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Biomedical subjects

R Bowman

Publications and source records attributed to R Bowman.

At least 37 records · Page 2Linked to original sources
PubMed1994

Intermuscular bupivacaine infusion for control of pain after renal surgery: a preliminary report.

OBJECTIVE: To assess the value of continuous bupivacaine wound infusion for post-operative pain relief after renal surgery. PATIENTS AND METHODS: The analgesic efficacy of continuous intermuscular wound infusion with 0.25% bupivacaine was studied in 10 patients (four men, six women), with a mean age of 47.5 years (range 25-71) and a mean weight of 71.2 kg (range 44-99), after renal surgery in a single-blind randomized trial. The results were compared with those of an age- and weight-matched control group of 10 patients (five men, five women) with a mean age of 47.7 years (range 27-73) and a mean weight of 67.3 kg (range 51-85). Post-operative pain was studied objectively by assessing individual patient's morphine requirements administered via a patient controlled analgesia system, and subjectively with pain scores. Patient mobility was assessed by ward nursing staff using mobility score charts. RESULTS: There was a lower demand for post-operative analgesia in the bupivacaine group compared with the control. Although there was no significant difference in the pain scores between the two groups, the bupivacaine group was significantly more mobile than the control group after surgery. There was no significant difference in the mean post-operative hospital stay between the two groups. CONCLUSION: Continuous intermuscular bupivacaine wound infusion is a simple and safe procedure which lowers the patients' post-operative analgesic requirements, allows for earlier mobility and may promote more rapid discharge from hospital.

Adult↗
PubMed1994

Selection of morphometric features that identify responders and nonresponders in stage IV Wilms' tumors.

Wilms' tumor is the most common renal malignancy of childhood. The use of histologic grade and stage has divided those patients into two main groups, responders and nonresponders, based on the absence or presence of extreme cytologic atypia (anaplasia). Patients with Wilms' tumor who have favorable histology experience excellent cure rates with relatively conservative treatment regimens. However, some patients with a favorable histologic diagnosis die of the disease. Destained hematoxylin and eosin-stained tissue sections were restained stoichiometrically with Feulgen stain, and 100 tumor cells per case were measured on a CAS 200 running CMP software. Using multivariant stepwise discriminant analysis on 13 cases of stage IV, favorable-histology Wilms' tumor, we successfully classified 92% of individuals into their correct prognostic groupings using 10 features of the quantitative morphology of tumor cells, including six Markovian textures. This morphometric technique may identify patients who can benefit from reduced therapy and those who must be treated with the more aggressive, classic therapy regimens.

Cell Nucleus↗
PubMed1993

Structure-activity relationships and binding model of novel aromatase inhibitors.

The use of aromatase inhibitors is an established therapy for oestrogen-dependent breast cancer in postmenopausal women. However, the sole commercially available aromatase inhibitor, aminoglutethimide, is not very selective. We have therefore developed fadrozole hydrochloride and CGS 20,267, which are both currently under clinical evaluation. This report will present an analysis of structure-activity relationships in the azole series of inhibitors and give an account of the further optimization of our development compounds, starting from CGS 20,267 over CGP 45,688 and leading to CGP 47,645, the most potent aromatase inhibitor in vivo reported to date. In addition, on the basis of comparisons of these azole-type inhibitors with the most potent steroidal inhibitors published in the literature, we propose a CAMM-generated model describing the relative binding modes of these two classes of compounds at the active site of the enzyme.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Syphilis serology in blood donors: a possible surrogate marker for human immunodeficiency virus risk.

We report a preliminary study on whether syphilis serology might be reactive in some blood donors at risk for human immunodeficiency virus (HIV) infection. We retrospectively analyzed voluntary blood donations with reactive Treponema pallidum antibody (TPA) tests according to the type of donation, the presence of other safety markers, confidential unit exclusion, syphilis diagnosis, and HIV risk factors. Over 2 years (1987-1988), 1 in 8,900 regular homologous donations (n = 258,610) was TPA positive as compared with 1 in 2,200 directed donations (n = 6,685) and 1 in 300 autologous donations (n = 8,870; p less than 0.05 for both). The rate in directed donations was not significantly higher than in first-time regular donors (1 in 4,800; n = 57,000). TPA-positive donations had higher rates of antibody to hepatitis B core antigen and confidential unit exclusion than TPA-negative donations. Ten TPA-positive homologous or directed donors had latent or previously treated syphilis (1 in 26,500 such donations), and 2 of these had HIV risk factors. None of the autologous donors were determined to have active syphilis. Syphilis serology in blood donors bears further scrutiny as a possible surrogate marker for HIV risk.

Biomarkers↗
PubMed1991

Prevention of cytomegalovirus infection following bone marrow transplantation: a randomized trial of blood product screening.

