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Introduction Fractures of the pelvis and acetabulum are associated with osteoporosis, and their incidence is rising in older adults. In the last decade an increasing number of these fractures are being operated in older patients in certain regions. The goal of this study was to describe the incidence of pelvic and acetabular fractures in Belgium between 1988 and 2018. Materials & methods This retrospective, nationwide, population-based study was conducted with the help of the national health insurance database from the Belgian National Institute for Health and Disability Insurance (NIHDI-RIZIV-INAMI). Multiple codes for the reimbursement of the diagnosis and treatment of pelvic and acetabular fractures were collated and (since 2006) linked to the patients' age group, sex and region. Results Between 1988 and 2018, 91.317 pelvic and acetabular fractures were diagnosed. The overall incidence increased from 15,8/100.000 persons per year in 1988 to 29,7/100.000 persons per year in 2006 and to 37,6/100.000 persons per year in 2018. These fractures showed a bimodal incidence, with a small peak in children (particularly boys), and an increasing incidence in older adults, particularly in women. Between 2006 and 2018, 5.957 (12,4%) patients underwent surgical treatment for their pelvic fracture. 2.088 patients underwent an osteosynthesis of the acetabulum and 3869 patients underwent an osteosynthesis of the pelvic ring. There were 3622 osteosynthesises (60.8%) in patients younger than 60 years old and 2335 (39,1%) in patients over 60 years old. Conclusion There is an increasing incidence of pelvic and acetabular fractures in Belgium with the majority of these fractures occurring in older people. Younger adults have the highest proportion of surgical treatment, but given the much higher incidence in older adults, there is a considerable amount of operations in older adults too.

The proximal interphalangeal (PIP) joint is particularly vulnerable to trauma. In comminuted fractures, arthroplasty with a silicone implant is a treatment option that may be controversial in an emergency setting. This joint destruction is usually accompanied by soft tissue injuries (skin and tendon damage, devascularization) making the reconstruction all the more complex. The aim of our work was to evaluate emergency finger silicone implants for complex and comminuted fractures of the PIP joint as well as clinical and radiological complications. In this single-center, retrospective study, 13 patients operated between January 2007 and January 2019 on an emergency basis with a Neuflex® PIP arthroplasty were reviewed. This PIP joint reconstruction was associated with the soft tissue repair at the same time (skin cover, tendons, nerves) in all patients. The average age was 57.7 years with a male predominance (92%). The injuries were caused by a domestic accident in 61% of cases. The average follow-up was 4.7 years. The average total active motion arc was 183.8°. The average QuickDASH score was 24. There was one case of broken implant with no functional consequence. No infection or instability was reported. Silicone implant arthroplasty is a simple, reliable, fast, and durable solution for complex PIP fractures when conservative treatment is impossible. This solution is an alternative to arthrodesis or even finger amputation.

A 63-year-old woman presented to the outpatient metabolic bone disease clinic with a 6-month history of lumbar and dorsal back pain. Initially, facet arthrosis was suspected and physical therapy suggested. See related editorial, page [339][1] Physical therapy for 1 month brought no improvement in

This systematic review and meta-analysis found low-quality evidence that orthogeriatric care is positively associated with diagnosis of osteoporosis, prescription of calcium and vitamin D supplements and bisphosphonates in older hip fracture patients. Evidence on fall and fracture prevention was scarce and inconclusive. Orthogeriatrics may reduce the treatment gap following hip fractures. Hip fracture patients are at imminent risk of additional fractures and falls. Orthogeriatric care might reduce the osteoporosis treatment gap and improve outcomes in these patients. However, the optimal orthogeriatric care model (geriatric liaison service, co-management, or geriatrician-led care) remains unclear. To summarize the association of different orthogeriatric care models for older hip fracture patients, compared to usual orthopaedic care, with fall prevention measures, diagnosis and treatment of osteoporosis and future falls and fractures. Two independent reviewers retrieved randomized controlled trials (RCTs) or controlled observational studies. Random effects meta-analysis was applied (PROSPERO ID: 165914). One RCT and twelve controlled observational studies were included, encompassing 20,078 participants (68% women, median ages between 75 and 85 years). Orthogeriatric care was associated with higher odds of diagnosing osteoporosis (odds ratio [OR] 11.36; 95% confidence interval [CI] 7.26–17.77), initiation of calcium and vitamin D supplements (OR 41.44; 95% CI 7.07–242.91) and discharge on anti-osteoporosis medication (OR 7.06; 95% CI 2.87–17.34). However, there was substantial heterogeneity in these findings. Evidence on fall prevention and subsequent fractures was scarce and inconclusive. Almost all studies were at high risk of bias. Evidence was insufficient to compare different care models directly against each other. Low-quality evidence suggests that orthogeriatric care is associated with higher rates of diagnosing osteoporosis, initiation of calcium and vitamin D supplements and anti-osteoporosis medication. Whether orthogeriatric care prevents subsequent falls and fractures in older hip fracture patients remains unclear.

The skeletal effects of renal transplantation are not completely understood, especially in patients managed with a steroid minimization immunosuppressive protocol and long term. We enrolled 69 adult transplant recipients (39 males; ages 51.1 ± 12.2 years), free of antiresorptive therapy and managed with a steroid minimization immunosuppressive protocol, into a 5-year prospective observational study to evaluate changes in areal bone mineral density (aBMD), mineral metabolism and bone remodelling. Dual energy X-ray absorptiometry, laboratory parameters of mineral metabolism (including parathyroid hormone, sclerostin and fibroblast growth factor 23) and non-renal cleared bone turnover markers (BTMs) (bone-specific alkaline phosphatase, trimeric N-terminal propeptide and tartrate-resistant acid phosphatase 5b) were assessed at baseline and 1 and 5 years post-transplantation. The mean cumulative methylprednisolone exposure at 1 and 5 years amounted to 2.5 ± 0.8 and 5.8 ± 3.3 g, respectively. Overall, bone remodelling activity decreased after transplantation. Post-transplant aBMD changes were minimal and were significant only in the ultradistal radius during the first post-operative year {median -2.2% [interquartile range (IQR) -5.9-1.2] decline, P = 0.01} and in the lumbar spine between Years 1 and 5 [median 1.6% (IQR -3.2-7.0) increase, P = 0.009]. BTMs, as opposed to mineral metabolism parameters and cumulative corticosteroid exposure, associated with aBMD changes, both in the early and late post-transplant period. Most notably, aBMD changes inversely associated with bone remodelling changes. In summary, in de novo renal transplant recipients treated with a steroid minimization immunosuppressive protocol, BMD changes are limited, highly variable and related to remodelling activity rather than corticosteroid exposure. ispartof: Nephrol Dial Transplant vol:35 issue:4 pages:697-705 ispartof: location:England status: published

