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R H Collins

Publications and source records attributed to R H Collins.

53 records · Page 3Linked to original sources

Effects of monosulfate esters of taurochenodeoxycholate on bile flow and biliary lipids in hamsters.

The effect of the 3 alpha- and 7 alpha-monosulfate esters of taurochenodeoxycholate on bile flow and biliary lipids was compared to the effect of unsulfated taurochenodeoxycholate. Test bile salts were infused directly into the portal circulation through a catheter introduced into the splenic pulp. Recovery of unsulfated and sulfated bile salts was complete; no biotransformation of any of the administered compounds was noted. Equivalent choleresis was noted in response to administration of each of the test bile salts. Of particular interest, the biliary cholesterol and phospholipid content was tightly linked to biliary bile salt monosulfates; the slope of the line describing the relationship between bile salts and lipids was similar to that for the unsulfated bile salt. The critical micellar concentration of the 3 alpha- and 7 alpha-monosulfate esters was 19 mM and 18 mM, respectively. Sulfation of taurochenodeoxycholate, therefore, does not impair its bile secretory function. Despite a higher critical micellar concentration, biliary lipid excretion with monosulfate esters is equivalent to that seen with unsulfated bile salt. The role of hydrophobic/hydrophilic balance in the promotion of biliary lipid excretion may need to be redefined.

Animals↗

Rat hepatic bile acid sulfotransferase: enzyme response to androgens and estrogens.

Rat liver bile sulfotransferase activity can be divided into a fraction that reacts with a monoclonal antibody (PK1B) and another fraction that does not. This work was performed to analyze the known response of hepatic bile acid sulfotransferase activity to androgens and estrogens by determining the effect of treatment on the proportion of bile acid sulfotransferase activity that possessed the epitope for PK1B monoclonal antibody. Activity in treated animals was further characterized by high-performance liquid chromatography (HPLC) analysis following purification by PK1B-immunoadsorption chromatography. The results indicate that estrogens and androgens affect the subset of enzyme activity that has the PK1B epitope more than the population that does not. HPLC demonstrates that increases and decreases in activity that follow treatment with androgens and estrogens are mirrored by the proportion of the PK1B-reactive protein that exhibits a relative molecular weight (Mr) greater than 170,000. Radial immunodiffusion assays of hepatic supernatant using a polyclonal antibody raised against PK1B-reactive bile acid sulfotransferase show that changes in specific activity that follow treatment are the result of changes in enzyme protein concentration.

Androgens↗

Compliance, mass, and shape of the canine left ventricle after global ischemia analyzed with two-dimensional echocardiography.

End-diastolic pressure (EDP)-volume (EDV) curves were constructed for the left ventricle (LV) in 10 dogs on cardiopulmonary bypass before and after 45 min of normothermic ischemic arrest. LVEDV and mass were calculated from three perpendicular two-dimensional echocardiographic sections using a Simpson's rule algorithm. The echocardiographic method employed was specially developed in earlier work for physiologic studies in dogs. Postmortem pressure-volume curves were measured for comparison by direct saline infusion into sealed ventricles. LVEDV was plotted against LVEDP (0-20 mm Hg) and data were analyzed by two-way analysis of variance and also by exponential curve fitting to the relation EDP = alpha e beta EDV, where beta is the derived exponential constant reflecting slope and thereby ventricular stiffness. Postischemic EDP-EDV curves shifted to the left and the beta constant increased (beta = 0.02 +/- 0.005 (SE) vs 0.05 +/- 0.01, P less than 0.05). LV eccentricity, the ratio between long- and short-axis measurements, was unchanged (1.43 +/- 0.05 vs 1.46 +/- 0.06 postischemia, NS), but LV mass increased (105 +/- 7 vs 128 +/- 9 g postischemia, P less than 0.001). Postischemic LV mass by echo was not significantly different from measured postmortem LV mass (r = 0.87). The nonparallel alteration in the EDP-EDV curves, lack of change in LV shape (eccentricity), and increase in LV mass in the postischemic ventricle suggest that increased ventricular stiffness rather than direct encroachment by the edematous endocardium on chamber volume is responsible for postischemic changes in LV diastolic properties.

Animals↗

Two-dimensional echocardiography in dogs. Variation of left ventricular mass, geometry, volume, and ejection fraction on cardiopulmonary bypass.

