Testicular Microlithiasis: Is Sonographic Surveillance Necessary? Single Centre 14 Year Experience in 442 Patients with Testicular Microlithiasis.

PURPOSE: Increased prevalence of germ cell tumour (GCT) is seen with testicular microlithiasis (TM) suggesting TM is a premalignant condition with US surveillance advocated. We present a cohort of patients with TM followed up in a single centre and deliberate on the value of US surveillance. MATERIALS AND METHODS: A retrospective analysis of subjects with underlying US diagnosis of TM between 1998 and 2012. One-yearly US follow-up was offered to all patients with TM and a database maintained. Any co-existing tumour at presentation with TM was recorded. TM was divided into limited (< 5 microliths/field), classical (≥ 5 microliths/field) and florid ('snowstorm' appearance). Patient demographics, follow-up details and the development of any scrotal abnormalities were recorded. The radiological and histological findings were documented when a testicular lesion occurred during the follow-up period. RESULTS: 20 224 patients were examined: 867/20 224 (4.3 %) had TM. 21/867 (2.4 %) patients had histology proven malignant tumours at presentation. All TM patients consented to follow-up with 442/867 (51.0 %) achieving this and entering into a follow-up program (mean duration 28 months, range 8 - 165 months). Two patients developed primary GCT during the follow up period. One patient (limited TM) had undergone a previous orchiectomy for contralateral GCT and developed a palpable mass at follow up month 21. The other (limited TM) had an atrophic testis; a tumour was found on US at follow up month 62. CONCLUSION: Two patients of 442 (0.5 %) followed up for all forms of TM in a single centre developed a GCT over a mean duration of 28 months, both had independent risk factors for the development of GCT. These findings suggest that US surveillance is not required when TM is the only abnormality in the absence of any clinical risk factors for the development of GCT.

TOOKAD® Soluble focal therapy: pooled analysis of three phase II studies assessing the minimally invasive ablation of localized prostate cancer.

PURPOSE: To evaluate the 6-month effects of the recommended drug and light dosage in focal vascular-targeted photodynamic therapy (VTP) using TOOKAD(®) Soluble in patients with localized prostate cancer (LPCa). METHODS: We performed a pooled analysis of 117 men with LPCa, PSA <10 ng/mL, and Gleason score ≤ 7 (3 + 4), from 3 studies who received a 10-min intravenous infusion of a single dose of 4 mg/kg TOOKAD(®) Soluble, activated by a 753-nm light at 200 J/cm delivered in the prostate by transperineal fibres under transrectal ultrasound guidance. Primary endpoint was 6-month negative biopsies in the treated lobe(s). PSA was measured at month 1, 3, and 6. Magnetic resonance imaging was performed at day 7, month 3, and 6. International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5) and adverse events were reported at day 7, month 1, 3, and 6. RESULTS: Month 6 negative biopsy rate was 68.4 % in the overall evaluable population (N = 114) and 80.6 % for patients treated by hemiablation with light density index (LDI) ≥ 1 (N = 67). Mean prostate necroses at week-1 were 76.5 and 86.3 %, respectively. In both groups, PSA levels at month 6 decreased by 2.0 ng/mL. Small changes from baseline for IPSS and IIEF-5 indicated a slight improvement in urinary function and a slight deterioration in sexual function. CONCLUSIONS: Focal VTP treatment with TOOKAD(®) Soluble at 4 mg/kg and 200 J/cm resulted in a negative 6-month biopsy rate of 68.4 % for the whole population and 80.6 % for patients treated by hemiablation with LDI ≥ 1. The treatment was well tolerated. Two phase III studies will reach completion in early 2015.

Improving postgraduate clinical assessment tools: the introduction of video recordings to assess decision making.

BACKGROUND: Competency in the management of acutely unwell patients has not previously been formally assessed as part of an objective structured clinical examination (OSCE). AIM: The reliability of the paediatric postgraduate OSCE was calculated. An objective structured video examination was designed to assess candidates' clinical decision making ability when managing acutely unwell children. METHODS: The performance of 3522 postgraduate paediatric trainees was assessed (2006-2008). OSCE reliability was determined using Cronbach's alpha and mean inter-item correlation. Performance in the video station was compared with overall performance (not including video station; Mann-Whitney U) and video station scores correlated with individual station scores (Spearman's Rho correlation coefficient). RESULTS: Clinical examination pass rates for the 684 UK graduates, 1608 overseas candidates training in the UK and 1104 overseas candidates training overseas were 69.7%, 28% and 22.3%, respectively (graduation information not available for 126 candidates). Cronbach's alpha was 0.62. Mean inter-item correlation was 0.15. Candidates who passed the OSCE overall had significantly higher scores on the video station (t(3520) = 14.48); p < 0.001). There was significant positive correlation between scores on the video station, individual stations and overall total score (r's = 0.300; p = 0.001). CONCLUSIONS: The postgraduate paediatric OSCE provides a sound and valid means of assessing clinical skills at the postgraduate level. The video station provides an important new method of assessment. Its use in other postgraduate clinical examinations should be explored.

