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Biomedical subjects

G S DiZerega

Publications and source records attributed to G S DiZerega.

17 recordsLinked to original sources

Clinical evaluation of 0.5% ferric hyaluronate adhesion prevention gel for the reduction of adhesions following peritoneal cavity surgery: open-label pilot study.

The objective of this study was to assess the safety and to make a preliminary assessment of the efficacy of 0.5% ferric hyaluronate adhesion prevention gel in reducing adhesions in patients undergoing peritoneal cavity surgery by laparotomy, with a planned 'second-look' laparoscopy. The study was a randomized, open-label, placebo-controlled, parallel-group design in patients desirous of fertility at the Women's and Children's Hospital, Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, California. Female patients aged 24 to 41 years received 300 ml 0.5% ferric hyaluronate adhesion prevention gel or lactated Ringer's solution as an intraperitoneal instillate at the completion of the laparotomy procedure. At second-look laparoscopy 4-12 weeks after the laparotomy, the presence of adhesions was evaluated. Haematology and serum chemistry were determined throughout the study interval. All patients tolerated the procedures well and did not manifest any serious adverse events. At second-look laparoscopy, patients treated with 0.5% ferric hyaluronate adhesion prevention gel had significantly fewer adhesions than control patients. When adhesions did form, they were significantly less extensive and less severe in patients who received 0.5% ferric hyaluronate adhesion prevention gel. In conclusion, 0.5% ferric hyaluronate adhesion prevention gel was safe and highly efficacious in the reduction of the number, severity and extent of adhesions throughout the entire abdomen following peritoneal cavity surgery.

Adult↗

Enhanced follicle regulatory protein levels accompany reinitiation of ovulatory function after parturition.

OBJECTIVES: We examined the changes in follicle regulatory protein, estrone-3-glucuronide, pregnanediol-3-glucuronide, and luteinizing hormone levels in first-morning urine samples from postpartum, fully breast-feeding women to characterize the reemergence of these urinary hormones after pregnancy ovarian quiescence and early postpartum period and to determine whether follicle regulatory protein could be used prospectively to predict the return of fertility. STUDY DESIGN: Twenty-five hundred urine samples collected from six postpartum women were evaluated. Daily urine samples collected from normally cycling women were used to establish normal urinary hormone and hormone metabolite cyclicity. Luteinizing hormone, estrone-3-glucuronide, and pregnanediol-3-glucuronide levels were measured by radioimmunoassay. Follicle regulatory protein level was assayed with a double-antibody enzyme-linked immunosorbent assay. RESULTS: Although follicle regulatory protein levels were found to be very low or undetectable in early postpartum urine, they began to rise with episodes of estrone-3-glucuronide and pregnanediol-3-glucuronide secretion. A chi 2 analysis suggests that increasing urinary follicle regulatory protein levels are most closely associated with the luteal phase of the first menstrual cycles in postpartum women. CONCLUSIONS: These results suggest that follicle regulatory protein is of little value in predicting either the onset of renewed ovarian activity or the fertile period.

Adult↗

[Modulation of postsurgical macrophage function by postsurgical polymorphonuclear leukocytes].

Rapid and transient influx of polymorphonuclear leukocytes (PMN) is observed prior to accumulation of macrophages after surgical trauma. Rabbits underwent intestinal reanastomosis and at various times peritoneal exudate cells were collected and separated using a Percoll gradient. Postsurgical macrophages were incubated with PMN spent media obtained from various postsurgical periods. Macrophage release of O2- had already increased at 2 hr after surgery, reached peak levels at 6 hr and decreased by 24 hr. PMN spent media from 6 hr postsurgical cells functioned as a suppressor, whereas 12 or 24 hr PMN spent media increased the O2- release from the macrophages harvested at 6 and 12 hr after surgery. Plasminogen activator (PA) activity in the macrophage spent medium was elevated at 24 hr after surgery by exposure to PMN spent media, however no effects were observed on macrophages harvested within 12 hr after surgery. PA inhibitory activity was reduced at 2 hr after surgery, and gradually increased, but no effects of PMN spent media on the PA inhibitory activity was observed. Thus, soluble factors secreted into the medium by PMN may modulate macrophage metabolism in stages as the macrophages differentiate and promote wound repair.

