Increased fracture rates in Turner's syndrome: a nationwide questionnaire survey

BACKGROUND AND OBJECTIVES: Reduced bone mineral content (BMC) and bone mineral density (BMD) have previously been reported in Turner's syndrome, although appropriate GH treatment and early induction of puberty seem to permit normal bone mass accumulation. Furthermore, an increased risk of fractures and osteoporosis have been reported in a registry study. The aim of the present study was to further characterize the risk of fractures in TS and to explore risk factors, in a historical follow-up survey based on a self-administered questionnaire. STUDY GROUPS: The questionnaire was issued to all females with TS (n = 632) in Denmark and to 1888 randomly selected controls (C) matched for age and geographical region. A total of 322 patients (51%) and 1169 controls (62%) returned the questionnaire. RESULTS: TS women were younger than C (30 years, range: 1-73 years vs. 34 years, range 2-82 years, P < 0.0005), smoked less often (17%vs. 27%, P < 0.0005), and had less frequent spontaneous menstruation (18%vs. 86%, P < 0.0005). In contrast, they used hormonal replacement therapy (HRT) more often (71%vs. 7%, P < 0.0005). The median age at start of HRT was 16 years (range 8-59 years) in TS vs. 42 years (range 12-53 years) in C (P < 0.0005). Above the age of 15 years, 83% of TS and 8% of C used HRT. GH had been used by 37% of TS but only 0.2% of C. Both type 1 and 2 diabetes were increased sevenfold among TS. Altogether, 77 individuals with TS had 109 fractures. The fracture risk was increased in TS [hazard ratio (HR, status) 1.35, confidence interval (CI) 1.04-1.75, P = 0.025]. Time to first fracture was reduced in TS (53 +/- 2 vs. 63 +/- 1; log-rank P = 0.03). Spontaneous menstruation was protective in females above 13 years of age (HR: 0.70, CI 0.54-0.93, P = 0.012). A history of parental fractures increased the risk (HR 1.92, CI 1.62-2.27, P < 0.001). Fractures of the forearm was more frequent among TS (P = 0.02). CONCLUSION: The present nationwide survey, based on questionnaires, confirms an increased risk of early fractures in TS, especially in those without ovarian function and with a positive family history of fracture and osteoporosis. It thereby emphasizes the need for being vigilant with respect to BMD measurements in these patients.     

Characterization of paroxysmal and persistent atrial fibrillation in the human left atrium during initiation and sustained episodes

INTRODUCTION: Atrial fibrillation (AF) in the left atrium (LA) is poorly defined in terms of regional differences in the degree of organization, characteristics of paroxysmal and persistent variants, and electrophysiologic events that develop at the onset of episodes. METHODS AND RESULTS: The study population consisted of 21 patients (15 men and 6 women; mean age 58+/-9.4 years) with paroxysmal (10 patients) or persistent (11 patients) AF. Mapping of the LA during sustained episodes and the onset of AF was performed with a 64-electrode basket catheter. At the onset of AF, repetitive beats starting with atrial premature complexes and ending with generation of the earliest fibrillatory activity were defined as intermediary rhythm. Patients with paroxysmal AF had longer AF cycle lengths and more pronounced regional differences than patients with persistent AF. In total, AF cycle lengths in the LA in patients with persistent AF were 20% shorter than in patients with paroxysmal AF. Initiation of AF was preceded by an intermediary rhythm of 5.5+/-2.5 cycles (6.3+/-2.7 cycles in paroxysmal AF vs 4.2+/-1.0 cycles in persistent AF; P = 0.026). At the onset of AF, the earliest generators of fibrillatory activity were located more frequently in the posterior wall of the LA. CONCLUSION: AF in the LA displays substantial regional differences in terms of AF cycle lengths and degree of organization. Patients with persistent AF have shorter cycle lengths and a higher degree of disorganized activity than patients with paroxysmal AF. Intermediary rhythms play an important role in initiation of AF via activation of generator regions in the LA.     

