Transitional cell metaplasia of fallopian tube fimbriae: a potential mimic of early tubal carcinoma in risk reduction salpingo-oophorectomies from women With BRCA mutations

Germline mutations in the hereditary breast/ovary carcinoma genes BRCA1 or BRCA2 confer increased lifetime risk for ovarian, fallopian tube, and primary peritoneal carcinoma. This risk can be minimized by prophylactic surgery. Risk-reducing salpingo-oophorectomy (RRSO) provides 2 potential benefits: long-term cancer risk reduction and immediate detection of occult early carcinoma, which frequently arises in the tubal fimbriae. Recognition of occult early tubal carcinoma is challenging because it is often microscopic in size and can be confined to the fimbrial epithelium without invasion. Transitional cell metaplasia is a benign epithelial alteration that is a common finding in the serosa of the tube but is underrecognized in the tubal fimbriae, where it may mimic tubal intraepithelial carcinoma. The aim of this study was to define the incidence, morphology, immunophenotype, and distribution of transitional cell metaplasia of the fimbriae in RRSO specimens from 96 women with BRCA germline mutations and to compare these features to those of tubal intraepithelial carcinoma in this cohort. RRSO specimens from an additional 30 women at increased risk for ovarian cancer based on strong family history were also studied, along with RRSO from 1 patient with Lynch syndrome, and 1 patient with PTEN mutation. Transitional cell metaplasia of the fimbriae was present in 26% of all RRSO specimens. It was commonly multifocal (67%), with involvement of the tip, edges, or base of the fimbrial plicae. Average size of a metaplastic focus was 1.3 mm (range: 0.1 to 10 mm). None of the metaplastic foci expressed p53 by immunohistochemistry nor was there increased staining for the proliferation marker MIB-1. Occult early carcinoma was detected in 6/128 RRSO specimens. Median tumor size was 2.7 mm (range: 1 to 11 mm). All expressed p53 and showed markedly increased MIB-1 staining. The key criteria distinguishing transitional cell metaplasia from tubal intraepithelial carcinoma were uniform cell size and shape, normal nucleus:cytoplasm ratios, lack of nuclear atypia, presence of nuclear grooves, lack of mitoses, and absence of p53 expression or increased staining for MIB-1. No particular clinical variables (BRCA 1 vs. BRCA 2 mutation, parity, personal history of breast cancer, prior abdomino-pelvic surgery, or intraoperative findings) or benign pathologic alterations in the RRSO specimens were associated with the presence of transitional cell metaplasia of the fimbriae. None of the patients with this finding developed peritoneal carcinoma during follow-up ranging from 1 month to 9 years. This study demonstrates that transitional cell metaplasia of the fimbriae is a common benign finding in RRSO specimens that should not be confused with the much less common finding of tubal intraepithelial carcinoma.     

Histological and molecular analysis of the biceps tendon long head post‐tenotomy

Tendinopathy is a vexing clinical problem as its onset and development is often asymptomatic and unrecognized until tendon rupture. While extensively studied in the rotator cuff, Achilles, and patellar tendons, no study to date has examined the histological and molecular characteristics of the tendinopathic biceps long‐head (LHB). The anatomy of the LHB is unique in that it comprises intra‐ and extra‐articular portions, each exposed to differing loading patterns. Eleven LHBs post‐tenotomy were sectioned, fixed in formalin, and stained (H&E; Alcian Blue), and gross structural organization of collagen measured using polarized light microscopy. Protein expression of intra‐ and extra‐articular portions of the tenotomized biceps for IGF‐I, collagen III, and MMP‐1, ‐2, ‐3, and ‐13 was determined with Western blot analyses. The intra‐articular LHB exhibited significantly greater histological evidence of tendinopathy inclusive of increased proteoglycan (p < 0.05) and decreased organization as measured by polarized light microscopy (p < 0.01). The intra‐articular LHB also had significantly increased expression of collagen type III (p < 0.01) and of MMP‐1 and 3 (p < 0.01, p < 0.05 respectively). No significant differences were found for IGF‐I or for MMP‐2 and ‐13. The intra‐articular LHB exhibited histological characteristics of tendinopathy. Protein expression of the intra‐articular LHB did not universally display signs of tendinopathy in comparison to the extra‐articular portion of the tendon. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1379–1385, 2009     

