Management of Advanced Prostate Cancer – Role of the Urologist

There now exists an enhanced opportunity for urologists to continue to successfully identify, treat, and manage advanced prostate cancer patients in partnership with our medical oncology and radiation oncology colleagues. For urologists and their supporting staff who are dedicated to caring for patients with advanced prostate cancer, there are novel therapies that delay disease progression, maintain – and oftentimes improve – quality-of-life metrics, and prolong overall survival. These therapies are not unusually difficult to manage, nor are they too intimidating with regard to understanding their mechanisms of action and respective safety profiles. They provide the opportunity to improve and enhance patient care, as well as to further augment the urological role in both the academic and community multidisciplinary prostate cancer clinic.     

Tumor necrosis factor receptor 2 contributes to ozone-induced airway hyperresponsiveness in mice

The purpose of this study was to determine whether tumor necrosis factor (TNF) contributes to airway hyperresponsiveness (AHR) and migration of polymorphonuclear leukocytes (PMN) into the airways following exposure to ozone (O(3)). Wild-type mice, TNF p55 or p75 receptor knockout mice (p55 TNFR -/- and p75 TNFR -/-), as well as double receptor knockout mice (p55/p75 TNFR -/-), were exposed to O(3). Three hours after cessation of O(3), airway responses to inhaled methacholine were determined by whole body plethysmography using changes in enhanced pause (Penh) as an index of airway narrowing. In wild-type mice, O(3) exposure (0.5 ppm, 3 h) caused a significant increase in airway responsiveness as indicated by a 1.2 log leftward shift in the methacholine dose- response curve. In contrast, in p55/p75 TNFR -/- mice, O(3) caused only a 0.5 log shift in the dose-response curve (p < 0.05 compared with wild-type). Similar results were obtained in p75 TNFR -/- mice. In contrast, O(3)-induced airway hyperresponsiveness was not different in WT and p55 TNFR -/- mice. During O(3) exposure (1 pm, 3 h), minute ventilation (V E) decreased by 64 +/- 4% in wild-type, but only 24 +/- 5% in p55/p75 TNFR -/- mice, indicating that despite their reduced O(3)-induced AHR, the TNFR-deficient mice actually inhaled a greater dose of O(3). Similar results were obtained in p75 -/- mice, whereas changes in V E induced by O(3) were the same in wild-type and p55 -/- mice. PMN numbers in bronchoalveolar lavage fluid recovered 21 h after cessation of exposure to O(3) (2 ppm, 3 h) were significantly increased compared with after air exposure but were not different in wild-type and p55/p75 TNFR -/- mice. Our results indicate that TNF contributes to the AHR but not the PMN emigration induced by acute O(3) exposure. Keywords: whole body plethysmography; polymorphonuclear leukocytes; minute ventilation; knockout mice; methacholine     

Prevalence and prognostic implication of restenosis or dilatation at the aortic coarctation repair site assessed by cardiovascular MRI in adult patients late after coarctation repair

Background

Cardiovascular magnetic resonance (CMR) is ideal for assessing patients with repaired aortic coarctation (CoA). Little is known on the relation between long-term complications of CoA repair as assessed by CMR and clinical outcome. We examined the prevalence of restenosis and dilatation at the repair site and the long-term outcome in patients with repaired CoA.

Methods and results

CMR imaging and clinical data for adult CoA patients (247 patients aged 33.0 ± 12.8 years, 60% male), were analyzed. The diameter of the aorta at the repair site was measured on CMR and its ratio to the aortic diameter at the diaphragm (repair site-diaphragm ratio, RDR) was calculated. Restenosis (RDR ≤ 70%) was present in 31% of patients (and significant in 9% [RDR < 50%]), and dilatation (RDR > 150%) in 13.0%. A discrete aneurysm at the repair site was observed in 9%. Restenosis was more likely after resection and end–end anastomosis, whereas dilatation after patch repair. Systemic hypertension was present in 69% of patients. Of the hypertensive patients, blood pressure (133 ± 20/73 ± 10 mm Hg) was well controlled in 93% with antihypertensive therapy. Mortality rate over a median length of 5.9 years was low (0.69% per year, 95% CI: 0.33–1.26), but significantly higher than age-matched healthy controls (standardised mortality ratio 2.86, CI 1.43–5.72, p < 0.001).

Conclusion

Restenosis or dilatation at the CoA repair site as assessed by CMR is not uncommon. Medium term survival remains good, however, albeit lower than in the general population. Life-long follow-up and optimal blood pressure control are likely to secure a good longer term outlook in these patients.     

Effects of Neonatal Enzyme Replacement Therapy and Simvastatin Treatment on Cervical Spine Disease in Mucopolysaccharidosis I Dogs

