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Biomedical subjects

L Wan

Publications and source records attributed to L Wan.

At least 19 recordsLinked to original sources
PubMed2005

Commercial low-citrate anticoagulation haemofiltration in high risk patients with frequent filter clotting.

This study assessed the safety and efficacy of a commercial low-citrate concentration-based pre-filter replacement fluid during continuous veno-venous haemofiltration (CVVH) in patients with frequent filter clotting and high risk of bleeding. We used a commercial low-citrate fluid as pre-dilution replacement fluid during CVVH (citrate: 11 mmol/l (33 meq/l), sodium: 140 mmol/l, chloride: 108 mmol/l and potassium: 1 mmol/l). A calcium and magnesium infusion was delivered separately by central line for the maintenance of serum ionized calcium (Cai) and total magnesium (Mg). In this prospective observational study, 30 patients, 124 filters and 1,515 treatment-hours were observed. Median filter life of citrate CVVH was 9.5 hours. Filter life in the 48 hours prior to citrate CVVH was also observed. In the patients on prior non-anticoagulant CVVH (n=14) filter life increased significantly with citrate (9.5 hours vs 5 hours; P<0.0001). In patients on prior heparin CVVH (n = 15), filter life was similar with citrate (10 hours vs 8 hours; P = 0.68). However, in patients with prior early/frequent filter clotting despite heparin (n = 11) filter life increased significantly (10 hours vs 7 hours; P=0.038). Of 411 serum Cai measurements, none showed a Cai < 0.85 mmol/l and, of 84 observations, none showed a serum Mg<0. 6 mmol/l. One patient with sepsis and shock needed to cease citrate CVVH because of progressive ionized hypocalcaemia and increasing anion gap. No other adverse effects were observed. In selected patients, CVVH with a commercial low-citrate concentration solution as pre-filter replacement fluid and a simultaneous calcium and magnesium infusion protocol appears generally safe. Filter life was acceptable and superior to that achieved with previous treatment.

Acute Kidney Injury↗
PubMed2005

A technique for the measurement of renal ATP in a large animal model of septic shock.

BACKGROUND: The mechanisms responsible for acute renal failure in sepsis are not understood. Measurement of tissue ATP might help to understand this process but, in the large animal, it is hampered by major technical difficulties. OBJECTIVE: To develop a technique to monitor ATP in the kidney of a large mammal during the induction of septic shock and then circulatory arrest. METHODS: Implantation of a custom-made phosphorus coil around the left kidney. Induction of septic shock by intravenous E. coli administration. Acquisition of 31 P magnetic resonance (MR) spectroscopic data at 3-tesla before and during septic shock over several hours. Induction of euthanasia and measurement of the same 31 P signal immediately and thirty minutes after circulatory arrest. RESULTS: Clear reproducible 31 P MR spectra were obtained before and after the induction of septic shock and euthanasia. They indicated limited changes in ATP during septic shock. An expected rapid and dramatic decrease in ATP occurred with euthanasia. CONCLUSIONS: It is possible to sequentially monitor renal bioenergetics in a large mammal during septic shock using an implanted custom-made phosphorus coil and 3-tesla MR technology. This technique offers a novel approach to the investigation of septic renal failure.

Acute Kidney Injury↗
PubMed2005

Low-dose citrate continuous veno-venous hemofiltration (CVVH) and acid-base balance.

OBJECTIVE: To evaluate the acid-base effect of low-dose regional citrate anticoagulation (RCA) during continuous veno-venous hemofiltration (CVVH). DESIGN: Prospective observational study. SETTING: ICUs of tertiary public and private hospitals. SUBJECTS: Thirty critically ill patients with acute renal failure at risk of bleeding or with a major contraindication to heparin-CVVH and/or short filter life. METHODS: We used a commercial citrate-based fluid (11 mmol/L, sodium: 140 mmol/L, chloride: 108 mmol/L and 1 mol/L of potassium) as pre-dilution replacement fluid during CVVH. Further potassium was added according to serum potassium levels. We measured all relevant variables for acid-base analysis according to the Stewart-Figge methodology. RESULTS: Before treatment, study patients had a slight metabolic acidosis, which worsened over 6 hours of RCA-CVVH (pH from 7.39 to 7.38, p < 0.005; bicarbonate from 23.2 to 21.6 mmol/L, p < 0.0001 and base excess from -2.0 to -3.0 mEq/L, p < 0.0001) due to a significant increase in SIG (from 5.8 to 6.6 mEq/L, p < 0.05) and a decrease in SIDa (from 37.5 to 36.6 mEq/L, p < 0.05). These acidifying effects were attenuated by hypoalbuminemia and a decrease in lactate (from 1.48 to 1.34 mmol/L, p < 0.005) and did not lead to progressive acidosis. On cessation of treatment, this acidifying effect rapidly self-corrected within six hours. CONCLUSIONS: Low dose RCA-CVVH induces a mild acidosis secondary to an increased strong ion gap and decreased SIDa which fully self-corrects at cessation of therapy. Clinicians need to be aware of these effects to correctly interpret changes in acid-base status in such patients.

