Origins of equine dentistry.

From the American West to the steppes of Eurasia, the domestic horse transformed human societies, providing rapid transport, communication, and military power, and serving as an important subsistence animal. Because of the importance of oral equipment for horse riding, dentistry is an essential component of modern horse care. In the open grasslands of northeast Asia, horses remain the primary form of transport for many herders. Although free-range grazing on gritty forage mitigates many equine dental issues, contemporary Mongolian horsemen nonetheless practice some forms of dentistry, including the removal of problematic deciduous teeth and the vestigial first premolar ("wolf tooth"). Here, we present archaezoological data from equine skeletal remains spanning the past 3,200 y, indicating that nomadic dental practices have great antiquity. Anthropogenic modifications to malerupted deciduous central incisors in young horses from the Late Bronze Age demonstrate their attempted removal, coinciding with the local innovation or adoption of horseback riding and the florescence of Mongolian pastoral society. Horse specimens from this period show no evidence of first premolar removal, which we first identify in specimens dating to ca. 750 BCE. The onset of premolar extraction parallels the archaeological appearance of jointed bronze and iron bits, suggesting that this technological shift prompted innovations in dentistry that improved horse health and horse control. These discoveries provide the earliest directly dated evidence for veterinary dentistry, and suggest that innovations in equine care by nomadic peoples ca. 1150 BCE enabled the use of horses for increasingly sophisticated mounted riding and warfare.

Clinical performance of Siemens digital breast tomosynthesis versus standard supplementary mammography for the assessment of screen-detected soft-tissue abnormalities: a multi-reader study.

AIM: To compare the diagnostic accuracy of standard screening images plus single-view digital breast tomosynthesis (DBT), using Siemens DBT equipment, with standard screening images plus supplementary mammographic views in non-calcific, screen-detected mammographic abnormalities. MATERIALS AND METHODS: Participants were unselected women aged 50-69 years recalled within a population-based European breast screening programme for assessment of soft-tissue mammographic abnormalities. Supplementary mammographic views (SMVs) and DBT were performed in all cases. A range of equipment was used for screening and supplementary mammography, but all DBT examinations were performed using the Siemens Mammomat Inspiration. A retrospective multi-reader study including 238 cases for whom either histology or at least 2 years' follow-up was available was performed with eight suitably accredited UK breast screening personnel reading all cases under both conditions, with temporal separation. Readers were blinded to case outcomes and findings from other examinations. Diagnostic accuracy using receiver operating characteristic (ROC) analysis was compared between screening plus SMV images and screening plus DBT images. The study was powered to detect a 3% inferiority margin in diagnostic accuracy between methods. RESULTS: The final sample with complete data available for analysis included 195 benign cases (1,560 reads) and 35 malignant cases (280 reads). The DBT method yielded a slightly higher area under the curve (AUC) value than the SMV method (0.870 versus 0.857), but the difference was not statistically significant (p=0.4890), indicating that the methods have equivalent accuracy. CONCLUSION: Siemens DBT demonstrates equivalent diagnostic accuracy according to ROC curve analysis when used in place of SMVs in screen-detected soft-tissue mammographic abnormalities.

Harmonic ratios: a quantification of step to step symmetry.

The harmonic ratio (HR), derived from the Fourier analysis of trunk accelerations, has been described in various ways as a measure of walking smoothness, walking rhythmicity, or dynamic stability. There is an increasing interest in applying the HR technique to investigate the impact of various pathologies on locomotion; however, explanation of the method has been limited. The aim here is to present a clear description of the mathematical basis of HRs and an understanding of their interpretation. We present harmonic theory, the interpretation of the HR using sinusoidal signals, and an example using actual trunk accelerations and harmonic analyses during limb-loading conditions. We suggest that the HR method may be better defined, not as a measure of rhythmicity or stability, but as a measure of step-to-step symmetry within a stride.

Age- and speed-related differences in harmonic ratios during walking.

