Persistent Bleeding After Laparoscopic Supracervical Hysterectomy

Background and Objectives:

In our clinical experience, there seemed to be a correlation between cervical stump bleeding and adenomyosis. Therefore, we wanted to conduct a study to determine whether there was an actual correlation and to identify other risk factors for persistent bleeding after a laparoscopic supracervical hysterectomy.

Methods:

The study included women who underwent laparoscopic supracervical hysterectomy from January 1, 2003, through December 31, 2012. Data were collected on age, postmenopausal status, body mass index (BMI), uterine weight, indication for hysterectomy, concomitant bilateral salpingo-oophorectomy (BSO), presence of endometriosis, surgical ablation of the endocervix, adenomyosis, presence of endocervix in the specimen, and postoperative bleeding.

Results:

The study included 256 patients, of whom 187 had no postoperative bleeding after the operation, 40 had bleeding within 12 weeks, and 29 had bleeding after 12 weeks. The 3 groups were comparable in BMI, postmenopausal status, uterine weight, indication for hysterectomy, BSO, surgical ablation of the endocervix, adenomyosis, and the presence of endocervix. However, patients who had postoperative bleeding at more than 12 weeks were significantly younger (P = .002) and had a higher rate of endometriosis (P < .001).

Conclusions:

Risks factors for postoperative bleeding from the cervical stump include a younger age at the time of hysterectomy and the presence of endometriosis. Therefore, younger patients and those with endometriosis who desire to have no further vaginal bleeding may benefit from total hysterectomy over supracervical hysterectomy. All patients who are undergoing supracervical hysterectomy should be counseled about the possible alternatives, benefits, and risks, including continued vaginal bleeding from the cervical stump and the possibility of requiring future treatment and procedures.     

Ethanol self-administration and nicotine treatment increase brain levels of CYP2D in African green monkeys

BACKGROUND AND PURPOSE

CYP2D6 metabolizes many centrally acting drugs, neurotoxins and endogenous neurochemicals, and differences in brain levels of CYP2D have been associated with brain function and drug response. Alcohol consumers and smokers have higher levels of CYP2D6 in brain, but not liver, suggesting ethanol and/or nicotine may induce human brain CYP2D6. We investigated the independent and combined effects of chronic ethanol self-administration and nicotine treatment on CYP2D expression in African green monkeys.

EXPERIMENTAL APPROACH

Forty monkeys were randomized into control, ethanol-only, nicotine-only and ethanol + nicotine groups. Two groups voluntarily self-administered 10% ethanol in sucrose solution for 4 h·day⁻¹, whereas two groups consumed sucrose solution on the same schedule. Two groups received daily s.c. injections of 0.5 mg·kg⁻¹ nicotine in saline bid, whereas two groups were injected with saline on the same schedule.

KEY RESULTS

Both nicotine and ethanol dose-dependently increased CYP2D in brain; brain mRNA was unaffected, and neither drug altered hepatic CYP2D protein or mRNA. The combination of ethanol and nicotine increased brain CYP2D protein levels to a greater extent than either drug alone (1.2–2.2-fold, P < 0.05 among the eight brain regions assessed). Immunohistochemistry revealed the induction of brain CYP2D protein within specific cell types and regions in the treatment groups.

CONCLUSIONS AND IMPLICATIONS

Ethanol and nicotine increase brain CYP2D protein levels in monkeys, in a region and treatment-specific manner, suggesting that CNS drug responses, neurodegeneration and personality may be affected among people who consume alcohol and/or nicotine.     

The Impact of COVID-19 on HIV Self-Management,Affective Symptoms,and Stress in People Living with HIV in the United States

AIDS and Behavior - COVID-19 has the potential to detrimentally impact HIV self-management in people living with HIV (PLHIV). Effective HIV-self management is critically important in managing...     

Syntheses and Antibacterial Activity of N-Acylated Ciprofloxacin Derivatives Based on the Trimethyl Lock

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Genetics of P450 oxidoreductase: sequence variation in 842 individuals of four ethnicities and activities of 15 missense mutations