Bisphenol A (BPA) and Diethylhexyl Phthalate (DEHP) are well-studied endocrine disrupting chemicals (EDCs), however, the effects of mixtures of these EDCs are not. To assess the consequences of prenatal exposure to a mixture of these EDCs, dams were orally administered either saline (control), BPA (5 μg/kg BW/day), high dose DEHP (HD-D; 7.5 mg/kg BW/day), or a combination of BPA with HD-D in experiment 1; saline, BPA (5 μg/kg BW/day), low-dose DEHP (LD-D; 5 μg/kg BW/day) or a combination of BPA with LD-D in experiment 2. Gestational weights, number of abortions, litter size and weights, number of live births and stillbirths were recorded. Morphometric measures were obtained at birth and body weight, food and water intake were monitored weekly from postnatal weeks 3–12. Offspring were sacrificed at 16–24 weeks of age and organ weights were measured. The abortion rate of dams exposed to HD-D and the mixtures, BPA + LD-D and BPA + HD-D were higher at 9, 14 and 27% respectively. Prenatal exposure to BPA or HD-D significantly decreased relative thymus weights in male but not female offspring. Apoptotic cells were detected in thymus sections of both male and female offspring prenatally exposed to DEHP. Relative heart weights increased in BPA + HD-D exposed male offspring compared to the other groups. The results indicate that a mixture of BPA and DEHP, produced a pronounced effect on pregnancy outcomes. Male offspring appear to be more susceptible to the programming effects of these EDCs or their mixture suggesting a need to reconsider the possible additive, antagonistic or synergistic effects of EDC mixtures.

Purpose: To provide updated evidence-based guidelines for the management of osteoporosis in postmenopausal women in Belgium. Methods: The Belgian Bone Club (BBC) gathered a guideline developer group. Nine “Population, Intervention, Comparator, Outcome” (PICO) questions covering screening, diagnosis, non-pharmacological and pharmacological treatments, and monitoring were formulated. A systematic search of MEDLINE, the Cochrane Database of Systematic Reviews, and Scopus was performed to find network meta-analyses, meta-analyses, systematic reviews, guidelines, and recommendations from scientific societies published in the last 10 years. Manual searches were also performed. Summaries of evidence were provided, and recommendations were further validated by the BBC board members and other national scientific societies’ experts. Results: Of the 3840 references in the search, 333 full texts were assessed for eligibility, and 129 met the inclusion criteria. Osteoporosis screening using clinical risk factors should be considered. Patients with a recent (, SCOPUS: ar.j, info:eu-repo/semantics/published

Osteocyte lacunae are small cavities within the bone matrix. Their dimensions and spatial arrangement affect bone mechanical properties. Furthermore, their size and shape affect the strain in bone tissue close to the lacunae; hence, they are supposed to affect the mechanosensory function of the osteocytes residing in the lacunae. It was the purpose of this study to quantify the morphological features of osteocyte lacunae, whether these are affected by aging and whether these vary among different anatomical location. In addition, we aimed at quantifying the vascular canals as these affect bone's microporosity too. We quantified the microporosity in the fibular midshaft of young-adult and old female C57BL/6 mice. Using micro-computed tomography (μCT), we found that advanced age was associated with a significantly decreased vascular canal number and volume density. In aged mice, the mean volume of the lacuna was significantly smaller than in young animals and they were more round. Lacuna number density close to the neutral axis of the fibula was higher in older mice than in young ones. The characterization of bone microporosity presents a first step in further unraveling their potential role in age-related reductions in bone strength.

The aim of this study is to analyze the patients' satisfaction after aesthetic abdominal etching or associated with an abdominoplasty.All records of patients who underwent abdominal etching between 2016 and 2017 were analyzed. Eligible patients were contacted, by telephone and submitted to a questionnaire of satisfaction. The patients were then divided into 3 groups according to the operative indication: aesthetic abdominal etching, abdominal etching for breast lipofilling and abdominal etching associated with an abdominoplasty.Twenty-two out of 30 patients agreed to answer the questionnaire: 6 in the aesthetic abdominal etching group, 9 in the breast lipofilling group and 7 in the abdominoplasty group. For 41% of patients, the result was entirely in line with their expectations. It was fairly consistent in 50% of cases and non-compliant in 9% of cases. 50% of the patients were completely satisfied with the stability of the result over time and 45% were quite satisfied, an average satisfaction of 95%. Fourteen percent of patients rated their result as excellent, 41% as very good, 32% as good and 14% as average. No patient rated his result as mediocre. For 96% of patients, the choice of intervention was a good or very good decision and 77% would do it again without hesitation.Abdominal etching provides a high overall patients' satisfaction. It has a positive impact on the patient's life, with a low risk of complications.

ispartof: GASTROENTEROLOGY vol:156 issue:5 pages:E4-E5 ispartof: location:United States status: Published online

Objectives To determine the association between frailty and short-term mortality in older adults hospitalized for coronavirus disease 2019 (COVID-19). Design Retrospective single-center observational study. Setting and participants: N = 81 patients with COVID-19 confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR), at the Geriatrics department of a general hospital in Belgium. Measure ments: Frailty was graded according to the Rockwood Clinical Frailty Scale (CFS). Demographic, biochemical and radiological variables, co-morbidities, symptoms and treatment were extracted from electronic medical records. Results Participants (N = 48 women, 59%) had a median age of 85 years (range 65 – 97 years), median CFS score of 7 (range 2 – 9), and 42 (52%) were long-term care residents. Within six weeks, eighteen patients died. Mortality was significantly but weakly associated with age (Spearman r = 0.241, P = 0.03) and CFS score (r = 0.282, P = 0.011), baseline lactate dehydrogenase (LDH) (r = 0.301, P = 0.009), lymphocyte count (r = -0.262, P = 0.02) and RT-PCR cycle threshold (Ct, r = -0.285, P = 0.015). Mortality was not associated with long-term care residence, dementia, delirium or polypharmacy. In multivariable logistic regression analyses, CFS, LDH and RT-PCR Ct (but not age) remained independently associated with mortality. Both age and frailty had poor specificity to predict survival. A multivariable model combining age, CFS, LDH and viral load significantly predicted survival. Conclusions and implications Although their prognosis is worse, even the oldest and most severely frail patients may benefit from hospitalization for COVID-19, if sufficient resources are available., Outcomes of frail older adults hospitalized for COVID-19, particularly long-term care residents, remain unclear. In this retrospective cohort, frailty predicted mortality independently of age or established biomarkers.

