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Biomedical subjects

L Barber

Publications and source records attributed to L Barber.

At least 37 records · Page 2Linked to original sources
PubMed1998

Localized versus systemic angiotensin II receptor inhibition of intimal hyperplasia in experimental vein grafts by the specific angiotensin II receptor inhibitor L158,809.

BACKGROUND: This study examines the effect of the angiotensin II receptor (type 1) antagonist (L158,809) on the formation of vein graft intimal hyperplasia in vivo, by both localized and systemic administration. METHODS: Forty New Zealand White rabbits underwent carotid interposition bypass grafting with the external jugular vein and were killed on postoperative day 28. To determine the effect of L158,809 on the development of intimal hyperplasia, 10 animals received long-term oral therapy with L158,809 (10 mg/kg/day, begun 5 days before operation and continued until harvest), 10 animals underwent coating of the grafts with a pluronic gel containing L158,809 (10(-5) mol/L), and 20 animals were controls (10 with and 10 without pluronic gel). These grafts were harvested for either histologic analysis (n = 6 per group) or in vitro isometric tension studies to angiotensin II (n = 4 per group). RESULTS: Long-term oral treatment with L158,809 produced a 43% decrease in intimal thickness from 76 +/- 6 microns (mean +/- SEM) in the control animals to 43 +/- 7 microns in the treated vein grafts (p = 0.002). There was also a significant decrease (44%) in the medial thicknesses between the control (75 +/- 4 microns) and L158,809-treated (42 +/- 6 microns) vein grafts (p = 0.007). The contractile responses to angiotensin II were abolished in the vein grafts by long-term L158,809 therapy. Local application by gel of L158,809 produced a significant decrease (33%) in the intimal thickness (48 +/- 3 microns) but no change in medical thicknesses (76 +/- 6 microns) compared with control grafts. The contractile responses to angiotensin II were unchanged in the vein grafts by local L158,809 therapy. CONCLUSIONS: This study shows that a local single application of L158,809 will reduce the intimal response but not the medial response in vein grafts, whereas long-term treatment will reduce intimal hyperplasia and the medial response in experimental vein grafts. Therefore angiotensin II acting through AT1 receptors mediates a significant part of the intimal hyperplastic response in vein grafts that appears to involve two phases: an acute intimal response requiring short-term therapy and a long-term medial response that requires prolonged therapy.

Angiotensin II↗
PubMed1997

Oral monoterpene therapy (perillyl alcohol) reduces vein graft intimal hyperplasia.

The development of intimal hyperplasia is recognized as a major impediment to graft patency. D-Limonenes are monoterpenes with a recognized cytostatic effect on cell proliferation by inhibiting posttranslational isoprenylation of p21ras and other small G-proteins. This study examines the effect of perillyl alcohol, an oral hydroxylated D-limonene, on the development of intimal hyperplasia and its associated smooth muscle cell physiological responses in an experimental model of vein bypass grafting. Twenty New Zealand white rabbits had a right carotid interposition bypass graft using the ipsilateral external jugular vein. Ten animals received chronic oral therapy with a perillyl alcohol (200 mg/kg/day; begun 5 days before surgery and continued until harvest) and 10 control animals received vehicle only. All animals were sacrificed on the 28th postoperative day. Vein grafts were harvested either for morphology/videomorphometry (n = 6 per group) or for in vitro isometric tension studies (n = 4; four 5-mm rings per graft). The cell proliferation and incorporation of [3H]thymidine into the cellular DNA of serum-stimulated rabbit aortic smooth muscle cells was also assessed in the presence of increasing concentrations of perillyl alcohol (10(-9)-10(-4) M). Perillyl alcohol treated vein grafts showed a 22% reduction in overall mean intimal thickness (54 +/- 4 microns vs 69 +/- 3 microns; P = 0.006) but a 25% increase in overall mean medial thickness (86 +/- 4 microns vs 61 +/- 3 microns). The intimal ratio of the perillyl alcohol treated vein grafts decreased by 27% compared to controls. Perillyl alcohol induced norepinephrine and serotonin hypersensitivity in vein grafts compared to controls. The IC50 for perillyl alcohol was 176 nM with maximal inhibition at 5 microM. Incubation of smooth muscle cell cultures with increasing concentrations of perillyl alcohol showed a dose-dependent decrease in in vitro cellular proliferation, maximal at 1 microM. Therapy with perillyl alcohol alters the early development of intimal hyperplasia reducing the intimal response but increasing the medial response without significant changes in the physiological responses of the smooth muscle cells. Modulating G-proteins will affect the intimal hyperplastic response in vein grafts.