Acute intermittent hypoxia enhances regeneration of surgically repaired peripheral nerves in a manner akin to electrical stimulation.

The intrinsic repair response of injured peripheral neurons is enhanced by brief electrical stimulation (ES) at time of surgical repair, resulting in improved regeneration in rodents and humans. However, ES is invasive. Acute intermittent hypoxia (AIH) - breathing alternate cycles of regular air and air with ~50% normal oxygen levels (11% O2), considered mild hypoxia, is an emerging, promising non-invasive therapy that promotes motor function in spinal cord injured rats and humans. AIH can increase neural activity and under moderately severe hypoxic conditions improves repair of peripherally crushed nerves in mice. Thus, we posited an AIH paradigm similar to that used clinically for spinal cord injury, will improve surgically repaired peripheral nerves akin to ES, including an impact on regeneration-associated gene (RAG) expression-a predictor of growth states. Alterations in early RAG expression were examined in adult male Lewis rats that underwent tibial nerve coaptation repair with either 2 days AIH or normoxia control treatment begun on day 2 post-repair, or 1 h ES treatment (20 Hz) at time of repair. Three days post-repair, AIH or ES treatments effected significant and parallel elevated RAG expression relative to normoxia control at the level of injured sensory and motor neuron cell bodies and proximal axon front. These parallel impacts on RAG expression were coupled with significant improvements in later indices of regeneration, namely enhanced myelination and increased numbers of newly myelinated fibers detected 20 mm distal to the tibial nerve repair site or sensory and motor neurons retrogradely labeled 28 mm distal to the repair site, both at 25 days post nerve repair; and improved return of toe spread function 5-10 weeks post-repair. Collectively, AIH mirrors many beneficial effects of ES on peripheral nerve repair outcomes. This highlights its potential for clinical translation as a non-invasive means to effect improved regeneration of injured peripheral nerves.

Clinical presentation and initial management of black men and white men with prostate cancer in the United Kingdom: the PROCESS cohort study.

BACKGROUND: In the United States, Black men have a higher risk of prostate cancer and worse survival than do White men, but it is unclear whether this is because of differences in diagnosis and management. We re-examined these differences in the United Kingdom, where health care is free and unlikely to vary by socioeconomic status. METHODS: This study is a population-based retrospective cohort study of men diagnosed with prostate cancer with data on ethnicity, prognostic factors, and clinical care. A Delphi panel considered the appropriateness of investigations and treatments received. RESULTS: At diagnosis, Black men had similar clinical stage and Gleason scores but higher age-adjusted prostate-specific antigen levels (geometric mean ratio 1.41, 95% confidence interval (95% CI): 1.15-1.73). Black men underwent more investigations and were more likely to undergo radical treatment, although this was largely explained by their younger age. Even after age adjustment, Black men were more likely to undergo a bone scan (odds ratio 1.37, 95% CI: 1.05-1.80). The Delphi analysis did not suggest differential management by ethnicity. CONCLUSIONS: This UK-based study comparing Black men with White men found no evidence of differences in disease characteristics at the time of prostate cancer diagnosis, nor of under-investigation or under-treatment in Black men.

Pathways to diagnosis for Black men and White men found to have prostate cancer: the PROCESS cohort study.

Black men in England have three times the age-adjusted incidence of diagnosed prostate cancer as compared with their White counterparts. This population-based retrospective cohort study is the first UK-based investigation of whether access to diagnostic services underlies the association between race and prostate cancer. Prostate cancer was ascertained using multiple sources including hospital records. Race and factors that may influence prostate cancer diagnosis were assessed by questionnaire and hospital records review. We found that Black men were diagnosed an average of 5.1 years younger as compared with White men (P<0.001). Men of both races were comparable in their knowledge of prostate cancer, in the delays reported before presentation, and in their experience of co-morbidity and symptoms. Black men were more likely to be referred for diagnostic investigation by a hospital department (P=0.013), although general practitioners referred the large majority of men. Prostate-specific antigen levels were comparable at diagnosis, although Black men had higher levels when compared with same-age White men (P<0.001). In conclusion, we found no evidence of Black men having poorer access to diagnostic services. Differences in the run-up to diagnosis are modest and seem insufficient to explain the higher rate of prostate cancer diagnosis in Black men.

