Full-field acoustomammography using an acousto-optic sensor.

In this Letter the authors introduce a wide-field transmission ultrasound approach to breast imaging based on the use of a large area acousto-optic (AO) sensor. Accompanied by a suitable acoustic source, such a detector could be mounted on a traditional mammography system and provide a mammographylike ultrasound projection image of the compressed breast in registration with the x-ray mammogram. The authors call the approach acoustography. The hope is that this additional information could improve the sensitivity and specificity of screening mammography. The AO sensor converts ultrasound directly into a visual image by virtue of the acousto-optic effect of the liquid crystal layer contained in the AO sensor. The image is captured with a digital video camera for processing, analysis, and storage. In this Letter, the authors perform a geometrical resolution analysis and also present images of a multimodality breast phantom imaged with both mammography and acoustography to demonstrate the feasibility of the approach. The geometric resolution analysis suggests that the technique could readily detect tumors of diameter of 3 mm using 8.5 MHz ultrasound, with smaller tumors detectable with higher frequency ultrasound, though depth penetration might then become a limiting factor. The preliminary phantom images show high contrast and compare favorably to digital mammograms of the same phantom. The authors have introduced and established, through phantom imaging, the feasibility of a full-field transmission ultrasound detector for breast imaging based on the use of a large area AO sensor. Of course variations in attenuation of connective, glandular, and fatty tissues will lead to images with more cluttered anatomical background than those of the phantom imaged here. Acoustic coupling to the mammographically compressed breast, particularly at the margins, will also have to be addressed.

Automated detection of microcalcification clusters for digital breast tomosynthesis using projection data only: a preliminary study.

Digital breast tomosynthesis (DBT) is a promising modality for breast imaging in which an anisotropic volume image of the breast is obtained. We present an algorithm for computerized detection of microcalcification clusters (MCCs) for DBT. This algorithm operates on the projection views only. Therefore it does not depend on reconstruction, and is computationally efficient. The algorithm was developed using a database of 30 image sets with microcalcifications, and a control group of 30 image sets without visible findings. The patient data were acquired on the first DBT prototype at Massachusetts General Hospital. Algorithm sensitivity was estimated to be 0.86 at 1.3 false positive clusters, which is below that of current MCC detection algorithms for full-field digital mammography. Because of the small number of patient cases, algorithm parameters were not optimized and one linear classifier was used. An actual limitation of our approach may be that the signal-to-noise ratio in the projection images is too low for microcalcification detection. Furthermore, the database consisted of predominantly small MCC. This may be related to the image quality obtained with this first prototype.

Motor control in children and adults during a non-speech oral task.

Although decreased accuracy and increased variability of movement is a common developmental finding, the nature of these performance patterns remains poorly understood. The present study examined the accuracy and stability of several aspects of oral motor control. Specifically, we examined the control of absolute timing (temporal parameterization), absolute amplitude (amplitude parameterization), and relative timing and amplitude (generalized motor programs) in children and adults during a lip plus jaw opening and closing task. As was the case with similar reports, we found that children were both less accurate and less stable in their assignment of temporal and amplitude parameters. However, we further found that although children's underlying movement patterns were less accurate than those of adults, children exhibited similar variability in their generalized motor programs. The results are discussed within the framework of a schema model of motor control (Schmidt, 1975) with reference to the strategic allocation of resources during motor learning (e.g., Clark & Robin, 1998).

Potential of computer-aided diagnosis to reduce variability in radiologists' interpretations of mammograms depicting microcalcifications.

PURPOSE: To evaluate whether computer-aided diagnosis can reduce interobserver variability in the interpretation of mammograms. MATERIALS AND METHODS: Ten radiologists interpreted mammograms showing clustered microcalcifications in 104 patients. Decisions for biopsy or follow-up were made with and without a computer aid, and these decisions were compared. The computer was used to estimate the likelihood that a microcalcification cluster was due to a malignancy. Variability in the radiologists' recommendations for biopsy versus follow-up was then analyzed. RESULTS: Variation in the radiologists' accuracy, as measured with the SD of the area under the receiver operating characteristic curve, was reduced by 46% with computer aid. Access to the computer aid increased the agreement among all observers from 13% to 32% of the total cases (P <.001), while the kappa value increased from 0.19 to 0.41 (P <.05). Use of computer aid eliminated two-thirds of the substantial disagreements in which two radiologists recommended biopsy and routine screening in the same patient (P <.05). CONCLUSION: In addition to its demonstrated potential to improve diagnostic accuracy, computer-aided diagnosis has the potential to reduce the variability among radiologists in the interpretation of mammograms.

