leading to the first use of human umbilical cord blood, material usually discarded, for the provision of stem/progenitor cells for clinical hematopoietic reconstitution. This prospect arose as a result of extensive studies of the harvesting and cryopreservation of cord blood and of its numerical content of progenitor cells demonstrable in vitro. A male patient with Fanconi anemia (FA) was conditioned with a modified regimen of cyclophosphamide and irradiation that accommodates the abnormally high sensitivity to these agents that is characteristic of FA. Cryopreserved cord blood had been retrieved at birth from a female sibling known from prenatal testing to be unaffected by FA and to be human leukocyte antigen (HLA)-compatible with the prospective sibling recipient. After conditioning and therapeutic infusion of thawed cord blood, successful hematopoietic reconstitution was indicated by the general health of the patient, who had previously required supportive transfusions, by satisfactory hematological criteria and by counts of hematopoietic progenitor cells of various types in the bone marrow. Complete engraftment of the myeloid system with donor cells was evident from cytogenetics, ABO typing, study of DNA polymorphisms, and normal cellular resistance to cytotoxic agents that reveal the fragility of FA cells; the blood contained a residuum of host lymphocytes exhibiting chromosomal damage, but the trend has been towards eliminating these damaged cells. This implies that cord blood from a single individual should provide sufficient reconstituting cells for effective hematopoietic repopulation of an autologous or an HLA-compatible allogeneic recipient.

Blood Transfusion↗
PubMed1990

Prenatal identification of potential donors for umbilical cord blood transplantation for Fanconi anemia.

Reported here are studies of Fanconi anemia fetal cells that led to the first use of umbilical cord blood for hematopoietic reconstitution in a clinical trial. Prenatal diagnosis and HLA typing were performed in fetuses at risk for Fanconi anemia (FA) to identify, prior to birth, those that were unaffected with the syndrome and were HLA-identical to affected siblings. Umbilical cord blood was harvested at the delivery of these infants; assays of progenitor cells indicated the presence of colony-forming units-granulocyte-macrophage (CFU-GM) in numbers similar to those of bone marrow CFU-GM that are associated with successful engraftment in HLA-matched allogeneic bone marrow transplantation. The possibility that umbilical cord blood from a single individual can be used as an alternative to bone marrow for hematopoietic reconstitution has now been demonstrated by the successful engraftment of two patients with FA. Progenitor cell assays of umbilical cord blood collected at the birth of a child affected with FA, who had been misdiagnosed on the basis of chorionic villus sampling (CVS) studies, indicated a profound deficiency in colony formation, consistent with previously reported abnormalities in the growth of FA cells in vitro. These results suggest that the hematopoietic disorder in FA is related to an underlying problem with cell proliferation.

Blood Cell Count↗
PubMed1989

Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells.

The purpose of this study was to evaluate human umbilical cord blood as an alternative to bone marrow in the provision of transplantable stem/progenitor cells for hematopoietic reconstitution. Although no direct quantitative assay for human hematopoietic repopulating cells is at present available, the granulocyte-macrophage progenitor cell (CFU-GM) assay has been used with success as a valid indicator of engrafting capability. We examined greater than 100 collections of human umbilical cord blood for their content of nucleated cells and granulocyte-macrophage, erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells, in many cases both before and after cryopreservation. First it was determined that granulocyte-macrophage, erythroid, and multipotential progenitor cells remained functionally viable in cord blood untreated except for addition of anticoagulant for at least 3 days at 4 degrees C or 25 degrees C (room temperature), though not at 37 degrees C, implying that these cells could be satisfactorily studied and used or cryopreserved for therapy after transport of cord blood by overnight air freight carriage from a remote obstetrical service. Granulocyte-macrophage progenitor cells from cord blood so received responded normally to stimulation by purified recombinant preparations of granulocyte-macrophage, granulocyte, and macrophage colony-stimulating factors and interleukin 3. The salient finding, based on analysis of 101 cord blood collections, is that the numbers of progenitor cells present in the low-density (less than 1.077 gm/ml) fraction after Ficoll/Hypaque separation typically fell within the range that has been reported for successful engraftment by bone marrow cells. Another observation of practical importance is that procedures to remove erythrocytes or granulocytes prior to freezing, and washing of thawed cells before plating, entailed large losses of progenitor cells, the yield of unwashed progenitor cells from unfractionated cord blood being many times greater. The provisional inference is that human umbilical cord blood from a single individual is typically a sufficient source of cells for autologous (syngeneic) and for major histocompatibility complex-matched allogeneic hematopoietic reconstitution.

Blood Preservation↗
PubMed1987

Surgical treatment for advanced epithelial carcinoma of the ovary.