The splicing factor SRSF6 is amplified and is an oncoprotein in lung and colon cancers

An increasing body of evidence connects alterations in the process of alternative splicing with cancer development and progression. However, a direct role of splicing factors as drivers of cancer development is mostly unknown. We analysed the gene copy number of several splicing factors in colon and lung tumours, and found that the gene encoding for the splicing factor SRSF6 is amplified and over‐expressed in these cancers. Moreover, over‐expression of SRSF6 in immortal lung epithelial cells enhanced proliferation, protected them from chemotherapy‐induced cell death and converted them to be tumourigenic in mice. In contrast, knock‐down of SRSF6 in lung and colon cancer cell lines inhibited their tumourigenic abilities. SRSF6 up‐ or down‐regulation altered the splicing of several tumour suppressors and oncogenes to generate the oncogenic isoforms and reduce the tumour‐suppressive isoforms. Our data suggest that the splicing factor SRSF6 is an oncoprotein that regulates the proliferation and survival of lung and colon cancer cells.     

Characterization of the orientation and isometry of Humphrey's ligament

Objectives/purposeThe purpose of this study was to examine the effect of flexion angle on isometry and fiber obliquity of the anterior meniscofemoral ligament (Humphrey's ligament (HL)).MethodsFollowing a medial parapatellar arthrotomy on 7 fresh frozen cadavers, the insertion points of the anterolateral (AL) and posteromedial (PM) bundles of the PCL, and HL were identified. Using a 9 mm circular software tool, virtual fibers were created. Within each virtual graft, a central fiber was calculated and used to generate anisometry profiles for the AL and PM bundles and HL at flexion angles of 0°, 30°, 60°, 90°, and 120°. Previously validated computer navigation software was used to re-create three dimensional bundles to measure fiber obliquity in the sagittal, frontal, and axial planes.ResultsHL length increased with knee flexion from 0 to 120°, and underwent similar length changes as the PCL bundles. In full extension and at 90°, the average length of the PM and AL bundles were not statistically different (p = 0.13 and p = 0.85 respectively). From 0 to 120°, the PM bundle was the most isometric, but the anisometry profile was statistically similar to the AL bundle and HL. In general, HL and the PM bundle had similar graphic trends in terms of fiber obliquity in all planes.ConclusionsUsing computer navigation, we have demonstrated that HL has similar isometry profiles as the PM and AL bundles of the PCL, and “mirrored” the obliquity of the PM bundle in all planes throughout flexion to 120°.     

CareCoor: Augmenting the coordination of cooperative home care work

ObjectivesThe present study aims to augment the network of home care around elderly. We investigate the nature of cooperative work between relatives and home care workers around elderly persons; present the CareCoor system developed to support that work; and report experiences from two pilot tests of CareCoor.MethodsWe employed ethnographic fieldwork methods and conducted participatory design workshops to throw light on the nature of cooperative home care work, and to elicit implications for the design of an IT system that would support the work of relatives and home care workers around elderly persons. The design implications led to the development of a prototype, called CareCoor, which is accessible via a tablet PC and on the Internet. CareCoor was subsequently evaluated in two pilot tests. The first lasted a week and included three elderly, their next of kin and the affiliated home care workers, while the second test lasted for six weeks and involved five elderly people, their next of kin and relevant home care workers.ResultsIn the paper we make three major points, namely, (1) home care work is highly cooperative in nature and involves substantial coordinative efforts on the part of the actors involved, (2) the network of care around elderly can be augmented with new technology that allows all members of the network to follow, influence and be a part of the cooperative care of the elderly, and (3) CareCoor, the prototype introduced in this study, shows promise as it was well received during test and evaluation.ConclusionHome care work is increasingly important due to the ageing populations of Europe, the USA and large parts of Asia. Home care work between relatives and home care workers is inherently a cooperative effort, and can be facilitated and augmented by new information technology such as CareCoor. The pilot tests of CareCoor revealed promising results and will be further developed and evaluated in a larger test.