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Biomedical subjects

T Moore

Publications and source records attributed to T Moore.

At least 109 records · Page 6Linked to original sources
PubMed1995

Post-operative problems following anterior cruciate ligament reconstruction.

Seventy adult patients were studied during the postoperative rehabilitation period following anterior cruciate ligament reconstruction in order to investigate the role of pre-, intra-, and postoperative factors in range of motion and graft problems. A standard bone-patellar tendon-bone autograft was used for the reconstruction. Pre- and intraoperative factors such as concomitant injuries, time from injury to surgery, age, sex, and tunnel placement were recorded. Tunnel placement was recorded on intraoperative radiographs of the final guide pin placement and compared to pin placement on cadaver knees. The results indicated a significant relation between early reconstruction (< 1 month) following the injury and range of motion problems during the early rehabilitation period (P < 0.001). This relation disappeared by the end of the first postoperative year. Prolonged surgery was also associated with early motion problems (P < 0.05). Graft laxity or failure was correlated with an earlier return of range of motion (P < 0.05). We hypothesized that graft failure can have a biologic cause rather than a mechanical one since intraoperative X-rays indicated a near-anatomic tunnel placement in this patient group when compared to ideal placement in the cadaver knees.

Adolescent↗
PubMed1995

Sustained-release transdermal glyceryl trinitrate patches as a treatment for primary and secondary Raynaud's phenomenon.

A randomized, double-blind, placebo controlled, cross-over study was conducted to determine the clinical efficacy of and patient tolerance to sustained-release glyceryl trinitrate (GTN) patches in the treatment of Raynaud's phenomenon. The patients studied were those with primary Raynaud's disease (n = 21) and patients with Raynaud's phenomenon secondary to systemic sclerosis (n = 21). GTN patches (0.2 mg/h) were found to be effective in reducing the number (P < 0.05) and severity of Raynaud's attacks (P < 0.05) in both groups of patients. Objective assessments by infrared thermography did not show any significant improvement when the patients were on GTN patches (P > 0.05). Headaches, refractory to treatment, led to the withdrawal of eight patients from the study and occurred in approximately 80% of the remaining patients. Thus, in spite of the subjective efficacy, the frequent headaches will limit the use of GTN patches in Raynaud's phenomenon. Elucidating the mechanism of action of the beneficial and adverse effects of GTN at the molecular level may shed light on the pathogenesis of Raynaud's phenomenon and its treatment.

Administration, Cutaneous↗
PubMed1995

Comparison of PCR and standard cytological staining for detection of Pneumocystis carinii from respiratory specimens from patients with or at high risk for infection by human immunodeficiency virus.

The detection of Pneumocystis carinii DNA by PCR was compared with routine cytologic staining techniques (CYT). A total of 284 clinical respiratory specimens, including 137 bronchoalveolar lavage (BAL), 63 bronchoalveolar washing, 63 sputum, and 21 induced sputum samples, obtained from patients with or at high risk for human immunodeficiency virus infection were evaluated. Eighty specimens were positive by PCR, and 69 were positive by CYT. PCR was able to detect P. carinii in more bronchoalveolar washing specimens (15 versus 11) and in comparable BAL specimens (53 versus 54) compared with CYT. PCR was particularly more sensitive than CYT in detecting P. carinii in expectorated sputum (12 versus 4 samples). Of the 19 patients whose respiratory specimens were positive for P. carinii by PCR but negative by CYT, 5 had P. carinii pneumonia (PCP) confirmed by subsequent BAL and transbronchial or mediastinal lymph node biopsy and 9 had a clinical course highly suggestive of acute PCP. Eleven (58%) of the 19 patients with discordant PCR and CYT results had received prior anti-PCP prophylaxis. In this clinical setting in particular and in the evaluation of sputum specimens, the ability of PCR to detect a low parasitic load suggests that this technique may become an important additional tool, along with current cytological methods, for the detection of P. carinii.

Adult↗
PubMed1994

Expression of CD43 on murine and human pluripotent hematopoietic stem cells.

