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Biomedical subjects

P Blair

Publications and source records attributed to P Blair.

At least 19 recordsLinked to original sources
PubMed2002

Epidemiological investigation of sudden infant death syndrome infants--recommendations for future studies.

In recent years the study of infant care practices within the sleeping environment has proved to be the single most important set of observations for reducing the risk of Sudden Infant Death Syndrome (SIDS). To further reduce the number of deaths and resolve the debate on safe infant care practice, a closer scrutiny of this environment is required. However, anecdotal observation from uncontrolled death-scene investigations and a reluctance to diagnose SIDS because of adverse social conditions or circumstantial evidence at the time of death is undermining future research. To investigate SIDS now means investigating the wider umbrella of all Sudden Unexpected Deaths in Infancy (SUDI) because of the potential for misdiagnosis. In trying to find out why SIDS infants die we have increasingly been forced to search for why infants survive in the first few months of life and it is this comparative component of epidemiological observation that has saved so many lives. A death-scene investigation is vital to any planned future investigation of SIDS but equally essential is a sleep-scene investigation of surviving infants to put any findings into context. SIDS infants are no longer scattered across the social strata and the cot is not the only environment in which they are found, social deprivation and use of the parental bed are now more discernable. Future studies should therefore reflect these changes with a second control group of surviving infants more closely matched to the type of environment in which SIDS infants might be found.

Case-Control Studies↗
PubMed2000

Preincubation with endothelial cell monolayers increases gene transfer efficiency into human bone marrow CD34(+)CD38(-) progenitor cells.

Retroviral gene transfer studies targeting bone marrow CD34(+)CD38(-) stem cells have been disappointing because of the rarity of these cells, their G(0) cell cycle status, and their low or absent expression of surface retroviral receptors. In this study, we examined whether preincubation of bone marrow CD34(+)CD38(-) stem cells with a hematopoietically supportive porcine microvascular endothelial cell line (PMVECs) could impact the cell cycle status and expression of retroviral receptors in pluripotent CD34+CD38- cells and the efficiency of gene transfer into these primitive target cells. PMVEC coculture supplemented with GM-CSF + IL-3 + IL-6 + SCF + Flt-3 ligand induced >93% of the CD34(+)CD38(-) population to enter the G(1) or G(2)/S/M phase while increasing this population from 1.4% on day 0 to 6.5% of the total population by day 5. Liquid cultures supplemented with the identical cytokines induced 73% of the CD34(+)CD38(-) population into cell cycle but did not maintain cells with the CD34(+)CD38(-) phenotype over time. We found no significant increase in the levels of AmphoR or GaLVR mRNA in PMVEC-expanded CD34(+)CD38(-) cells after coculture. Despite this, the efficiency of gene transfer using either amphotropic vector (PA317) or GaLV vector (PG13) was significantly greater in PMVEC-expanded CD34(+)CD38(-) cells (11.4 +/- 5.6 and 10.9 +/- 5.2%, respectively) than in either steady state bone marrow CD34(+)CD38(-) cells (0.6 +/- 1.7 and 0.2 +/- 0.6%, respectively; p < 0.01 and p < 0.01) or liquid culture-expanded CD34(+)CD38(-) cells (1.4 +/- 3.5 and 0.0%, respectively; p < 0.01 and p < 0.01). Since PMVEC coculture induces a high level of cell cycling in human bone marrow CD34(+)CD38(-) cells and expands hematopoietic cells capable of in vivo repopulation, this system offers potential advantages for application in clinical gene therapy protocols.

ADP-ribosyl Cyclase↗
PubMed1999

Night-time non-nutritive sucking in infants aged 1 to 5 months: relationship with infant state, breastfeeding, and bed-sharing versus room-sharing.

AIM: Epidemiological studies suggest that pacifier use may be protective against SIDS but little is known of the relationship between pacifier use and other forms of non-nutritive sucking (NNS) in infancy, or of patterns of NNS during the night, when most SIDS deaths occur. We report the first longitudinal study of NNS by direct overnight observations in healthy infants in a sleep laboratory. METHODS: Healthy, breast fed term infants (n = 10) were enrolled at birth, and sequential overnight polygraphic and infrared video recordings of infants with their mothers performed at monthly intervals from 1 to 5 months. Each month, mother baby pairs were randomized to 1 night bed-sharing (BN) then 1 room-sharing (RN), or vice versa. 'Episodes' of pacifier, own digit and mother's digit sucking (> 1 min) were identified and compared with state-matched control periods without sucking or feeding before and after each such episode. RESULTS: 329 episodes of NNS were identified in 749 h of video recording. The prevalence of pacifier sucking decreased with age, whilst digit sucking increased. Routine pacifier users rarely sucked their digits. There were temporal differences throughout the night in the distribution of different types of sucking and in infant state during and around sucking episodes. Sleeping in the 'non-routine' location was associated with a larger percentage of nights with sucking episodes and increased sleep latency. Bed sharing (routinely or on a given night) was associated with less sucking behavior and more breastfeeding. Non-nutritive sucking was not, however, associated with decreased total time breastfeeding per night or number of feeds per night. CONCLUSION: Patterns of NNS during the night change with age and are affected by maternal proximity. Digit sucking has state modulating effects, and may be suppressed by pacifier use. Thus any benefits of pacifier use must be set against the potential loss of a self-directed ability to modulate state during the night, and possible shortening of breastfeeding duration.