Administration, Oral↗
PubMed1997

Plasma clearance, biodistribution and therapeutic properties of mitoxantrone encapsulated in conventional and sterically stabilized liposomes after intravenous administration in BDF1 mice.

Mitoxantrone can be efficiently loaded into large unilamellar vesicles using a transmembrane pH gradient. Release studies indicate that these drug-loaded carriers are highly stable and even after dissipation of the residual pH gradient retain more than 85% of encapsulated mitoxantrone following dialysis at 37 degrees C for 5 days. In murine studies we have compared the plasma clearance and biodistribution of both mitoxantrone and liposomal lipid following intravenous administration of free drug or mitoxantrone encapsulated in either conventional or sterically stabilized liposomes. In contrast to the rapid blood clearance observed for free mitoxantrone, both liposomal systems provided extended circulation lifetimes, with over 90% of the drug present 1 h after administration and 15-30% remaining at 24 h. In agreement with previous reports, longer plasma half-lives were observed for sterically stabilized liposomes than for conventional systems. In addition, a strong correlation between drug and carrier biodistribution was seen, with uptake occurring mainly in the liver and spleen and paralleling plasma clearance. This would suggest that tissue disposition reflects that of drug-loaded liposomes rather than the individual components. Liposomal encapsulation also significantly reduced mitoxantrone toxicity, allowing administration of higher, more efficacious drug doses. In a murine L1210 tumour model, for example, no long-term survivors were seen in animal groups treated with free drug, whereas at the maximum therapeutic dose of liposomal mitoxantrone survival rates of 40% were observed.

Animals↗
PubMed1997

Acute effects of treadmill running on lipoprotein(a) levels in males and females.

This investigation examined the acute response of serum lipoprotein(a) (Lp(a)) concentration immediately after, and during several days following, level and downhill motorized treadmill running. Eight males ran for 1 h on a level motorized treadmill at an intensity producing 90% maximum heart rate (MHR). On a separate occasion, three males and three females performed downhill (negative 13.4% incline) treadmill running at an intensity producing 75-80% MHR. For both protocols, serial blood samples were taken pre- and post-exercise and at the same time of day 1, 3, 5, and 7 days following exercise. Levels of Lp(a), creatine kinase (CK), C-reactive protein (CRP), and ferritin were measured. Repeated measures statistical analysis (Friedman ANOVA) showed no significant change in the median level of Lp(a) (level run, 5.0 mg.dl-1; downhill run, 7.45 mg.dl-1) across time following either protocol. After level running, ferritin levels 5 and 7 d post-exercise were significantly (P < 0.05) lower compared with immediately and 1 d post-exercise measures (Friedman ANOVA). Following level running, the Wilcoxon signed rank test showed significant (P < 0.05) elevations in CK levels immediately, 1 and 5 d post-exercise compared with pre-exercise values. Following downhill running. CK level was significantly elevated up to 3 d post-exercise (Wilcoxon signed rank). Calculated plasma volume did not change significantly following either protocol. These data suggest that Lp(a) does not change acutely in response to level or downhill treadmill running up to 60 min duration.

Acute-Phase Proteins↗
PubMed1997

A crisis intervention program. Staff go the extra mile for client improvement.

1. Community mental health centers are faced with clients with dual and triple diagnoses who do not respond to traditional treatment. 2. A crisis team, with its inherent flexibility, may be able to engage multi-need clients and enable them to become connected to the Community mental health center. 3. Although these clients will continue to require inpatient services, provision of crisis team services can shorten inpatient length of stay. Plans to transition clients to more comprehensive services are necessary.

Adult↗
PubMed1996

Comparative study of three PCR assays with antigenaemia and serology for the diagnosis of HCMV infection in thoracic transplant recipients.