From 1983 to 1987, cytomegalovirus seronegative allogeneic bone marrow recipients were randomized to receive screened cytomegalovirus (CMV) seronegative or unscreened blood products and 125 patients were available for analysis. CMV infection occurred in 18% of patients in the screened versus 38% in the unscreened blood product group. However, only two of 64 patients in the screened group and seven of 61 in the unscreened group developed culture or biopsy-proven CMV infections. Bone marrow donor CMV seropositivity was associated with an increased risk of developing CMV infection (21% with seronegative and 46% with seropositive donor), and CMV infection was not prevented by blood product screening if the bone marrow donor was sero = positive (62% for screened, 42% for unscreened group, p = 0.80). One year survival censored for relapse was 52% in the screened group versus 68% in the unscreened group (p = 0.08). Gram negative bacteremia complicated bone marrow transplantation (BMT) in 35% of patients receiving screened and 15% of those receiving unscreened blood products (p = 0.02). Relapse did not differ in the screened and unscreened groups. By multivariate analysis, high risk disease (p = 0.0002), CMV infection (p = 0.004), screened blood products group (p = 0.011), recipient age greater than 17 (p = 0.027), chronic graft-versus-host disease (p = 0.014) and gram negative bacteremia (p = 0.004) independently had a negative influence on survival. We conclude that blood product screening was effective in preventing CMV infections following BMT if both the recipient and bone marrow donor were CMV seronegative.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Highly selective inhibition of estrogen biosynthesis by CGS 20267, a new non-steroidal aromatase inhibitor.

CGS 20267 is a new non-steroidal compound which potently inhibits aromatase in vitro (IC50 of 11.5 nM) and in vivo (ED50 of 1-3 micrograms/kg p.o.), CGS 20267 maximally inhibits estradiol production in vitro in LH-stimulated hamster ovarian tissue at 0.1 microM with an IC50 of 0.02 microM and does not significantly affect progesterone production up to 350 microM. In ACTH-stimulated rat adrenal tissue in vitro, aldosterone production was inhibited with an IC50 of 210 microM (10,000 times higher than the IC50 for estradiol production); no significant effect on corticosterone production was seen at 350 microM. In vivo, in ACTH-treated rats, CGS 20267 does not affect plasma levels of corticosterone or aldosterone at a dose of 4 mg/kg p.o. (1000 times higher than the ED50 for aromatase inhibition in vivo). In adult female rats, a 14-day treatment with 1 mg/kg p.o. daily, completely interrupts ovarian cyclicity and suppresses uterine weight to that seen 14 days after ovariectomy. In adult female rats bearing estrogen-dependent DMBA-induced mammary tumors, 0.1 mg/kg p.o. given daily for 42 days caused almost complete regression of tumors present at the start of treatment. Thus compared to each other, CGS 16949A and CGS 20267 are both highly potent in inhibiting estrogen biosynthesis in vitro and in vivo. The striking difference between them is that unlike CGS 16949A, CGS 20267 does not affect adrenal steroidogenesis in vitro or in vivo, at concentrations and doses several orders of magnitude higher than those required to inhibit estrogen biosynthesis.

Animals↗
PubMed1990

Novel aromatase inhibitors.

Aminoglutethimide (AG), an inhibitor of the aromatase enzyme, inhibits the biosynthesis of estrogens and displays well-documented anti-tumor efficacy in breast-cancer. However, this efficacy is accompanied by a relative lack of specificity in inhibiting aromatase and moderate tolerability. We report on two new non-steroidal aromatase inhibitors (CGS 16949A and CGS 18320B) which are more potent, selective and efficacious in their inhibition of aromatase than AG. Both compounds inhibit aromatase more potently in vitro and in vivo (over 400 and 1000 times respectively) than AG. They are both more selective in their inhibition of aromatase with CGS 18320B showing an improved selectively over CGS 16949A. When administered to adult female rats, both compounds elicit responses in serum hormones similar to those seen after ovariectomy. The duration of action of CGS 18320B, however, appears to be longer than that of CGS 16949A. CGS 18320B and CGS 16949A cause almost complete regression of DMBA-induced mammary tumors in adult female rats and almost completely suppress the appearance of new tumors. Thus CGS 16949A and CGS 18320B represent significant advances in the search for novel aromatase inhibitors which are more potent, selective and efficacious than aminoglutethimide.

Animals↗
PubMed1988

Limiting-dilution analysis of T cells extracted from solid human lung tissue: comparison of precursor frequencies for proliferative responses and lymphokine production between lung and blood T cells from individual donors.