Harmonic ratios (HRs), derived from trunk accelerations, measure smoothness of trunk motion during gait; higher ratios indicate greater smoothness. Previous research indicates that young adults optimize HRs at preferred pace, exhibiting reduced HRs at speeds faster and slower than preferred. Recent studies examining HRs and other trunk acceleration measures challenge this finding. The purpose of this study was to examine age-related differences in HRs across a range of self-selected overground walking speeds. Anteroposterior (AP), vertical (VT), and mediolateral (ML) HRs were examined in 13 young adults (ages 20-23), 13 healthy older adults (ages 60-69), and 13 healthy old-old adults (ages 80-86) while walking overground at very slow, slow, preferred, fast, and very fast speeds. Young and older adults exhibited similar HRs in all directions of motion across speeds, while old-old adults exhibited lower AP- and VT-HRs. All groups exhibited reduced HRs at speeds slower than preferred. However, there were no differences in HRs between preferred and faster speeds, with the exception of reduced VT-HRs in the very fast condition for the older groups. The ML-HR was not different between groups, and varied less across speeds. Stride time variability exhibited inverse relations with, and independently contributed to, HRs across speeds; lower stride time variability was associated with greater smoothness of trunk motion. Older groups were not disproportionately affected by walking more slowly and smoothness of trunk motion did not show a clear pattern of optimization at preferred pace for any group.

Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor-2 inhibits type 1 interferon signalling by targeting interferon-stimulated gene factor-3.

Kaposi's sarcoma-associated herpesvirus (KSHV) encodes four viral interferon regulatory factors (vIRF-1-4). We investigated the mechanism and consequences of vIRF-2-mediated inhibition of interferon-response element signalling following type I interferon (IFN) induction. Western blot and electrophoretic mobility-shift assays identified the interferon-stimulated gene factor-3 (ISGF-3) components STAT1 and IRF-9 as the proximal targets of vIRF-2 activity. The biological significance of vIRF-2 inhibition of ISGF-3 was demonstrated by vIRF-2-mediated rescue of the replication of the IFN-sensitive virus encephalomyocarditis virus. This study provides both a mechanism and evidence for KSHV vIRF-2-mediated suppression of the consequences of type 1 IFN-induced signalling.

Immunovirological correlates in human rabies treated with therapeutic coma.

A 37-year-old woman was admitted to hospital and over the next 5 days developed a progressive encephalitis. Nuchal skin biopsy, analyzed using a Rabies TaqMan(c) PCR, demonstrated rabies virus RNA. She had a history in keeping with exposure to rabies whilst in South Africa, but had not received pre- or post-exposure prophylaxis. She was treated with a therapeutic coma according to the "Milwaukee protocol," which failed to prevent the death of the patient. Rabies virus was isolated from CSF and saliva, and rabies antibody was demonstrated in serum (from day 11 onwards) and cerebrospinal fluid (day 13 onwards). She died on day-35 of hospitalization. Autopsy specimens demonstrated the presence of rabies antigen, viral RNA, and viable rabies virus in the central nervous system.

Planning and control of sequential rapid aiming in adults with Parkinson's disease.

Eight people with Parkinson's disease (PD), 8 age-matched older adults, and 8 young adults executed 3-dimensional rapid aiming movements to 1, 3, 5, and 7 targets. Reaction time, flight time, and time after peak velocity to the 1st target indicated that both neurologically healthy groups implemented a plan on the basis of anticipation of upcoming targets, whereas the PD group did not. One suggested reason for the PD group's deficiency in anticipatory control is the greater variability in their initial force impulse. Although the PD group scaled peak velocity and time to peak velocity similarly to the other groups, their coefficients of variation were greater, making consistent prediction of the movement outcome difficult and thus making it less advantageous to plan too far in advance. A 2nd finding was that the PD group exhibited increased slowing in time after peak velocity in the final segments of the longest sequence, whereas the other 2 groups did not. The increased slowing could be the result of a different movement strategy, increased difficulty modulating the agonist and antagonist muscle groups later in the sequence, or both. The authors conclude that people with PD use more segmented planning and control strategies than do neurologically healthy older and young adults when executing movement sequences and that the locus of increased bradykinesia in longer sequences is in the deceleration phase of movement.