Background: Hypophosphatasia (HPP) is a rare metabolic bone disorder caused by mutations in the alkaline phosphatase (ALPL) gene, and characterized by low circulating alkaline phosphatase (ALP) levels and bone, muscle, dental and systemic manifestations. In this case series we investigate the clinical spectrum, genetic and biochemical profile of adult HPP patients from the University Hospitals Leuven, Belgium. Methodology: Adults with HPP were identified through medical record review. Inclusion criteria were: 1) age ≥ 16 years; 2) consecutively low ALP levels not explained by secondary causes; 3) one or more of the following supporting criteria: biochemical evidence of elevated enzyme substrates; subtrochanteric fractures, metatarsal fractures or other typical clinical features; family history of HPP; a known or likely pathogenic ALPL mutation. Results: 19 patients met our inclusion criteria (n=2 infantile, n=6 childhood, n=10 adult-onset HPP and one asymptomatic carrier). Fractures and dental abnormalities were the most reported symptoms. Fatigue was reported in n=7/19 patients (37%), three of which had previously been misdiagnosed as having chronic fatigue syndrome and/or fibromyalgia. Empirical pyridoxine therapy in four patients (without seizures) did not provide symptomatic relief. N=7/19 patients (37%) were inappropriately treated or planned to be treated with antiresorptive treatment. Two patients developed atypical femoral fractures following exposure to bisphosphonates and/or denosumab. Patients detected by screening were less severely affected, while patients with homozygous or compound heterozygous mutations had the most severe symptoms, significantly lower circulating ALP levels (p=0.013) and significantly higher pyridoxal-5’-phosphate (p=0.0018) and urinary phosphoethanolamine (p=0.0001) concentrations. Conclusions: Screening may detect mainly less severely affected individuals, which may nevertheless avoid misdiagnosis and inappropriate antiresorptive drug exposure. Patients with biallelic mutations had more severe symptoms, significantly lower ALP and higher substrate levels. Whether the latter finding has implications for the classification and treatment of HPP should be investigated further in larger cohorts. ispartof: JOURNAL OF CLINICAL DENSITOMETRY vol:23 issue:3 pages:340-348 ispartof: location:United States status: published

Kidney transplant recipients are at increased risk of fractures. This prospective observational study investigated whether areal bone mineral density (aBMD) as assessed by dual-energy x-ray absorptiometry can predict incident fragility fractures in de novo kidney transplant recipients and whether bone turnover markers increase diagnostic accuracy. Parameters of bone mineral metabolism including parathyroid hormone (PTH), fibroblast growth factor 23, sclerostin, calcidiol and calcitriol, and bone turnover markers were assessed in blood samples collected immediately prior to kidney transplantation in 518 adult recipients. aBMD was measured at several skeletal sites within 14 days posttransplant. Thirty patients had a history of a fragility fracture at the time of transplantation, and osteopenia or osteoporosis at the femoral neck was observed in 77%. Bone turnover markers were inversely correlated with aBMD at all skeletal sites. Low aBMD and low PTH were associated with history of fragility fracture at the time of transplantation, independent of age, gender, and comorbidity. During a median post-transplant follow-up of 5.2 years, 38 patients sustained a fragility fracture, corresponding to a fracture incidence of 14.1 per 1000 person-years. Low aBMD at the hip and lumbar spine were associated with incident fractures, independent of classical determinants, including history of fracture. PTH and bone turnover markers at the time of transplantation failed to predict incident fractures. In conclusion, aBMD is low, correlates inversely with bone turnover, and predicts incident fractures in de novo kidney transplant recipients. ispartof: KIDNEY INTERNATIONAL vol:95 issue:6 pages:1461-1470 ispartof: location:United States status: published

Bone's microporosity plays important roles in bone biology and bone mechanical quality. In this study, we explored the accuracy and reproducibility of nondestructive desktop μCT for 3D visualization and subsequent morphometric analysis of mouse cortical bone microporosity including the vascular canal network and osteocyte lacunae. The accuracy of measurements was evaluated in five murine fibula using confocal laser scanning microscopy (CLSM) in conjunction with Fluorescein isothiocyanate (FITC) staining as the reference method. The reproducibility of μCT-derived cortical bone microstructural indices was examined in 10 fibulae of C57Bl/6J male mice at a nominal resolution of 700 nanometer. Three repeated measurements were made on different days. An excellent correlation between μCT and CLSM was observed for both mean lacuna volume (r = 0.98, p = 0.002) and for mean lacuna orientation (r = 0.93, p = 0.02). Whereas the two techniques showed no significant differences for these parameters, the mean lacuna sphericity acquired from μCT was significantly higher than CLSM (p = 0.01). Reproducibility was high, with precision errors (PE) of 1.57-4.69% for lacuna parameters, and of 1.01-9.45% for vascular canal parameters. Intraclass correlation coefficient (ICC) showed a high reliability of the measurements, ranging from 0.998-1.000 for cortical parameters, 0.973-0.999 for vascular canal parameters and 0.755-0.991 for lacuna parameters. In conclusion, desktop μCT is a valuable tool to quantify the 3D characteristics of bone vascular canals as well as lacunae which can be applied to intact murine bones with high accuracy and reproducibility. Thus, μCT might be an important tool to improve our understanding of the physiological and biomechanical significance of these cannular and lacunar structure in cortical bone. ispartof: PLoS One vol:12 issue:8 ispartof: location:United States status: published

IF 1.331; International audience; The human amniotic membrane (hAM) has been successfully used as a natural carrier containing amniotic mesenchymal stromal cells, epithelial cells and growth factors. It has a little or no immunogenicity, and possesses useful anti-microbial, anti-inflammatory, anti-fibrotic and analgesic properties. It has been used for many years in several indications for soft tissue repair. We previously reported that hAM represents a natural and preformed sheet containing highly potent stem cells, and could thus be used for bone repair. Indeed, native hAM possesses pre-osteoblastic potential that can easily be stimulated, even as far as mineralization, by means of in vitro osteogenic culture. However, cell culture induces damage to the tissue, as well as to cell phenotype and function. The aim of this study was to evaluate new bone formation by fresh and in vitro osteodifferentiated hAM, alone or associated with an additional scaffold presenting osteoinductive properties. Moreover, we also aimed to determine the effect of in vitro hAM pre-osteodifferentiation on its in vivo biocompatibility/tissue degradation. Results showed that neither fresh nor osteodifferentiated hAM induced ectopic bone formation, whether or not it was associated with the osteoinductive scaffold. Secondly, fresh and osteodifferentiated hAM presented similar in vivo tissue degradation, suggesting that in vitro hAM pre-osteodifferentiation did not influence its in vivo biocompatibility.

Bone is an endocrine tissue expressing androgen and estrogen receptors as well as steroid metabolizing enzymes. The bioactivity of circulating sex steroids is modulated by sex hormone-binding globulin and local conversion in bone tissue, for example, from testosterone (T) to estradiol (E2) by aromatase, or to dihydrotestosterone by 5α-reductase enzymes. Our understanding of the structural basis for gender differences in bone strength has advanced considerably over recent years due to increasing use of (high resolution) peripheral computed tomography. These microarchitectural insights form the basis to understand sex steroid influences on male peak bone mass and turnover in cortical vs trabecular bone. Recent studies using Cre/LoxP technology have further refi ned our mechanistic insights from global knockout mice into the direct contributions of sex steroids and their respective nuclear receptors in osteoblasts, osteoclasts, osteocytes, and other cells to male osteoporosis. At the same time, these studies have reinforced the notion that androgen and estrogen defi ciency have both direct and pleiotropic effects via interaction with, for example, insulin-like growth factor 1, inflammation, oxidative stress, central nervous system control of bone metabolism, adaptation to mechanical loading, etc., This review will summarize recent advances on these issues in the fi eld of sex steroid actions in male bone homeostasis. ispartof: Asian Journal of Andrology vol:16 issue:2 pages:213-222 ispartof: location:China status: published