Evaluation of ideal irrigation fluid in 'Greenlight' photoselective vapourization of the prostate.

Although many anecdotal opinions are available that water gives a better visual quality, no studies have analysed the differences in the visual quality of the operative field with the use of either saline or sterile water. As part of a prospective audit we wished to assess the effect of differing irrigant fluids on intraoperative visibility during Greenlight photoselective vapourization of prostate (PVP). Twenty-nine consecutive patients with prostates less than 100 cm(3) who underwent PVP were studied. The irrigation fluid used was randomly connected on a bag-by-bag basis, with the surgeon blinded to the bag's contents. Towards the end of each bag the surgeon gave a score to the quality of vision. All surgeons were familiarized with the vision scoring system in advance. The scores were analysed in two ways. The mean scores for water and saline were compared. In addition, a mean score for each fluid in each patient where both fluids were used (n=24) was separately calculated and the means for each fluid compared. One hundred and twenty-four bags of fluid in 29 operative cases were analysed. The mean overall vision scores were 3.94% for saline and 4.01% for water (P=0.62). The paired data were analysed using the Student's t-test and there was no statistically significant difference (P=0.34). We showed no significant difference in visual quality between water and saline during PVP. Although fluid absorption is almost unknown with PVP, there seems to be no justification for using water irrigation if saline is available, particularly with a theoretical risk of absorption.

Racial origin is associated with poor awareness of prostate cancer in UK men, but can be increased by simple information.

Prostate cancer is the second most common cause of cancer death in UK men. We have shown a higher incidence and disease stage in black British men (unpublished), however there is no evidence regarding their awareness of prostate cancer and screening. We assessed the level of prostate cancer awareness and attitudes in Black and White men in the UK, and to see if written information would modify awareness. Information was collected from two groups of 871 men without prostate cancer using a new, validated, prostate cancer awareness questionnaire. The first group was asked to fill in the questionnaire, whereas the second group was initially given printed information on prostate cancer and requested to fill in the questionnaire. Data were compared between the two ethnic groups using SPSS statistical package. Changes in knowledge and attitudes after providing prostate health education were analysed. There was a significantly lower response from Black men. In the first group, Black men were unaware of their increased risk of developing the disease and demonstrated poor knowledge about the symptoms of prostate cancer (P<0.001) and also more negative attitudes about its control and treatment (P<0.01). In the second group, there were significant improvements in knowledge, risk awareness and attitudes following targeted education: this was true for Black and White men. Although Black British men have a high risk of prostate cancer, their knowledge of the disease is poor. Simple education methods can significantly improve awareness and knowledge in both Black and White men.

The drebrin/EB3 pathway drives invasive activity in prostate cancer.

Prostate cancer is the most common cancer in men and the metastatic form of the disease is incurable. We show here that the drebrin/EB3 pathway, which co-ordinates dynamic microtubule/actin filament interactions underlying cell shape changes in response to guidance cues, plays a role in prostate cancer cell invasion. Drebrin expression is restricted to basal epithelial cells in benign human prostate but is upregulated in luminal epithelial cells in foci of prostatic malignancy. Drebrin is also upregulated in human prostate cancer cell lines and co-localizes with actin filaments and dynamic microtubules in filopodia of pseudopods of invading cells under a chemotactic gradient of the chemokine CXCL12. Disruption of the drebrin/EB3 pathway using BTP2, a small molecule inhibitor of drebrin binding to actin filaments, reduced the invasion of prostate cancer cell lines in 3D in vitro assays. Furthermore, gain- or loss-of-function of drebrin or EB3 by over-expression or siRNA-mediated knockdown increases or decreases invasion of prostate cancer cell lines in 3D in vitro assays, respectively. Finally, expression of a dominant-negative construct that competes with EB3 binding to drebrin, also inhibited invasion of prostate cancer cell lines in 3D in vitro assays. Our findings show that co-ordination of dynamic microtubules and actin filaments by the drebrin/EB3 pathway drives prostate cancer cell invasion and is therefore implicated in disease progression.

Sensorimotor stimulation to improve locomotor recovery after spinal cord injury.