Herpes simplex type 1 shedding is associated with reduced hospital survival in patients receiving assisted ventilation in a tertiary referral intensive care unit.

The impact of shedding of herpes simplex virus type 1 (HSV-1) on hospital survival of patients receiving assisted ventilation in an adult tertiary referral, acute trauma intensive care unit was assessed. The study was designed to address a clinical impression linking HSV-1 recovery with poor survival. Two hundred and forty-one males and 152 females were enrolled into a longitudinal cohort study. Combined throat swabs and tracheal secretions were tested for HSV-1 shedding using a nested nucleic acid amplification protocol; patients were ranked as nonshedders, shedders, and high-level shedders. Nonparametric analysis assessed the impact of shedding on hospital survival and logistic regression measured the confounding influence of sex, age, and the Acute Physiology, Age and Chronic Health Evaluation (APACHE II) score. Linear-by-linear association determined the influence of the level of shedding on hospital survival. The observed mortality rate was 113/393 (28.8%). Patients shedding HSV-1 106/393 (27%) had a significant reduction in hospital survival 66/106 (62%) in HSV-1 shedders compared with 217/287 (75.6%) in nonshedders (P = 0.002). This difference remained significant when adjusted for age and sex (P = 0.026). Respective mortality figures for HSV-1 shedders and nonshedders were 43/106 (40.6%) and 70/287 (24.4%) (P = 0.002). HSV-1 shedding was associated with a significant reduction in hospital survival amongst patients receiving assisted ventilation. Hospital mortality in HSV-1 shedders was increased by 16.2% over nonshedders. The role of HSV-1 in this setting needs to be addressed.

Neurotrophin receptor expression and responsiveness by postnatal cerebral oligodendroglia.

The low affinity neurotrophin receptor (p75(NTR)) is implicated in promoting oligodendrocytic death after nerve growth factor (NGF) stimulation but NGF and neurotrophin-3 (NT-3) can also potentiate oligodendrocytic survival. We show regional variability in p75(NTR) expression within the central nervous system of the postnatal rat; expression is readily detectable by immunohistochemistry upon a subset of CNPase-positive oligodendroglia in optic nerve but not within the cerebrum. Nevertheless, oligodendroglia isolated from the cerebrum and cultured for 16 hours express p75(NTR) as well as the trkC but not the TrkA gene. Viability was not, however, influenced by exposure to either NGF or NT-3. Cells overexpressing p75(NTR) remained unresponsive to NGF but exhibited potentiated survival with NT-3, correlating with the differential expression profile of their high affinity receptors.

Indomethacin compared with localized irradiation for the prevention of heterotopic ossification following surgical treatment of acetabular fractures.

BACKGROUND: There is controversy surrounding the relative effectiveness of local irradiation and oral indomethacin for prophylaxis against heterotopic ossification following surgical treatment of acetabular fractures. The purpose of this study was to compare the efficacy of these two commonly used methods in a prospective, randomized trial. METHODS: From July 1992 to June 1999, 166 patients in whom a fracture of the acetabulum was treated surgically through a posterior, extensile, or combination approach were randomized to receive either indomethacin or radiation therapy postoperatively. Seventy-eight patients received 800 cGy of local radiation therapy within seventy-two hours after surgery, and seventy-two patients received a six-week course of indomethacin (25 mg three times a day) beginning within twenty-four hours after surgery. Sixteen additional patients were randomized but did not receive treatment with either prophylactic regimen. At an average of fourteen months, the extent of heterotopic ossification was assessed on plain radiographs with use of the classification of Brooker et al. The grade of ossification was correlated with hip motion. RESULTS: There was no significant difference between treatment groups with regard to patient age, gender, Glasgow Coma Scale, operative time, estimated operative blood loss, duration of follow-up, or presence of closed head injury. The Injury Severity Score appeared to be the only covariate that was significantly different between the groups (p = 0.019). Grade-III or IV ossification developed in eight (11%) of the patients in the indomethacin group and three (4%) in the radiation therapy group. The difference was not significant (p = 0.22; 95% confidence interval, -1.1%, +15.7%). No complications related to the prophylaxis were noted in either group. Heterotopic ossification developed in all sixteen patients who did not receive prophylaxis, with six demonstrating grade-III or IV changes. The overall prevalence of grade-III or IV heterotopic ossification was 7% (eleven of 150) in the treated groups and 38% (six of sixteen) in the untreated group. We did not find any association between the prevalence of heterotopic ossification and fracture type (p = 0.296) or posterior hip dislocation (p = 0.306). Grade-I, II, and III heterotopic ossification did not decrease the range of motion of the hip except in flexion. CONCLUSIONS: Both local radiation therapy and indomethacin were found to provide effective prophylaxis against heterotopic ossification following surgical treatment of acetabular fractures through a posterior or extensile approach. We detected no significant difference in efficacy between the two prophylactic regimens.