A bridge between neuroscience and oncology: prostate cancer genesis. A 'negative' consequence of learning?

Prostate cancer has become the most commonly diagnosed cancer in men over recent years. The initiating mechanism for tumorigenesis within the prostate remains an unknown. The observation, that the cancer incidence in patients with chronic neurological disabilities is significantly lower than in the normal population lead to the hypothesis, that changed processing due to a barrage of aberrant sensory information within a healthy CNS can trigger events within the prostate cell, that cause malignant transformation. There is a broad overlap of cellular mechanism of gene expression, that lead to either long term potentiation, learning and memory storage or deregulated differentiation and malignant transformation.

The male chronic pelvic pain syndrome.

Suffering chronic pain is a common and debilitating problem that significantly impairs the quality of life of affected patients. Because we continue to struggle with chronic pelvic pain disorders both diagnostically and therapeutically, a neuro-behavioral perspective should be used in an attempt to explain pathways and neurophysiological mechanisms, and to improve diagnostics and treatment of male pelvic pain. First, however, malignant and acute/chronic bacterial disease has to be excluded as a cause of chronic pain in every single case. Then diagnostic approaches should screen for lower urinary tract dysfunction, pelvic floor functional disorders, and disturbed reflex integrity within the pelvic area. Treatment approaches for the male chronic pelvic pain syndrome could be divided into causal and symptomatic. Causal treatment approaches try to influence basic mechanisms generating and supporting chronic pain. In most cases a symptomatic approach is needed to relieve pain immediately. Because generally accepted treatment protocols and studies are missing, the following approach in the individual patient is recommended: (1) symptomatic treatment for immediate pain relief, (2) diagnostic work-up, (3) causal treatment trial.

Chronic perineal pain and lower urinary tract dysfunction--a clinical feature of the "Gulf War syndrome"?

A Persian Gulf War veteran presented to the University Neuro-Urology service for management of severe chronic perineal pain. The overall physical and neurological exam was unremarkable. However, the rectal exam and the urodynamic study revealed a severe pelvic floor dysfunction. A neuro-behavioral approach is recommended and discussed.

Long-term effectiveness of sacral nerve stimulation for refractory urge incontinence.

OBJECTIVES: To evaluate the long-term efficacy of sacral nerve stimulation for refractory urinary urge incontinence. STUDY DESIGN AND METHODS: Urge incontinent patients qualified for surgical implantation of a neurostimulator system after trial screening with percutaneous test stimulation. Surgical implantation of the InterStim System (Medtronic Inc., Minneapolis, Minn., USA) was performed in cases where a >50% reduction in incontinence symptoms was documented during the 3- to 7-day test stimulation period. The InterStim System consists of an implantable pulse generator, a transforamenally placed quadripolar lead, and an extension that connects these two devices for unilateral stimulation of the S3 or S4 sacral nerve. Efficacy for 96 implanted patients was based on urinary symptom changes as quantified in voiding diaries collected at baseline and annually after surgical implantation. RESULTS: As compared to baseline, the group of 96 implanted patients demonstrated significant reductions in urge incontinent symptoms at an average of 30.8+/-14.8 (range 12-60) months with respect to the number of urge incontinent episodes per day, severity of leaking, and the number of absorbent pads/diapers replaced per day due to incontinence (all p<0.0001, respectively). Gender, pretreatment variables, and age were not found to be relevant factors that affected these results. 11 of the 96 patients underwent device explant due to lack of efficacy, pain or bowel dysfunction. These data were conservatively included in the efficacy results. No permanent injuries associated with the devices or therapy were reported. CONCLUSION: Sacral nerve stimulation is an effective treatment for refractory urge incontinence with sustained long-term benefit through an average of 30.8 months.

Efficacy of sacral nerve stimulation for urinary retention: results 18 months after implantation.