Acid-Base Equilibrium↗
PubMed2004

Suppression of human peripheral blood lymphocyte proliferation by immortalized mesenchymal stem cells derived from bone marrow of Banna Minipig inbred-line.

This study sought to investigate whether mesenchymal stem cells (MSC) derived from Banna Minipig Inbred-line (BMI-MSC) suppressed human peripheral blood lymphocyte (hPBLs) proliferation in a one-way mixed lymphocyte reaction system. BMI-MSC failed to stimulate proliferative responses by hPBLs, which were activated by allogenic endothelial cells, BMI-PBLs and non-specific mitogenic stimuli. Furthermore, BMI-MSC also suppressed proliferation of hPBLs stimulated by mismatched allogenic, as well as xenogenic PBLs, and the mitogenic stimulus ConA. The suppression occurred in dose-dependent fashion when the ratio of hPBLs to BMI-MSC varied from 1 to 5 fold; fewer, BMI-MSC (0.001 to 0.01 times) showed no obvious suppression. When BMI-MSC were added to hPBLs stimulated for 72 hours, the proliferative suppression was still evident. Addition of anti-FasL or anti-TGF-beta1 antibody attenuated the proliferative suppression, while antibody against IL-10 had no effect on it. Further immunofluorescence analysis demonstrated that FasL and TGF-beta1 constitutively expressed BMI-MSC. These findings suggest that BMI-MSC suppress hPBLs proliferation relying on FasL and TGF-beta1 mediated pathways.

Animals↗
PubMed2004

Prolonged daily intermittent renal replacement therapy in ICU patients by ICU nurses and ICU physicians.

OBJECTIVES: Prolonged daily intermittent renal replacement therapy (PDIRRT) has been proposed as a new form of treatment for severe acute renal failure (ARF). However, this treatment has so far implied a) full dependence on nephrological input, b) lack of any convective clearance and c) limited purification of dialysate water. The aim of this study was to establish the feasibility and safety of performing PDIRRT in the ICU with a) no nephrological input, b) the addition of some convective clearance with on-line fluid replacement and c) a new advanced water purification system. DESIGN: Prospective observational study. PATIENTS: Fourteen patients treated with PDIRRT. SETTING: ICU of tertiary institution. INTERVENTIONS: Treatment of patients with severe ARF and critical illness with PDIRRT. Prescription of treatment by ICU physicians. Conduct of treatment by ICU nurses. Use of combined convective and diffusive therapy with on-line generation of fluid replacement, application of a double-filtration water purification system. MEASUREMENTS AND MAIN RESULTS: We prospectively collected demographic, biochemical, hemodynamic and clinical data in 14 patients, who received 30 PDIRRT treatments for a cumulative treatment time of 205.4 hours. The mean age was 57.9 +/- 16.0. Eight patients were male and 6 female. Their mean APACHE II score was 24.6 +/- 5.9 and their SAPS II score was 41.7 +/- 18.8. PDIRRT was used after at least 24 hours of initial stabilization with continuous veno-venous hemofiltration (CVVH). Blood flow was kept at 100 ml/min dialysate flow at 200 ml/min and convective clearance varied from 21 ml/min to 33 ml/min. All patients were either anuric or oliguric (UO < 400 ml/day). Ten patients were on mechanical ventilation and 11 patients on vasopressor support. Mean treatment session time was 6.9 +/- 1.8 hours. The mean pre-PDIRRT urea was 19.2 +/- 6.9 mmol/L and the creatinine was 274 +/- 116 micromol/L. The mean pre-PDIRRT lactate was 2.95 +/- 2.24 mmol/L. Following treatment, all had significantly decreased to 13.2 +/- 6.3 mmol/L, 215 +/- 95 micromol/L and 2.25 +/- 1.61 mmol/L, respectively (p=<0.0001, <0.0001, <0.05). Bicarbonate levels remained stable during treatment (23.0 +/- 3.8 mmol/L to 23.1 +/- 2.5 mmol/L). Mean norepinephrine dose changed from 8.8 +/- 11.9 microg/min to 12.9 +/- 27.0 microg/min after treatment (NS). There were no complications of therapy. Patient ICU survival was 71.4%. CONCLUSIONS: PDIRRT with combined diffusive and convective clearance is an efficacious form of renal replacement, which can be safely and effectively conducted by ICU nurses following prescription by ICU physicians without any nephrological involvement and with adequate double filtration water purification.

