Application of cephalosporins to obstetrics and gynecology: Transfer of cefazolin and cephalothin to uterine tissue

Antibiotics should be administered so as to maintain effective therapeutic levels in target organs. In routine clinical treatment, however, doses of antibiotics are determined on the basis of their achievable concentrations in blood. To determine the optimum doses of antibiotics against obstetric and gynecologic infections, the authors gave a single intravenous dose of 2 gm of cefazolin or cephalothin to 51 patients before hysterectomy and measured the levels of the antibiotics in uterine tissues and compared them with corresponding serum levels. The maximum tissue levels of cefazolin were generally about 6 to 7 times higher than those of cephalothin: In the perimetrium, levels were 154 μg/gm for cefazolin and 24.1 μg/gm for cephalothin; in the myometrium, 109.5 μg/gm for cefazolin, and 15.5 μg/gm for cephalothin; and in the endometrium, 98.9 μg/gm for cefazolin and 10.4 μg/gm for cephalothin. In the tissues, however, cephalothin reached peak levels more rapidly than cefazolin. Comparisons of the tissue levels and MIC of cefazolin and cephalothin revealed that cefazolin was maintained at over 12.5 μg/gm for at least 150 minutes in the perimetrium, myometrium, and endometrium, whereas cephalothin was maintained at these levels for 40 to 50 minutes only in the perimetrium and myometrium. The ratio of tissue levels to serum levels was 40–70 to 100 for cefazolin and about 30 or less to 100 for cephalothin.     

Endometrial tissue in peritoneal fluid

Peritoneal fluid (PF) was studied for the presence of endometrial tissue in a consecutive series of 67 women (with documented tubal patency) undergoing diagnostic laparoscopy, tubal lavage, and hysteroscopy. PF was completely aspirated from the cul-de-sac both before and after uterine irrigation. The PF was then analyzed for the presence of endometrial tissue. In native PF no significant difference in the incidence of endometrial tissue between patients with (19%) and without (11%) endometriosis (P = 0.6) was observed. Refluxed PF, obtained after uterine irrigation, showed a significantly higher incidence of endometrial tissue in women with endometriosis (76%) as compared to controls (42%) (P = 0.03). We propose two models to explain the development of endometriosis. These are not mutually exclusive, may be independent of each other, and may represent two distinct pathophysiologic disease processes.     

Recovery of Chlamydia trachomatis from endometrial and fallopian tube biopsies in women with infertility of tubal origin

In order to examine the role of chronic active chlamydial infection in tubal infertility, cultures for Chlamydia trachomatis were performed on endometrial biopsies from 38, and fallopian tube biopsies from all, of 52 women undergoing tubal surgery for infertility. C. trachomatis was recovered from one or both sites in 8 of 52 (15%). Five of 6 women with positive fallopian tube cultures had endometrial cultures performed, and of these, 4 (80%) were positive. Three culture-positive women had been treated with tetracycline or doxycycline. Multiple blind passage in tissue culture was required for recovery of all six fallopian tube and four of the six endometrial isolates. No specific anatomic lesion was associated with documented infection. Chronic active chlamydial infection is frequently associated with tubal infertility, may persist despite therapy, and often can be detected by endometrial biopsy culture.     

Effects of clomiphene citrate on cytosolic estradiol and progesterone receptor concentrations in secretory endometrium

Cytosolic estradiol and progesterone receptor concentrations were measured in luteal phase endometrial biopsy samples obtained from 12 anovulatory or oligoovulatory women on clomiphene citrate therapy and from 40 normal control subjects. Clomiphene citrate treatment (250 to 750 mg per cycle) decreased both endometrial estradiol and progesterone receptor concentrations. Estradiol receptor levels were nondetectable in seven tissue samples and progesterone receptor levels in four samples from the 12 subjects given clomiphene citrate compared to nondetectable estradiol receptor concentrations in one tissue sample and progesterone receptor concentrations in two samples from the 40 normal control subjects. In histologically dated endometrium, mean estradiol receptor concentrations on days 20 to 23 and progesterone receptor levels on days to 24 to 27 were lower than the values observed in the comparable dated endometrium of normal ovulatory women. Steroid receptor concentrations correlated negatively with the duration of clomiphene citrate therapy, which implies a time-dependent suppressive effect of clomiphene citrate on measurable cytosolic estradiol and progesterone receptor concentrations during the luteal phase of the cycle.     