Beds↗
PubMed1999

Stage B Prostate Cancer: Correlation of DNA Ploidy Analysis With Histological and Clinical Parameters.

BACKGROUND: The ability to accurately predict tumor behavior and patient survival is a problem in managing patients with prostate cancer. Prognostic variables in predicting death from tumor include prostate-specific antigen (PSA) level, histological grade, and clinical stage. Observer subjectivity is inherent in determining grade and stage; thus, criteria that are more objective are needed to identify patients for appropriate treatment. METHODS: The authors correlated flow cytometric nuclear DNA ploidy with Gleason score, PSA level, and recurrence risk in patients who underwent radical retropubic prostatectomy and bilateral pelvic lymphadenectomy between 1987 and 1993 for histopathologic stage B prostate cancer (T2, N0, M0). RESULTS: Of the tumors analyzed, 64% were DNA diploid with a low proliferative fraction, 25% were DNA diploid with a high proliferative fraction, and 11% were DNA aneuploid. DNA aneuploidy was associated with high Gleason grade (7-10). All Gleason grade 10 tumors were DNA aneuploid. Both DNA aneuploidy and high proliferative fraction (S+G2M) were statistically correlated with high Gleason grade and adverse prognosis but not with PSA level or patient age. CONCLUSIONS: A direct relationship is shown between both DNA aneuploidy and a high proliferation index with aggressive biological behavior in stage B prostatic cancer. Objective tumor criteria are needed to choose treatment more selectively for individual patients.

Journal Article↗
PubMed1996

Disease in the scurfy (sf) mouse is associated with overexpression of cytokine genes.

The murine X-linked lymphoproliferative disease scurfy is similar to the Wiskott-Aldrich syndrome in humans. Disease in scurfy (sf) mice is mediated by CD4+ T cells. Based on similarities in scurfy mice and transgenic mice that overexpress specific cytokine genes, we evaluated the expression of cytokines in the lesions of sf mice by Northern blotting, quantitative reverse-transcription polymerase chain reaction (RT-PCR) and by hybridization in situ. Overall, the phenotypic characteristics of scurfy disease correlated well with increased interleukin (IL)-4 (lymphadenopathy), IL-6 (B cell proliferation, hypergammaglobulinemia), IL-7 (dermal inflammatory cell infiltration), and high levels of tumor necrosis factor-alpha (wasting).

Animals↗
PubMed1996

A study of bereavement care after a sudden and unexpected death.

Bereaved parents' perceptions of care after the sudden, unexpected death of their child (from 1 week to 12 years), and the care that was or could be offered by statutory and voluntary agencies, was assessed in 11 health districts in seven regions of England and Wales. In these 11 districts, 185 families were identified who met the criteria of the study. Permission to contact these families was given by only 72 general practitioners. Of these, 42 families responded (58%). Sudden infant death syndrome accounted for 43% of the deaths. The results from postal questionnaires sent to both parents showed that hospital care was perceived as good on the whole, although parents would like more choices. Most parents felt that community care was inadequate, leaving many feeling isolated. In contrast, questionnaires from health visitors and general practitioners in the same health districts showed that they believed that they were the most appropriate professionals to give follow up care, but as there were few policies to guide them and little training provided, felt unable to offer support.

Attitude of Health Personnel↗
PubMed1995

The mouse homolog of the Wiskott-Aldrich syndrome protein (WASP) gene is highly conserved and maps near the scurfy (sf) mutation on the X chromosome.