Acute Kidney Injury↗
PubMed2004

Kidney failure associated with liver transplantation or liver failure: the impact of continuous veno-venous hemofiltration.

BACKGROUND AND AIMS: The short-term outcome of critically ill patients with kidney failure combined with severe liver failure or orthotopic liver transplantation (OLTx) is poor. We sought to test the hypothesis that, with the exclusive use of continuous veno-venous hemofilration (CVVH) with minimal heparin-anticoagulation, the short and long-term outcomes of these patients would be improved. PATIENTS: Sixty-six consecutive patients with combined liver and kidney failure SETTING: Intensive Care Unit of tertiary hospital DESIGN: Retrospective interrogation of prospectively collected databases INTERVENTION: Treatment of all patients with continuous veno-venous hemofiltration (CVVH) by protocol with 2L/h of ultrafiltration rate and minimal use of circuit heparinization. Retrieval of specific information on demographic, clinical, therapeutic and outcome details. MEASUREMENTS AND MAIN RESULTS: From July 1995 to April 2004, 66 patients with combined liver and renal failure received continuous veno-venous hemofiltration (CVVH). Of these, 26 received liver transplantation and 40 did not. There were no significant differences in age, APACHE II score, bilirubin, ALT, INR or albumin on admission. The average duration of CVVH was 9.5 days for OLTx patients and 5 days for non-transplanted patients (p=0.013). Heparin anticoagulation was used in only 12% of OLTx patients and 20% of non-transplanted patients. ICU mortality was 15% in OLTx patients and 63% in non-transplanted patients (p<0.0005); hospital mortality was 23% compared to 70% (p<0. 001). Mean survival time at follow up was 1,120 days compared to 358 days (p<0.0001). CONCLUSIONS: ARF associated with OLTx has a much better outcome than ARF without OLTx. Furthermore, management based on a conservative anticoagulation policy and CVVH as the exclusive form of renal support was associated with the best ICU, hospital and long term survival reported so far.

Cause of Death↗
PubMed2001

Nanostructure. Epitaxial diamond polytypes on silicon.

Carbon is unique in the variety of configurations it can adopt with itself and other elements. Here we show how ion beams can be used to nanostructure various diamond polytypes, epitaxially aligning them to a silicon substrate. The ready controllability of ion beams, which are already used to manufacture submicrometre-scale devices, means that our findings should enable new carbon and non-carbon materials to be nanostructured for a host of applications.

Journal Article↗
PubMed2001

Levonorgestrel concentrations during 7 years of continuous use of Jadelle contraceptive implants.

Serum levonorgestrel concentrations were assayed in a multicenter, 7-year study of 199 users of Jadelle rod implants. We examined drug levels, patterns of changes, factors affecting drug levels, and concentrations at which pregnancies occurred. Mean levonorgestrel concentrations declined from 435 pg/mL at 1 month of use to 64% of that value (280 pg/mL) at the end of 3 years. Between the end of the third and fifth years neither mean nor median serum levels varied markedly. At 5 years the mean concentration was again 64% of the first month's mean. Declining levels were observed thereafter through the end of 7 years when the mean, 224 pg/mL, was 52% of the 1-month value. Last measured drug concentrations of women who became pregnant during Jadelle use had mean and median values of 152 and 144 pg/mL, respectively, and a maximum value of 180 pg/mL. Analyses indicated ponderal index, body weight, duration of use, and a single clinical center were the most important variables affecting measured levonorgestrel levels. Approximately one-third of assays in the sixth and seventh years were found to be below 180 pg/mL, suggesting that Jadelle levonorgestrel implants would not maintain sufficiently high levels of effectiveness against pregnancy after 5 years and that heavier women would then be at greater risk of pregnancy.

Adolescent↗
PubMed2001

Transgenic mice with overexpression of human scavenger receptor A on endothelial cells.