Prevalence and degree of sexual dysfunction in a sample of women seeking bariatric surgery

BackgroundSexual functioning has been shown to be impaired in women who are obese, particularly those seeking bariatric surgery. However, most previous studies evaluating sexual function in these populations have not used validated measures. We used the validated Female Sexual Function Index (FSFI) to assess the prevalence of female sexual dysfunction (FSD) in a sample of >100 women evaluated for bariatric surgery.MethodsThe FSFI was administered to reportedly sexually active women during their preoperative evaluation. The scores for the individual FSFI domains (desire, arousal, lubrication, orgasm, satisfaction, and pain) ranging from 0 (or 1.2) to 6 were summed to produce a FSFI total score (range 2–36). A FSFI total cutoff score of ≤26.55 was used to identify participants with FSD. The participants' FSFI total and domain scores were compared with previously published norms available for women diagnosed with female sexual arousal disorder and healthy controls.ResultsOf the 102 women, 61 (59.8%) had FSFI total scores of ≤26.55, indicative of FSD. Older age and menopause were associated with FSD. Compared with published norms, bariatric surgery candidates had FSFI domain scores that were lower than those of the control group (all P values < 0.0001) but greater than those of the female sexual arousal disorder group (all P values < 0.0001), except for desire, for which the scores were similar.ConclusionWomen seeking bariatric surgery are clearly a population with substantial sexual function impairment, with 60% of participants reporting FSD. These findings highlight the need to initiate routine assessment of sexual functioning in this population and examine whether the weight loss after bariatric surgery contributes to a reversal of FSD.     

Lung inflation with direct injection of agarose: a technique for simultaneous molecular and morphometric measurements

The usual methods for preparing lungs for morphologic study involve the instillation of fixatives that modifyproteins and RNA such that the tissue is unsuitable for molecular studies. To develop a technique suitable for molecular studies, pieces of adult rat lungs were infiltrated with agarose, glutaraldehyde, or paraformaldehyde and the consistency of alveolar inflation was compared to lungs inflated with 10% formalin. Only direct injection with 1% agarose resulted in comparable inflation of lung tissue and preserved RNA and protein. Thus, this technique enables simultaneous molecular and morphometric analysis of the lung on small pieces of lung tissue in heterogeneous lung diseases.     

Depressive symptoms and heart rate variability in postmenopausal women

BACKGROUND: Depressive symptoms have been associated with increased cardiac morbidity and mortality rates, but the pathophysiologic mechanism linking depressive symptoms to cardiovascular outcome has yet to be fully understood. Lower heart rate variability has also been associated with increased risk of cardiac events in healthy individuals and in patients with coronary artery disease. Findings regarding a relationship between depressive symptoms and heart rate variability that could explain increased cardiovascular risk have been inconsistent across studies. METHODS: As an ancillary study to the Women's Health Initiative Observational Study, 3372 postmenopausal women aged 50 to 83 years were enrolled for further evaluation using 24-hour ambulatory electrocardiographic monitoring. A shortened version of the Center for Epidemiological Studies Depression Scale and the Diagnostic Interview Schedule were administered. Women with adequate electrocardiographic data and depressive symptom information and without coronary artery disease were analyzed (n = 2627). RESULTS: Two hundred sixty-nine women (10.2%) had depressive symptoms as measured using the 2 instruments. Women with depressive symptoms had a higher mean +/- SD heart rate (77.4 +/- 9.6 vs 75.5 +/- 8.5 beats/min) and lower heart rate variability than women without depressive symptoms. All differences remained significant after adjusting for age (P<.01). CONCLUSIONS: Women with depressive symptoms had significant reductions in heart rate variability and higher heart rates, suggestive of increased sympathetic tone. These findings may contribute to the increased cardiac morbidity and mortality rates associated with depression in other studies.     

HIV,pathology and epigenetic age acceleration in different human tissues

GeroScience - Epigenetic clocks based on patterns of DNA methylation have great importance in understanding aging and disease; however, there are basic questions to be resolved in their...