Functional recovery after CNS injury may depend, in part, upon reorganization of undamaged neural pathways. Spinal cord circuits are capable of significant reorganization, in the form of both activity-dependent and injury-induced plasticity. This plasticity is manifest behaviourally in the ability of spinal animals to learn new locomotor tasks. Recent work with spinal-injured humans demonstrates that training can improve functional locomotor abilities. New methodologies to enhance limb movement are designed to exploit further the plastic capabilities of the spinal cord by reinforcing appropriate connections in an activity-dependent manner. In the future, these methods might also prove useful in guiding and strengthening functional synaptogenesis of regenerating axons to maximize their contribution towards restoration of function.

Lycopene inhibits DNA synthesis in primary prostate epithelial cells in vitro and its administration is associated with a reduced prostate-specific antigen velocity in a phase II clinical study.

Interest in lycopene has focused primarily on its use in the chemoprevention of prostate cancer (CaP); there are few clinical trials involving men with established disease. In addition, most data examining its mechanism of action have been obtained from experiments using immortal cell lines. We report the inhibitory effect(s) of lycopene in primary prostate epithelial cell (PEC) cultures, and the results of a pilot phase II clinical study investigating whole-tomato lycopene supplementation on the behavior of established CaP, demonstrating a significant and maintained effect on prostate-specific antigen velocity over 1 year. These data reinforce the justification for a large, randomized, placebo-controlled study.

Instability in the place field location of hippocampal place cells after lesions centered on the perirhinal cortex.

The perirhinal cortex appears to play a key role in memory, and the neighboring hippocampus is critically involved in spatial processing. The possibility exists, therefore, that perirhinal-hippocampal interactions are important for spatial memory processes. The purpose of the present study was to investigate the contribution of the perirhinal cortex to the location-specific firing ("place field") of hippocampal complex-spike ("place") cells. The firing characteristics of dorsal CA1 place cells were examined in rats with bilateral ibotenic acid lesions centered on the perirhinal cortex (n = 4) or control surgeries (n = 5) as they foraged in a rectangular environment. The activity of individual place cells was also monitored after a delay period of either 2 min, or 1 or 24 hr, during which time the animal was removed from the environment. Although the perirhinal cortex lesion did not affect the place field size or place cell firing characteristics during a recording session, it was determined that the location of the place field shifted position across the delay period in 36% (10 of 28) of the cells recorded from lesioned animals. In contrast, none of the place cells (0 of 29) recorded from control animals were unstable by this measure. These data indicate that although the initial formation of place fields in the hippocampus is not dependent on perirhinal cortex, the maintenance of this stability over time is disrupted by perirhinal lesions. This instability may represent an erroneous "re-mapping" of the environment and suggests a role for the perirhinal cortex in spatial memory processing.

Beliefs about illness and quality of life among men with erectile dysfunction.

The objective of the study was to apply an illness representations framework to examine patients' beliefs about erectile dysfunction (ED) and the association between those beliefs and reported quality of life. A total of 41 patients attending two secondary care clinics at a teaching hospital completed questionnaires examining quality of life, sexual functioning, illness representations (cause, time-line, coherence, consequences, cure, control and emotion) and perceptions of masculinity. Masculinity, sexual function, emotions and beliefs about consequences were found to be significantly correlated with quality of life. Multiple regression analysis revealed a model that accounted for almost 35% of the variance in quality of life of ED patients. The strongest predictor of higher quality of life was better sexual functioning (beta = -0.342, P < 0.05) followed by more positive beliefs about the effects of ED on masculinity (beta = 0.323, P < 0.05). The results suggest that when assessing the quality of life of men with ED, patients' illness representations should be considered along with their level of sexual functioning and the effects of ED on masculinity. Patients may benefit from an intervention programme that includes an educational component, thereby providing patients with more information about treatment options and available support.

Determining the biomass fraction of mixed waste fuels: A comparison of existing industry and (14)C-based methodologies.

(14)C analysis of flue gas by accelerator mass spectrometry (AMS) and liquid scintillation counting (LSC) were used to determine the biomass fraction of mixed waste at an operational energy-from-waste (EfW) plant. Results were converted to bioenergy (% total) using mathematical algorithms and assessed against existing industry methodologies which involve manual sorting and selective dissolution (SD) of feedstock. Simultaneous determinations using flue gas showed excellent agreement: 44.8 ± 2.7% for AMS and 44.6 ± 12.3% for LSC. Comparable bioenergy results were obtained using a feedstock manual sort procedure (41.4%), whilst a procedure based on selective dissolution of representative waste material is reported as 75.5% (no errors quoted). (14)C techniques present significant advantages in data acquisition, precision and reliability for both electricity generator and industry regulator.