OBJECTIVES: To establish a new transgenic mouse model for determining the function and role of human scavenger receptor A (SR-A) in atherosclerosis in vivo. METHODS: Human scavenger receptor minigene-driven mouse tie-1 promoter was constructed and confirmed by endonuclease digestion and sequence analysis. Transgenic mice were generated via the microinjection method. PCR and Southern blot were used to screen the positive transgenic mice. RT-PCR and immunohistochemical analysis were used to detect the level and location of human SR-AI expression in transgenic mice. The activity of human SR-AI was determined by morphologic observation of aortic endothelial cells of transgenic mice under transmission electron microscopy. RESULTS: The electrophoresis assay showed the expected 4 fragments of 0.9 kb, 1.1 kb, 1.2 kb and 4.2 kb in the Sma I digest and 2 fragments of 0.8 kb and 6.7 kb in Bgl II digest of plasmids pTie-1/hSR-A. The fragment sequence of tie-1 promoter and human SR-A cDNA in plasmids pTie-1/hSR-A was correct and no ATG before the translation initiation sites of human SR-A was found by sequence analysis. 561 injected and surviving embryos with the purified human SR-A minigene were implanted into the oviducts of 19 ICR pseudopregnant mice. Among the 54 surviving pups from 13 foster mothers, 7 were identified by PCR and Southern blot analysis. The results of RT-PCR and immunohistochemical analysis showed human SR-A was specifically expressed on vascular endothelial cells of the aorta and renal artery, as well as hepatic sinusoidal endothelial cells in transgenic mice. Transmission electron microscope (TEM) of aorta of transgenic mice showed that a large number of vesicles, multivesicle bodies and swollen mitochondria filled the plasma of endothelial cells. CONCLUSIONS: A transgenic mouse model with overexpression of human SR-A in endothelial cells was successfully established. The transgene was integrated and transmitted into the chromosome of transgenic mice. Tie-1 promoter controlled the transgene to express in endothelial cells in mice. Pinocytic activity of aortic endothelial cells in transgenic mice was higher than that of C57BL/6J mice. Our studies will provide a new transgenic model for investigation of atherosclerosis and functions of human SR-A.

Animals↗
PubMed2000

Mutational definition of RNA-binding and protein-protein interaction domains of heterogeneous nuclear RNP C1.

The heterogeneous nuclear ribonucleoprotein (hn- RNP) C proteins, among the most abundant pre-mRNA-binding proteins in the eukaryotic nucleus, have a single RNP motif RNA-binding domain. The RNA-binding domain (RBD) is comprised of approximately 80-100 amino acids, and its structure has been determined. However, relatively little is known about the role of specific amino acids of the RBD in the binding to RNA. We have devised a phage display-based screening method for the rapid identification of amino acids in hnRNP C1 that are essential for its binding to RNA. The identified mutants were further tested for binding to poly(U)-Sepharose, a substrate to which wild type hnRNP C1 binds with high affinity. We found both previously predicted, highly conserved residues as well as additional residues in the RBD to be essential for C1 RNA binding. We also identified three mutations in the leucine-rich C1-C1 interaction domain near the carboxyl terminus of the protein that both abolished C1 oligomerization and reduced RNA binding. These results demonstrate that although the RBD is the primary determinant of C1 RNA binding, residues in the C1-C1 interaction domain also influence the RNA binding activity of the protein. The experimental approach we described should be generally applicable for the screening and identification of amino acids that play a role in the binding of proteins to nucleic acid substrates.

Amino Acid Sequence↗
PubMed2000

Ambient sulfate concentration and chronic disease mortality in Beijing.

In this study, ecological analysis was used to assess the relationship between ambient air pollution and human mortality. All the data on environmental measures and related factors, population size and number of deaths were collected for the city of Beijing, PR China and its eight districts for the years 1980-1992. In this study the concentration of SO(4)2- was selected as a main indicator of environmental pollution for the following reasons: (i) SO(4)2- data are available to cover all urban and suburban areas in Beijing compared with other air pollutants during the study period; (ii) SO(4)2- levels indicate the concentration of sulfide (include sulfate) and acid fog in the air, and they are significantly lower in cleaner districts than in others; and (iii) analyses showed that SO(4)2- levels are significantly correlated with daily mean concentrations of sulfur dioxide and nitrogen oxide, annual coal combustion, number of households using gas fuel, counts of motor vehicles and population density. Age-standardised mortality rates due to specific diseases were calculated using the Chinese population census data in 1990. Statistically significant correlations were observed between SO(4)2- concentration and total mortality and mortality due to cardiovascular disease, malignant tumour and lung cancer (r > 0.50 in all cases). The correlations were not only found between the current SO(4)2- concentration and these mortalities, but also for SO(4)2- levels measured up to 12 years prior to death, which may suggest long-term effects of air pollution. No significant correlations were observed for mortality from respiratory diseases and cerebrovascular diseases (r = 0.30-0.50). This study indicates that the concentration of SO(4)2- in air is a useful air pollution indicator in the areas where coal is used as the main source of energy. Areas with high levels of SO(4)2- experienced higher mortality due to a variety of chronic diseases.