Three PCR assays were evaluated for the detection of human cytomegalovirus (HCMV) infection in heart and lung transplant recipients in comparison with HCMV antigenaemia and serology assay. Polymorphonuclear leucocyte (PMNL) samples taken at regular intervals after transplantation were tested for HCMV DNA using primer sets homologous to the glycoprotein B (gp58), major immediate early (IE1), and structural phosphoprotein (pp150) regions. The detection of HCMV infection at various times after transplantation showed all three primer sets to have a sensitivity of 100% and a specificity of 92.3% for the detection of HCMV infection although overall the gp58 primer set was found to be significantly more frequently associated with a positive PCR result than the IE1 (P = 0.0228) and pp150 (P = 0.0015) primer sets. The positive PCR result had a positive predictive value of 27.8% for HCMV disease. Detection of HCMV infection was first by the PCR assay, and significantly before the HCMV antigenaemia assay. Of nine patients who received antiviral therapy while PCR positive, only one patient cleared HCMV DNA from PMNLs during treatment but became positive again 17 days later. Quantitative PCR methodologies may improve the predictive value of PCR for HCMV disease and its value for monitoring antiviral therapy.

Antigens, Viral↗
PubMed1996

The temporal sequence of G-protein expression in intimal hyperplasia.

The universal response of a blood vessel to intimal injury is the development of intimal hyperplasia. The etiology of this lesion is not fully understood but is assumed to involve stimulation of receptors on smooth muscle cells with their subsequent proliferation. Many receptor-mediated processes are coupled to G-proteins but little information exists regarding the expression of G-proteins during the development of intimal hyperplasia. This study examines the kinetics of G-protein expression in experimental vein grafts. Male New Zealand White rabbits had a right carotid interposition bypass graft using the ipsilateral external jugular vein. These were harvested on days 1, 3, 5, 7, 14, and 28 postoperatively for histology (n = 3), for in vitro isometric tension studies of potassium chloride, serotonin, bradykinin, and histamine (n = 3), or for Western blot analysis (n = 3) of the G-protein subunits (alpha(i1), alpha(i2), alpha(i3), alpha(S) and beta). The results show that expression of alpha(i3) developed de novo, was detectable by day 1, and continued to increase through day 7, paralleling the development of intimal hyperplasia. The expression of alpha(S) (52 kDa) increased significantly by day 1 and also continued to increase until day 7. In contrast, expression for alpha(i2), alpha(S) (45 kDa) and beta subunits increased at a much slower rate from 1 to 7 days and remained constant thereafter. No alpha(i1) was detected. The contractile response to potassium chloride was significantly reduced (36% of the response in the jugular vein) over the first 7 days and increased to 196% of the jugular vein response at 14 and 28 days. There was minimal response to serotonin, bradykinin, and histamine over the first 7 days. Contractile responses to serotonin increased while those to bradykinin and histamine decreased from 7 to 28 days. This study demonstrates that there are specific changes in alpha(i) and alpha(S) subunits within 24 hr of grafting and that increases in all G-proteins occur in a time dependent manner up to 7 days postoperatively. Microscopic development of intimal hyperplasia occurs from days 3 to 5 and increases rapidly between 7 and 14 days. Changes in the expression of G-proteins in the vein grafts, particularly the alpha(i3) subunit, parallel this formation of intimal hyperplasia. These alterations in G-protein expression do not appear to correlate with G-protein-mediated, contractile responses in the vein grafts.

Animals↗
PubMed1996

Lazaroid therapy (methylaminochroman: U83836E) reduces vein graft intimal hyperplasia.