子宫输卵管造影诊断符合率及诊断一致性分析

目的:研究不同医师对子宫输卵管造影的诊断符合率以及诊断一致性。方法:选取60例接受宫、腹腔镜手术患者的造影片,由4位临床医师读片诊断。诊断结果分成输卵管积水、输卵管近端阻塞、输卵管远端阻塞、盆腔粘连以及子宫内膜息肉,分别分析各医师的诊断结果与宫、腹腔镜诊断结果的符合率以及一致性(以κ值表示)。结果:造影诊断符合率分别为输卵管积水敏感度83.33%~100.00%,特异度97.22%~98.15%;输卵管近端阻塞敏感度75.00%~83.33%,特异度88.89%~92.60%;输卵管远端阻塞敏感度85.71%~92.86%,特异度77.78%~81.11%;子宫内膜息肉敏感度12.50%~25.00%,特异度94.23%~100.00%;盆腔粘连敏感度58.93%~64.26%,特异度45.31%~64.06%。各医师诊断一致性(κ值):输卵管积水为0.758,输卵管近端阻塞为0.815,输卵管远端阻塞为0.277,盆腔粘连为0.431,子宫内膜息肉为0.658。结论:造影诊断输卵管积水符合率较高;诊断近端阻塞及子宫内膜息肉不易误诊,但易漏诊;诊断远端阻塞不易漏诊,但易误诊;诊断盆腔粘连敏感度及特异度均较低,临床价值有限。不同医师诊断输卵管近端阻塞和输卵管积水一致性较高,输卵管远端阻塞和盆腔粘连诊断一致性较低。     

Histopathological changes in ovary and endometrium after tubal ligation: a rat model

BACKGROUND: To evaluate the histopathological effects of tubal ligation on ovary and endometrium in a rat model. METHODS: Twenty-four female Wistar albino rats weighing 220-260 g were used. The rats were assigned randomly into tubal ligation and control groups. While tubal ligation was applied to the first group of rats, only a laparotomy was performed in the second group. Six weeks later, a second laparotomy was performed and uterine horns and ovaries of the rats in the two groups were excised for histopathological assessment. A pathologist blinded to the groups made histopathological examination including quantification of endometrial phases, presence of endometrial inflammation and counting the number of tertiary follicles and corpora lutea in each ovary. RESULTS: We found no significant difference between tubal ligation and control groups related to the number of tertiary follicles and corpora lutea (p > 0.05). However, in the tubal ligation group, endometrial inflammatory infiltration was significantly higher than in the control group (p < 0.05). CONCLUSION: Tubal ligation does not affect ovarian histology as an indicator of ovarian function. However, endometrial inflammation may occur after tubal ligation and lead to menstrual irregularities as an early complication.     

育龄期功能失调性子宫出血患者子宫内膜组织中雌、孕激素及其受体的变化与意义

目的:研究育龄期功能失调性子宫出血患者子宫内膜组织中雌、孕激素及其受体的变化。方法:随机采集2005年8月至2006年11月北方学院附属第一医院妇产科门诊育龄期功血35例患者的静脉血及子宫内膜功能层组织为研究组,以20例月经正常健康女性排卵后期标本为对照组。(1)采用放免法测定研究组及对照组血清及子宫内膜组织中雌二醇(E2)、孕激素(P)的含量;(2)HE染色后对子宫内膜进行组织学诊断;(3)用TUNEL原位标记技术精确测定子宫内膜功能层细胞凋亡指数;(4)用免疫组化法检测子宫内膜中雌、孕激素受体(ER、PR)的表达。结果:育龄期功血患者以排卵型为主(30/35),其子宫内膜组织中E2含量高于对照组(P<0.05),而P含量低于对照组(排卵后期的子宫内膜),二者差异有统计学意义(P<0.05);两组血清中E2、P差异无统计学意义(P>0.05),但血清、子宫内膜中E2和P呈正相关(rE2=0.74,PE2<0.01;rP=0.65PP<0.01);育龄期功血患者子宫内膜中ER、PR表达及凋亡指数较对照组显著增高,差异有统计学意义(P<0.01)。结论:育龄期功血绝大多数可能系体内作用于子宫内膜的雌、孕激素产生的时间、数量及其受体比例失衡所致,细胞凋亡也参与了功血的发生。     

Relationship between endometrial Arias-Stella phenomenon and concentrations of urinary chorionic gonadotropin and serum human placental lactogen.