To understand regulation of hemopoiesis, it would be helpful to identify physiologically relevant function-associated molecules on stem cells. Here, we report the detailed examination of CD43 expression on murine and human pluripotent hemopoietic stem cells. Mouse stem cells were found within the Ly6+Lin-CD43high subpopulation of bone marrow. These cells, upon transfer into SCID mice, caused rapid repopulation of thymus, spleen, and bone marrow. Retransfer of bone marrow cells from primary SCID recipients of Ly6+Lin-CD43high cells into secondary recipients resulted in repopulation of lymphohemopoietic cells. All Ly6+Lin-CD43high cells were found to express high levels of c-kit. In contrast, Ly6+Lin-CD43-/low cells caused limited and variable thymic and splenic repopulation. These cells failed to repopulate the marrow cavity and did not contain retransplantable stem cells. These data indicate that murine pluripotent stem cells express high levels of CD43. Examination of human fetal bone marrow cells revealed a population of CD34+CD38-CD43+ cells. When single sorted cells with this phenotype were cultured in vitro, they were able to produce colonies with a dispersed growth pattern. Cells with this growth pattern have previously been shown to have myeloid and lymphoid growth potentials and extensive self-renewal capacity. Furthermore, CD34+CD38-HLA-DR+ cells, recently shown to be highly enriched in stem cell activity, expressed relatively high levels of CD43. Because CD43 has recently been shown to bind to intercellular adhesion molecule-1, these data suggest a possible role for CD43 in the regulation of hemopoiesis.

ADP-ribosyl Cyclase↗
PubMed1994

Effect of free-radical scavengers and hyperbaric oxygen on random-pattern skin flaps.

OBJECTIVE: To determine whether treatment with the combination of hyperbaric oxygen and free-radical scavengers or inhibitors would result in increased skin-flap survival. DESIGN: An animal model with male Sprague-Dawley rats was used. The flap was a cranial-based dorsal 3 x 12-cm random-pattern skin flap that included the panniculus carnosus. Rats were randomly assigned to one of 10 treatment groups. INTERVENTIONS: The radical scavengers superoxide dismutase, catalase, and alpha-tocopherol acetate and the inhibitor allopurinol were used to combat or scavenge radicals. Oxygen (100%) treatments were for 90 minutes at 2.5 atm absolute daily. MAIN OUTCOME MEASURES: At 7 days, the flaps were examined for survival by fluorescein injection. Lipid peroxidation as a measure of tissue damage was measured by thiobarbituric acid-malondialdehyde analysis. RESULTS: The combination of treatments resulted in significantly increased flap survival compared with untreated controls (P < .05) except in the group treated with allopurinol and hyperbaric oxygen. Lipid peroxidation was inhibited by the superoxide dismutase plus catalase and the alpha-tocopherol treatments but not by treatment with allopurinol. CONCLUSION: Moderate doses of radical scavengers or antioxidants coupled with a conservative hyperoxic exposure regimen can result in the increased survival of random-pattern skin flaps.

Allopurinol↗
PubMed1994

Clinical development of anticancer agents from natural products.

Recent years have seen the introduction into clinical trials of new classes of chemotherapeutic agents which are derived from natural sources and have novel mechanisms of action. Examples of some of these newer classes of agents are presented here to illustrate both the opportunities they represent with respect to cancer treatment applications and the challenges which they represent from the clinical development perspective. Cumulatively the problems encountered with the development of the agents described are representative of the spectrum of issues encountered in the development of natural products, ranging from initial characterization and purification through the difficulties encountered in obtaining sufficient quantities of material for preclinical studies and then ultimately for clinical trials. Since these agents have unique mechanisms of action and are often exquisitely dose- and schedule-dependent in pre-clinical studies, they represent significant complexities with respect to determining the optimal regimen of administration clinically. The particular agents chosen for description here represent the spectrum of natural source-derived materials as well as mechanisms of action. The taxanes are derived from tree sources and interfere with the mitotic spindle apparatus; the camptothecins, while also derived from trees, appear to exert their activity through interactions with topoisomerase I. Bryostatin, derived from a marine animal, has powerful effects on protein kinase C (PKC), and therefore affects signal transduction pathways within cells. Fumagillin analogs appear to exhibit their important antitumor activity not through a direct effect on cancer cells but rather through effects on the tumor neovasculature. Taken as a whole, the spectrum of agents and activities described here confirms the continued importance of natural products in current anticancer agent development and reflects the complexities involved in this area of clinical research.