Androgens have well-established anabolic actions on skeletal muscle, although the direct effects of the androgen receptor (AR) in muscle remain unclear. We generated satellite cell-specific AR-knockout (satARKO) mice in which the AR is selectively ablated in satellite cells, the muscle precursor cells. Total-limb maximal grip strength is decreased by 7% in satARKO mice, with soleus muscles containing ∼10% more type I fibers and 10% less type IIa fibers than the corresponding control littermates. The weight of the perineal levator ani muscle is markedly reduced (-52%). Thus, muscle AR is involved in fiber-type distribution and force production of the limb muscles, while it is a major determinant of the perineal muscle mass. Surprisingly, myostatin (Mstn), a strong inhibitor of skeletal muscle growth, is one of the most androgen-responsive genes (6-fold reduction in satARKO) through direct transcription activation by the AR. Consequently, muscle hypertrophy in response to androgens is augmented in Mstn-knockout mice. Our finding that androgens induce Mstn signaling to restrain their own anabolic actions has implications for the treatment of muscle wasting disorders.-Dubois, V., Laurent, M. R., Sinnesael, M., Cielen, N., Helsen, C., Clinckemalie, L., Spans, L., Gayan-Ramirez, G., Deldicque, L., Hespel, P., Carmeliet, G., Vanderschueren, D., and Claessens, F. A satellite cell-specific knockout of the androgen receptor reveals myostatin as a direct androgen target in skeletal muscle.

Estrogens and androgens influence the growth and maintenance of the mammalian skeleton and are responsible for its sexual dimorphism. Estrogen deficiency at menopause or loss of both estrogens and androgens in elderly men contribute to the development of osteoporosis, one of the most common and impactful metabolic diseases of old age. In the last 20 years, basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies have changed considerably the landscape of our understanding of bone biology as well as the relationship between sex steroids and the physiology and pathophysiology of bone metabolism. Together with the appreciation of the side effects of estrogen-related therapies on breast cancer and cardiovascular diseases, these advances have also drastically altered the treatment of osteoporosis. In this article, we provide a comprehensive review of the molecular and cellular mechanisms of action of estrogens and androgens on bone, their influences on skeletal homeostasis during growth and adulthood, the pathogenetic mechanisms of the adverse effects of their deficiency on the female and male skeleton, as well as the role of natural and synthetic estrogenic or androgenic compounds in the pharmacotherapy of osteoporosis. We highlight latest advances on the crosstalk between hormonal and mechanical signals, the relevance of the antioxidant properties of estrogens and androgens, the difference of their cellular targets in different bone envelopes, the role of estrogen deficiency in male osteoporosis, and the contribution of estrogen or androgen deficiency to the monomorphic effects of aging on skeletal involution.

Aging hypogonadal men are at increased risk of osteoporosis and sarcopenia. Testosterone is a potentially appealing strategy to prevent simultaneous bone and muscle loss. The androgen receptor (AR) mediates antiresorptive effects on trabecular bone via osteoblast-lineage cells, as well as muscle-anabolic actions. Sex steroids also modify the skeletal response to mechanical loading. However, it is unclear whether the effects of androgens on bone remain effective independent of mechanical stimulation or rather require indirect androgen effects via muscle. This study aims to characterize the effects and underlying mechanisms of androgens on disuse osteosarcopenia. Adult male mice received a unilateral botulinum toxin (BTx) injection, and underwent sham surgery or orchidectomy (ORX) without or with testosterone (ORX + T) or dihydrotestosterone (ORX + DHT) replacement. Compared to the contralateral internal control hindlimb, acute trabecular number and bone volume loss was increased by ORX and partially prevented DHT. T was more efficient and increased BV/TV in both hindlimbs over sham values, although it did not reduce the detrimental effect of BTx. Both androgens and BTx regulated trabecular osteoclast surface as well as tartrate-resistant acid phosphatase expression. Androgens also prevented BTx-induced body weight loss but did not significantly influence paralysis or muscle atrophy. BTx and ORX both reduced cortical thickness via endosteal expansion, which was prevented by T but not DHT. In long-term follow-up, the residual trabecular bone volume deficit in sham-BTx hindlimbs was prevented by DHT but T restored it more efficiently to pre-treatment levels. Conditional AR deletion in late osteoblasts and osteocytes or in the satellite cell lineage increased age-related trabecular bone loss in both hindlimbs without influencing the effect of BTx on trabecular osteopenia. We conclude that androgens have antiresorptive effects on trabecular disuse osteopenia which do not require AR actions on bone via muscle or via osteocytes. publisher: Elsevier articletitle: Androgens have antiresorptive effects on trabecular disuse osteopenia independent from muscle atrophy journaltitle: Bone articlelink: http://dx.doi.org/10.1016/j.bone.2016.09.011 content_type: article copyright: © 2016 Elsevier Inc. All rights reserved. ispartof: Bone vol:93 pages:33-42 ispartof: location:United States status: published

Sex hormone-binding globulin (SHBG) is the high-affinity binding protein for androgens and estrogens. According to the free hormone hypothesis, SHBG modulates the bioactivity of sex steroids by limiting their diffusion into target tissues. Still, the in vivo physiological role of circulating SHBG remains unclear, especially since mice and rats lack circulating SHBG post-natally. To test the free hormone hypothesis in vivo, we examined total and free sex steroid concentrations and bioactivity on target organs in mice expressing a human SHBG transgene. SHBG increased total androgen and estrogen concentrations via hypothalamic-pituitary feedback regulation and prolonged ligand half-life. Despite markedly raised total sex steroid concentrations, free testosterone was unaffected while sex steroid bioactivity on male and female reproductive organs was attenuated. This occurred via a ligand-dependent, genotype-independent mechanism according to in vitro seminal vesicle organ cultures. These results provide compelling support for the determination of free or bioavailable sex steroid concentrations in medicine, and clarify important comparative differences between translational mouse models and human endocrinology.

to the editor: Cooke et al. provided in their recent review a comprehensive insight into the estrogenic regulation of male physiology ([1][1]). This brings us a good opportunity to revisit our current knowledge on serum estradiol (E2) concentrations in aging men and their potential associations with

Gender is one of the strongest predictors of osteoporotic fracture risk, second only to ageing. A recent systematic review of worldwide epidemiology revealed that hip fracture incidence is about twofold lower in men compared to women, despite greater than tenfold variation between geographic regions [1]. This lower fracture incidence occurs despite persisting underdiagnosis and undertreatment of osteoporosis in men, which probably explains why hip fracture incidence may be decreasing in women but not men [2–5]. It is well known that men generally have a more robust body composition; even after correction for an average 10 % greater height and bone length, men at the age of peak bone mass have 25 % greater bone mineral content [6], almost 50 % greater muscle mass and power and half the fat mass of women [7]. Conversely, late-onset male hypogonadism increases the risk of bone loss, muscle atrophy and fat accumulation [3, 8]. Understanding the underlying mechanisms involved in this gender dimorphism in body composition may thus identify additional therapeutic targets not only for osteoporosis, but also for sarcopenia and obesity.