Serum placental lactogen (HPL) and urinary chorionic gonadotrophin (HCG) were measured in 14 patients with the endometrial Arias-Stella phenomenon and in 35 comparable patients without this reaction in order to explore a possible causative relationship between the hormonal levels and the endometrial changes. The concentrations of HPL and HCG were similar in both groups of patients, indicating a lack of correlation between the levels of these two hormones and endometrial changes.     

Effects of trophoblast invasion on the distribution of leukocytes in uterine and tubal implantation sites.

OBJECTIVE: To distinguish endocrine and paracrine influences on leukocyte subpopulations at uterine and tubal implantation sites. DESIGN: Retrospective immunohistochemical study. SETTING: Departments of Anatomy, and Obstetrics and Gynecology, School of Medicine, RWTH University of Aachen, Aachen, Germany. PATIENT(S): Ten women with a viable ectopic pregnancy (EP), 25 women who had undergone elective first-trimester termination of pregnancy, and 4 women who had undergone hysterectomy with adnexectomy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Quantitative analysis of leukocyte subpopulations at the implantation sites and their corresponding noninvaded tissues, decidual tissue from patients with EP, and tubal mucosa from normal menstrual cycle. RESULT(S): Similar numbers and characteristic distribution patterns of macrophages, T cells, and B cells were found at both normal intrauterine and tubal implantation sites. Natural killer (NK) cells were always absent from tubal mucosa. The number and distribution of leukocytes within decidual tissue from women with EP corresponded to those in the noninvaded decidual compartment in intrauterine pregnancy (IUP). CONCLUSION(S): Leukocyte populations present in the tubal and uterine mucosa are an intrinsic characteristic of these tissues. The distinct leukocyte distribution pattern at the implantation sites suggests that the invading trophoblast exerts a paracrine influence on endometrial and endosalpingeal leukocytes. The absence of natural killer cells from the tubal wall may be one reason for the higher degree of invasiveness of the trophoblast at the tubal implantation site.     

Reactivity of two monoclonal antibodies (Troma 1 and CAM 5.2) on tissue sections--as a histological trophoblast marker in normal pregnancy and trophoblastic disease

In normal and molar pregnancy, non-villous trophoblasts which exist in the placental bed are thought to be difficult to be distinguished morphologically from the surrounding maternal cells. We examined the reactivities of two monoclonal antibodies (Troma 1 and CAM 5.2) by an immunoperoxidase technique and analyzed their usefulness as histological trophoblast markers. Materials were taken from 41 uteri of normal pregnancy, 7 uteri of hydatidiform mole, 2 uterine gestational choriocarcinoma, 1 tubal tissue of non-gestational choriocarcinoma and 5 non-gestational uteri. The reactivity of Troma 1 was observed on frozen sections and paraffin sections were employed in the analysis of CAM 5.2. The reactivities of these antibodies were the same. In nongestational tissue, they reacted with endometrial gland epithelia and endometrial covering epithelia. In placental bed of normal pregnancy, they reacted with villous and non-villous trophoblasts, besides endometrial gland epithelia. In molar sections, they reacted with gland epithelia, villous trophoblasts and also non-villous trophoblasts which proliferated towards maternal tissue. In choriocarcinoma, they reacted with carcinoma cells specifically. Since endometrial gland epithelia are easily identified histologically, it was concluded that these antibodies could work as histological trophoblast markers in normal pregnancy and trophoblastic disease.     

