Inhibition of tooth movement by osteoprotegerin vs. pamidronate under conditions of constant orthodontic force

The undesired movement of anchor teeth, and relapse of previously moved teeth, are major clinical problems in orthodontics. Dental implants are increasingly used to preserve anchorage, but these are costly and require invasive surgical procedures. An alternative strategy for maintaining anchorage may be the use of biological inhibitors of osteoclastic bone resorption. In the present study, we investigated the relative efficacy of pamidronate vs. osteoprotegerin (OPG) in inhibiting bone resorption and tooth movement, using a new orthodontic model in mice in which maxillary molars are moved for prolonged periods by near-constant, clinically relevant forces. Osteoclast influx to compression sites was initiated on day 3, was maximal on day 4, and persisted until at least day 12 after force application. Tooth movement paralleled osteoclast numbers. Minimal osteoclast apoptosis was observed, suggesting that recruitment, rather than programmed cell death, is a critical regulatory mechanism under conditions of constant force. Osteoclasts were reduced at compression sites by both OPG (95%) and pamidronate (70%); tooth movement was more dramatically inhibited by OPG (77% vs. 34%). Our findings indicate that constant orthodontic force regulates the recruitment, activation, and viability of osteoclasts, and that OPG could have clinical utility in preventing undesired tooth movement.     

Outcome of obstetric anal sphincter injuries (OASIS)—role of structured management

Introduction and hypothesis  Prospective studies up to 1 year after repair of obstetric anal sphincter injuries (OASIS) report anal incontinence in 33% of women and up to 92% have a sonographic sphincter defect. The aim of this study is to determine the outcome of repair by doctors who have undergone structured training using a standardized protocol. Methods  Doctors repaired OASIS after attending a training workshop. The external anal sphincter was repaired by the end-to-end technique when partially divided and the overlap method when completely divided. Endoanal ultrasound was performed prior to suturing and 7 weeks later. A validated bowel symptom questionnaire was completed prior to delivery, at 7 weeks postpartum, and at 1 year postpartum. Results  Fifty-nine women sustained OASIS. At 7 weeks, six (10%) had a defect on ultrasound. There was no significant deterioration in symptoms of fecal urgency, incontinence, or quality of life at 1 year after delivery. Conclusions  The 1-year outcome after repair of OASIS appears to be good when repaired by doctors after structured training.     

Neurobehavioural Toxicity of Iron Oxide Nanoparticles in Mice

Postnatal development of the cerebellar cortex was studied in rats administered with a single dose (2 mg/g) of the cytotoxic agent hydroxyurea (HU) on postnatal day (P) 9 and collected at appropriate times ranging from 6 h to 45 days. Quantification of several parameters such as the density of pyknotic, mitotic, BrdU-positive, and vimentin-stained cells revealed that HU compromises the survival of the external granular layer (EGL) cells. Moreover, vimentin immunocytochemistry revealed overexpression and thicker immunoreactive glial processes in HU-treated rats. On the other hand, we also show that HU leads to the activation of apoptotic cellular events, resulting in a substantial number of dying EGL cells, as revealed by TUNEL staining and at the electron microscope level. Additionally, we quantified several features of the cerebellar cortex of rats exposed to HU in early postnatal life and collected in adulthood. Data analysis indicated that the analyzed parameters were less pronounced in rats administered with this agent. Moreover, we observed several alterations in the cerebellar cortex cytoarchitecture of rats injected with HU. Anomalies included ectopic placement of Purkinje cells and abnormities in the dendritic arbor of these macroneurons. Ectopic granule cells were also found in the molecular layer. These findings provide a clue for investigating the mechanisms of HU-induced toxicity during the development of the central nervous system. Our results also suggest that it is essential to avoid underestimating the adverse effects of this hydroxylated analog of urea when administered during early postnatal life.     

Altered white matter microstructure in the corpus callosum in Huntington's disease: Implications for cortical “disconnection”

