Reproductive Hormones and Longitudinal Change in Bone Mineral Density and Incident Fracture Risk in Older Men: The Concord Health and Aging in Men Project

The objectives of this study were to examine relationships between baseline levels of reproductive hormones in older men and (1) change in bone mineral density (BMD) over 5 years and (2) incident fractures over an average of 6 years' follow‐up. A total of 1705 men aged 70 years and older from the Concord Health and Ageing in Men Project (CHAMP) study were assessed at baseline (2005–2007), 2 years follow‐up (2007–2009), and 5 years follow‐up (2010–2013). At baseline, testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) were measured by liquid chromatography–tandem mass spectrometry (LC‐MS/MS), and sex hormone–binding globulin (SHBG), luteinizing hormone (LH), and follicle‐stimulating hormone (FSH) by immunoassay. Hip BMD was measured by dual X‐ray absorptiometry (DXA) at all three time‐points. Fracture data were collected at 4‐monthly phone calls and verified radiographically. Statistical modeling was by general estimating equations and Cox model regression. Univariate analyses revealed inverse associations for serum SHBG, FSH, and LH and positive association for E1 but not DHT or E2 with BMD loss at the hip across the three time points. Serum levels of SHBG (β = –0.071), FSH (β = –0.085), LH (β = –0.070), and E1 (β = 0.107) remained significantly associated with BMD loss in multivariate‐adjusted models; however, we were unable to identify any thresholds for accelerated BMD loss according to reproductive steroids. Incident fractures (all, n = 171; hip, n = 44; and nonvertebral, n = 139) were all significantly associated with serum SHBG, FSH, and LH levels in univariate models but none remained significantly associated in multivariate‐adjusted model. Serum T, DHT, E2, and E1 levels were not associated with incident fractures in univariate or multivariate‐adjusted analyses. In older men, lower serum SHBG, FSH, and LH and higher E1 levels protected against loss of BMD without increasing fracture rate. This means these reproductive variables may be considered as novel biomarkers of bone health during male aging. © 2015 American Society for Bone and Mineral Research.     

Long-term bowel disorders following radial cystectomy: an underestimated issue?

Purpose

Patients after radical cystectomy (RC) frequently complain about bowel disorders (BDs). Reports addressing related long-term complications are sparse. This cross-sectional study assessed changes in bowel habits (BH) after RC.

Methods

A total of 89 patients with a minimum follow-up ≥1 year after surgery were evaluated with a questionnaire. Patients with BD prior to surgery were excluded. Symptoms such as diarrhea, constipation, bloating/flatulence, incomplete defecation, uncontrolled stool loss, and impact on quality of life (QoL) were assessed.

Results

A total of 46.1 % of patients reported changes in BH; however, only 25.8 % reported experiencing related dissatisfaction. Primary causes of dissatisfaction were diarrhea and uncontrolled stool loss. The most common complaints were bloating/flatulence and the feeling of incomplete defecation, but these symptoms did not necessarily lead to dissatisfaction or impairment in quality of life. No difference was identified between an orthotopic neobladder and ileal conduit, and even patients without bowel surgery were affected. QoL, health status, and energy level were significantly decreased in unsatisfied patients.

Conclusions

About 25 % of patients complain about BDs after RC. More prospective studies assessing symptoms, comorbidities, and dietary habits are necessary to address this issue and to identify strategies for follow-up recommendations.

     

Visibility of Sutures of the Orbit and Periorbital Region Using Multidetector Computed Tomography

Objective

Knowledge of cranial suture morphology is crucial in emergency medicine, forensic medicine, and maxillofacial reconstructive surgery. This study assessed the visibility of sutures of the orbit and periorbital region on multidetector computed tomography.

Materials and Methods

Multidetector computed tomography scans of 200 patients (127 males, 73 females; mean age 51.3 years; range, 6-92 years) were evaluated retrospectively. The slice thicknesses varied from 0.5 to 1 mm, and the tube current from 25 to 370 mAs, depending on the CT indication. The visibility of sutures was estimated according to a 4-point scale from "not visible" to "well visible". The chi-squared test was used to test the association of the visibility of sutures with the slice thickness, tube current, and age of patients. Statistical significance was assumed at p < 0.05.

Results

Overall, best visibility was found for the sutura frontozygomatica (98%), sutura frontonasalis (88.5%), and sutura sphenozygomatica (71.5%), followed by the sutura zygomaticomaxillaris (65.8%), sutura temporozygomatica (41.8%), sutura frontomaxillaris (44.5%), and sutura sphenofrontalis (31%). Poor visibility was found for the sutura frontolacrimalis (16.8%) and sutura frontoethmoidalis (1.3%). The sutura ethmoidomaxillaris, sutura lacrimomaxillaris, and sutura ethmoidolacrimalis were not visible.

Conclusion

Although the sutures of the superior, lateral, and inferior orbit are well visible, those of the medial orbit are poorly visible on CT scans.     

Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression.

Deep brain stimulation (DBS) to different sites allows interfering with dysfunctional network function implicated in major depression. Because a prominent clinical feature of depression is anhedonia--the inability to experience pleasure from previously pleasurable activities--and because there is clear evidence of dysfunctions of the reward system in depression, DBS to the nucleus accumbens might offer a new possibility to target depressive symptomatology in otherwise treatment-resistant depression. Three patients suffering from extremely resistant forms of depression, who did not respond to pharmacotherapy, psychotherapy, and electroconvulsive therapy, were implanted with bilateral DBS electrodes in the nucleus accumbens. Stimulation parameters were modified in a double-blind manner, and clinical ratings were assessed at each modification. Additionally, brain metabolism was assessed 1 week before and 1 week after stimulation onset. Clinical ratings improved in all three patients when the stimulator was on, and worsened in all three patients when the stimulator was turned off. Effects were observable immediately, and no side effects occurred in any of the patients. Using FDG-PET, significant changes in brain metabolism as a function of the stimulation in fronto-striatal networks were observed. No unwanted effects of DBS other than those directly related to the surgical procedure (eg pain at sites of implantation) were observed. Dysfunctions of the reward system--in which the nucleus accumbens is a key structure--are implicated in the neurobiology of major depression and might be responsible for impaired reward processing, as evidenced by the symptom of anhedonia. These preliminary findings suggest that DBS to the nucleus accumbens might be a hypothesis-guided approach for refractory major depression.     

