Higher fracture prevalence and smaller bone size in patients with hEDS/HSD-a prospective cohort study

Increased fracture risk in patients with Ehlers-Danlos syndromes has been reported, but the reasons for it are incompletely understood. We aimed to investigate possible determinants of this increased risk and found that hEDS/HSD patients present with a cortical bone size deficit compared with control subjects, possibly related to lower mechanical loading. Introduction The Ehlers-Danlos syndromes (EDS) comprise a group of heritable connective tissue disorders caused by defects in the biosynthesis, secretion, and/or organization of fibrillar collagens which might impair bone strength. Our aim was to compare fracture prevalence, volumetric and areal bone mineral density (BMD), bone geometry, muscle size and the muscle-bone interaction, body composition and longitudinal changes therein between patients with hypermobile EDS (hEDS) or hypermobility spectrum disorder (HSD), and healthy control subjects. Methods Cross-sectional data comprised 39 female hEDS/HSD patients (age 41 +/- 11 years) and 43 age-matched controls. After 8 years, 27 hEDS/HSD and 17 control subjects were re-evaluated. Tibial trabecular and cortical volumetric BMD, bone mineral content (BMC), cortical bone geometry, and lower leg muscle cross-sectional area (CSA) were measured using pQCT. Body composition, areal BMD, and BMC were determined by DXA. Results At baseline, patients with hEDS/HSD presented with a smaller cortical bone area, smaller cortical thickness and muscle CSA, and a higher fracture prevalence than control subjects (all p < 0.05). No differences in areal or volumetric BMD were found. Longitudinally, muscle CSA decreased in both groups and muscle density decreased in the hEDS/HSD group (p < 0.001) whereas all bone parameters remained unchanged. Conclusion hEDS/HSD patients have a cortical bone size deficit compared with controls, possibly contributing to their increased fracture risk. They presented with decreased muscle CSA but normal bone/muscle area ratio, suggesting that this bone size deficit is likely secondary to decreased mechanical loading. Further, there were no arguments for accelerated bone loss in hEDS/HSD subjects

Vestibular Infant Screening (VIS)–Flanders : results after 1.5 years of vestibular screening in hearing-impaired children

Due to the close anatomical relationship between the auditory and vestibular end organs, hearing-impaired children have a higher risk for vestibular dysfunction, which can affect their (motor) development. Unfortunately, vestibular dysfunction often goes unnoticed, as vestibular assessment in these children is not standard of care nowadays. To timely detect vestibular dysfunction, the Vestibular Infant Screening–Flanders (VIS–Flanders) project has implemented a basic vestibular screening test for hearing-impaired infants in Flanders (Belgium) with a participation rate of 86.7% during the first year and a half. The cervical Vestibular Evoked Myogenic Potentials (cVEMP) test was applied as vestibular screening tool to map the occurrence of vestibular (mainly saccular) dysfunction in this population. At the age of 6 months, 184 infants were screened. No refers on vestibular screening were observed in infants with permanent conductive hearing loss. In infants with permanent sensorineural hearing loss, a cVEMP refer rate of 9.5% was observed. Failure was significantly more common in infants with severe-profound compared to those with mild-moderate sensorineural hearing loss (risk ratio = 9.8). Since this is the first regional study with a large sample size and successful participation rate, the VIS–Flanders project aims to set an example for other regions worldwide

In vitro activity of menogaril and N-demethylmenogaril in a human tumor cloning assay

The activity of menogaril and its major metabolite in animals and humans, N-demethylmenogaril, has been investigated in the human stem cell assay as developed by Salmon et al. Among 31 evaluable samples, four were sensitive to menogaril, including one which responded to N-demethylmenogaril. Three samples resistant to menogaril responded to N-demethylmenogaril. None was sensitive to doxorubicin. Overall, one out of seven ovarian samples and one out of three breast samples responded to menogaril. Our data confirm the in vitro activity of menogaril in ovarian and breast cancer; in addition, they suggest incomplete cross-resistance between doxorubicin and menogaril and, considering the concentrations of N-demethylmenogaril in animals and humans, a minor role for this metabolite in the overall antitumor activity of the parent compound. © 1986.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Evaluation of spermatogenesis and number of spermatogonia.