Quantitative two-dimensional echocardiography was evaluated in 39 open-chest dogs placed on cardiopulmonary bypass. The correlation coefficient of left ventricular end-diastolic volume against postmortem pressure-volume curves was r = 0.89 to 0.93 (347 measurements in 15 dogs, 0 to 24 mm Hg). Ejection fraction was validated against roller pump flow and echo left ventricular end-diastolic volume (r = 0.83, n = 13). Left ventricular mass in vivo was compared with postmortem left ventricular mass (r = 0.81 in 21 early studies, r = 0.91 in 10 later studies with updated equipment) and was found to increase with ischemic injury as well as cardiopulmonary bypass with hemodilution. Left ventricular mass increased (p less than 0.001) from 119 +/- 5 (standard error of the mean) to 138 +/- 6 gm (n = 23) after 2 1/2 hours on cardiopulmonary bypass and moderate hemodilution. With the addition of ischemic arrest, left ventricular mass increased from 119 +/- 7 to 148 +/- 11 gm (p less than 0.01, n = 8), and myocardial water content increased by 2.0% +/- 0.4%, which accounted for at least 65% of the observed mass change. Mean left ventricular wall thickness increased from 13.8 to 15.5 mm (p = 0.02) after ischemia. Ventricular shape became more spherical with increasing left ventricular end-diastolic pressure. We conclude that two-dimensional echocardiography can be reliably used for accurate, serial measurements in physiological studies. The demonstrated variability in left ventricular mass is important, yet frequently ignored. Recognizing left ventricular mass changes may facilitate the detection of myocardial injury reflected as edema.

Animals↗

Effect of cardiopulmonary bypass and global ischemia on human and canine left ventricular mass: evidence for interspecies differences.

Previous studies in dogs suggest that global ischemia with cardiopulmonary bypass causes increased left ventricular (LV) mass and water content. To investigate effects in humans, we developed a simplified method for mass determination by intraoperative two-dimensional echocardiography. LV mass was measured as echocardiographic short-axis myocardial area. This was validated by linear regression versus postmortem LV mass in 10 dogs (r = 0.89) and versus single-plane angiography in 18 patients (r = 0.73). According to this method, there was no change in LV mass (209 gm versus 208 gm; NS) at constant preload in 20 patients during routine operations (eight coronary revascularizations, 10 aortic valve replacements, and two mitral valve replacements). The same method used in 10 dogs after 2 hours of bypass, 60 minutes of normothermic global ischemia, and reperfusion revealed an LV mass increase from 113 +/- 13 gm (SE) to 150 +/- 16 gm (p less than 0.01) at matched preload. In addition, in 14 dogs after 2 hours of bypass alone, LV mass was unchanged (98 +/- 5 gm versus 101 +/- 5 gm; NS) at matched preload. Data recently derived from a separate study in our laboratory revealed a statistically significant increase in canine LV mass when conditions of human cardiopulmonary bypass and cardioplegic arrest were reproduced. We conclude that uncomplicated cardiac operations in humans do not alter LV mass. This supports the safety of crystalloid cardioplegia in humans. While present evidence is not conclusive, it appears that the threshold for edema formation after ischemic injury may be higher in humans than it is in dogs. The clinical relevance of studies of cardioplegia in edematous dog hearts thus deserves careful scrutiny.

Animals↗

Left ventricular ejection fraction during cardiac surgery: a two-dimensional echocardiographic study.

Although long-term effects have been studied, the immediate effect of surgery for acquired heart disease on left ventricular function is not well defined. Accordingly, 44 adults with acquired heart disease underwent intraoperative two-dimensional echocardiography with a gas-sterilized transducer before and immediately after cardiopulmonary bypass. Ejection fraction was measured by short-axis area change at the maximum left ventricular cross section (SAAC-EF) and also by a method using multiple sections. Correction of both mitral and aortic regurgitation produced a significant intraoperative decrease in ejection fraction from 0.49 +/- 19 (SD) to 0.32 +/- 0.16 (p less than .02) and from 0.41 +/- 0.13 to 0.30 +/- 0.17 (p less than .0005), respectively. Relief of aortic stenosis and mitral stenosis resulted in an intraoperative increase in ejection fraction from 0.45 +/- 0.10 to 0.55 +/- 0.09 (p less than .02) and from 0.41 +/- 0.05 to 0.50 +/- 0.07 (p less than .05), respectively. Ejection fraction after coronary artery bypass grafting was unchanged. Preload (end-diastolic area) was significantly decreased after correction of aortic regurgitation (p less than .02) but unchanged in other lesions. We conclude that (1) correction of pure mitral and aortic valvular lesions produces characteristic alterations in ejection fraction in the immediate postoperative period; (2) with the possible exception of patients with aortic regurgitation, the observed change in ejection fraction does not appear to reflect changes in preload; (3) noninvasive assessment of left ventricular function by two-dimensional echocardiography during cardiac surgery appears feasible and could provide data important for clinical decision making in the early postoperative period.

Aged↗

Angioplasty for femoral artery occlusion: comparison with surgery.