Animals↗

[A role of postsurgical macrophage activation by peritoneal injury].

At a site of peritoneal injury after abdominal surgery, macrophages are thought to be a principle type of inflammatory cells. Therefore, we determined the metabolic activities of postsurgical peritoneal exudate macrophages using standardized rabbit model. Rabbits underwent midline laparotomy followed by resection and reanastomosis of the ileum. At various days after surgery, peritoneal exudate macrophages were recovered from lavage fluid. Postsurgical Day-5 macrophages expressed significantly high potential to produce superoxide anion even without PMA stimulation compared to non-surgical control macrophages, although an activity of Day-10 macrophages was similar to control. The conditioned media from postsurgical Day-1 macrophage culture strongly inhibited urokinase type plasminogen activator (PA) and this plasminogen activator inhibitor (PAI) activities decreased following the extension of postsurgical time. Conversely, PA activities of macrophage-conditioned media decreased by day 1 and then gradually increased reaching control levels by day 10. Elastase activities of macrophage-conditioned media gradually decreased until postsurgical day 10. These data suggest that surgical injury activates postsurgical exudate macrophages. However, a time course of metabolic activities of these cells was dependent upon each secretory products. This differential secretion might express the stage of activation and differentiation of postsurgical macrophages. Moreover, postsurgical activated macrophages may control the tissue repair through a digestion of injured matrix and fibrinolytic process.

Animals↗

The effect of intraperitoneal administration of sodium tolmetin-hyaluronic acid on the postsurgical cell infiltration in vivo.

Intraperitoneal administration of sodium tolmetin-hyaluronic acid reduced the formation of adhesions at early postsurgical time points. In addition, at 6, 48, 72, and 96 hr following surgery, there was a significant reduction in the number of red blood cells (RBC) recovered from peritoneal lavage. This effect was not the result of fluid or viscous solution in the peritoneal cavity since intraperitoneal administration of Ringer's lactate or Hyskon (a 32% solution of Dextran 70) did not affect RBC recovery. In contrast, the influx of leukocytes into the peritoneal cavity was elevated at 12 hr after surgery, but suppressed at 96 hr. These data may suggest a mechanism by which sodium tolmetin in hyaluronic acid reduced adhesion formation.

Animals↗

The mitogenic activity of peritoneal tissue repair cells: control by growth factors.

The purpose of this study was to determine the proliferative activity of tissue repair fibroblasts recovered directly from injured peritoneum at various times after surgery and to test the mitogenic response of tissue repair cells (TRC) to growth factors. Rabbits underwent bilateral peritoneal abrasion (5 X 5 cm) with sterile gauze until punctate bleeding developed. Postsurgical (Days 2, 5, 7, and 10) tissue repair cells were recovered from the injured peritoneum by scraping with a scalpel blade. Although tissue repair cells consisted of a mixed cell type after 4 days in culture, recovered cells were essentially fibroblasts. These TRC were then pulsed with [3H]thymidine after 4 days in culture. The incorporation of thymidine into Postsurgical Day 5 TRC increased significantly compared to that of Day 2 TRC (P less than 0.05). Incorporation then decreased with time following surgery. Fibroblast growth factor (FGF) and epidermal growth factor (EGF) stimulated the incorporation of thymidine into TRC. However, the response of Postsurgical Day 7 and 10 TRCs to 1 microgram/ml EGF was significantly greater than those of Postsurgical Day 2 and 5 TRCs (Day 2 TRC, 166 +/- 7.4; Day 10 TRC, 420 +/- 96% of control cells without EGF, P less than 0.05). Platelet-derived growth factor (PDGF, 10 ng/ml) also stimulated the incorporation of thymidine into Day 10 TRCs, but this stimulatory activity (129.9 +/- 8.5% of control) was less than EGF or FGF. IL-1 alpha and IL-2 did not stimulate the incorporation of thymidine into TRC at a concentration of 100 pg/ml, but these cytokines did stimulate protein synthesis by TRC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Production of protease inhibitors by postsurgical macrophages.