Elution characteristics of tobramycin from polycaprolactone in a rabbit model.

This study investigated the elution characteristics of tobramycin from polycaprolactone, a bioabsorbable polymer, in a rabbit model. Sixty rabbits were divided into two groups. Group 1 had polycaprolactone rods impregnated with 6% tobramycin surgically implanted into the proximal femoral intramedullary canal. Group 2 received polymethylmethacrylate rods of like size, shape, and antibiotic concentration. Serum and urine samples were obtained, and tobramycin levels were determined via fluorescent immunosorbent assay. Rabbits were sacrificed as long as 56 days after surgery. Local bone tobramycin concentration was determined using the agar diffusion method. Polycaprolactone delivered a significantly higher peak bone concentration of tobramycin (22.4 microg/mL) than did polymethylmethacrylate (13.59 microg/mL). Polycaprolactone also had a more gradual decrease in local tobramycin concentration than did polymethylmethacrylate. Neither polycaprolactone nor polymethylmethacrylate yielded consistently detectable (> 0.1 microg/mL) serum tobramycin levels. Urine concentrations mirrored those seen in bone, with polycaprolactone achieving significantly higher tobramycin concentrations than did polymethylmethacrylate. Polycaprolactone had superior elution characteristics compared with polymethylmethacrylate in this lapine model, suggesting that polycaprolactone might be a promising local antibiotic delivery vehicle for the treatment of osteomyelitis.

In vitro elution of tobramycin from bioabsorbable polycaprolactone beads.

OBJECTIVES: To compare the in vitro elution characteristics of tobramycin impregnated beads made of polycaprolactone (PCL) and polymethylmethacrylate (PMMA). DESIGN: Six-millimeter PCL and PMMA beads with 6% tobramycin were formed and placed in phosphate-buffered saline or newborn calf serum and incubated at room temperature or 37 degrees C. Aliquots were taken at intervals for eight weeks. Tobramycin levels were determined by fluorescent assay and antibacterial efficacy was assessed by measuring the zones of inhibition against Staphylococcus aureus and Pseudomonas aeruginosa on agar diffusion plates. RESULTS: Tobramycin elution rates at room temperature were similar up to three weeks. At three weeks, elution rates from PCL beads were twice those from PMMA beads, and at eight weeks, elution from PCL was quadruple that from PMMA. At 37 degrees C, tobramycin elution rates from PCL were eight times greater than those from PMMA by eight weeks. Total tobramycin eluted from PCL beads was 38.9% and 20% in PMMA beads. All samples showed bacteriostatic activity against S. aureus and P. aeruginosa at eight weeks. CONCLUSIONS: These in vitro results show that PCL has superior antibiotic elution characteristics compared with PMMA, and this may translate into a more effective antibiotic delivery vehicle. In addition, PCL is a bioabsorbable polymer, which may decrease the need for a second surgical procedure to remove retained beads.

Radiologic case study. Pigmented villonodular synovitis.

