Hydrosalpinges adversely affect markers of endometrial receptivity

While in-vitro fertilization (IVF) was initially developed in women with tubal factor infertility, recent clinical studies have suggested that the presence of hydrosalpinges lowers implantation and pregnancy rates. We postulated that these hydrosalpinges cause impaired endometrial receptivity. A total of 103 women with hydrosalpinges were prospectively evaluated, and compared with 55 infertile and 44 fertile controls. All women had endometrial biopsies during the window of implantation, analysed by conventional histological criteria, and also stained for three integrin markers of endometrial receptivity (alpha1beta1, alpha4beta1 and alpha vbeta3). Women with hydrosalpinges (cases) expressed significantly less of the alpha vbeta3 integrin compared with controls. There was no difference in expression of alpha1beta1 or alpha4beta1 among groups. A significantly greater number of cases had out of phase histology and missing alpha vbeta3 (type I defects) and absent integrin expression despite normal histological maturation (type II) defects, compared with controls. Of 20 women with impaired endometrial receptivity who were also biopsied after hydrosalpinx surgery, 70% demonstrated increased alpha vbeta3 expression. Seventy-seven percent of type I and 57% of type II defects were corrected postoperatively. Using markers of endometrial receptivity, this study demonstrates that inflammatory hydrosalpinges have an adverse effect on endometrial receptivity, which in some cases may be overcome by surgical treatment of the hydrosalpinx.      

Symptomatic peripheral arterial disease: the value of a validated questionnaire and a clinical decision rule

BACKGROUND: If a validated questionnaire, when applied to patients reporting with symptoms of intermittent claudication, could adequately discriminate between those with and without peripheral arterial disease, GPs could avoid the diagnostic measurement of the ankle brachial index. AIM: To investigate the Edinburgh Claudication Questionnaire (ECQ) in general practice and to develop a clinical decision rule based on risk factors to enable GPs to easily assess the likelihood of peripheral arterial disease. DESIGN OF STUDY: An observational study. SETTING: General practice in The Netherlands. METHOD: This observational study included patients of > or =55 years visiting their GP for symptoms suggestive of intermittent claudication or with one risk factor. The ECQ and the ankle brachial index were performed. The prevalence of peripheral arterial disease, defined as an ankle brachial index <0.9, was related to risk factors using logistic regression analyses, on which a clinical decision rule was developed and related to the presence of peripheral arterial disease. RESULTS: Of the 4790 included patients visiting their GP with symptoms suggestive of intermittent claudication, 4527 were eligible for analyses. The prevalence of peripheral arterial disease in this group was 48.3%. The sensitivity of the ECQ was only 56.2%. The prevalence of peripheral arterial disease in a clinical decision rule that included age, male sex, smoking, hypertension, hypercholesterolemia, and a positive ECQ, increased from 14% in the lowest to 76% in the highest category. CONCLUSION: This study indicates that the ECQ alone has an inadequate diagnostic value in detecting patients with peripheral arterial disease. The ankle brachial index should be performed to diagnose peripheral arterial disease in patients with complaints suggestive of intermittent claudication, although our clinical decision rule could help to differentiate between extremely high and lower prevalence of peripheral arterial disease.     

Expression of alpha-smooth muscle actin by and contraction of cells derived from synovium

Cells derived from synovium have drawn interest as donor cells for articular cartilage tissue engineering because they have been implicated in certain cartilage repair processes in vivo and the chondrogenic potential of the cells has been demonstrated in vitro. Studies have demonstrated that several other types of musculoskeletal connective tissue cells--including chondrocytes, fibrochondrocytes, ligament fibroblasts and osteoblasts, and mesenchymal stem cells can express the gene for the contractile actin isoform, alpha-smooth muscle actin (SMA), and can contract analogs of extracellular matrix in vitro. Although the physiological roles of SMA-enabled contraction of these cells have yet to be established, cell-mediated contraction of scaffolds employed for tissue engineering can alter the pore diameter of the matrix and distort its overall shape, and thus needs to be addressed. Toward this goal, the objective of this study was to investigate the expression of SMA by synovial cells and to evaluate their contraction of collagen-glycosaminoglycan (GAG) scaffolds. Synovial membranes obtained from the knees (stifle joints) of six adult dogs were evaluated for the presence of SMA by immunohistochemistry. Cells isolated from the synovial tissue were expanded through seven passages in monolayer culture, with samples from each passage allocated for Western blot analysis of SMA. Cells from passage 4 were seeded into porous type I collagen-GAG matrices and cultured for 4 weeks. Synovial cell-mediated contraction of the scaffolds was determined by measuring the diameters of the cell-seeded scaffolds and nonseeded controls every other day. Synovium-derived cells cultured as micropellets or in collagen-GAG matrices were incubated in chondrogenic medium with and without fetal bovine serum and evaluated for chondrogenesis by type II collagen immunohistochemistry. Immunohistochemistry revealed the presence of SMA in some cells (less than 10% of the cells) in the intimal layer of synovium from four of the five animals analyzed. Western blot analysis demonstrated a regular increase in the amount of SMA in the synovium-derived cells with passage number. Synovial cell-mediated contraction of the collagen-GAG scaffolds reached a value of 43% of the original diameter after 4 weeks, comparable to that found with other musculoskeletal cell types. Incubation of micropellet cultures of synovium-derived cells with chondrogenic medium revealed trace amounts of type II collagen production by immunohistochemistry. The findings of this study indicate that control of SMA-enabled contraction may be important when employing synovial cells for cartilage repair procedures, and warrant further investigation into the physiological role of SMA expression in synovial cells.     