The corpus callosum (CC) is the major conduit for information transfer between the cerebral hemispheres and plays an integral role in relaying sensory, motor and cognitive information between homologous cortical regions. The majority of fibers that make up the CC arise from large pyramidal neurons in layers III and V, which project contra-laterally. These neurons degenerate in Huntington's disease (HD) in a topographically and temporally selective way. Since any focus of cortical degeneration could be expected to secondarily de-afferent homologous regions of cortex, we hypothesized that regionally selective cortical degeneration would be reflected in regionally selective degeneration of the CC. We used conventional T1-weighted, diffusion tensor imaging (DTI), and a modified corpus callosum segmentation scheme to examine the CC in healthy controls, huntingtin gene-carriers and symptomatic HD subjects. We measured mid-sagittal callosal cross-sectional thickness and several DTI parameters, including fractional anisotropy (FA), which reflects the degree of white matter organization, radial diffusivity, a suggested index of myelin integrity, and axial diffusivity, a suggested index of axonal damage of the CC. We found a topologically selective pattern of alterations in these measures in pre-manifest subjects that were more extensive in early symptomatic HD subjects and that correlated with performance on distinct cognitive measures, suggesting an important role for disrupted inter-hemispheric transfer in the clinical symptoms of HD. Our findings provide evidence for early degeneration of commissural pyramidal neurons in the neocortex, loss of cortico-cortical connectivity, and functional compromise of associative cortical processing.     

Anal and urinary incontinence 4 years after a vaginal delivery

Introduction and hypothesis

Our purpose was to establish the incidence of anal and urinary incontinence 4 years following vaginal delivery in women with and without obstetric anal sphincter injuries (OASIS).

Methods

This was a prospective study of 241 having their first vaginal delivery who had independent verification and repair of OASIS by trained obstetricians. All obstetricians performing OASIS repairs had undergone structured hands-on training and were then directly supervised while repairing OASIS until they were deemed competent to repair independently. Patients were followed up for 4 years with validated bowel and urinary questionnaires. In order to minimise nonresponders, contact details were verified and obtained from their general practitioners, the local primary care trust and electoral roll.

Results

Two hundred and fifty-four women were invited, and 241 (95 %) participated. Fifty-nine (25 %) women sustained OASIS. One hundred and forty-nine were contactable 4 years later, and 86 (58 %) agreed to participate in the study at 4 years. No woman had faecal incontinence, and there was no difference in rates of flatus incontinence prior to delivery up to 4 years postpartum, regardless of whether OASIS occurred or not. Urinary incontinence was more than four times more common after vaginal birth, and this was not affected by whether OASIS occurred and resulted in a significant deterioration in quality of life.

Conclusions

The previously reported higher rates of anal incontinence following OASIS can be minimised up to 4 years after delivery if repaired by trained doctors. There is a significant increase in urinary incontinence following vaginal delivery, and the mechanism for this is not linked to anal sphincter disruption.     

RSSDI Guidelines for the management of hypertension in patients with diabetes mellitus

International Journal of Diabetes in Developing Countries - Hypertension and diabetes mellitus (DM) are two of the leading lifestyle diseases in the Indian and South Asian populations that often...     

Clinical Presentation and Outcomes Associated with Different Treatment Modalities for Pediatric Bark Scorpion Envenomation

Introduction

Scorpion envenomation is potentially life-threatening and affects children in the Southwestern USA. An FDA-approved antivenom is available, but its high cost has led to use of off-label antivenom dosing or supportive care alone as alternatives to FDA-recommended dosing. This study sought to determine whether treatment approach influences outcomes in envenomated children.

Methods

A retrospective cohort study of children with grade III or IV scorpion envenomation evaluated in Phoenix Children’s Hospital ED between September 1, 2011, and March 31, 2014. Patients were grouped based on treatment: group 1, supportive care only; group 2, FDA-recommended dosing (3-vial initial dose); group 3, “off label” dosing (1–2 vial initial dose). Primary outcomes were ED length of stay and hospital admission. Secondary outcomes were mechanical ventilation and aspiration pneumonia.

Results

One hundred fifty-six patients were included with 58 patients in group 1, 16 patients in group 2, and 82 patients in group 3. Group 1 was significantly older than the antivenom groups (p < 0.001), and group 2 was younger than group 3 (p = 0.024). Envenomation grade was also different, with group 1 having fewer grade IV then groups 2 and 3 (p < 0.001). Three percent of group 1, 56 % of group 2, and 28 % of group 3 had respiratory distress (p < 0.001). ED LOS was not significantly different between groups. Hospital admission occurred in 3.4 % group 1, no group 2, and 8.5 % group 3 patients. Two intubations and two aspirations occurred in group 3.

Conclusions

In this study, clinical presentation appeared to influence treatment. Groups that received antivenom had a higher envenomation grade than the group that received supportive care. The FDA-recommended dosing group was younger and had more respiratory distress than those treated with initial doses of 1–2 vials. Outcomes were not significantly different between groups. Prospective studies may identify the ideal population for each treatment approach.