Sex steroids are chief regulators of gender differences in the skeleton, and male gender is one of the strongest protective factors against osteoporotic fractures. This advantage in bone strength relies mainly on greater cortical bone expansion during pubertal peak bone mass acquisition and superior skeletal maintenance during aging. During both these phases, estrogens acting via estrogen receptor-α in osteoblast lineage cells are crucial for male cortical and trabecular bone, as evident from conditional genetic mouse models, epidemiological studies, rare genetic conditions, genome-wide meta-analyses, and recent interventional trials. Genetic mouse models have also demonstrated a direct role for androgens independent of aromatization on trabecular bone via the androgen receptor in osteoblasts and osteocytes, although the target cell for their key effects on periosteal bone formation remains elusive. Low serum estradiol predicts incident fractures, but the highest risk occurs in men with additionally low T and high SHBG. Still, the possible clinical utility of serum sex steroids for fracture prediction is unknown. It is likely that sex steroid actions on male bone metabolism rely also on extraskeletal mechanisms and cross talk with other signaling pathways. We propose that estrogens influence fracture risk in aging men via direct effects on bone, whereas androgens exert an additional antifracture effect mainly via extraskeletal parameters such as muscle mass and propensity to fall. Given the demographic trends of increased longevity and consequent rise of osteoporosis, an increased understanding of how sex steroids influence male bone health remains a high research priority.

Study design. A prospective cross-sectional analytic study. Objectives. To assess in patients with chronic low back pain whether the presence or absence of pain originating from the lumbar zygapophysial joints correlates with changes seen on computed tomography. Summary of Background Data. Results of studies have been divided as to whether or not radiologic imaging is able to predict those patients with pain originating from the zygapophysial joints. Methods. Sixty-three patients with low back pain lasting for longer than 3 months underwent computed tomography and blocks of the zygapophysial joints at L5-S1, L4-L5, and L3-L4. The zygapophysial joints of all images were scored by three independent, masked radiologists. Results. Interobserver agreement was poor with intraclass correlation coefficients of 0.34-0.66 using total joint scores for all three assessors. Using the results of a repeat assessment with two radiologists there was no statistically significant difference in joint scores between those with and those without pain originating from the zygapophysial joint. Conclusions. Computed tomography has no place in the diagnosis of lumbar zygapophysial joint pain

OBJECTIVES--To determine the prevalence of pain arising from the zygapophysial joint in patients with chronic low back pain and to determine whether any clinical features could distinguish patients with and without such pain. METHODS--Sixty three patients with chronic low back pain were studied prospectively. All patients underwent a detailed history and physical examination as well as a series of intra-articular zygapophysial joint injections of 0.5% bupivacaine starting at the symptomatic level to a maximum of three levels or until the pain was abolished. They also received injections of normal saline into paraspinal muscles to act as controls. RESULTS--All patients proceeded with the injections. Twenty (32%; 95% confidence interval (CI) 20 to 44%) obtained greater than 50% relief of their pain following the administration of saline. Fifty seven patients completed the study; 23 of them (40%; 95% CI 27 to 53%) failed to obtain relief following the injection of saline but obtained relief following one or more intra-articular injections of local anaesthetic. None of the historical features or clinical tests could discriminate those patients with and those without zygapophysial joint pain. CONCLUSION--Pain originating from the zygapophysial joint is not uncommon, but this study failed to find any clinical predictors in patients with such pain.

Children increasingly participate in horseback riding, especially young girls, with more and more accidents during this activity. The severity of the injuries caused by horses seems to be higher than in other sports.In a retrospective study, we reviewed 303 accidents of children younger than 15 years of age during the past 13 years. Our study only investigated children who were hospitalized after their accident.Eighty-two percent of the injured children were girls, but there was no difference between girls and boys in terms of severity. In most cases, children were hurt by falling from the horse (87 %). In the other cases, they were kicked or bitten by the animal. The most frequent trauma sustained was fracture (50 %). The upper extremity was injured in 40 % of the traumas followed by the head (32 %). The lower limbs, the abdomen, the spine, or the thorax were injured in less than 10 % of the incidents. The severity of the accidents was studied with the Injury Severity Score and we compared groups of children. Children younger than 11 years old were more severely injured than older children (P=0.0002).The youngest horseback riders should be supervised carefully to avoid severe injuries during this activity.

Patients are increasingly seeking health information on the Internet, but to the best of our knowledge, this has not been previously studied in haematology. We aimed to characterise online health information use and associated variables among adult outpatients in our tertiary-care centre in Flanders, Belgium. During a 6-week period, we distributed 477 anonymous self-administered questionnaires and received 451 (response rate 94.5%), of which 444 (93.1% of total) contained information on Internet use for health information, the primary outcome. Two hundred and thirty-two respondents (52.3%) had ever sought any health information online, and 187 (33.1%) conducted searches pertaining to their haematological disease in the past year. The latter was independently associated with younger age and a higher level of education in multivariate analysis. Internet users ranked the Internet higher and other resources lower as health information resources. Among Internet users, 196 (89.5%) would be interested in a list of reliable websites about their disease. Patients reported positive and negative aspects of online health information-seeking; it increased anxiety in some while it stimulated coping in others. We conclude that haematological patients commonly use the Internet for health information and report both positive and negative aspects of using this medium.

Background Intravenous infusion of lidocaine decreases postoperative pain and speeds the return of bowel function. The authors therefore tested the hypothesis that perioperative lidocaine infusion facilitates acute rehabilitation protocol in patients undergoing laparoscopic colectomy. Methods Forty patients scheduled to undergo laparoscopic colectomy were randomly allocated to receive intravenous lidocaine (bolus injection of 1.5 mg/kg lidocaine at induction of anesthesia, then a continuous infusion of 2 mg.kg.h intraoperatively and 1.33 mg.kg.h for 24 h postoperatively) or an equal volume of saline. All patients received similar intensive postoperative rehabilitation. Postoperative pain scores, opioid consumption, and fatigue scores were measured. Times to first flatus, defecation, and hospital discharge were recorded. Postoperative endocrine (cortisol and catecholamines) and metabolic (leukocytes, C-reactive protein, and glucose) responses were measured for 48 h. Data (presented as median [25-75% interquartile range], lidocaine vs. saline groups) were analyzed using Mann-Whitney tests. P Results Patient demographics were similar in the two groups. Times to first flatus (17 [11-24] vs. 28 [25-33] h; P Conclusions Intravenous lidocaine improves postoperative analgesia, fatigue, and bowel function after laparoscopic colectomy. These benefits are associated with a significant reduction in hospital stay.