P450 oxidoreductase (POR) is an electron-donating flavoprotein required for the activity of all microsomal cytochrome P450 enzymes. We sequenced 5,655 bp of the POR gene in a representative population of 842 healthy unrelated individuals in four ethnic groups: 218 African Americans, 260 Caucasian Americans, 179 Chinese Americans, and 185 Mexican Americans. One hundred forty SNPs were detected, of which 43 were found in >/=1% of alleles. Twelve SNPs were in the POR promoter region. Fifteen of 32 exonic variations altered the POR amino acid sequence; 13 of these 15 are previously undescribed missense variations. We found eight indels, only one of which was in the coding region. A previously described variant, A503V, was found on 27.9% of all alleles with some ethnic predilection (19.1% in African Americans, 26.4% in Caucasian Americans, 36.7% Chinese Americans, and 31.0% in Mexican Americans). We built cDNA expression vectors for the 13 previously undescribed missense variants, expressed each protein lacking 27 N-terminal residues in Escherichia coli, and assayed the apparent K(m) and V(max) of each in four assays: reduction of cytochrome c, oxidation of NADPH, 17alpha-hydroxylase activity of P450c17, and 17,20 lyase activity of P450c17. The catalytic activities of several missense mutants differed substantially in these assays, indicating that each POR mutant must be assayed separately with each potential target P450 enzyme. The activity of A503V was reduced to a modest but statistically significant degree in all four assays, suggesting that it may play an important role in interindividual variation in drug response.     

Thrombin causes subsecond changes in protein phosphorylation of platelets

We have developed a general quenched-flow approach to study platelet function as early as 0.3 seconds after stimulation. Phosphorylation of 20- and 40-kd proteins has been analyzed during the first five seconds of platelet response to thrombin from 0.1 to 5.0 U/mL and compared with the progress of aggregation and serotonin secretion. The onset time for aggregation and phosphorylation of both proteins was less than one second, although with lowest (less than 0.5 U/mL) thrombin levels, a lag of up to 0.6 seconds occurred before 40K phosphorylation increased. The thrombin sensitivity of aggregation and 20K phosphorylation was approximately twice that of 40K phosphorylation, with Ka values of 0.51 and 0.53 v 1.10 U/mL, respectively. External calcium was necessary for maximal 20K phosphorylation, since EDTA inhibited this by 30%. The 40K phosphorylation was not affected by EDTA. Platelet activation by thrombin thus induced biochemical changes well before one second. The quenched-flow approach may help to reveal relationships between phospholipase activation, calcium fluxes, and protein phosphorylation during these early periods of platelet function.     

Bryostatin 1, a unique biologic response modifier: anti-leukemic activity in vitro

Bryostatin 1, a macrocyclic lactone isolated from the marine bryozoan Bugula neritina, has demonstrated both antineoplastic activity against the murine P388 leukemia line in vivo and stimulatory activity against mouse and human hematopoietic progenitors. We studied the effects of bryostatin 1 on the growth of human leukemias in vitro. Bryostatin 1 inhibited 1 to 4 logs of clonogenic leukemia cell growth from three of four leukemia cell lines. Bryostatin 1 also inhibited, by at least 1 log, the proliferation of clonogenic acute nonlymphocytic leukemia (ANLL) cells from 10 to 12 patients with newly diagnosed or relapsed ANLL. Maximal inhibition of leukemic growth occurred at 10(-9) to 10(-7) mol/L bryostatin 1. Interestingly, bryostatin 1 also inhibited the growth of hematopoietic progenitors from eight patients with myelodysplastic syndromes (MDS). Leukemia cells exposed to bryostatin 1 for up to 96 hours and then washed, demonstrated no substantial inhibition of clonogenic growth, indicating that the anti-leukemic effect of bryostatin 1 is cytostatic. The phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) produced more potent inhibition of clonogenic leukemia growth, and this inhibition was blocked by bryostatin 1. Thus, the anti-leukemic activity of bryostatin 1 may be mediated through activation of protein kinase C. Bryostatin 1 inhibits clonogenic leukemia cells at concentrations that stimulate normal hematopoietic progenitors. The differential effects of bryostatin 1 on normal and abnormal hematopoiesis suggest that bryostatin 1 may have value in the treatment of leukemias and MDS.     

Electron microscopy shows periodic structure in collagen fibril cross sections.

X-ray diffraction was used to monitor the effects of electron microscope fixation, staining, and embedding procedures on the preservation of the three-dimensional crystalline order in collagen fibrils of rat tail tendon. A procedure is described in which the characteristic 3.8-nm lateral spacing is preserved, with increased contrast, in the diffraction pattern of the embedded fiber. This spacing is correlated with the separation between the tangentially oriented equally spaced lines of density observed in electron microscope ultrathin fibril cross sections of the same material. Optical diffraction of electron micrographs gives an objective measure of the periodicity and suggests that the fibril is composed of concentrically oriented crystalline domains. These observations, when combined with a recent interpretation of the native x-ray diffraction data [Hulmes, D. J. S. & Miller, A. (1979) Nature (London) 282, 878-880] suggest a tentative model for the three-dimensional structure of collagen fibrils.