The development of intimal hyperplasia is now recognized as a major impediment to graft patency and recent studies suggest that the infiltration of polymorphonucleocytes and oxygen free radical mediated injury are involved in the early development of intimal hyperplasia. This study examines the effect of a methylaminochroman, U83836E (Upjohn Company), a second generation lazaroid, in controlling the development of intimal hyperplasia and its associated smooth muscle cell physiological responses in an experimental model of vein bypass grafting. Twenty New Zealand White rabbits had a right carotid interposition bypass graft using the ipsilateral external jugular vein. Ten animals received chronic oral therapy with U83836E (10 mg/kg/day; begun 5 days before surgery and continued until harvest) and 10 control animals received vehicle only. All animals were sacrificed on the 28th postoperative day. Vein grafts were harvested either for morphology/videomorphometry (n = 6 per group) or for in vitro isometric tension studies (n = 4; four 5-mm rings per graft). The incorporation of [3H]thymidine into the cellular DNA of serum-stimulated rabbit aortic smooth muscle cells (passage 6th to 9th) was also assessed in the presence of increasing concentrations of U83836E (10(-9) to 10(-4) M). Treatment with U83836E produced a 41% decrease in overall mean intimal thickness in the U83836E-treated vein grafts compared to untreated vein grafts (P = 0.003). There were no differences in the medial thicknesses or luminal dimensions of the control and treated vein grafts. U83836E induced norepinephrine hypersensitivity in both jugular veins and vein grafts compared to controls. Other physiological contractile responses of the jugular veins and vein grafts were unaltered by U83836E. U83836E did not inhibit the in vitro [3H] thymidine incorporation in a dose-dependent manner until very high concentration when there was a significant and precipitous response with an IC(50) of 67 microM (114 microgram/ml) and a maximal inhibition of 97 +/- 2% (mean +/- SEM) at 80 microM (137 microgram/ml). Therapy with the methylaminochroman, U83836E, is beneficial in controlling the early development of intimal hyperplasia without significant changes in the physiological responses of the smooth muscle cells.

Administration, Oral↗
PubMed1996

Characterisation of angiotensin II receptor mediated responses and inhibition of intimal hyperplasia in experimental vein grafts by the specific angiotensin II receptor inhibitor, L158,809.

OBJECTIVES: This study characterises pharmacologically the angiotensin II receptor in experimental vein grafts and examines the effect of the angiotensin II receptor (type 1) antagonist (L158,809) on the formation of vein graft intimal hyperplasia in vivo, as well as the in vitro physiological response to angiotensin II of vein grafts after chronic oral L158,809 treatment. MATERIALS: Thirty New Zealand White rabbits had a right carotid interposition bypass graft using the external jugular vein and were killed on the 28th postoperative day. DESIGN: To characterise the angiotensin II receptors, concentration response curves to angiotensin II were obtained in vitro in the presence or absence of L158,809. To determine the effect of L158,809 on the development of intimal hyperplasia, 10 animals received chronic oral therapy with L158,809 (10 mg/kg/day; begun 5 days before surgery and continued until harvest) and 10 animals received vehicle only as controls. These grafts were harvested either for histology (n = 6 per group) or for in vitro isometric tension studies to angiotensin II. RESULTS: The monophasic contractile response to angiotensin II in the untreated vein grafts could be inhibited in a concentration dependent manner by L158,809 with first order kinetics. Chronic oral treatment with L158,809 produced a 48% decrease in intimal thickness from 82 +/- 1 micron (mean +/- S.E.M.) in the controls to 43 +/- 7 microns in the treated vein grafts (p = 0.002). There was also a significant decrease (45%) in the medial thickness between the control (76 +/- 6 microns) and L158,809 treated (42 +/- 6 microns) vein grafts (p = 0.007). The responses to angiotensin II were abolished in the vein grafts by chronic L158,809 therapy. CONCLUSIONS: This study suggests that vein graft angiotensin II responses are mediated through a type 1 receptor and that chronic inhibition with L158,809, significantly reduces intimal hyperplasia and medial hypertrophy in experimental vein grafts and concomitantly abolishes the in vitro responses to angiotensin II. Therefore, angiotensin II acting through AT1 receptors mediates a significant part of the intimal hyperplastic response in vein grafts.

Angiotensin II↗
PubMed1995

Differences in adhesion markers, activation markers, and TcR in islet infiltrating vs. peripheral lymphocytes in the NOD mouse.