PURPOSE: We investigate the efficacy of sacral neurostimulation in patients with idiopathic urinary retention in a prospective, randomized multicenter trial. MATERIALS AND METHODS: A total of 177 patients with urinary retention refractory to standard therapy were enrolled in the study. Greater than 50% improvement in baseline voiding symptoms during a 3 to 7-day percutaneous test stimulation qualified a patient for surgical implantation of an InterStim parallel system. Of the patients who qualified for implantation 37 were randomly assigned to a treatment and 31 to a control group. Patients in the treatment group underwent early surgical implantation of the sacral nerve stimulation system, while implantation was delayed in the control group for 6 months. Followup evaluations, including voiding diary analysis and temporary deactivation of the stimulator at 6 months, were conducted at 1, 3, 6, 12 and 18 months after implantation in the treatment group, and after 3 and 6 months in the control group. RESULTS: Compared to the control group, patients implanted with the InterStim system had statistically and clinically significant reductions in the catheter volume per catheterization (p <0.0001). Of the patients treated with implants 69% eliminated catheterization at 6 months and an additional 14% had a 50% or greater reduction in catheter volume per catheterization. Therefore, successful results were achieved in 83% of the implant group with retention compared to 9% of the control group at 6 months. Temporary inactivation of sacral nerve stimulation therapy resulted in a significant increase in residual volumes (p <0.0001) but effectiveness of sacral nerve stimulation was sustained through 18 months after implant. CONCLUSIONS: Results of this prospective, randomized clinical study demonstrate that sacral nerve stimulation is effective for restoring voiding in patients with retention who are refractory to other forms of treatment.

Long-term results of a multicenter study on sacral nerve stimulation for treatment of urinary urge incontinence, urgency-frequency, and retention.

Many patients have chronic, debilitating symptoms of voiding dysfunction that are refractory to conventional medical or surgical therapies. This multicenter, prospective study evaluated the long-term effectiveness of sacral nerve stimulation using the implantable Medtronic InterStim therapy for urinary control in patients with otherwise intractable complaints of urinary urge incontinence, urgency-frequency, or retention. Each patient first underwent temporary, percutaneous sacral nerve test stimulation. If at least a 50% reduction in target symptoms was documented for at least 3 days, patients received a permanent Medtronic InterStim sacral nerve stimulation system that includes a surgically implanted lead and neurostimulator. Regular follow-up was conducted with outcome data. We report here on patients who have been observed from 1.5 to 3 years postimplantation. The results demonstrate that after 3 years, 59% of 41 urinary urge incontinent patients showed greater than 50% reduction in leaking episodes per day with 46% of patients being completely dry. After 2 years, 56% of the urgency-frequency patients showed greater than 50% reduction in voids per day. After 1. 5 years, 70% of 42 retention patients showed greater than 50% reduction in catheter volume per catheterization. We conclude that the Medtronic InterStim therapy for urinary control system is an effective therapy with sustained clinical benefit for patients with intractable symptoms of urinary urge incontinence, urgency-frequency, or retention.

Similarity of distributions of spinal c-Fos and plasma extravasation after acute chemical irritation of the bladder and the prostate.

PURPOSE: Persistent pain in referred areas and voiding dysfunction are characteristic symptoms of chronic abacterial prostatitis. Since referred pain from visceral organs is considered a neurological event, it appeared reasonable to hypothesize that the persistent pain associated with prostatitis might also be explained by neural mechanisms. Neurogenic plasma extravasation and c-fos expression in the spinal cord, after chemical irritation of the rat prostate, was identified as a method to investigate the neurogenic aspect of prostatic inflammation. MATERIALS AND METHODS: The distribution of plasma extravasation using Evans blue dye was determined after chemical irritation of the prostate and bladder of the rat, and the distribution of dye extravasation was analyzed. c-fos expression within the spinal cord was determined immunocytochemically after chemical irritation of the prostate, bladder and superficial somatic region determined by the dye extravasation as a referred pain area (tail root). RESULTS: Chemical irritation of the prostate resulted in plasma extravasation in L5 to S2 dermatomes (primarily in L6 and S1). In rats receiving bladder irritation, the distribution of plasma extravasation showed a similar pattern to that observed in animals receiving prostatic irritation. Chemical irritation of the 3 structures resulted in expression of c-fos positive cells within the lumbosacral spinal cord. With each treatment the majority of c-fos positive cells were in the L6 and S1 segments. In all 3 groups the highest percentages of c-fos positive cells were observed in deeper laminae, including the dorsal commissure and sacral parasympathetic nucleus. CONCLUSIONS: Our results strongly suggest that referred pain status in inflammation of the bladder and prostate is neurogenically mediated. Based on these studies, there should be significant overlaps of nociceptive neurons within the spinal cord, which receive nociceptive inputs from pelvic soma and viscera.