Pigmented villonodular synovitis is a benign, locally aggressive disorder characterized by a unique clinical radiographic, and histopathologic presentation. While it is considered to be a rare disorder, a delay in diagnosis and treatment can potentially result in severe disruption of joint function due to subchondral invasion. Once the diagnosis is confirmed, treatment should consist of complete synovectomy. Recurrence is common, but malignant transformation is rare. The etiology of PVNS is still unknown, and perhaps its future discovery will assist in the definitive treatment of this disorder.

Postoperative pain control using epidural catheters after anterior spinal fusion for adolescent scoliosis.

STUDY DESIGN: A prospective review of patients undergoing epidural catheter placement after anterior spinal fusion and instrumentation for adolescent scoliosis was performed. Data were collected using visual analog pain scores reflecting the patients' perception of their pain control. OBJECTIVES: To present the authors' technique for epidural catheter placement and dosing protocol, and to demonstrate the results from postoperative pain control after anterior spinal instrumented fusion for 10 consecutive patients. SUMMARY OF BACKGROUND DATA: The literature regarding the benefits of epidural catheters after spinal surgery is contradictory, even with controlled studies comparing epidural catheters with intravenous morphine patient-controlled anesthesia. The authors believe that this lack of consensus stems from varied epidural dosing protocols and techniques in catheter placement, which they have witnessed anecdotally at their own institution. This prompted the authors to develop and refine a standardized dosing and catheter placement protocol for pain control after spinal surgery. METHODS: Epidural catheters were placed intraoperatively before wound closure, then removed on postoperative Day 5. Dosing consisted of fentanyl (1 microg/kg) and hydromorphone (5 microg/kg) diluted in preservative-free saline (0.2 mL/kg). After surgery, dosing consisted of 0.1% ropivacaine and hydromorphone (10 microg/ml) continuously infused at 0.2 mL/kg/hour. Postoperative pain control was assessed on each postoperative day using a visual analog pain scale with choices ranging from 0 to 10. RESULTS: The arithmetic mean of the median pain scores after surgery was 2.1. The mean of the maximum pain scores for the 5 days was 4.1. Three patients required an epidural bolus and a 20% increase in the epidural infusion rate. One patient was judged to be excessively sleepy, so the epidural infusion rate was decreased by 20%. Pruritus requiring diphenhydramine developed in three patients. No other adverse effects related to epidural analgesia were noted. No catheters were accidentally pulled out or disconnected. CONCLUSION: By following the dosing protocol described, epidural catheters can be used safely and effectively to control postoperative pain after anterior instrumentation and spinal fusion for adolescent scoliosis.

There is no loss of motor neurons in the rat spinal cord during postnatal maturation.

Motor neurons are lost during embryonic development, but it remains controversial whether motor neuron cell death occurs during postnatal life. In this study we investigated the effect of postnatal maturation on the number of intact spinal motor neurons in the rat using retrograde labelling with model-based counting, and an unbiased stereological counting technique. To determine the number of motor neurons innervating a specific forelimb muscle in rats of different postnatal ages FluoroGold was injected into the flexor carpi radialis. Before postnatal day 21 there were higher numbers of retrogradely labelled motor neurons than in adult rats, suggesting a 'loss' with postnatal maturation. This loss may be attributed to tracer diffusion to adjacent muscles and to the permeability of the muscle spindle capsule in younger animals. To obtain an unbiased estimate of the number of motor neurons in the C7 and C8 segments of the postnatal rat cervical spinal cord the fractionator/optical disector counting technique was used. This method did not show a loss of spinal motor neurons between birth and adulthood. The main conclusion from this study is that there is no loss of spinal motor neurons during postnatal maturation.

Systemic administration of antisense p75(NTR) oligodeoxynucleotides rescues axotomised spinal motor neurons.