Antineoplastic Agents, Phytogenic↗
PubMed1994

Correlation of perinatal transmission of human immunodeficiency virus type 1 with maternal viremia and lymphocyte phenotypes.

OBJECTIVE: To determine whether maternal transmission of human immunodeficiency virus (HIV) is correlated with increased quantities of HIV, decreased frequencies of CD4+ T cells, or increased levels of CD8+ T cells in the transmitting mother. METHODS: Peripheral blood obtained from HIV-infected women at different times during pregnancy was used to measure quantitative cell-associated HIV-1 and CD3+CD4+ and CD3+CD8+ proportions; the plasma was used to perform measurements of quantitative viremia by culture and subsequently to measure quantitative HIV-1 ribonucleic acid levels. These measurements were analyzed with respect to their association with HIV transmission to the baby, which occurred in one fourth of the cases. The children were also studied to determine whether HIV-1 was detected near birth or not until 1 to 8 weeks of life. RESULTS: Increased clonal frequencies of HIV-1-infected peripheral blood mononuclear cells were found in mothers of infected children; fivefold fewer cells were required for a positive culture result (median cell numbers of 10(4.5) vs 10(5.2); p = 0.008). Higher frequencies of infected cells were seen in mothers of babies with evidence of infection at birth than in mothers of infected babies without evidence of infection at birth (p < 0.05). Plasma viremia was measured in 10% of cultures without regard to whether the mothers transmitted virus to their babies. Increased levels of ribonucleic acid as detected by the branched-chain DNA method were measurable more often (45% vs 17%) in the mothers of infected children than in mothers of uninfected children. Proportions of CD4+ and CD8+ T cells were indistinguishable in these two groups of women. CONCLUSIONS: Increased viremia was present in mothers who transmitted HIV to their offspring. This variable could be used to select women at highest risk of transmitting HIV to their offspring for treatment to decrease the HIV burden five-fold.

CD4-CD8 Ratio↗
PubMed1994

Effects of antiviral therapy on the production of anti-human immunodeficiency virus-specific immunoglobulin in infants and children.

The effect of zidovudine therapy on human immunodeficiency virus (HIV)-specific antibody production was studied in 64 HIV-1-infected infants and children > 6 months old. HIV-specific in vitro antibody production (IVAP) was measured in cultures of peripheral blood mononuclear cells (PBMC). IVAP decreased in 85% of children after zidovudine was initiated (mean decline, 1 log within 2 months). Effects were seen as early as 1 week after starting zidovudine. No change in IVAP was seen in children not treated. In comparison, plasma core (p24) antigen levels declined and CD4+ lymphocytes increased in only 42% and 52%, respectively, of treated subjects. Thus, the production of antibody to HIV-1 decreases rapidly after the initiation of antiretroviral therapy. This response to therapy may provide a simple and sensitive method of monitoring antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Sensing of aromatic compounds by the DmpR transcriptional activator of phenol-catabolizing Pseudomonas sp. strain CF600.