Forty-six patients with superficial femoral artery occlusions (range, 1-20 cm) had percutaneous transluminal angioplasty. The primary success rate was 76% with a late closure in six patients. Life table analysis showed a 1 year patency of 56.8%, maintained at 2 years among the group in whom the successful was 4 cm, while in those in whom the lesion was not crossed, it was 9 cm. Over the same period, 133 femoropopliteal bypass grafts were performed. The patients were comparable as to runoff, incidence of diabetes, and distal ischemia. The 1 year patency was 60.2% and the 2 year patency, 42.1%, largely because of the poor performance of grafts other than saphenous vein. Angioplasty seems to be the treatment of choice for short segment occlusions, and should be used in longer occlusions if saphenous vein is not going to be used.

Angioplasty, Balloon↗

Rat hepatic bile acid sulfotransferase: identification of the catalytic polypeptide and evidence for polymeric forms in female rats.

A monoclonal antibody, PK1B, directed against rat liver bile acid sulfotransferase was used for the purification and characterization of the enzyme. Incubation of rat liver supernatant with the antibody followed by immunoprecipitation with Staphylococcus aureus cells demonstrated that PK1B reacted with 90% of the enzymatic activity present in the liver supernatant from female rats and 40 to 50% of the activity in male liver preparations. Immunoadsorption chromatography with PK1B bound to Sepharose isolated active enzyme which was purified greater than 75-fold. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of this preparation in the presence of 2-mercaptoethanol demonstrated three polypeptides: Mr 29,500; 32,500, and 34,000. Western blot analysis indicated that PK1B recognized an epitope which was found only on the Mr 29,500 polypeptide. Two-dimensional gel electrophoresis associated the enzymatic activity with this Mr 29,500 band. High-pressure liquid chromatographic analysis of immunopurified enzyme defined three distinct, enzymatically active protein populations: I (Mr 400,000 to 170,000); II (Mr 130,000), and III (Mr 43,000). An Mr 29,500 polypeptide was the sole constituent of Peaks I and III and a major constituent of Peak II. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence and absence of 2-mercaptoethanol indicated that in Peak II, catalytically active Mr 29,500 protein is associated with the other two polypeptides by disulfide bonds. In contrast, Peak I consists of a polymer of Mr 29,500 polypeptide which is independent of disulfide interaction.

Animals↗

Transfusion of donor buffy coat cells in the treatment of persistent or recurrent malignancy after allogeneic bone marrow transplantation.

BACKGROUND: Patients who experience relapse after allogeneic bone marrow transplantation have a poor prognosis. However, preclinical and clinical data have strongly suggested the existence of an immune-mediated anti-tumor effect of allogeneic bone marrow transplantation. This effect, termed graft-versus-leukemia, may be harnessed purposefully in patients with posttransplant relapses by the administration of immune cells obtained by leukapheresis of the original bone marrow donor. STUDY DESIGN AND METHODS: Thirteen patients with persistent or recurrent hematologic malignancy after HLA-matched sibling-donor allogeneic bone marrow transplantation were treated with transfusion of buffy coat cells collected from the original bone marrow donors. Mononuclear cell dose ranged from 1.18 to 4.28 x 10(8) per kg. Alpha-interferon (1.5-3 x 10(6) U/m2 3-5x/week) was given to seven patients. Patients were observed for the development of graft-versus-host disease and disease response. RESULTS: Three of five patients with chronic myelogenous leukemia had complete remissions. One of five patients with active acute leukemia attained complete remission. A sixth acute leukemia patient treated with buffy coat transfusion after the induction of remission with chemotherapy relapsed 12 months later. One patient with myeloma had a complete but transient response. A patient with Hodgkin's disease did not respond. Four patients remain in remission 4, 16, 17, and 29 months after attaining complete remission. Graft-versus-host disease occurred in eight patients, including all of those with a complete response. One patient developed transient pancytopenia. CONCLUSION: The transfusion of donor buffy coat cells has significant anti-tumor activity in patients with relapsed hematologic malignancy after allogeneic bone marrow transplantation. This effect is strongly associated with graft-versus-host disease.

Adolescent↗

Efficacy of percutaneous angioplasty in lower extremity arterial occlusive disease.

One hundred and twenty four percutaneous transluminal angioplasties performed over a 5 year period for lower extremity arterial occlusive disease were reviewed to evaluate clinical efficacy and define parameters of success. Technical success was achieved in 82%, clinical success in 71%. The important predictive variables were severity of disease, anatomic site and length of diseased vessel segment. Best results (94% success rate) were obtained in the proximal single segment lesion with lesser initial disease as reflected by flow study, calf vessel runoff and claudication as the indication for treatment. The poorest results (33% success rate) were obtained in distal vessels with multisegmental disease where limb salvage was the indication for intervention. Stenosing or recently occluded bypass grafts were successfully dilated in 7 of 8 patients. With a complication rate of 3%, percutaneous angioplasty is clearly a highly effective treatment for lower extremity arterial insufficiency in the properly selected patient judged by immediate and relatively short term follow-up observations.

Aged↗