Air Pollutants↗
PubMed2000

Membrane-associated GAIP is a phosphoprotein and can be phosphorylated by clathrin-coated vesicles.

GAIP (G alpha interacting protein) is a member of the RGS (regulators of G protein signaling) family and accelerates the turnover of GTP bound to Galphai, Galphaq, and Galpha13. There are two pools of GAIP-a soluble and a membrane-anchored pool. The membrane-anchored pool is found on clathrin-coated vesicles (CCVs) and pits in rat liver and AtT-20 pituitary cells. By treatment of a GAIP-enriched rat liver fraction with alkaline phosphatase, we found that membrane-bound GAIP is phosphorylated. By immunoprecipitation carried out on [(32)P]orthophosphate-labeled AtT-20 pituitary cells stably expressing GAIP, (32)P-labeling was associated exclusively with the membrane pool of GAIP. Phosphoamino acid analysis revealed that phosphorylation of GAIP occurred largely on serine residues. Recombinant GAIP could be phosphorylated at its N terminus with purified casein kinase 2 (CK2). It could also be phosphorylated by isolated CCVs in vitro. Phosphorylation was Mn(2+)-dependent, using both purified CK2 and CCVs. Ser-24 was identified as one of the phosphorylation sites. Our results establish that GAIP is phosphorylated and that only the membrane pool is phosphorylated, suggesting that GAIP can be regulated by phosphorylation events taking place at the level of clathrin-coated pits and vesicles.

Animals↗
PubMed2000

Prolonged effectiveness of Norplant(R) capsule implants: a 7-year study.

Soft tubing Norplant(R) contraceptive implants were studied in 1210 women for 7 years to measure the duration of effectiveness and the magnitude of the pregnancy rates over that time. Mean age at enrollment was 27.4 years. Of the enrollees, 42% were US residents. One-sixth (16.1%) weighed >/=70 kg at the time of implant placement. At the end of 5 years, the cumulative pregnancy rate was 1.1/100; at the end of 7 years, it was 1.9/100. No pregnancies occurred to any of the 400 women who enrolled in the study at age >/=30 years and who weighed <100 kg. Among women aged 18-33 years, the 7-year Norplant pregnancy rates are comparable to the median pregnancy rates of tubal sterilization methods for women of the same age and duration of use. For women aged >/=34 years, without regard to weight at admission, the 7-year effectiveness of soft tubing Norplant equals or surpasses that of tubal sterilization. For continuing implant users, annual pregnancy rates <1.0/100 in years 6 and 7, together with low cumulative pregnancy rates, testify that Norplant capsule implants remain highly effective for 7 years.

Adolescent↗
PubMed2000

HIV-1 Nef protein binds to the cellular protein PACS-1 to downregulate class I major histocompatibility complexes.

Major-histocompatibility-complex (MHC) proteins are used to display, on the surface of a cell, peptides derived from foreign material - such as a virus - that is infecting that cell. Cytotoxic T lymphocytes then recognize and kill the infected cell. The HIV-1 Nef protein downregulates the cell-surface expression of class I MHC proteins, and probably thereby promotes immune evasion by HIV-1. In the presence of Nef, class I MHC molecules are relocalized from the cell surface to the trans-Golgi network (TGN) through as-yet-unknown mechanisms. Here we show that Nef-induced downregulation of MHC-I expression and MHC-I targeting to the TGN require the binding of Nef to PACS-1, a molecule that controls the TGN localization of the cellular protein furin. This interaction is dependent on Nef's cluster of acidic amino acids. A chimaeric integral membrane protein containing Nef as its cytoplasmic domain localizes to the TGN after internalization, in an acidic-cluster- and PACS-1-dependent manner. These results support a model in which Nef relocalizes MHC-I by acting as a connector between MHC-I's cytoplasmic tail and the PACS-1-dependent protein-sorting pathway.

Animals↗
PubMed2000

The role of tissue factor in regulating endometrial haemostasis: implications for progestin-only contraception.