Mucopolysaccharidosis I (MPS I) is a lysosomal storage disease characterized by deficient α‐L‐iduronidase activity, leading to the accumulation of poorly degraded glycosaminoglycans (GAGs). Children with MPS I exhibit high incidence of spine disease, including accelerated disc degeneration and vertebral dysplasia, which in turn lead to spinal cord compression and kyphoscoliosis. In this study we investigated the efficacy of neonatal enzyme replacement therapy (ERT), alone or in combination with oral simvastatin (ERT + SIM) for attenuating cervical spine disease progression in MPS I, using a canine model. Four groups were studied: normal controls; MPS I untreated; MPS I ERT‐treated; and MPS I ERT + SIM–treated. Animals were euthanized at age 1 year. Intervertebral disc condition and spinal cord compression were evaluated from magnetic resonance imaging (MRI) images and plain radiographs, vertebral bone condition and odontoid hypoplasia were evaluated using micro–computed tomography (µCT), and epiphyseal cartilage to bone conversion was evaluated histologically. Untreated MPS I animals exhibited more advanced disc degeneration and more severe spinal cord compression than normal animals. Both treatment groups resulted in partial preservation of disc condition and cord compression, with ERT + SIM not significantly better than ERT alone. Untreated MPS I animals had significantly lower vertebral trabecular bone volume and mineral density, whereas ERT treatment resulted in partial preservation of these properties. ERT + SIM treatment demonstrated similar, but not greater, efficacy. Both treatment groups partially normalized endochondral ossification in the vertebral epiphyses (as indicated by absence of persistent growth plate cartilage), and odontoid process size and morphology. These results indicate that ERT begun from a very early age attenuates the severity of cervical spine disease in MPS I, particularly for the vertebral bone and odontoid process, and that additional treatment with simvastatin does not provide a significant additional benefit over ERT alone. © 2014 American Society for Bone and Mineral Research.     

The lubricating activity of human synovial fluids

The lubricating abilities of human synovial fluids were measured using a rotating cartilage-on-glass apparatus. A total of 247 human fluids were lubricationtested. Of these, 20 of the 180 knee fluids from patients with degenerative/traumatic joint disease lubricated less well than normal bovine synovial fluid. The remainder of the fluids from the knee and other joints were equivalent to normal bovine synovial fluid in their lubricating properties. The concentrations of hyaluronic acid, protein, and sialic acid and the relative viscosity of 117 human fluid samples were determined, but no relationships between the gross composition and the lubricating abilities were apparent.     

Fenestrated capillaries in the periodontal ligaments of the erupting and erupted rat molar

Quantitative ultrastructural studies were conducted on eight rats (four aged 21 days and four aged 8 weeks) using the periodontal tissues around the mesial root of the mandibular first molar. The periodontal ligament of the erupting tooth contained significantly more capillary fenestrations than the erupted tooth, both in terms of the number per unit area of endothelium (2.2/microns2) and in terms of total number per cubic millimetre of tissue (30.5 X 10(6)/mm3). Differences were also discerned with respect to the percentage of capillaries in the tissue. Thus, the periodontal vasculature demonstrates marked morphological changes which may be related to the eruptive phase of the tooth.     

Projections from the trigeminal nuclear complex to the cochlear nuclei: a retrograde and anterograde tracing study in the guinea pig

In addition to input from auditory centers, the cochlear nucleus (CN) receives inputs from nonauditory centers, including the trigeminal sensory complex. The detailed anatomy, however, and the functional implications of the nonauditory innervation of the auditory system are not fully understood. We demonstrated previously that the trigeminal ganglion projects to CN, with terminal labeling most dense in the marginal cell area and secondarily in the magnocellular area of the ventral cochlear nucleus (VCN). We continue this line of study by investigating the projection from the spinal trigeminal nucleus to CN in guinea pig. After injections of the retrograde tracers FluoroGold or biotinylated dextran amine (BDA) in VCN, labeled cells were found in the spinal trigeminal nuclei, most densely in the pars interpolaris and pars caudalis with ipsilateral dominance. The anterograde tracers Fluoro-Ruby or BDA were stereotaxically injected into the spinal trigeminal nucleus. Most labeled puncta were found in the marginal area of VCN and the fusiform cell layer of dorsal cochlear nucleus (DCN). A smaller number of labeled puncta was located in the molecular and deep layers of DCN and the magnocellular area of VCN. The trigeminal projection to CN may provide somatosensory information necessary for pursuing a sound source or for vocal production. These projections may have a role in the generation and modulation of tinnitus.     

A comparison of schizophrenic patients in different community support treatment approaches

Recent advances in the care of the chronically mentally ill in the community have resulted in a community support system approach to maintaining chronically mentally ill persons outside the hospital. Yet, very little is known of what a community support system actually is for the chronic mental patient. This paper looks at three different sorts of community support programs and compares a sample of patients within them with respect to network variables, role performance, and demographic variables. Implications regarding the use of network oriented approaches are discussed and directions for further research are explored.     

Atrioventricular septal defect with a well developed primary component of the atrial septum ("septum primum")

A heart is described with an atrioventricular septal defect in which the lower part of the atrial septum ("septum primum") was well developed and in which superior and inferior bridging leaflets were attached neither to the crest of the ventricular septum nor the inferior rim of the atrial septum. Diagnostic pre-operative angiographic and echocardiographic features and the method of surgical correction are outlined.     

Temporal aspects of the visuotactile congruency effect

We report an experiment designed to investigate the temporal dynamics of the visuotactile crossmodal congruency effect. Vibrotactile targets were presented randomly to the index finger (top side of a hand-held cube) or thumb (bottom side) of either hand while visual distractors were presented randomly from one of the same four possible locations. The stimulus onset asynchrony (SOA) between the vibrotactile target and the visual distractor was varied on a trial-by-trial basis. Participants made speeded discrimination responses regarding the elevation of the vibrotactile targets (i.e., upper versus lower) while trying to ignore the visual distractors. The largest crossmodal congruency effects (defined as the difference in performance between incongruent and congruent elevation distractor trials) were obtained when the visual distractor preceded the vibrotactile target by 50-100 ms, although significant effects were also reported when the distractor followed the target by as much as 100 ms. These results are discussed in terms of the conjoint influence of response competition, crossmodal perceptual interactions (i.e., the ventriloquism effect), and exogenous spatial attention on the crossmodal congruency effect. The distinct temporal signatures of each of these effects are also highlighted.