Serum levels of endometrial proteins during transcervical resection of the endometrium

Objective To study the potential for dissemination of endometrial tissue substances during transcervical resection of the endometrium (TCRE).
Design Prospective study.
Setting One university and two county hospitals.
Participants Forty-eight women with dysfunctional bleeding.
Interventions The serum levels of two endometrial proteins, insulin-like growth factor binding protein-1 (IGFBP-1) and placental protein 14 (PP14), were measured before and every 10 min during the operations. Blood loss was also measured by a photometer together with absorption of the irrigating fluid containing glycine 1.5% and ethanol 1% by expired-breath tests, and serum sodium and volumetric fluid balances.
Main outcome measures Linear correlations between changes in IGFBP-1 and PP14 during TCRE and operating parameters such as operating time, blood loss and fluid absorption.
Results The baseline levels of IGFBP-1 were normal but PP14 could only be detected in one third of the patients, which was due, in part, to pre-operative treatment with danazol. The highest levels of IGFBP-1 and PP14 during surgery correlated positively with the baseline concentrations. Fluid absorption (median 405 ml, range 0–2177) was the only surgical factor associated with increasing serum levels of endometrial proteins.
Conclusion Absorption of the solution used to irrigate the uterus is associated with dissemination of endometrial products in the bloodstream during TCRE.     

Metallothionein expression and infiltration of cytotoxic lymphocytes in uterine and tubal implantation sites

INTRODUCTION: In spite of increasing number of immune cells in the endometrium during the decidualization, the integrity of endometrial tissue in each menstrual cycle is maintained by adaptive changes in expression of several factors that regulate activity of immune cells and concomitant hormonal alterations during the menstrual cycle. This regulatory function of endometrium is also related to resistance to apoptosis, in which metallothionein (MT) may play a role. MATERIALS AND METHODS: Study group included 26 women with spontaneous abortion and 18 patients with tubal ectopic pregnancy. Control group included 17 women whose endometrial tissue samples were taken during the normal secretory cycle phase. Expression of metallothionein (MT), CD56 and CD69 were assessed in tissue samples by immunohistochemistry. RESULTS: The number of CD56-positive cells was significantly higher in women with ruptured than unruptured ectopics. MT expression was higher in tubal mucosa distant from the implantation site in ruptured compared to unruptured ectopics. It was found also to be significantly lower than in decidua taken from women with spontaneous abortion. CD69 expression was similar in women with spontaneous abortion as well as patients with ruptured ectopics compared to the control group. On the other hand, CD69 expression in unruptured ectopics was significantly lower than in women with spontaneous abortion and the control group. CONCLUSION: The concentration of immune cells and increase of their activity in tubal mucosa, with insufficient protection against immune-mediated apoptosis assessed by MT expression, might result in tubal rupture during ectopic pregnancy.     

Antibiotic prophylaxis for hysterectomy and cesarean section: Amoxicillin-clavulanic acid versus cefazolin

Objective

To compare amoxycillin-clavulanic acid with cefazolin as short term antibiotic prophylaxis in women undergoing hysterectomy and elective cesarean section.

Method

Sixty women undergoing hysterectomy were randomly assigned either to 2.4g intravenous amoxycillin-clavulanic acid (AMX/CL) or 2g cefazolin 30 min before hysterectomy. One hundred and twenty two women delivered by elective cesarean were randomized to a single dose of either of the above antibiotics at cord clamping. Each patient was assessed daily until discharge for evidence of febrile status and the presence of infection at the operative site and urinary tract.

Results

Infectious morbidity was found in 11% and 12.5% of hysterectomy patients in AMX/CL and cefazolin groups respectively. Ten women had post-cesarean infections (six AMXCL, four cefazolin, P=0.51)

Conclusion

Broad spectrum amoxycillin-clavulanic acid was not superior to cefazolin in the prevention of postoperative infection when given as prophylaxis in hysterectomy and elective cesarean cases.     

Localization of Chlamydia trachomatis infection by direct immunofluorescence and culture in pelvic inflammatory disease