The deposition and lysis of fibrin are important processes in normal peritoneal healing. Since macrophages secrete a neutral plasminogen activator, we studied the production of plasminogen-dependent, fibrinolytic activity by postsurgical macrophages. Peritoneal exudate macrophages were collected from rabbits after resection and reanastomosis of their ileum. Intracellular plasminogen activator (PA) activity of resident (nonsurgical) macrophages was 8.4 +/- 1.8 milli-Plough units (mPU)/10(6) cells. Postsurgical Day 1 macrophages had significantly less activity (0.33 +/- 0.056 mPU/10(6) cells) compared to resident cells. Thereafter, the PA activity gradually increased and reached control levels by Postsurgical Day 7. The PA activity secreted by postsurgical macrophages into serum-free medium after 48 hr of culture was also determined. Conditioned medium from macrophages collected on Postoperative Days 1-5 exhibited less PA activity than buffer controls. PA activity was detected after acid treatment of the conditioned medium to remove acid-labile inhibitors. The activities of PA in acid-treated conditioned medium increased gradually and reached nonsurgical levels by Postsurgical Day 7. In spent medium from macrophages collected on Postsurgical Days 1-3, high levels of urokinase inhibitory activities were secreted; production gradually decreased during the later postoperative period. This inhibitory activity of macrophage-conditioned medium on urokinase-like PA activity was partially diminished by acidification of the media. These results support the hypothesis that macrophages in the postsurgical exudate may play an important role in the fibrinolytic process during peritoneal wound healing, perhaps through production and secretion of plasminogen activator as well as acid-labile and resistant protease inhibitors.

Animals↗

Kinetics of interleukin-1 secretion by murine macrophages recovered from the peritoneal cavity after surgery.

Macrophages play a central role in wound healing after surgical injury possibly through the secretion of soluble factors like interleukin-1 (IL-1). IL-1 has many biological activities which regulate most of the cell types that appear in postsurgical wounds. In this study, we determined the levels of IL-1 production by murine macrophages harvested from postsurgical exudate at several time points after standardized peritoneal surgery. To further characterize the level of functional activities of postsurgical macrophages, the IL-1 levels were determined with or without stimulating the cells with lipopolysaccharide (LPS) and phorbol myristate acetate (PMA). After surgery, the number of macrophages harvested by peritoneal lavage increased, reached peak levels on Postsurgical Day 3, and then decreased. IL-1 levels secreted by macrophages cultured without stimuli gradually increased after surgery, reaching peak levels on Day 10. In conditioned media from LPS-PMA-stimulated macrophages, IL-1 levels were significantly greater than in media from unstimulated macrophages and peaked on Postsurgical Day 3. These data suggest that the susceptibility of postsurgical macrophages to stimuli changes during the postsurgical wound healing process. Accordingly, IL-1 may play an important role in the late rather than in the early phase of peritoneal repair.

Animals↗

Modulation of proline and glucosamine incorporation into tissue repair cells by peritoneal macrophages.

The purpose of this study was to determine the patterns of [14C]proline and [14C]glucosamine incorporation by tissue repair cells (TRC) as modulated by postsurgical macrophages. Rabbits underwent a midline laparotomy followed by resection (2.0 cm) and reanastomosis of their ileum. Another group of rabbits underwent peritoneal wall abrasion with sterile gauze until punctate bleeding developed. Postoperative (1-28 days) exudate cells (PEC) were recovered from the peritoneal cavity after reanastomosis, and (TRC) were obtained directly from the injured peritoneal surface after abrasion. Since the postsurgical exudate was composed mainly of macrophages, we examined the effect of postsurgical macrophage-spent media on the incorporation of [14C]proline, [14C]glucosamine, and [3H]thymidine by TRC. After 7 days of culture, Postsurgical Day 7 TRC were incubated with spent media from postsurgical PEC (greater than 90% macrophages). When TRC were cultured with macrophage-spent media, the number of TRC increased significantly compared to that of fresh medium-treated controls. The incorporation of [3H]thymidine by TRC was also enhanced by macrophage-spent media. The incorporation of [14C]proline and [14C]glucosamine by TRC was also enhanced when incubated with macrophage-spent medium. However, when data were expressed on a per cell basis, incorporation of [14C]proline and [14C]glucosamine by TRC cultured with macrophage-spent media was the same or less than that by cells incubated with fresh medium. These data suggest that the increase in incorporation of glucosamine and proline into connective tissue protein by postsurgical repair cells may be directly modulated by macrophages recruited in response to surgical injury and that this increase is due to the fibroproliferative effect of postsurgical macrophages.