The mouse WASP gene, the homolog of the gene mutated in Wiskott-Aldrich syndrome, has been isolated and sequenced. the predicted amino acid sequence is 86% identical to the human WASP sequence. A distinct feature of the mouse gene is an expanded polymorphic GGA trinucleotide repeat that codes for polyglycine and varies from 15 to 17 triplets in different Mus musculus strains. The genomic structure of the mouse WASP gene is expressed as an approximately 2.4-kb mRNA in thymus and spleen. Chromosomal mapping in an interspecific M. Musculus/M. spretus backcross placed the Wasp locus near the centromere of the mouse X chromosome, inseparable from Gata1, Tcfe3, and scurfy (sf). This localization makes Wasp a candidate for involvement in scurfy, a T cell-mediated fatal lymphoreticular disease of mice that has previously been proposed as a mouse homolog of Wiskott-Aldrich syndrome. Northern analysis of sf tissue samples indicated the presence of WASP mRNA in liver and skin, presumably as a consequence of lymphocytic infiltration, but non abnormalities in the amount or size of mRNA present.

Amino Acid Sequence↗
PubMed1991

Selective decontamination of the digestive tract: a stratified, randomized, prospective study in a mixed intensive care unit.

To evaluate the use of selective decontamination of the digestive tract (SDD) (polymyxin, amphotericin, tobramycin, and intravenous cefotaxime) in a mixed intensive care unit, we performed a stratified, randomized, prospective study. The 331 patients were recruited over an 18-month period, with 256 patients remaining more than 48 hours. Stratification by acute physiology and chronic health evaluation (APACHE II) preceded randomization to control (standard antibiotic therapy) or treatment (SDD) groups. Nosocomial infection was significantly reduced in the SDD group (16.7%; 21 of 126 patients) compared with the control group (30.8%; 40 of 130 patients; p = 0.008). No difference was found in overall mortality rate or length of stay between the two groups. Those patients with admission APACHE II scores 10 to 19 demonstrated the most significant reduction in nosocomial infection (23 of 70 control vs 13 of 76 SDD; p = 0.03) and mortality (15 of 70 control vs 8 of 76 SDD; p = 0.07). Emergence of multiresistant microorganisms was not a clinical problem, but a definite change occurred in the ecology of environmental and colonizing bacteria. With the exception of cefotaxime, a reduction was noted in systemic antibiotic usage in the SDD group. We conclude that SDD is useful in selected patients in a mixed intensive care unit.

Adolescent↗
PubMed1990

Contribution of ventral blood island mesoderm to hematopoiesis in postmetamorphic and metamorphosis-inhibited Xenopus laevis.

In an effort to label very early erythrocyte and lymphocyte populations and to follow their fate in normally developing postmetamorphic frogs and goitrogen-treated permanent larvae, diploid (2N) and triploid (3N) ventral blood island (VBI) mesoderm was exchanged between neurula stage embryos (about 16-22 hr old). Beginning at 15 days of age, half of the 2N or 3N hosts were treated with sodium perchlorate to prevent thyroxine-induced developmental changes. At larval stages 55-59 (41-48 days) and at 1-2 months postmetamorphosis (110-120 days), the untreated control chimeras and age-matched perchlorate-treated chimeras were killed for analysis of the VBI contribution to blood, spleen, and thymus populations by flow cytometry. The data suggest that grafting of ventral blood island mesoderm is an effective way to label an early larval erythrocyte population that declines after metamorphosis. In perchlorate-blocked permanent larvae this early VBI-derived erythrocyte population persists. In contrast, grafting of VBI mesoderm was less useful as a method to label a larvally distinct lymphocyte population in the thymus and spleen. At the late larval stages that we examined, the proportion of VBI-derived cells in thymus and spleen was not different from that observed after metamorphosis. Inhibition of metamorphosis interfered with the thymocyte expansion that normally occurs after metamorphosis, but the proportion of VBI-derived cells in thymus and spleen was not affected. This suggests that lymphopoiesis occurring in late larval life and after metamorphosis uses a stable persisting population of VBI-derived stem cells as well as dorsally derived stem cells.

Animals↗
PubMed1990

Organ-specific hematopoietic changes induced by a recombinant human interferon-alpha in mice.