The 75 kD low-affinity neurotrophin receptor (p75(NTR)) is expressed in developing and axotomised spinal motor neurons. There is now convincing evidence that p75(NTR) can, under some circumstances, become cytotoxic and promote neuronal cell death. We report here that a single application of antisense p75(NTR) oligodeoxynucleotides to the proximal nerve stumps of neonatal rats significantly reduces the loss of axotomised motor neurons compared to controls treated with nonsense oligodeoxynucleotides or phosphate-buffered saline. Our investigations also show that daily systemic intraperitoneal injections of antisense p75(NTR) oligodeoxynucleotides for 14 days significantly reduce the loss of axotomised motor neurons compared to controls. Furthermore, we found that systemic delivery over a similar period continues to be effective following axotomy when intraperitoneal injections were 1) administered after a delay of 24 hr, 2) limited to the first 7 days, or 3) administered every third day. In addition, p75(NTR) protein levels were reduced in spinal motor neurons following treatment with antisense p75(NTR) oligodeoxynucleotides. There were also no obvious side effects associated with antisense p75(NTR) oligodeoxynucleotide treatments as determined by behavioural observations and postnatal weight gain. Our findings indicate that antisense-based strategies could be a novel approach for the prevention of motor neuron degeneration associated with injuries or disease.

A dual epidural catheter technique to provide analgesia following posterior spinal fusion for scoliosis in children and adolescents.

BACKGROUND: The authors report their experience with the use of a dual epidural catheter technique in controlling pain following long posterior spinal fusion and instrumentation for scoliosis in children and adolescents. METHODS: Following completion of the surgical procedure and prior to wound closure, the upper catheter was inserted with the tip directed cephalad to T1-4 while the tip of the lower catheter was positioned at the L1-4 level. As the surgical wound was being closed, the catheters were dosed with fentanyl and hydromorphone followed by a continuous infusion of ropivacaine plus hydromorphone. Postoperative pain was assessed every 2-4 h using a visual analogue score or an observational behavioural score (0=no pain, 10=worst imaginable pain). There were 14 patients ranging in age from 5-17 years (12.7 +/- 3.5) and in weight from 19-68 kg (44.3 +/- 17.5). The epidural catheters were left in place until the fifth postoperative day. RESULTS: The mean of the median pain score from each patient was 1.5 +/- 1.6, 1.6 +/- 1.5, 1.4 +/- 1.3, 1.1 +/- 1.1 and 0.9 +/- 0.9, respectively, on postoperative days 1 through 5. The mean of the maximum pain scores was 3.5 +/- 2.3 (range 0-7), 4 +/- 1.6 (range 2-6), 3.1 +/- 1.7 (range 1-6), 2.4 +/- 1.5 (range 0-4) and 2.2 +/- 1.4 (range 0-4), respectively, on postoperative days 1 through 5. CONCLUSION: No adverse effects related to epidural analgesia were noted.

A potential role for the p75 low-affinity neurotrophin receptor in spinal motor neuron degeneration in murine and human amyotrophic lateral sclerosis.

INTRODUCTION: The p75 neurotrophin receptor has been recognized as a death-signalling molecule under certain circumstances. Its role in motor neuron degeneration in amyotrophic lateral sclerosis (ALS) was analysed in SOD1-G93A transgenic mice and in spinal cords from human amyotrophic lateral sclerosis. METHOD: The precise loss of motor neurons in SOD1-G93A transgenic mice from birth to adulthood was established using the unbiased fractionator/optical dissector neuronal counting technique. RESULTS: This study showed an early trend in the loss of lumbar motor neurons in SOD1-G93A mice, beginning at birth and progressing to a massive 80% reduction by 4 months of age, when the disease is severe. This study also found that the p75 neurotrophin receptor was expressed in lumbar motor neurons in symptomatic SOD1-G93A mice and in motor neurons in the cervical spinal cords of patients with ALS. CONCLUSIONS: The murine and human ALS data suggest that the p75 neurotrophin receptor may play a death-signalling role in the pathogenesis of motor neuron degeneration. The precise mechanism by which this receptor drives the apoptotic process, both in murine SOD1-G93A motor neuron degeneration and in human amyotrophic lateral sclerosis, remains to be determined.