Animals↗

A postulated role for naturally occurring aromatase inhibitors in follicle selection.

The studies reviewed here indicate that follicle regulatory protein (FRP) alters aromatase and 3B-hydroxysteroid dehydrogenase activity in porcine, human, and rat granulosa cells. The inhibitory effect of FRP on granulosal aromatase activity depend upon the response of the cell to FSH: large amounts of FSH can partially overcome FRP inhibition while relatively small amounts of FSH sensitize the granulosal aromatase system to FRP. Although androgens potentiate FSH-mediated granulosal functions, they also sensitize granulosa cell steroidogenic enzymes to inhibition by FRP. The demonstration that FRP acts primarily on granulosa cells of less mature antral follicles to inhibit aromatase supports the hypothesis that FRP may facilitate follicle selection and suggests a role for FRP in atresia. Most of the effects of FRP on granulosal activities reflect an interplay between the systemic endocrine and local paracrine systems. That FRP functions, at least in part, by modulating follicular response to FSH is consistent with the hypothesis that paracrine effectors are important mediators of folliculogenesis in the presence of gonadotropins.

3-Hydroxysteroid Dehydrogenases↗

Prevention of postoperative tubal adhesions. Comparative study of commonly used agents.

Tubal abrasions were surgically induced in 25 rhesus monkeys following demonstration of tubal patency. Five monkeys received dexamethasone, promethazine, and ampicillin perioperatively, five received intraperitoneal 10% dextran 40, five received intraperitoneal 32% dextran 70, and 10 received no additional therapy. Fimbrial biopsies were obtained from two additional monkeys treated with 32% dextran 70 before and postoperatively on days 2, 5, and 7. Only those treated with 32% dextran 70 retained tubal patency and avoided development of adhesions, involving fimbria, omentum, ovary, uterus, and bladder. Histologic examination of fimbrial biopsies demonstrated sufficient epithelial repair to have occurred during the 5 days 32% dextran 70 remained in the pelvin cavity to prevent adhesion formation.

Ampicillin↗

Fluorescence localization of luteinizing hormone/human chorionic gonadotropin uptake in the primate ovary: characterizatin of the preovulatory ovary.

A fluorescent derivative of human chorionic gonadotropin (hCG) for binding studies was prepared by conjugation of hightly purified hCG with fluorescein isothiocynate (FITC-hCG) in a molar ratio of 3:1. The resulting FITC-hCG conjugate retained full cross-reactivity with antibodies directed against intact hCG, the hCG beta-subunit, the carboxyl-terminal peptide sequence of beta-hCG. The fluorescent hormone retained binding activity similar to that of native hCG, and the capacity to induce progesterone production from primate corpora luteal cells in vitro. After intravenous administration to female rhesus monkeys, FITC-hCG was localized within the theca cell layer of certain antral follicles, including the dominant follicle, but no fluorescence was noted around preantral follicles. Areas of fluorescence were also localized to discrete groups of interstitial gland cells in the stroma. The degree of fluorescence associated with these cells was indistinguishable from that observed in the thecal cells. The development of a fluorescent derivative that is biologically and immunologically similar to native hCG has permitted differential microscopic localization of luteinizing hormone/hCG uptake in the preovulatory ovary.

Animals↗

Bacteremia in post-Cesarean section endomyometritis: differential response to therapy.

Presented are blood culture results obtained from 200 patients with post-cesarean section endomyometritis treated with either penicillin-gentamicin or clindamycin-gentamicin. Their clinical course is correlated to their blood culture results by the fever index. Fifty-three percent of the 60 organisms isolated from 48 patients were anaerobic bacteria. Patients from whose blood cultures anaerobic bacteria were recovered had higher fever indexes than did those with aerobic isolates (P less than .05). Clindamycin-gentamicin patients from whose blood cultures anaerobic organisms were isolated had less febrile morbidity than did comparable penicillin-gentamicin patients. Patients with Bacteroides fragilis bacteremia had the highest fever indexes overall. Therefore, patients with post-cesarean section endomyometritis have less febrile morbidity if they are initially treated with a drug effective against anaerobic bacteria, especially B fragilis.

Anti-Bacterial Agents↗