The three surgical steps in the management of carcinoma of the ovary--staging laparotomy, cytoreductive operation and second-look laparotomy--must be critically re-evaluated. During the past decade much data has been assembled on platinum based combination chemotherapy. The results of this type of chemotherapy questions the importance of these procedures. Whereas staging laparotomy will continue to determine important issues in the management of early disease, the use of cytoreduction and second-look laparotomy must be questioned as a routine or important determinant of current treatment results.

Carcinoma↗
PubMed1985

Colposcopic screening of women with atypical Papanicolaou smears.

A retrospective study was done on 575 patients with atypical Papanicolaou smears obtained during a ten-year period (1974-83) at Bellevue Hospital-New York University Medical Center. The smears were classified into three categories. The first consisted of 463 patients (81%) with inflammatory atypia specifically treated for Trichomonas, Monilia, Chlamydia, Gardnerella and atrophic vaginitis. Of them, 162 patients (35% of the group) had persistent inflammatory atypia 90 days after the beginning of therapy and were subjected to colposcopic examination. The second group consisted of 86 patients (15%) with squamous atypia. That group underwent colposcopic examination. The third group, 26 patients (4%), had endocervical atypia and underwent colposcopy and endocervical curettage. Overall, of 162 patients with persistent inflammatory atypia, 36 (22%) were found to have cervical intraepithelial neoplasia (CIN); of 86 with squamous atypia, 60 (70%) had CIN; and of 26 with endocervical atypia, 15 (58%) had CIN. Fifty-eight (28%) of all the patients with CIN had lesions of severity greater than CIN 1. It appears that all patients with persistent inflammation or squamous or endocervical atypia would benefit from colposcopic screening.

Biopsy↗
PubMed1980

Intravenous dexamethasone for prevention of neonatal respiratory distress: A prospective controlled study.

A trial of intravenous dexamethasone for prevention of neonatal respiratory distress syndrome was carried out prospectively. There were 112 treated and 188 control patients, matched for gestational age, birth weight, rupture of membranes, and antepartum diagnosis. No short-term deleterious effects on mother or infant were demonstrable. There was an increased incidence of cesarean section and puerperal infection in the treated patients. This was not related to the steroid therapy. There was no increased incidence of infection in the treated neonates. At 28 to 33 weeks' gestation, the treated newborn infants had one half the perinatal mortality and one fourth the incidence of severe respiratory distress syndrome seen in the controlls. Under 28 weeks, and from 34 to 36 weeks, no difference between treated and control groups was observed. Intravenous dexamethasone is effective in reducing perinatal mortality from respiratory distress syndrome in premature infants delivered between 28 to 33 weeks' gestation.

Bacterial Infections↗
PubMed1980

The role of colposcopy in the management of cervical intraepithelial neoplasia during pregnancy and postpartum.

We made a colposcopic study of 149 pregnant patients with suspicious or positive Papanicolaou smears. Characteristic changes in the colposcopic images were noted to be physiologic eversion of the squamocolumnar junction, glandular hypertrophy and decidual reaction. Fourteen percent of the patients with suspicious Papanicolaou smears were normal by colposcopic examination. Sixteen percent of colposcopic interpretations of the pregnant cervix suggested CIN when in fact none was present on tissue specimens obtained by directed biopsies. There was a good correlation between colposcopic clinical diagnosis and directed tissue biopsies (79%). Furthermore, there was a strong correlation between colposcopically directed tissue biopsies and subsequent cone and hysterectomy specimens (29 cases). All cases with suspicious cytology and CIN based on colposcopic findings (130 patients with satisfactory colposcopic examinations) were managed conservatively. No invasive neoplasia was subsequently detected in this group. Morbidity for colposcopically directed biopsies in pregnancy was negligible. No massive hemorrhage, premature labor, abortion or infection occurred. Treatment for CIN was accomplished following the puerperium by cryocauterization (101 cases), conization (8 cases) or hysterectomy (21 cases). Colposcopy cannot be a substitute for histologic diagnosis. However, it supplies enough data to avoid unnecessary cone biopsies. Only 19 diagnostic cone biopsies were performed during pregnancy with the indication of positive cytology and unsatisfactory colposcopy.

Adolescent↗
PubMed1973

In-use evaluation of a commercially available set of quality control cultures.

Increasing awareness of the need for a uniform quality control program prompted an evaluation of a commercially available set (Bact-Chek) of eight organisms. A protocol was designed in which this set of control cultures was tested simultaneously in the clinical microbiology laboratory of a 400-bed hospital (the Berkshire Medical Center) and in the reference laboratories of the Bacteriology Section of the Center for Disease Control. The results indicate that the Bact-Chek organisms are essentially as advertised: they constitute a basic set of cultures for a quality control program in clinical microbiology. Ninety per cent of the media and reagents (excluding mycobacterial media and reagents) in the clinical laboratory were checked with this set of eight cultures. Additional cultures not in the set were used to check the remaining 10% of the media and reagents.

Bacteria↗