Fifty-five women with suspected pelvic inflammatory disease underwent diagnostic laparoscopy and endometrial and tubal biopsy, with specimens for isolation of Chlamydia trachomatis and for staining with a species-specific monoclonal fluorescein-conjugated antibody to C. trachomatis were obtained from the urethra, rectum, endocervix, endometrium, tubes, and cul-de-sac. C. trachomatis was isolated from 21 patients (38%), including 10 (18%) who had positive endometrial or tubal cultures. The fluorescein-conjugated antibody stain was positive for 43 (86%) of 50 culture-positive specimens, for 14 (18%) of 78 culture-negative specimens from 21 patients who had positive cultures from other sites, and for one (0.5%) of 192 specimens from 34 patients who had negative cultures at all sites. Thus the sensitivity of direct fluorescein-conjugated antibody for culture-positive specimens was 86% and the specificity for specimens from culture-negative patients was 99%. Twelve upper genital tract specimens were positive by fluorescein-conjugated antibody only. Fluorescein-conjugated antibody staining of 50 paraffin-embedded endometrial aspirates showed extracellular or intracellular elementary bodies and or cytoplasmic inclusions in all of seven culture-positive specimens, in four of six culture-negative specimens from patients who had positive cultures at other sites, and in none of 34 specimens from patients with negative cultures. Thus fluorescein-conjugated antibody staining is useful for confirming the role of C. trachomatis in endometritis and salpingitis. It is more sensitive than culture for detection of chlamydia in endometrial or tubal specimens and is able to confirm that the organism is actually present in endometrial tissue (rather than simply reflecting contamination from the cervix) in women with clinical evidence of pelvic inflammatory disease.     

女性下生殖道沙眼衣原体及解脲支原体感染与输卵管妊娠的相关性

目的探讨女性下生殖道沙眼衣原体(CT)、解脲支原体(UU)感染与输卵管妊娠发生的关系以及夫妻双方接受敏感抗生素治疗CT、UU感染的输卵管妊娠患者术后输卵管通畅情况。方法 (1)对暨南大学附属第一医院2009年9月至2011年9月135例手术治疗的输卵管妊娠患者(研究组)和68例卵巢囊肿、子宫肌瘤患者(对照组)宫颈分泌物行性传播疾病病原体检测和药敏试验。(2)对有生育要求的65例CT、UU阳性的输卵管妊娠患者根据治疗情况分成夫妻双方同时接受敏感抗生素治疗的治疗组35例和预防性使用抗生素治疗的预防组30例,两组患者在手术当天均预防性使用抗生素,前者再根据药敏试验结果选择敏感抗生素对夫妻双方进行规范治疗,后者手术24h后不再使用抗生素。3个月后行子宫输卵管碘油造影(HSG),检查输卵管通畅情况。结果 (1)研究组CT、UU、CT+UU混合感染、淋病奈瑟菌(NG)检出率分别为19.3%(26/135)、40.7%(55/135)、8.9%(12/135)、3.7%(5/135);对照组CT、UU、CT+UU混合感染、NG的检出率分别为4.4%(3/68)、17.6%(12/68)、0(0/68)、、0(0/68)。两组CT、UU、CT+UU混合感染检出率差异有统计学意义(均P<0.05)。(2)HSG显示敏感抗生素治疗组患者患侧输卵管通畅31例(88.6%),阻塞或通而不畅4例(11.4%);预防性抗生素使用组患者患侧输卵管通畅20例(66.7%),阻塞或通而不畅10例(33.3%)。两组差异有统计学意义(均P<0.05)。结论以CT和UU为主的性传播病原体感染与输卵管妊娠的发生有关;根据药敏试验结果对CT和UU阳性的夫妻加强治疗,可能有助于提高术后3个月的输卵管复通率及减少输卵管妊娠的再发。     

Incidence of genital tuberculosis in infertile patients submitted to diagnostic laparoscopy: recent experience in an Italian university hospital.

The incidence of genital tuberculosis is decreasing in industrialized countries. The authors report their experience in 254 patients with primary or secondary infertility. Out of 101 patients with a tubal factor of infertility, two patients were diagnosed as having tuberculosis by both endometrial biopsy and endometrial culture. In a third patient, even in the presence of laparoscopic findings suggesting genital tuberculosis Mycobacterium tuberculosis was isolated only from the urine.     

Bilateral cornual abscess after endometrial ablation following Essure sterilization

Endometrial ablation is used extensively to treat dysfunctional bleeding. Since the introduction of Essure tubal sterilization, this permanent contraception method has been widely used. Both endometrial ablation and Essure sterilization are procedures reported to have only a few complications. We describe a serious infectious complication shortly after an endometrial ablation in a patient with Essure microinserts in situ. To our knowledge, this complication has not been reported before in patients with Essure microinserts in situ. We suggest administering prophylactic antibiotics before endometrial ablation in women with Essure microinserts in situ.     