Insulin dependent diabetes mellitus (IDDM) in the non-obese diabetic (NOD) mouse is the result of a cellular mediated autoimmune event that destroys pancreatic islet beta cells. This destruction is characterized by a progressive lymphocytic infiltration into the islets as well as circulating autoantibodies and T cells reactive with islet antigens. To gain a better understanding of the cells responsible for islet destruction we isolated lymphocytes from the islets of prediabetic NOD mice and conducted a comparative phenotypic analysis with the analogous subpopulations of lymphocytes isolated from peripheral blood and lymph node (LN) of the same mice. CD3+ cells were analysed for T cell receptor (TcR); cell bearing gamma delta TcR were consistently observed at a higher frequency in the infiltrating T cells than in the periphery. Lymphocytes were also characterized for the expression of CD4 and CD8 T cell markers and, within each population, for the expression of activation markers (CD25, CD69) and adhesion markers (CD51, CD54, CD11b, CD49e, L-selectin). Significantly increased levels of CD4+CD8+ double-positive and CD4-CD8- double-negative T cell populations were observed in the infiltrating lymphocytes as compared with peripheral lymphocytes. In addition, within both CD4 and CD8 subpopulations isolated from islet infiltrates, CD11b+ and CD49e+ cells were increased with respect to the same subset of cells isolated from the periphery. In contrast, the level of cells that expressed L-selectin was significantly higher in the periphery for both CD4+ and CD8+ cells than for infiltrating cells. These data describe the phenotype of islet reactive T cells in the NOD mouse and identify possible targets for therapeutic intervention.

Animals↗
PubMed1995

Control of accelerated vein graft atheroma with the nitric oxide precursor: L-arginine.

Hyperlipidemia contributes to the development of intimal hyperplasia and subsequent accelerated atherosclerosis in vein bypass grafts. This study examines the effect of dietary supplementation with L-arginine on the development of intimal hyperplasia and the vasomotor function of vein grafts in hypercholesterolemic animals. Thirty male New Zealand White rabbits had a right carotid vein bypass graft and were sacrificed at 28 days postoperatively. Twenty animals received a 1% cholesterol diet for 4 weeks prior to surgery and this diet was continued until harvest. Of these, 10 also received L-arginine (2.25%, 2 g/kg, p.o.) 7 days preoperatively and thereafter until harvest. The last 10 animals were controls. Vein grafts were harvested either for morphology or for in vitro isometric tension studies. Cumulative dose-response curves to norepinephrine, serotonin, and bradykinin were recorded, and following norepinephrine precontraction, relaxation to acetylcholine and sodium nitroprusside were determined. After in situ pressure fixation, intimal thicknesses of the vein grafts were measured by videomorphometry. The addition of L-arginine doubled the serum arginine concentrations. Intimal hyperplasia of both groups of hypercholesterolemic vein grafts contained foam cells and lipid-laden endothelial and smooth muscle cells. There was a 24% reduction in the intimal thickness of vein graft intimal hyperplasia in the L-arginine group compared to that in the hypercholesterolemia group (P < 0.05). All hypercholesterolemic vein grafts were two-fold thicker than in the control group. L-arginine supplementation resulted in the preservation of acetylcholine-mediated relaxation but did not change hypercholesterolemia-induced contractile agonist supersensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The influence of the combined presence of diabetes mellitus and hypercholesterolaemia on the function and morphology of experimental vein grafts.

OBJECTIVES: Diabetes and hypercholesterolaemia are known risk factors for the development of atherosclerosis and are considered to influence the development of vein graft intimal hyperplasia. This study examines the combined effect of diabetes for 12 weeks (alloxan-induced) and hypercholesterolaemia for 8 weeks (1% cholesterol diet) on the formation of intimal hyperplasia and the vasomotor function of vein grafts. MATERIALS AND DESIGN: Thirty-two New Zealand White rabbits underwent a carotid vein bypass graft. Eight were controls, eight were diabetic, eight were hypercholesterolaemic and eight had both diabetes and hypercholesterolaemia. All vein grafts were harvested at 4 weeks postoperatively for morphology (n = 4) or contractility studies (n = 4). RESULTS: Compared to controls, both diabetes and hypercholesterolaemia increased intimal thickness by 20% and 63% respectively; medial thicknesses of these vein grafts were unchanged compared to control. In contrast, diabetes with hypercholesterolaemia dramatically increased intimal and medial thickness (1.8 fold and 1.6 fold respectively, compared to control). Smooth muscle cell contractility was enhanced in both the diabetic and hypercholesterolaemic groups. The presence of diabetes with hypercholesterolaemia did not further alter the enhanced smooth muscle cell contractile responses. CONCLUSIONS: This study suggests that the combination of both the atherogenic risk factors, hypercholesterolaemia and diabetes, significantly augments the formation of intimal hyperplasia in experimental vein grafts.