<p>a) A UCHL1 staining was performed to evaluate the number of spermatogonia (white arrow) per tubule. All pictures show testis sections of prepubertal treated rats. Left row: DAPI, middle row: UCHL1, right row: merge UCHL1+DAPI. b) A HE staining was performed to evaluate spermatogenesis. All pictures show testis sections of prepubertal treated rats. Thirty percent of the rats that received the combined treatment at prepubertal age showed SCO tubules. FC: fertile controls, O: rats treated with unilateral orchiectomy, B: rats treated with busulfan, O+B: rats treated with busulfan and unilateral orchiectomy.</p

Mating.

<p>Number of litters produced during the whole mating experiment per adult (a) or prepubertal (c) treated rat per gestation period during 4 months of mating. Mean number of pups per litter produced per adult (b) or prepubertal (d) treated rat per gestation period. Variables with a different letter are statistically different. If no letters are indicated, no statistical differences were found in the graph. FC: fertile controls, O: rats treated with unilateral orchiectomy, B: rats treated with busulfan, O+B: rats treated with busulfan and unilateral orchiectomy.</p

Testis weight.

<p>Bodyweight (A) and testicular weight (B) of the adult treated rats at the time of euthanasia. Bodyweight (C) and testicular weight (D) of the prepubertal treated rats at the time of euthanasia. Variables with a different letter are statistically different. If no letters are indicated, no statistical differences were found in the graph. FC: fertile controls, O: rats treated with unilateral orchiectomy, B: rats treated with busulfan, O+B: rats treated with busulfan and unilateral orchiectomy.</p

Testosterone levels.

<p>Evolution of testosterone levels of rats treated at adult (a) or prepubertal (b) age. Variables with a different letter are statistically different. FC: fertile controls, O: rats treated with unilateral orchiectomy, B: rats treated with busulfan, O+B: rats treated with busulfan and unilateral orchiectomy, D: day.</p

Phase II study of ametantrone in a human tumor cloning assay

The anticancer activity of ametantrone was investigated in a human tumor cloning assay. Tumor samples were freshly obtained from 105 patients. Cells were exposed for 1 hr to drug concentrations of 1 and 10 μg/ml. A reduction in the number of tumor colony-forming units by 50% or more was seen in 2 31 breast cancers, 2 25 ovarian cancers, 1 10 primaries of unknown origin, 1 10 melanomas, 2 8 non-small cell lung cancers, 1 5 small cell lung cancers and 1 3 colon cancers. Only three of these in vitro responses were consistently obtained at the probably more relevant concentration of 1 μg/ml. These findings indicate that low efficacy should be expected in cancer patients with ametantrone. The predictive value of these in vitro phase II data remains to be demonstrated. © 1985.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Phase II study of carminomycin in a human tumor cloning assay

The anticancer activity of carminomycin was investigated in a human tumor cloning assay. No efficacy could be identified in the WiDr and the MCF7 cell lines which were highly responsive to doxorubicin. In addition, drug testing experiments were carried out in samples of various malignancies freshly obtained from 86 patients of whom 54 had not received prior anthracyclines. A reduction in the number of tumor colony forming units by 50% or more was seen in 1/26 breast cancers, 1/22 ovarian cancers and 1/7 melanomas. Cross-resistance studies indicated that eight tumors were responsive to doxorubicin only and one to carminomycin only whereas two were sensitive to both and 73 were resistant to both. This in vitro Phase II study corroborates the disappointing clinical results achieved with carminomycin. © 1984 Martinus Nijhoff Publishers.SCOPUS: ar.jinfo:eu-repo/semantics/publishe