In vitro study of prolactin secretion by ectopic endometrial stromal cells]

OBJECTIVE: To investigate the relationship between prolactin (PRL) secretion by ectopic endometrial stromal cells and elevated PRL concentrations of peritoneal fluid in patients with endometriosis. METHODS: Twelve samples of each ectopic endometrium and normal endometrium were separated and cultured in vitro. After stimulated with progesterone(10(-8) mol/L) for 6 days, PRL levels in the media of cultured stromal cells from both tissue types were measured by enzyme-labeled immunosorbent assay(ELISA). A study of correlation between PRL level in culture supernatant of stromal cells from ectopic endometrium and American Fertility Society (AFS) classification of endometriosis score was performed. The expression of PRL protein of stromal cells from both tissue types were determined by immunocytochemical method. RESULTS: PRL was secreted in similar concentrations by stromal cells from both tissue types. The mean levels of PRL in ectopic and normal endometria were (21.8 +/- 8.0) and (24.5 +/- 7.9) micrograms.L-1.6 d-1 per, respectively (P > 0.05). There is significant positive correlation between PRL secretion by ectopic endometrial stromal cells and the scoring of endometriosis (P < 0.05). There were no significant difference in the immunostaining integral score of PRL between the two groups. CONCLUSION: Production of PRL by ectopic implants of endometriosis is likely to be a contributing factor of the elevated peritoneal fluid PRL in patients with endometriosis.     

Cyclooxygenase-2 expression in deep endometriosis and matched eutopic endometrium

OBJECTIVE: To identify any relationship between cyclooxygenase-2 expression and the intensity of severe, endometriosis-related dysmenorrhea. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Patients with deep endometriosis. INTERVENTION(S): During surgery, paired samples of tissue representing deep endometriosis and eutopic endometrium were obtained from 46 patients. Control endometrial tissue samples were obtained from 34 fertile women who underwent laparoscopic tubal ligation or reversal of tubal sterilization. Pain assessment for dysmenorrhea was done with a 10-point linear analogue scale. MAIN OUTCOME MEASURE(S): The percentage of surface immunostained for Cox-2 was determined by an immunohistochemical technique. Relationships between pain score for dysmenorrhea and Cox-2 expression were analyzed. RESULT(S): Cox-2 expression was significantly higher in eutopic endometrial stromal cells from patients with deep endometriosis than in stroma from controls during the early, mid, and late secretory phases. In endometriosis patients, Cox-2 expression in eutopic endometrial stromal cells was significantly higher in women with more severe dysmenorrhea (pain score > or =7 vs. <7) during early and mid secretory phases. CONCLUSION(S): Elevated Cox-2 expression in stromal cells in eutopic endometrium from patients with deep endometriosis may play a role in severe, endometriosis-related dysmenorrhea.     

Comparison of trace element concentrations in cancerous and noncancerous human endometrial and ovary tissues

Question of whether trace metal concentrations in tissues are increased or decreased in cancerous patients in comparison with noncancerous patients has not been answered yet, due to the fact that the data known in this field are rare and have contradictory results. Although Zn and Cu concentrations in serum and tissues of cancerous patients have extensively been studied, the precise role of these metals in carcinogenesis is not clearly understood. There are few studies on the concentrations of essential and toxic trace/minor metals in human tissue samples in comparison with serum and plasma samples. Trace metal concentrations including Cd, Cu, Zn, Fe, Mg, Ca, and Ni in both cancerous and noncancerous endometrial, ovary, and cervix uteri tissues were determined by atomic absorption spectrometry. The tissue samples were digested by using microwave energy. Slotted tube atom trap was used to improve the sensitivity of copper and cadmium in flame atomic absorption spectrometry determination. The concentrations of iron in cancerous endometrial tissues were found to be significantly higher than those in noncancerous samples (P < 0.01). On the contrary Fe, Zn concentration in cancerous endometrial tissue was found to be lower significantly than those in noncancerous samples (P= 0.005), whereas the other studied metals were not observed different. Furthermore, Cu and Ca concentrations in cancerous ovary samples were observed to be higher than those in noncancerous ovary tissues (P < 0.01 for Cu and P= 0.1 for Ca), whereas Mg, Fe, and Zn levels in cancerous ovary samples were not found to be different than those in noncancerous tissues.