Animals↗
PubMed1995

Haematopoietic radioprotection by Cremophor EL: a polyethoxylated castor oil.

The polyethoxylated castor oil, Cremophor EL (Cremophor) is approved for human use as a vehicle for oral and intravenous administration of water-insoluble compounds. Cremophor has also previously been shown to reverse the multidrug resistance phenotype at clinically acceptable doses. This study demonstrates that doses of Cremophor in the range of 25-50 microliters/kg intravenously (i.v.) administered 1 day prior to near-lethal irradiation protected the regenerative capacity of the marrow, resulting in haematopoietic radioprotection and long-term survival of near-lethally-irradiated mice. In normal mice, Cremophor administration (1) markedly reduced the level of serum haematopoietic inhibitory activity 4-8 h following injection; (2) resulted in a transient decrease in femoral bone marrow cellularity and upregulated B220 (B cells), and 7/4 (neutrophils and activated macrophages), but not Thy-1 (T-cells) surface antigen expression in bone marrow cells within 24 h of injection; and (3) transiently elevated the incidence of both primitive and committed haematopoietic progenitor cells detected in clonal agar culture within 48 h of injection. Bone marrow progenitor cell content, and peripheral blood white cell, platelet and reticulocyte counts were unaffected. This suggests that the haematopoietic radioprotection and recovery observed in irradiated mice pretreated with Cremophor may be the result of accessory cell activation and/or modulation of accessory factors regulating haematopoietic progenitor cells. Our data suggest a potential clinical use of Cremophor as an adjunct to, or as a substitute for, cytokines to minimize myelosuppression following cytotoxic therapy.

Animals↗
PubMed1995

Detection of human cytomegalovirus antigenaemia: a rapid diagnostic technique for predicting cytomegalovirus infection/pneumonitis in lung and heart transplant recipients.

BACKGROUND: New rapid diagnostic techniques offer the opportunity of early diagnosis of human cytomegalovirus (CMV) infection in immunocompromised patients at risk of developing CMV disease. The use of human CMV antigenaemia as a predictor of clinical CMV infection and disease in lung and heart transplant recipients was studied prospectively. METHODS: Twenty three heart and nine lung transplant recipients who survived 40 days were observed by standard CMV surveillance with serological testing, culture, and by sequential testing for CMV antigenaemia. CMV antigenaemia testing is a rapid and quantifiable technique in which a viral lower matrix protein is detected in cytospin preparations of peripheral blood polymorphonuclear leucocytes (PMNLs) by immunofluorescent staining. RESULTS: Eleven patients developed CMV infection and five developed CMV disease (four pneumonitis, one duodenitis). These clinical events occurred at a median of 65 days following transplantation. CMV antigenaemia occurred in 17 patients at a median of 35 days following transplantation. Detection of CMV antigenaemia had a sensitivity of 100%, a specificity of 93.7%, and a positive predictive value of 94.1% for CMV related illness. CMV antigenaemia was positive at a significant interval before the clinical event. High levels of CMV antigenaemia (> 50 CMV antigen positive cells/2 x 10(5) PMNLs) occurred in 11 patients and five of these developed disease. CMV antigenaemia of > 50 CMV antigen positive cells/2 x 10(5) PMNLs had a positive predictive value of 45.5% for disease but a negative predictive value of 100%. Patients with disease had higher levels of antigenaemia than those without disease. CONCLUSIONS: CMV antigenaemia is a rapid diagnostic technique which can identify patients likely to develop CMV disease, potentially allowing early treatment.

Antigens, Viral↗
PubMed1995

Ramipril and experimental vein graft intimal hyperplasia.

Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce the intimal proliferation in animal models of arterial angioplasty and vein bypass grafting. This study examines the effect of high-dose ramipril, an ACE inhibitor that does not contain a sulfhydryl group, on the development of intimal hyperplasia in experimental vein bypass grafts. Twenty New Zealand White rabbits underwent common carotid interposition bypass grafting. Twelve were treated with ramipril (2 mg/kg/day; po) five days prior to surgery and thereafter until harvest. The remaining 8 animals were used as controls. Vein grafts were harvested at twenty-eight days by pressure fixation (80 mmHg). The grafts were sectioned into proximal, middle, and distal thirds, and the thickness of the intima and the media and the area of the lumen from each segment were determined by videomorphometry. The effect of ramipril on the [H3]thymidine incorporation into DNA of serum-stimulated smooth muscle cells (culture passage 6 to 12) was also assessed. There was a 50% mortality rate in the rabbits that received ramipril, and this was assumed to be related to the high dose of the drug. Ramipril treatment reduced mean vein graft intimal area by 34% (P > 0.05), but this was accompanied by an increase of 73% in the mean medial area of the vein grafts as compared with controls. These changes resulted in a decrease in the mean intimal ratio (intima/[intima + media]) by 39% in the ramipril group as compared with controls. Ramipril did not inhibit [H3]thymidine incorporation into DNA of serum-stimulated smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

How accurate is size measurement of pancreas cancer masses by computed axial tomography (CT) scanning?

With the advent of preoperative radiotherapy for pancreas cancers, their measurement by imaging is rendered more important, so that outcome data from various treatment programs may be compared. Two radiologists have examined tumor size measurements from 29 patients by CT scans obtained within a week of measurement in the Pathology Department after resection. The radiologists assessed these scans independently from one another and blinded from the pathologic measurement. The largest diameter of their readings was compared to the largest diameter of the tumor measured by the Pathology technician. The correlation between radiologists (P < 3 x 10(-8) was excellent. Correlation between the average of the two radiologic estimates of greatest tumor diameter and actual tissue measurement is excellent for tumors (n = 21) greater than 2 and less than 5 cm in diameter (P < 0.03), but of four specimens measured in the Pathology laboratory as less than 2 cm, all were measured by the radiologists as being at least 1.5 cm larger. Twenty of the 29 cancers (69%) were measured by two radiologists to be within 1 cm of the actual diameter. The nine specimens producing the greatest errors were two with diffuse mucinous tumors throughout the gland (radiologists undercalled by 2.5 cm), one 7 cm mass with a cystic center composed of necrotic cells (overcalled by 2.5 cm, perhaps because of deformity or release of fluid in Pathology), four small masses (1, 1.5, 1.5, and 1.5 cm in diameter), smaller than the normal diameter of the pancreas head, and two tumors with inexplicably inaccurate size estimates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1995

Modified thrombopoietic response to 5-FU in mice following transplantation of Lin-Sca-1+ bone marrow cells.

An experimental murine model of bone marrow transplantation (BMT) has been used to study the mechanisms of platelet production following transplantation. A defined primitive population of hematopoietic bone marrow cells (1000 Lin-Sca-1+) was isolated and transplanted into lethally irradiated (13 Gy) syngeneic recipient mice. Platelet counts, but neither red nor white blood cell (WBC) counts, were low 30 days after transplantation. By 90 days, platelet levels had normalized in transplanted mice, but this occurred from a reduced megakaryocyte progenitor (CFU-Mk) pool, implying that altered bone marrow control was involved in platelet production. To assess the capacity of the bone marrow of these compensated mice to sustain platelet production, the rate and degree of recovery were examined following administration of 150 mg/kg of 5-fluorouracil (5-FU) 90 days after transplantation. Transplanted mice showed a delay, both in platelet recovery and rebound thrombocytosis, after 5-FU administration when compared to normal littermates treated with 5-FU. The regeneration and expansion of bone marrow CFU-Mk and mature megakaryocytes was retarded in the transplanted mice and explained the altered platelet kinetics. The onset of increased platelet and mature megakaryocyte size, however, was not different between the two groups, indicating that the transplanted mice responded normally to the mechanisms controlling megakaryocyte development and platelet formation. The data suggest that following BMT a limitation in the proliferative capacity of primitive hematopoietic cells results in a smaller pool of megakaryocyte precursors. Compensatory adjustment within the megakaryocyte lineage, nevertheless, results in normalization of megakaryocyte and platelet number. The ability of transplanted mice to sustain platelet production when challenged with increased platelet demand is not limited by megakaryocytic maturation but by a restriction in proliferation or differentiation from the stem cell pool.

Animals↗