Interferon-alpha (IFN-alpha) is a naturally occurring cytokine that mediates numerous biological activities and has demonstrated therapeutic potential in a variety of malignancies. Encouraging activity against HIV-1 replication has also been observed with IFN-alpha in the treatment of AIDS, although hematotoxicity has been a frequently observed side effect. In addition, in vitro studies have suggested that IFN-alpha may function as a down-regulator of myelopoiesis. A recombinant hybrid of subtypes of human IFN-alpha, rHuIFN-alpha A/D, has antiviral activity in murine cells in vitro and in vivo. This study examines the effect of acute and subchronic exposure to rHuIFN-alpha A/D on hemopoietic and immune parameters in C57Bl/6 mice. IFN-alpha was administered ip at 0, 1000, 10,000, and 100,000 units/day for either 1 or 10 consecutive days. Many of the known effects of IFN-alpha in humans such as anemia, leukopenia, and thrombocytopenia were observed in mice following subchronic exposure, with the latter two effects also manifested following acute exposure. Further analysis showed that this leukopenia was not selective. Both splenic and bone marrow cells were examined following 10 days of dosing with the high dose of IFN-alpha. Lymphocytes were reduced in both compartments, while granulocytes were increased in both compartments. Bone marrow cells programmed to differentiate into granulocytes (CFU-G) were suppressed, while macrophage progenitors (CFU-M) were stimulated. Erythroid cells decreased in the marrow but increased in the spleen, suggesting that the microenvironment may play a significant role in the effect of IFN-alpha. The proliferative capacity of both B and T splenic lymphocytes was significantly suppressed in a dose-related fashion following multiple exposure to IFN-alpha. Clinically, IFN-alpha is most often given in multiple doses and the present data suggest that such a regimen is toxic to both erythroid and myeloid cells, as well as being immunotoxic to splenic B and T lymphocytes.

Alanine Transaminase↗
PubMed1990

Expression of class II major histocompatibility complex antigens on adult T cells in Xenopus is metamorphosis-dependent.

Class II major histocompatibility complex (MHC) antigens are expressed predominantly on B lymphocytes and macrophages of tadpoles of the South African clawed frog, Xenopus laevis, as is the pattern in lymphocyte populations of most mammals. However, unlike most mammals, young postmetamorphic frogs show expression of class II MHC antigens on a high proportion of thymocytes and most peripheral T and B lymphocytes. Using the J-strain of Xenopus and the anticlass II monoclonal antibody, 14A2, we have studied, by indirect immunofluorescence, whether inhibition of metamorphosis would alter the pattern of expression of class II antigens during ontogeny. In control animals, class II antigens were virtually absent from thymic lymphocytes and peripheral T cells of normal untreated larvae, but could be found in increasing numbers in both populations after metamorphosis (10-12 weeks of age). In contrast, larvae, whose metamorphosis was inhibited by treatment with sodium perchlorate, had relatively few class II+ thymic lymphocytes throughout the 6-month period of study, and the proportion of class II+ splenic lymphocytes was approximately equal to that of IgM+ B lymphocytes. Thus, perchlorate-treated animals retained the larval pattern of class II expression, suggesting that emergence of class II+ T cells is dependent on metamorphosis.

Animals↗
PubMed1990

Evaluation of amino-oxyacetic acid as a palliative in tinnitus.

Amino-oxyacetic acid (AOAA) was evaluated as a palliative in tinnitus. Sixty-six patients with tinnitus presumed to be of cochlear origin were given either a placebo or 75 mg of AOAA four times a day for 1 week. Response was evaluated by both audiometric measurement of tinnitus loudness and subjective rating by patients of change or no change in tinnitus severity. Because loudness measurements and self-rating have not been shown to be independent, and since the aim of clinical treatment of tinnitus is the alleviation of subjective distress, greater weight was given to the patient's self-rating. A total of 21% of all patients reported a subjective decrease in tinnitus severity, usually within 3 to 4 days after the start of AOAA use. Patients with tinnitus caused by presbycusis or Meniere's disease were the most likely to respond to AOAA treatment with a reduction in tinnitus severity, whereas those with drug-induced tinnitus were the least likely to respond. Nausea and dysequilibrium were the most common side effects of AOAA use. Of the 21% of patients who responded to AOAA, 71% developed some type of side effect. Amino-oxyacetic acid produces a reduction in the severity of tinnitus in about 20% of patients; however, the incidence of side effects makes the drug unacceptable for clinical use.

Acetates↗
PubMed1989

Identification of the sigma 1S protein in reovirus serotype 2-infected cells with antibody prepared against a bacterial fusion protein.

A bacterial expression vector, pATH 3, was used to produce high levels of a fusion protein composed of a portion of the trpE protein of Escherichia coli and the putative sigma 1S coding region from the S1 gene of reovirus serotype 2. The fusion protein was purified and injected into rabbits to prepare antisera. This antibody was able to detect sigma 1S being synthesized in L929 cells infected with reovirus serotype 2 by means of immunoprecipitation and immunoblotting techniques. The peak of sigma 1S accumulation in type 2-infected cells was shown to occur approximately 20 hr after infection. This report represents the first description of sigma 1S production in reovirus serotype 2-infected cells.

Antibodies, Viral↗