Background Dermatofibrosarcoma protuberans (DFSP) is a rare malignant tumour of the skin, with an estimated incidence of 0.8 to five cases per 1 million people per year. Objective To study epidemiological, immunohistochemical and clinical features, delay in diagnosis, type of treatment and outcome of DFSP from 1982 to 2002. Methods Using data from the population-based cancer registry, 66 patients with pathologically proved DFSP were included (fibrosarcomatous DFSP were excluded). Each patient lived in one of the four departments of Franche-Comte (overall population of 1 million people) at the time of diagnosis. The main data sources came from public and private pathology laboratories and medical records. The rules of the International Agency for Research on Cancer were applied. Results The estimated incidence of DFSP in Franche-Comte was about three new cases per 1 million people per year. Male patients were affected 1.2 times as often as female patients were. The trunk (45%) followed by the proximal extremities (38%) were the most frequent locations. DFSP occurred mainly in young adults between 20 and 39 years of age. Mean age at diagnosis was 43 years, and the mean delay in diagnosis was 10.08 years. Our 66 patients initially underwent a radical local excision. Among them, 27% experienced one or more local recurrences during 9.6 years of follow-up. There was one regional lymph node recurrence without visceral metastases. These recurrences were significantly related to the initial peripheral resection margins. We observed a local recurrence rate of 47% for margins less than 3 cm, vs. only 7% for margins ranging from 3 to 5 cm [P = 0.004; OR = 0.229 (95%, CI = 0.103–0.510)]. The mean time to a first local recurrence was 2.65 years. Nevertheless, there was no death due to the DFSP course at the end of the follow-up, and the final outcome was favourable. Conclusion Our study emphasizes the importance of wide local excision with margins of at least 3 cm in order to prevent local recurrence. However, the recent development of inhibitors of signal transduction by the PDGFB pathway should soon modify the surgical strategy, which is often too mutilating.

Several studies have shown a high prevalence of rash induced by nevirapine. However, there is little knowledge about the risk factors associated with nevirapine-induced rash. The aim of this study was to identify risk factors associated with the occurrence of rash during the treatment with nevirapine of HIV-infected patients.A retrospective study was conducted in the dermatology department of Besançon university teaching hospital between November 1998 and September 2001. The study included all HIV-infected patients receiving HAART regimens that included nevirapine. The following data were collected: age, sex, CDC classification of HIV, CD4 and CD8 lymphocyte counts, plasma HIV RNA load, hepatitis B, C and cytomegalovirus serostatus, history of drug allergy, concomitant medication (other antiretroviral drugs, corticosteroids, antihistamines). Univariate analysis was performed using a Chi2 test or Fischer's test and Student's t test. Fischer's test and the Cox proportional hazards model were used in the multivariate analysis.During the study period, 101 HIV-infected patients (74 men and 27 women; mean age: 41.6 +/- 10.3 years) were treated with HAART regimens including nevirapine. Fourteen developed cutaneous drug-reactions attributable to nevirapine (13.86%). We observed 13 cases of maculopapular exanthema and 1 case of DRESS. In the univariate analysis, female gender (p=0.002), plasma HIV RNA load10,000 copies/ml (p=0.05), heterosexual transmission (p=0.002) and abacavir treatment (p=0.05) constituted risk factors associated with rash. In the multivariate analysis, only female gender (p0.0001) and plasma HIV RNA load10,000 copies/ml (p=0.0007) were associated with rash.The results of this study confirm the high frequency of toxidermy associated with nevirapine therapy. The risk factors associated with occurrence of rash due to nevirapine therapy were female gender and plasma RNA10,000 copies/ml. Several studies showed absence of any protective effect of antihistamines and corticosteroids in preventing the cutaneous adverse reactions associated with nevirapine. The identification of risk factors closely associated with nevirapine-induced rash could help physicians determine new strategies for safer use of nevirapine in the HAART regimen.

Adult-onset Still's disease (AOSD) is a systemic affection characterized by intermittent fever, evanescent rash, polyarthralgia or arthritis and neutrophilic leucokytosis. We report a new case of AOSD with persistent pigmented plaques in a Vietnamese woman.A 23 year-old woman had presented within several months: inflammatory polyarthralgia, intermittent fever, asthenia, myalgia, weigh loss, polyadenopathy and an evanescent cutaneous rash. In addition, she presented pigmented skin plaques on the trunk. The investigations noted: neutrophilia (10000/mm3) and a high level of serum ferritin (42,000 microg/l). The erythrocyte sedimentation rate was 55mm in the first hour. C reactive protein was normal. HIV and syphilis serologies, antinuclear antibodies and rheumatoid factor were negative. No growth of micro-organisms was observed in repeated blood and urine cultures. The histology of the persistent plaque and lymph node were not specific. It required a high dose of corticosteroid to obtain remission.The existence of persistent plaques in AOSD is uncommon. Nevertheless, the exact relationship between the fixed cutaneous lesions and AOSD remains unclear. But their synchronous evolution with systemic symptoms and response to therapy suggest that they represent a specific manifestation of the disease.

Summary Background Angiogenesis has been reported as a parameter of potential prognostic value in solid tumours, as it may facilitate tumour growth and metastasis. One of the most important growth factors involved in angiogenesis is vascular endothelial growth factor (VEGF). Objectives To determine the predictive value of circulating VEGF levels in a cohort of patients with melanoma. Methods In a prospective cohort study, 324 patients with cutaneous melanoma at different clinical stages were investigated over 2 years (2002–04). VEGF was measured in plasma using enzyme-linked immunosorbent assay. Two hundred and eight patients were able to be followed up for progression of their disease and for blood sample collection (mean ± SD follow-up 13·4 ± 0·8 months). Data were compared with the extent of the disease and the clinical course. Results A significant increase in plasma VEGF levels was found in patients with melanoma compared with healthy controls, with statistically significant differences between patients in stages I, II and III vs. those in stage IV, but not between patients in stages I, II and III. When considering the 237 patients in stages I and II, no statistical correlation was found between plasma VEGF levels and tumour thickness. Baseline plasma VEGF levels were not significantly higher in patients who relapsed compared with nonprogressing patients. Among the 35 patients (two stage I, eight stage II and 25 stage III) who experienced a progression during follow-up, an increase in plasma VEGF level to > 100 pg mL−1 was found in 20 (sensitivity 57·1%), while 38 of the 173 remaining nonprogressing patients demonstrated an increase in VEGF level, indicating a specificity of 78%. In addition, an increase in plasma VEGF level was found in 58 patients during follow-up, of whom 20 showed evidence of progression, indicating a positive predictive value of 34·5%. However, among the 150 remaining patients who did not demonstrate any increase in plasma VEGF level during follow-up, only 15 experienced a progression, indicating a negative predictive value of 90%. Conclusions Our data confirm that blood VEGF levels are significantly increased in patients with melanoma and, more interestingly, that the absence of plasma VEGF level increase during follow-up appears to be associated with remission.

The concept of postoperative acute rehabilitation was introduced to accelerate postoperative recovery and improve outcome. We investigated whether intravenous lidocaine infusion, which decreases postoperative pain and speeds the return of bowel function, can be used instead of epidural analgesia in an acute rehabilitation protocol for patients undergoing laparoscopic colectomy.Twenty eight consecutive patients scheduled for laparoscopic colectomy were prospectively included in this case series study. Segmental colectomy was performed only for benign pathology. Intraoperative opioid use was restricted. After a bolus injection of lidocaine 1.5 mg x kg(-1), an infusion (2 mg x kg(-1) x h(-1), i.v.) was started before pneumoperitoneum. Balanced analgesia was used to reduce postoperative opioid consumption. Patients were allowed to drink 6 h postoperatively. The day after surgery, patients were allowed to eat a normal breakfast. Enforced mobilisation and ambulation were required from the patients. Our goal was to discharge patients within 3 days after surgery. Postoperative pain was measured. Time to first flatus, defecation, and hospital discharge were recorded.Mean postoperative pain at rest and mobilisation remained below 30 mm on a 100 mm visual analogue scale. Time to first flatus, defecation, and hospital discharge were 29 +/- 13 h, 38 +/- 13 h, and 3.0 +/- 1.0 days, respectively.Acute rehabilitation after laparoscopic colectomy using i.v. lidocaine gives similar outcomes to those reported using epidural analgesia.