This study evaluates the frequency and functions of immunocompetent T cells at the clonal level in solid human lung tissue versus peripheral blood. Enzymatic digestion of slices of histologically normal human lung yielded 18-42 x 10(6) viable mononuclear cells per gram wet weight tissue, of which 60-72% were lymphocytes; based upon these recoveries and the known weight of adult lung, the (median) lung parenchymal lymphocyte population can be estimated as 6 x 10(9), being of the same order as the blood pool and 15-30-fold that recoverable by broncho-alveolar lavage. Flow cytometric analysis indicated that the bulk of these lymphocytes was OKT3+/T11+ (CD3/CD2) T cells. Purified blood and lung T cells from each subject were cultured at limiting dilution in the presence of PHA, irradiated feeder cells and recombinant human IL-2. The mean frequency estimates for PHA-responsive T cells in these populations were 1 in 1.23 (81%) and 1 in 3.22 (31%) for blood and lung, respectively. This difference was seen for T cells from each donor and was highly significant by paired t-test (P less than 0.002). Analysis of surface phenotypes and functions of individual blood and T-cell clones indicated comparable frequencies for OKT4 (CD4) and OKT8 (CD8) expression, TNF production and mitogen-induced cytotoxicity. However, a striking inverse relationship was observed between the overall frequency of IL-2-producing clones (79% for blood versus 47% for lung) and interferon-gamma (IFN-gamma)-producing clones (46% versus 87%). These differences were found for each subject, and both were highly significant (P less than 0.001) by paired t-test. The available literature suggests that the majority of these lung T cells represent transient immigrants derived from the blood. Accordingly, the functional differences we have observed suggest either selective trapping within the lung vascular bed of peripheral blood T cells of certain functional phenotypes or alternatively selection/modulation of T cells by lung-derived factors during their transit through the tissue.

Adult↗
PubMed1984

Does prostacyclin prevent cognitive deficits after open heart surgery?

Two groups of open heart surgery patients, one receiving prostacyclin and one placebo, were assessed one week pre-operatively and 3 months post-operatively, using a battery of clinical tests measuring a variety of cognitive functions. No significant differences between the groups were detected, apart from a visual retention deficit at 3 months in the prostacyclin group. The results cast doubt on previous findings suggesting that prostacyclin reduces cognitive deficits following open heart surgery.

Cardiac Surgical Procedures↗
PubMed1983

Treatment of primary osteosarcoma with intra-arterial and intravenous high-dose methotrexate.

In an effort to achieve high concentrations and prolonged exposure times, high-dose methotrexate (MTX) was administered by the intra-arterial route over 6 hours at a dose of 12.5 g/m2 to nine patients with osteosarcoma. This was followed by citrovorum factor (CF) rescue, which was initiated 12 hours after completion of the infusion (MTX-CF). The regimen achieved high local concentrations over a finite period. No toxicity was encountered. Treatment was administered at weekly intervals, during which intravenous MTX-CF was interposed if facilities for intra-arterial administration were not available. However, despite increases in local venous concentrations and exposure times, only four of nine patients (44%) responded. This is similar to responses achieved with 7.5 g/m2 (48%) with CF initiated 2 hours after completion of the infusion. Higher MTX doses, intra-arterial administration, and prolongation of cytotoxic exposure time did not confer a therapeutic advantage as opposed to "conventional" intravenous high doses.

Adolescent↗
PubMed1981

Emergency PaO2 estimates in one minute with a transcutaneous oxygen sensor.

Blood was applied directly to the electrode surface of a transcutaneous oxygen sensor (PtcO2) and the oxygen tension value obtained was compared to oxygen tension value from a conventional blood gas machine. Three hundred and seventeen blood samples were analyzed at four PtcO2 electrode temperatures: 37, 40, 42, and 45 degrees C. A linear regression of PO2 vs. PtcO2 blood drop (PbdO2) produced correlation coefficients (r) from 0.99 to 0.93 and standard errors from 3.2 to 4.7 torr at these temperatures. The mean time for stabilization was 51 sec. The PO2 ranged from 4--150 torr. The authors conclude that an accurate PO2 of blood can be obtained within 1 min by placing a drop of blood on the surface of a PtcO2 electrode.

Blood Gas Analysis↗
PubMed1980

Continuous transcutaneous oxygen monitoring during respiratory failure, cardiac decompensation, cardiac arrest, and CPR. Transcutaneous oxygen monitoring during arrest and CPR.

The transcutaneous oxygen sensor (PtcO2), which has been used to predict PaO2 in neonates, recently has been shown to follow changes in oxygen delivery, rather than PaO2 during shock and hypoxia in dogs. Six preterminal patients were continuously monitored with PtcO2 and monitored hemodynamically at frequent intervals during cardiac decompensation, arrest, and cardiopulmonary resuscitation (CPR). The weighted mean correlation coefficients between PtcO2 and O2 delivery as well as between PtcO2 and cardiac output were 0.94 and 0.96, respectively. Five patients died of severe ARDS and 1 patient died intraoperatively of hemorrhagic shock. Four patients were monitored 1-7 days before shock occurred. The correlation between PtcO2 and PaO2 was 0.91 during periods of normal cardiac output in the preterminal period. During cardiac decompensation, the cardiac output, PtcO2, and mixed venous oxygen tension (PcO2) of 25 torr was reached, the PtcO2 fell below the PvO2. This also corresponded to a decrease in VO2. The mean VO2 was 142 +/- 24 ml/min x M2 for PtcO2 values > torr, and 75 +/- 15 ml/min x M2 for PtcO2 < 25 torr (p < 0.01). A PtcO2 of > 40 torr corresponded to normal cardiac index, O2 delivery, VO2, PvO2, and arterial pH (pHa) while a PtcO2, of < 25 torr corresponded to large reductions of these variables. A PtcO2 of < 25 torr preceded cardiac arrest by 43 +/- 28 min.

Cardiac Output↗