Abnormal uterine bleeding accounts for the unacceptably high discontinuation rate of progestin-only contraceptives. Previously, we found that in-vivo and in-vitro decidualization of human endometrial stromal cells was associated with elevated concentrations of tissue factor (TF), the primary initiator of haemostasis. Moreover, enhanced TF expression required progesterone receptor (PR) and epidermal growth factor receptor (EGFR) mediation. In the current study, endometrial biopsies were sampled from bleeding (BL) and non-bleeding (NBL) sites under camera-directed hysteroscopic guidance after Depo-provera injections. When compared with control biopsies, immunohistochemical examination revealed that 3 months of Depo-provera contraception reduced TF concentrations at the BL sites. However, there were ample EGFR and PR concentrations at BL and NBL sites. Moreover, there was a trend towards the appearance of pathologically enlarged blood vessels at the BL sites. The use of Western blotting revealed that after 3 months of Depo-provera, concentrations of both PRB and PRA isoforms were lower at BL versus NBL sites with decreased PRA concentrations attaining statistical significance. Separate sampling of endometrial BL and NBL sites as shown here for Depo-provera contraception could prove particularly useful in identifying local factors that determine the onset of bleeding during the more protracted time-course of Norplant contraception.

Biopsy↗
PubMed2000

Characterization of dFMR1, a Drosophila melanogaster homolog of the fragile X mental retardation protein.

Fragile X syndrome is the most common inherited form of mental retardation. It is caused by loss of FMR1 gene activity due to either lack of expression or expression of a mutant form of the protein. In mammals, FMR1 is a member of a small protein family that consists of FMR1, FXR1, and FXR2. All three members bind RNA and contain sequence motifs that are commonly found in RNA-binding proteins, including two KH domains and an RGG box. The FMR1/FXR proteins also contain a 60S ribosomal subunit interaction domain and a protein-protein interaction domain which mediates homomer and heteromer formation with each family member. Nevertheless, the specific molecular functions of FMR1/FXR proteins are unknown. Here we report the cloning and characterization of a Drosophila melanogaster homolog of the mammalian FMR1/FXR gene family. This first invertebrate homolog, termed dfmr1, has a high degree of amino acid sequence identity/similarity with the defined functional domains of the FMR1/FXR proteins. The dfmr1 product binds RNA and is similar in subcellular localization and embryonic expression pattern to the mammalian FMR1/FXR proteins. Overexpression of dfmr1 driven by the UAS-GAL4 system leads to apoptotic cell loss in all adult Drosophila tissues examined. This phenotype is dependent on the activity of the KH domains. The ability to induce a dominant phenotype by overexpressing dfmr1 opens the possibility of using genetic approaches in Drosophila to identify the pathways in which the FMR1/FXR proteins function.

Amino Acid Motifs↗
PubMed2000

Effects of norplant on endometrial tissue factor expression and blood vessel structure.

Abnormal uterine bleeding after Norplant administration is primarily responsible for the high discontinuation rate of this safe and effective long-acting implantable progestin-only contraceptive agent. Although tissue factor (TF) is the primary initiator of hemostasis, previous studies indicated that Norplant-associated bleeding persists despite relatively high TF levels in the stromal compartment. Recently, we determined that progestin-enhanced TF expression during decidualization of human endometrial stromal cells involves both the epidermal growth factor receptor and progesterone receptor (PR]. The current study evaluated TF levels in endometrial bleeding (BL) and nonbleeding (NBL) sites obtained by camera-guided hysteroscopy during Norplant contraception. After 1 yr of therapy, immunohistochemical TF levels were unexpectedly higher at BL than at NBL sites. Use of immunohistochemistry and Western blotting indicated that both sites displayed elevated epidermal growth factor receptor levels and that the BL sites exhibited high levels of the PR, as well as the PR(A) and the PR(B) isoforms. Microscopic examination of 1-yr biopsies revealed that significantly larger numbers of enlarged, distended vessels were present in BL, compared with NBL sites. Elevated TF levels and abnormally enlarged blood vessels in the BL sites are consistent with the recently discovered angiogenic role of TF. By promoting aberrant angiogenesis, chronic endometrial overexpression of TF could produce fragile vessels, which are at increased risk to bleed. Analysis of endometrial BL and NBL sites, during Norplant contraception, offers the potential of elucidating local mechanisms that control enhanced TF expression, leading to abnormal angiogenesis at specific endometrial sites.

Adult↗