High risk human papillomaviruses (HPV) have emerged as risk factors for anal carcinoma particularly in HIV-infected patients who demonstrate a high rate of anal HPV infection. Considering the relationship between the presence of anal infection and the development of neoplastic lesions, we wished to assess the capacity of imiquimod to eradicate latent HPV infection in HIV-infected patients.We conducted a prospective, randomized, double-blind and vehicle controlled study. Two consecutive anal swabs were taken at 2 month intervals and only patients with two consecutive tests positive for the detection of HPV-DNA (Hybrid Capture II) were included. Patients with persistent latent HPV infection were divided into 2 groups who applied imiquimod versus vehicle during 6 weeks. HPV-DNA presence was then investigated 2 and 4 months following the onset of treatment.Among the 80 HIV-infected patients, 26 (32.5 p. 100) had 2 positive consecutive assays, and 19 patients were included in the study. After randomization, 9 patients received imiquimod and 10 vehicle. There was no significant difference between treatment groups according to the following criteria: gender, route of HIV transmission, CDC stage, prior medical history of sexually transmitted diseases or anogenital warts. 33.3 p. 100 (3/9) of patients treated with imiquimod were negative at M2, whereas 100 p. 100 (10/10) vehicle treated-patients remained positive (p=0.08). Similar results were observed at the M4 visit.Our study confirmed the increased prevalence of latent HPV-DNA infection in HIV-infected patients. In spite of the low number of treated patients, we did not observe a statistically significant decrease in HPV-DNA in anal swabs from imiquimod-treated patients as compared to placebo-treated patients.

Cutaneous leiomyoma is a benign tumor, the discovery of which may suggest a hereditary form. We report a family in which 5 generations developed cutaneous and uterine leiomyomas. The originality of this report lies in the large number of generations developing the disease and the association with chronic myeloid leukemia.We have studied 16 members of a family with cutaneous and uterine leiomyomas spanning five generations. Eight members of the family (6 women and 2 men) presented with cutaneous leiomyomas. All 6 women also had uterine myomas with complications (menometrorrhagia, miscarriage, premature delivery and hysterectomy). Pathological association was also confirmed: polycythemia (1 case), papillary renal carcinoma (1 case) and chronic myeloid leukemia (1 case).Piloleiomyoma can develop sporadically or can be transmitted genetically. To our knowledge, we report the fifth case of a family of more than 2 generations presenting with piloleiomyoma. By studying the family tree, we were able to confirm the dominant autosomal nature of the mode of transmission found by other authors. The association of piloleiomyoma and uterine myoma is classified as Reed's syndrome. In such cases, the uterine myoma requires particularly careful monitoring since it is associated with significant risk of gynecological complications (menometrorrhagia, miscarriage, premature delivery and postpartum hemorrhage). Moreover, in our observations we describe diseases associated with piloleiomyoma: polycythemia (1 case), papillary renal carcinoma (1 case), but also the association of piloleiomyoma with chronic myeloid leukemia (1 case). A previous report described the same genetic deletion in uterine myoma as in chronic myeloid leukemia, which gives further weight to this association.

The aim of this study was to explore anti-Candida albicans systemic and mucosal humoral responses against Candida virulence antigens such as somatic antigen and secreted aspartic proteases (Saps) in HIV-infected patients with oral candidiasis. Twenty-eight subjects were included in the study: 11 HIV-positive patients without oral candidiasis (group A), 6 HIV-positive patients with oral candidiasis (group B) and 11 HIV-negative healthy controls (group C). Total IgA, IgG and IgM concentrations and antibodies to C. albicans (somatic antigen, Sap1, Sap6) were measured in serum and saliva. We developed a time-resolved immunofluorometric assay with biotin and europium-labeled streptavidin for this purpose. Salivary total IgA, IgG and IgM concentrations were higher in group B. IgA, IgG and IgM anti-C. albicans antibodies (against somatic antigen, Sap1, Sap6) were higher in saliva and serum from patients from group B compared with patients from group A and controls. Our results suggest that, in oral candidiasis, HIV-infected patients have a high mucosal response, specifically directed against C. albicans virulence antigens, such as somatic antigen, Sap1 and Sap6.

Oropharyngeal candidiasis (OPC), mainly caused by Candida albicans, is commonly observed in HIV-infected patients. Secreted aspartic proteinases (Saps) are virulent agents involved in adherence to the mucosal surface and in tissue invasion. The immune secretory response to these agents was investigated in 15 HIV-infected patients, during oral yeast colonization and episodes of oropharyngeal candidiasis (OPC), in a 1-year longitudinal study. We developed an avidin-biotin-amplified immunofluorometric assay for the detection of specific immunoglobulins G, A, and M against somatic, Sap2 and Sap6 antigens. We report increases in anti-somatic, anti-Sap2, and anti-Sap6 salivary antibodies in patients with OPC. Over the 1-year period, not only OPC episodes but also variations in yeast colonization levels were correlated with variations in salivary anti-Sap6 antibody levels. Our results show the ability of HIV-infected patients to produce high levels of salivary antibodies; however, these antibodies were not efficient in limiting candidal infection, probably because of cellular cooperation deficiency and the enhanced virulence of the infecting strain.

HIV-infected patients, like renal transplant recipients, are at increased risk of developing skin cancer in photoexposed areas. Previous studies demonstrated that prolonged ultraviolet (UV)-induced erythema and a decreased and delayed tanning could be correlated with an increased risk of skin cancers.As HIV-infected patients are at an increased risk of developing skin cancers, we aimed to assess the cutaneous response to UV irradiation in these patients.Twelve HIV-infected patients and 12 healthy volunteers were included in a prospective case-control study. No patient or volunteer had a history of skin cancer or photodermatosis. The minimal erythemal dose (MED) was determined using a solar simulator UV source, and, then, each subject underwent an exposure of 6 MED. The erythemal and pigmentation responses were studied using a visual scale and a tristimulus colorimeter over a 4-week period.We failed to demonstrate any significant differences between HIV-infected patients and controls for erythema and delayed pigmentation. No difference was found for MED between the two groups although most HIV-infected patients received potentially photosensitive drugs.Our results suggest that, as a group, the HIV-infected patients without a history of photosensitivity or skin cancer did not demonstrate a greater susceptibility to intense UV irradiation in terms of erythema and pigmentation induced by intense UV exposition.