The dmp operon of the pVI150 catabolic plasmid of Pseudomonas sp. strain CF600 encodes the enzymes involved in the catabolism of phenol and methylphenols. The regulator of this dmp pathway, DmpR, is a member of the NtrC family of transcriptional activators and controls transcription of the dmp operon in response to aromatic effector compounds (V. Shingler, M. Bartilson, and T. Moore, J. Bacteriol. 175:1596-1604, 1993). Using a lux gene fusion reporter system, in which the DmpR-regulated operon promoter controls the expression of luciferase activity, we have shown in the study reported here that DmpR is activated by, but responds differentially to, the presence of a wide range of aromatic compounds. In many microbial regulatory systems, including some members of the NtrC family, the response to environmental fluctuations involves information transfer from surface sensory proteins to transcriptional regulators. However, DmpR-mediated activation of phenol metabolism in response to aromatic compounds occurs in the absence of a specific sensory protein. We used hybrids between DmpR and XylR, a structurally related regulator of toluene and xylene metabolism, to demonstrate that it is the amino-terminal domains of these regulators that determine the specificity of transcriptional activation. The results suggest that it is the direct interaction of aromatic compounds with the DmpR and XylR proteins that regulates their transcriptional promoting activity.

Amino Acid Sequence↗
PubMed1994

FUNCTION OF THE TENSOR MUSCLE IN THE CICADA TIBICEN LINNEI

The calling song and the disturbance squawk of the cicada Tibicen linnei (Insecta: Homoptera) are described in terms of their physical parameters. The calling song is composed of quiet parts, which are very similar to the disturbance squawk, and loud parts, which are amplitude- and rate-modulated. The role of the tensor muscle acting on the tymbal frame in modulating the sound pulse amplitude was investigated. We demonstrate by tensor nerve recordings, by mechanical mimicking of the tensor muscle action and by electrical stimulation of the tensor nerve, that the contraction of the tensor muscle is responsible for (a) initiating sound production and (b) modulating the sound pulse amplitude. These results allow us to construct a model which suggests that the tensor shifts the tymbal into a mechanical working range that enables sound production and modulation of the sound pulse amplitude.

Journal Article↗
PubMed1994

AUDITORY THRESHOLD CHANGE IN SINGING CICADAS

The hearing sensitivity in singing cicadas is reduced during sound production by a folding of the tympanal membranes. Using electrophysiological recording and nerve stimulation techniques, we have shown an effect of the folded tympanum on the auditory threshold of two species of cicadas, Tibicen linnei and Okanagana rimosa. Auditory thresholds of both species increased by about 20 dB when the tympana folded during singing. In T. linnei the increase in threshold affected the whole frequency range, from 1 to 16 kHz, in a similar way. Electrical stimulation of one or both auditory nerves resulted in a folding of both tympanal membranes in a way very similar to that seen in singing animals. We have demonstrated that a cicada male is able to adjust its auditory threshold within a range of about 20 dB by the tympanal folding mechanism.

Journal Article↗
PubMed1994

Effects of gamma irradiation on the human immunodeficiency virus. A study in frozen human bone-patellar ligament-bone grafts obtained from infected cadavera.

We studied the effects of several different doses of gamma radiation, ranging from 20,000 to 40,000 gray (2.0 to 4.0 megarad), with respect to the inactivation of the human immunodeficiency virus in fresh-frozen, whole bone-patellar ligament-bone grafts. Although the International Atomic Energy Agency has recommended the use of 25,000 gray of gamma radiation for the sterilization of medical products, the dose required for the inactivation of the human immunodeficiency virus in frozen allografts has not been established. Using one of the most sensitive and specific tests for the detection of the human immunodeficiency virus, the polymerase-chain-reaction test, we found that doses of 20,000 or 25,000 gray of gamma radiation did not destroy the genes of the human immunodeficiency virus effectively; DNA of the virus was detectable in the DNA of bone-marrow tissue obtained from grafts treated with these doses. However, DNA of the human immunodeficiency virus was not detectable in the grafts treated with 30,000 or 40,000 gray of gamma radiation. We conclude that a dose of 30,000 gray of gamma radiation or more is necessary for the sterilization of a fresh-frozen bone-patellar ligament-bone allograft, so that it can be used for reconstructive procedures without the risk of transmission of the virus to the recipient.