Topical diclofenac sodium, dexamethasone and placebo compared in a model of immunogenic uveitis in rabbits

Unacceptable side effects involved in topical steroid usage for uveitis have prompted the search for alternative antiinflammatory drugs for the treatment of ocular inflammation. Cyclooxygenase inhibitors have been widely used for systemic inflammatory conditions over the last two decades and are therefore natural candidates to be studied for uveitis therapy. Previous studies of cyclooxygenase inhibitors in uveitis models yielded inconclusive and sometimes contradicting results. The authors compared the clinical effect of topical dexamethasone, diclofenac and placebo in an immunogenic uveitis model produced in ovalbumin immunized NZW rabbits challenged with ovalbumin in the vitreous. Nine clinical parameters of inflammation were compared employing a double blind placebo controlled protocol. Three groups of 16 eyes each, were assigned for each preparation and were followed for nine days with biomicroscopic examinations. Diclofenac was superior or equal to dexamethasone for iris hyperemia (p=0.059) and conjunctival injection (p=0.02), equal for corneal haziness and AC fibrin, yet inferior for corneal endothelial debris, iris fibrin and AC cells and flare (p<0.05). Placebo was inferior (p<0.05) to the other groups for the above mentioned parameters excluding fibrin precipitation on the iris that was greater in diclofenac treated eyes. While some clinical criteria of inflammation responded better to steroids than to diclofenac, the results of this study show that others responded better or equal to diclofenac. The authors hypothesize that although diclofenac reduces prostaglandin levels it may induce high levels of leukotrienes that maintain cellular exudation.     

HRT and cardiovascular disease

Conclusions influencing clinical decisions about the effects of hormone replacement therapy (HRT) on cardiovascular disease have undergone major revisions over the last 30 years. Assumptions in the early 1970s that HRT would increase thromboembolic conditions were reversed in the 1980s, when the first formal studies seemed to indicate a cardioprotective effect. The Heart and Estrogen/progestin Replacement Study (HERS) has, however, very recently suggested that HRT does not affect the incidence of coronary heart disease (CHD) one way or the other. These roller-coaster changes of direction have made decisions by doctors and their patients about the long-term use of HRT extremely difficult and need to be replaced by the stability that only further randomised controlled trials (RCTs) can now provide.     

Neurochemical diversity of dystrophic neurites in the early and late stages of Alzheimer's disease

We examined the neurochemical and morphological diversity of abnormal neurites associated with beta-amyloid plaque formation in the early and late stages of Alzheimer's disease. Preclinical Alzheimer's disease was characterised by the presence of abnormal neurites containing either neurofilament or chromogranin A immunoreactivity. All clustered dystrophic neurites in these cases were associated with beta-amyloid plaques. Neurofilament immunoreactive dystrophic neurites in preclinical Alzheimer's disease could be further subclassified into bulb- and ring-like structures, and these abnormal neurites contained both phosphorylated and dephosphorylated neurofilament epitopes. Dystrophic neurites in Alzheimer's disease could be subdivided into predominantly neurofilament, tau, or chromogranin A immunolabeled forms. Some neurofilament immunoreactive neurites had a core region labeled for tau. The neurofilaments of the dystrophic neurites in Alzheimer's disease had the same complement of phosphorylation- and dephosphorylation-dependent epitopes as observed in preclinical cases. Therefore, an abnormal accumulation of variably phosphorylated neurofilaments represent the earliest cytoskeletal alteration associated with dystrophic neurite formation. Furthermore, these data indicate that dystrophic neurites may "mature" through neurofilament-abundant forms to the neurites containing the profoundly altered filaments labeled for tau. The precise morphological and neurochemical changes associated with dystrophic neurite formation suggests that beta-amyloid plaques are causing physical damage to surrounding axons. The resultant axonal sprouting and profound cytoskeletal alterations would follow the chronic stimulation of the stereotypical reaction to such physical trauma.     

Hypotensive ischemic optic neuropathy and peritoneal dialysis.

PURPOSE: To report anterior ischemic optic neuropathy associated with systemic hypotension in a patient undergoing continuous ambulatory peritoneal dialysis. METHODS: Case report. A 58-year-old man undergoing continuous ambulatory peritoneal dialysis developed painless blurred vision in both eyes and bilateral optic disk swelling with an altitudinal field defect in the left eye. Twenty-four-hour ambulatory blood pressure monitoring was requested in addition to other routine investigations. RESULTS: Routine blood pressure measurement in the clinic was 130/86 mm Hg, but ambulatory blood pressure monitoring demonstrated pronounced early morning hypotension with individual readings as low as 91/41 mm Hg. CONCLUSIONS: Renal dialysis can render patients hypotensive, and this may be associated with anterior ischemic optic neuropathy. The overnight drop in blood pressure may not be appreciated with routine blood pressure measurement. Therefore, 24-hour ambulatory blood pressure monitoring should be considered when investigating patients with suspected anterior ischemic optic neuropathy who are undergoing renal replacement.