The incidence of condyloma acuminata is increasing in all developed countries with highest rates recorded for young sexually males and females, between the ages of 16 and 25 years. Subclinical and latent genital human papillomavirus (HPV) infections are highly prevalent. Direct correlation between number of sexual partners and presence of HPV is evident. Clinical HPV infections such as condylomas (acuminata and papular) are easily recognized, but acetowhite flat macular condylomas require colposcopic examination. High grade IN (cervical CIN II, III, vulvar VIN, anal AIN, penile PIN) are considered to be related to HPV type 16 and 18 (less frequently other types 31, 33, 35, 51), the oncogenic potential of which was demonstrated by in vitro transformation assays and by the fact that they are detected in 50 to 90% of genital neoplasia. Clinical HPV infections (condylomas and low grade IN) are associated with "low risk" HPV types 6/11. The requirement for routine HPV-DNA typing is limited and in general, management is based on clinical and conventional light microscope evaluation. Immunosuppression is a most important risk-factor for the development, the progression and the recurrences of cervical and anal condylomas and neoplasia. Whatever treatment is applied a 30% recurrences rates occur, implying a regular clinical follow up after treatment to prevent recurrences development and neoplasia.

Methylisothiazolinone chloride (Kathon CG) and its derivatives, used as preservatives in cosmetics, have been shown to be allergenic when used in humans although preliminary studies in Guinea pigs failed to reveal any sensitization. Dibromodicyanobutane, associated with phenoxyethanol in Euxyl K400, has been proposed to replace the isothiazolinone derivatives in cosmetics. Preliminary study has shown that these thiazolinone derivatives are not allergenic in Euxyl K400. The similarity of these situations led us to hypothesize that dibromodicyanobutane could become allergenic.We tested 0.1 p. 100 dibromodicyanobutane in vaseline in the additional battery of the ICDRG battery in patients with contact eczema. Among the 310 patients tested, 1.94 p. 100 had a positive test for this allergen (during this same period, 1.29 p. 100 of the patients were positive for isothiazolinones). Three patients were hospitalized because of generalized eczema and 1 patient had changed occupation with no effect because the crems containing the allergen had not been avoided.Dibromodicyanobutane is a new allergen. Numerous cases of allergy have developed as use of the product becomes more widespread. The consequences of this sensitization may have an economic impact. Animal experimentation has been unable to predict this allergenic effect. Cosmetic products must be precisely labeled with a single international term for each specific molecule and the name of the preservative added to the active substance.

The Biohit HPV Screening and Typing kits for in situ hybridization of human papillomavirus (HPV) DNA are now commercially available. The HPV Screening kit contains a cocktail of HPV probes, and the Typing kit contains separated hybridization probes for HPV 6, 11, 16, 18, 31, and 33. They were evaluated by comparison with an in situ hybridization (ISH) method, using the Pathogene HPV probes 6/11, 16/18, 31/33/51. One hundred anogenital biopsies from 78 women and 22 men were tested. Among them, 43% showed normal or inflammatory mucosa, 44%, koilocytosis or mild dysplasia, and 13%, moderate to severe dysplasia. Altogether, 60 specimens were positive with the ISH reference method: 17 with the HPV 6/11 probe, 12 with the HPV 16/18 probe, 16 with the HPV 31/33/51 probe, and 15 had mixed infections. The agreement between the Screening test and the homemade ISH is 91%. The Screening test has a sensitivity of 93% and a specificity of 87%. As for the Biohit Typing test, four false-negative samples, and partial or total discordance in nine and four samples, respectively, were observed when compared to our reference method. Thus the agreement between both typing ISH tests is 92%. The sensitivity of the Biohit Typing test is 93%, and the specificity, 91%. The sensitivity decreases to 72% when the 31 and 33 probes are evaluated separately. The Biohit Screening assay is simple, reliable, reproducible, and suitable for rapid routine screening. The Biohit Typing test allows the detection of a specific type of HPV DNA and also permits, in mixed HPV infection, definition of the type of associated HPV DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

The tertiary cutaneous syphilis is now extremely rare. We report a case of tubercular cutaneous syphilis associated with neurological dysfunction. We emphasize the difficulties to interpret serologic and CSF tests for the diagnosis of neurosyphilis.A 63 year-old-woman had nodular, purplish and painless cutaneous lesions on forehead and forearm for 6 months. The biopsy showed a dermohypodermic lymphoplasmocytic granuloma, without necrosis, with endothelitis. Syphilis serologic tests were positive: VDRL = 512 U; TPHA = 40,960 U; FTA abs: IgG = 72,000 U; IgM = 1,350 U; Nelson test = 100 p. 100 (1,200 U). HIV test was negative. There was a past history of a positive syphilis serologic test when the patient was 20-year-old. The patient complained of shaking and her family spoke of gradual mental deterioration and behaviour troubles. The neurological examination showed a major frontal syndrome, cerebellar dysfunction with dysarthria and a major labial and lingual tremor. There is no lymphocytosis nor increased protein in the CSF; VDRL test was negative, TPHA test was positive, FTA abs = 4,000 U (IgG), and TPHA was increased. Penicillin G 16 millions units/day was given intravenously for 20 days; a slow increase was made in association with steroids at the beginning. The cutaneous lesions regressed in 14 days, but the neurologic state did not change. Six months later, there was still no IgM, TPHA decreased and VDRL was unchanged.While the diagnosis of tertiary cutaneous syphilis was correct, the neurological abnormalities are difficult to classify. The symptoms were those of general paresis, but there is no argument favouring biological CSF activity (no increase in protein or lymphocytosis, negative VDRL). Nevertheless, in the context of very positive serologic tests and tertiary cutaneous syphilis, we treated this case as a neurological syphilis. The treatment regimen and the need of current cures are still under discussion.

1,25-dihydroxycholecalciferol (1,25 (OH)2 D3) causes dose-dependent inhibition of fibroblast growth and collagen synthesis and has numerous immunoregulatory activities. We assessed the effects of oral 1,25 (OH)2 D3 in the treatment of patients with systemic sclerosis (SS). Eleven patients with SS entered an open prospective study. Oral 1,25(OH)2 D3 was given at a mean dose of 1.75 micrograms/day. The effects of the treatment were evaluated using clinical examination and physical measurements. After the treatment period (6 months to 3 years), a significant improvement, as compared with baseline values, was observed. No serious side-effects were observed. These results suggest that high-dose 1,25 (OH)2 D3 may be a useful therapeutic agent for scleroderma.

OBJECTIVE--To determine whether two adults with stress fractures receiving low weekly doses of methotrexate had methotrexate osteopathy. CASE REPORTS--Two adult patients developed features consistent with methotrexate osteopathy while receiving low weekly doses of methotrexate. METHODS--Iliac crest biopsy samples were taken and bone histomorphometry carried out. RESULTS--Symptoms resolved when the methotrexate was discontinued. Bone histology showed changes consistent with osteoblast inhibition by methotrexate. CONCLUSIONS--When given in low doses for prolonged periods, methotrexate may have adverse effects on bone, particularly in post-menopausal women.

Pseudoxanthoma elasticum (PXE) is a rare form of congenital dystrophy of the elastic tissue, which is characterized by cutaneous, ocular and vascular impact. There are four clinical forms which correspond to 4 different genetic types (I or II, dominant or recessive). The vascular damage caused by the illness general limits the obstetric prognosis. Under our observation, the pregnancy of a woman 34 years of age suffering from type II PXE proceeded without problem.