Bone Transplantation↗
PubMed1994

Alteration in the proportion of CD4 T lymphocytes in a subgroup of human immunodeficiency virus-exposed-uninfected children.

OBJECTIVE: The age-related changes in the proportion of CD4 and CD8 lymphocytes in human immunodeficiency virus (HIV)-seronegative children born to HIV-infected mothers (seroreverters) were compared with the changes in these lymphocyte subsets in children born to seronegative women to assess a possible effect of exposure to HIV without infection. DESIGN: There were 146 seroreverter and 72 seronegative children. The median CD4 and CD8 percentages for each of these two groups of children were compared retrospectively at 3-month intervals from birth through 27 months and at a tenth interval for the time beyond 27 months. The weighted average of the within-subject rate of change of CD4 and CD8 percentages were also compared between the two groups. Finally, for each subject, the proportion of the subject's CD4 percentage assays which were <10th percentile of the entire study population (30%) was calculated, and the distributions of the subject-specific proportions were then compared between the seronegative and seroreverter groups using the Wilcoxon rank sum test. The proportion of CD8 assays <10th percentile (12%) or > 90th percentile (26%) were also computed for each subject, and the distributions of the proportions were compared similarly. . RESULTS: The median CD4 percentage of seroreverter children was lower than that for the seronegative children at every interval from birth through 27 months and for the last interval for values obtained at greater than 27 months, although the comparison was statistically significant only at the 4- to 6-month period. The weighted average of the within-subject rate of change of CD4 percentage was -0.09 and -3.0 per year (P = .04), and of CD8 percentage was 1.3 and 1.0 (P = .67), for the seroreverter and seronegative children, respectively. There were significantly more children in the seroreverter group than in the seronegative group who had repeated assays in which the CD4 percentage was < 10th percentile for age (P < .00005). In addition, there was a subset of 10 seroreverter children (6.8%) who had CD4 percentages < 30% on > 50% of their assays, as compared with only one (1.4%) seronegative child. The proportion of CD8 assays < 10th percentile or > 90th percentile were not significantly different between the two groups of children. CONCLUSIONS: The CD4 proportions were persistently lower in the seroreverter than in the seronegative population, although only reaching statistical significance in 1 of 10 3-month intervals. This finding may be due to a subgroup of seroreverter children who have persistently low CD4 lymphocyte percentages.

CD4-CD8 Ratio↗
PubMed1993

Understanding variation in rates of referral among general practitioners: are inappropriate referrals important and would guidelines help to reduce rates?

OBJECTIVES: To determine the extent to which variation in rates of referral among general practitioners may be explained by inappropriate referrals and to estimate the effect of implementing referral guidelines. SETTING: Practices within Cambridge Health Authority and Addenbrooke's Hospital, Cambridge. MAIN OUTCOME MEASURES: Data on practice referral rates from hospital computers, inappropriate referrals as judged by hospital consultants, and inappropriate referrals as judged against referral guidelines which had been developed locally between general practitioners and specialists. Effect of referral guidelines on referral patterns as judged by general practitioners using the guidelines in clinical practice. RESULTS: There was 2.5-fold variation in referral rates among general practices. According to the specialists, 9.6% (95% confidence interval 6.4% to 12.9%) of referrals by general practitioners and 8.9% (2.6% to 15.2%) of referrals from other specialists were judged possibly or definitely inappropriate. Against locally determined referral guidelines 15.9% of referrals by general practitioners were judged possibly inappropriate (11.8% to 20.0%). Elimination of all possibly inappropriate referrals could reduce variation in practice referral rates only from 2.5-fold to 2.1-fold. An estimate of the effect of using referral guidelines for 60 common conditions in routine general practice suggested that application of guidelines would have been unlikely to reduce rates of referral in hospital (95% confidence interval -4.5% to 8.6% of consultations resulting in referral). CONCLUSION: The variation in referral rates among general practitioners in Cambridge could not be explained by inappropriate referrals. Application of referral guidelines would be unlikely to reduce the number of patients referred to hospital.

Decision Making↗