Locomotor plasticity after spinal injury in the chick.

Functional recovery after spinal cord injury likely depends, in part, on the reorganization of undamaged spinal circuitry. Segmental afferent input from the limbs remains largely intact after spinal injury and may provide an important source of activation and regulation of the spinal circuits that have lost descending input as a result of the injury. This purpose of this study was to investigate the contribution of cutaneous afferent inputs to the recovery of motor function after spinal injury in the chick. After lateral thoracic spinal hemisection, the motion of the ipsilateral limb was impaired during both walking and swimming. By 2 weeks postoperatively, limb motion recovered to preoperative values for walking but not for swimming. It was hypothesized that phasic afferent inputs experienced during walking, but not swimming, contributed to recovery of limb motion during walking. When a source of phasic cutaneous input was provided during swim training sessions, limb motion gradually improved to preoperative values. After 2 weeks of training, this improved motion was retained even after the source of cutaneous stimulation was removed. The proposed mechanism is an experience-dependent strengthening of the circuits activated during the improved limb motion, leading to a permanent change in limb action during swimming. Thus, the afferent inputs experienced during movement repetition are important during the acquisition of learned movements after spinal injury. These results are discussed in terms of behavioral, physiological, and anatomical evidence for spinal plasticity in other species. It is concluded that the spinal cord has significant plastic capabilities, and efforts should be directed toward maximizing the contribution of this plasticity to functional recovery after spinal cord injury.

A randomized trial of family caregiver support in the home management of dementia.

A randomized trial of family caregiver support for the home management of older people suffering from moderate to severe progressive irreversible dementia was conducted in an urban center in southern Ontario. Thirty caregivers were allocated to receive the experimental intervention consisting of: caregiver-focused health care, education about dementia and caregiving, assistance with problem solving, regularly scheduled in-home respite, and a self-help family caregiver support group. Thirty control subjects received conventional community nursing care. Before completion of the intervention, 18 (30%) were withdrawn, almost equally from each group. The most frequent reason was long-term institutionalization of the demented relative (n = 10). At baseline, caregivers in both groups were suffering from above-average levels of depression and anxiety. After the six-month intervention period, we found neither experimental nor control group improved in these areas. However, the experimental group showed a clinically important improvement in quality of life, experienced a slightly longer mean time to long-term institutionalization, found the caregiver role less problematic, and had greater satisfaction with nursing care than the control group.

Possible use of phosphohexose isomerase as a preliminary to exfoliative cytology in screening for cervical carcinoma.

The activities of phosphohexose isomerase and 6-phosphogluconate dehydrogenase have been studied in the vaginal fluid of women from the gynaecological departments. Women from these departments gave a very high false positive rate, though no cases of carcinoma in situ were not detected by estimating phosphohexose isomerase levels. It gave considerably better results in malignancy than 6-phosphogluconate dehydrogenase. It is suggested that the use of phosphohexose isomerase might be of value in screening well women during a mass cytology programme.

A trial of phosphohexose isomerase as a means of detecting cervical carcinoma.

Phosphohexose isomerase activity has been studied in a well women's clinic with an automated method. In this series, in which freeze drying was used, the assay was not a reliable screening technique, as it was found that the method caused considerable loss of enzyme activity.

Vaginal fluid enzyme patterns in benign and malignant lesions of the female genital tract.

The enzymes phosphohexose isomerase, lactate dehydrogenase, hydroxybutyrate dehydrogenase, isocitric dehydrogenase, glutamate dehydrogenase, and sorbital dehydrogenase were assayed in cases of known carcinoma of the cervix and of carcinoma in situ. Phosphohexose isomerase, lactate dehydrogenase, and isocitric dehydrogenase were also assayed in a number of normal women and in those with benign lesions. It is unlikely that vaginal fluid enzymology will provide a screening test for cervical carcinoma.

An evaluation of the automated assay of urinary oestrogens in pregnant women.

An automated assay suitable for estimating urinary oestrogens in pregnant women has been investigated. Fluorimetry was found to have considerable advantages over colorimetry. The fluorimetric assay was simpler, more precise, more sensitive, and eliminated the need for correction for non-specific chromogens; in the assay of oestriol in pregnant women there was no need for correction for non-specific fluorescence. Spectrofluorimetric and photometric analyses, recoveries, and reproducibility show that the method offers a robust means of providing values for urinary oestrogen in pregnant women on a scale of up to 100 tests a day, the time of the assay being one and a half hours.