Propensity score matching without conditional independence assumption—with an application to the gender wage gap in the United Kingdom

Summary Propensity score matching is frequently used for estimating average treatment effects. Its applicability, however, is not confined to treatment evaluation. In this paper, it is shown that propensity score matching does not hinge on a selection on observables assumption and can be used to estimate not only adjusted means but also their distributions, even with non‐i.i.d. sampling. Propensity score matching is used to analyze the gender wage gap among graduates in the UK. It is found that subject of degree contributes substantially to explaining the gender wage gap, particularly at higher quantiles of the wage distribution.     

Pseudarthrosis in fibrous dysplasia treated with bone morphogenetic protein

We present a case of pseudarthrosis in a patient suffering from polyostotic fibrous dysplasia of the right part of the body that was successfully treated with bone morphogenetic protein. Pseudarthrosis occurred after proximal femoral shaft fracture due to a motorcycle accident initially treated by intramedullary nailing. After revision, the patient was treated by pseudarthrosis debridement and grafting of bone morphogenetic protein-7/osteogenic protein-1, resulting in callus formation that allowed indolent full weight-bearing after 6 weeks. The underlying disease as well as the described treatment is discussed.     

Tolerability of N-chlorotaurine plus ammonium chloride in the rabbit and human eye - a phase 1 clinical study

Background  N-chlorotaurine (NCT), an endogenous mild antiseptic, is well-tolerated by application to the human conjunctiva and has been shown to offer beneficial effects in infectious conjunctivitis. Animal tests revealed improved efficacy of a combination of NCT with ammonium chloride in adenoviral conjunctivitis. The aim of this study was to evaluate the tolerability of NCT plus ammonium chloride in the healthy rabbit and human eye. Methods  First, a tolerability study was performed in rabbits. In a blinded and randomized fashion, one eye was treated with the test medication, the other one with 0.9% saline. Twenty-one animals (three per concentration) were treated with one drop every 2 hours for 6 days. Second, in two volunteers one drop of a defined concentration was applied to one eye every 15 min for 1 hour, saline to the control eye. Four different concentrations were tested on different days. Third, a double-blind, randomized phase 1 study in 13 healthy volunteers was performed. One drop of 0.1% NCT plus 0.1% NH₄Cl versus saline was applied every 15 min within the first hour, followed by four drops every 2 hours. This regimen was done daily for 5 days. Results  In rabbits, no side effects were seen with 0.1% NCT plus 0.1% NH₄Cl, while higher concentrations sometimes caused short-time and minimal conjunctival injection and secretion after dosing. By 1% NCT plus 1% NH₄Cl, these effects were moderate, but disappeared again without any detectable residues. In the pilot study with two volunteers, treatment with 0.5% NCT plus 0.1% NH₄Cl caused medium-scale eye burning for 30 seconds, while 0.1% NCT plus 0.1% NH₄Cl was very well-tolerated, with no or minimal burning for a few seconds. In the subsequent phase 1 study, 0.1% NCT plus 0.1% NH₄Cl was well-tolerated by all subjects except for minimal eye burning for a few seconds after dropping. No objective signs of eye changes could be detected in the human beings. Conclusion  The results of this study clearly demonstrate the good tolerability of a promising NCT formulation with improved activity.     

Impact of cell culture media on the expansion efficiency and T-cell receptor Vbeta (TRBV) repertoire of in vitro expanded T cells using feeder cells.

BACKGROUND: The effects of different cell culture media on expansion efficiency and alterations in T-cell receptor V beta (TRBV) expression of in vitro expanded lymphocytes are not well established. MATERIAL/METHODS: Low numbers of CD3+ T cells from peripheral blood lymphocytes of healthy donors were subjected to polyclonal in vitro expansion in the presence of autologous CD3-depleted mononuclear cells as feeder cells (FCs) and their numbers and TRBV expressions were compared in media containing human (HS-RPMI) or fetal bovine serum (FBS-RPMI), Panserin413, or X-Vivo 15TM designed for lymphocyte culture. RESULTS: During three courses of restimulation within 28 days with CD3-antibody (OKT-3), IL-2, and initial CD3+, T-cell: FC ratios of 1:50 lowered to 1:5 and T cells expanded more than 1,000-fold in the media containing complete sera. Loss of cluster formation, associated with expansion failure, was only observed in cultures using synthetic media and resulted in only about 70-fold expansion. Whereas TRVB expression as determined by real-time PCR was substantially altered after 14 days of culture in X-Vivo 15, at day 28 only T cells from long-term culture in HS-RPMI presented the initial TRBV composition. CONCLUSIONS: Culture media have substantial impact on in vitro T-cell expansion. In the presence of FCs, medium containing human serum is superior to synthetic media and FBS-RPMI for long-term culture regarding T-cell number and TRBV repertoire. In contrast, the synthetic media Panserin413 and XVivo15 show lower expansion efficiency and reproducibility and, as RPMI1640+10%FBS, can contribute to overstimulation of certain TRBVs at advanced culture time points.