Lung cancer proliferation correlates with [F-18]fluorodeoxyglucose uptake by positron emission tomography.

Tumor proliferation has prognostic value in resected early-stage non-small cell lung cancer (NSCLC). We evaluated whether [F-18]fluorodeoxyglucose (FDG) uptake of NSCLC correlates with tumor proliferation and, thus, could noninvasively grade NSCLCs (refining patient prognosis and therapy). Thirty-nine patients with potentially resectable NSCLC underwent whole-body FDG positron emission tomography (PET) 45 min after i.v. injection of 10 mCi of FDG. Tumor FDG uptake was quantitated with the maximum pixel standardized uptake value (maxSUV). The lesion diameter from computed tomography was used to correct the maxSUV for partial volume effects using recovery coefficients determined for the General Electric Advance PET scanner. Thirty-eight patients underwent complete surgical staging (bronchoscopy and mediastinoscopy, with or without thoracotomy). One stage IV patient by PET underwent bronchoscopic biopsy only. Immunohistochemistry for Ki-67 (proliferation index marker) was performed on all of the 39 NSCLC specimens (35 resections, 1 percutaneous, and 3 surgical biopsies). The specimens were reviewed for cellular differentiation (poor, moderate, well) and tumor type. Lesions ranged from 0.7 to 6.1 cm. The correlation found between uncorrected maxSUV and lesion size (Rho, 0.56; P = 0.0006) disappeared when applying the recovery coefficients (Rho, -0.035; P = 0.83). Ki-67 expression (percentage of positive cells) correlated strongly with FDG uptake (corrected maxSUV: Rho, 0.73; P < 0.0001). The correlation was stronger for stage I lesions (11 stage IA, 15 stage IB): Rho, 0.79; P < 0.0001) and strongest in stage IB (Rho, 0.83; P = 0.0019). A significant association (P < 0.0001) between tumor differentiation and corrected SUV was noted. FDG PET may be used to noninvasively assess NSCLC proliferation in vivo, identifying rapidly growing NSCLCs with poor prognosis that could benefit from preoperative chemotherapy.

Perisphincteric injection of botulinum toxin type A. A treatment option for patients with chronic prostatic pain?

BACKGROUND: Chronic prostatic pain is still a diagnostic and therapeutic problem. The clinical observation that prostatic and pelvic pain is accompanied by motoric and sensoric disorders of the pelvic floor muscles led to the hypothesis that prostatic pain roots in a changed processing of afferent and efferent information with the central nervous system (CNS). METHODS: Neuro-urological work-up of 11 male patients with chronic prostatic pain was completed. This included a clinical evaluation of pelvic floor function, urodynamic investigation of bladder and urethra function and a cystoscopy to exclude morphological aberrations. A transurethral perisphincteric injection of 200 units botulinum toxin type A (BTX) was followed by a 2- to 4-week visit to evaluate their influence on the neuro-urological symptomatology. RESULTS: All chronic prostatic pain patients suffered from a pathological pelvic floor tenderness, an inability of sufficient conscious pelvic floor control, a urethral hypersensitivity/hyperalgesia and a urethral muscle hyperactivity. Basic parameters of bladder function (capacity, sensitivity, compliance) were normal. The BTX injection was followed by a pelvic floor muscle weakening and a relief of prostatic pain and urethral hypersensitivity/hyperalgesia. A botulinum-related decrease of the functional urethral length, the urethral sphincter closure pressure, the postvoid residual volume and an increase of the peak and average uroflow were objectivated. CONCLUSION: A weakening of the urethral sphincter muscle via blocking acetylcholine release by BTX injection is followed by pain relief and symptom improvement. It can therefore be concluded that a barrage of nociceptive information from the dysfunctional pelvic floor overflood the CNS and induce a changed CNS processing. Interrupting the efferent branch of the disturbed central circle is one opportunity to treat chronic prostatic pain.

Central nervous system neurons labeled following the injection of pseudorabies virus into the rat prostate gland.

BACKGROUND: The human prostate gland plays an important role in male fertility and is involved in different functional pathologies of the male lower urinary tract (LUT). The role of the prostate in these medical disorders is mainly unknown. Traditional surgical therapeutic attempts often fail to help these patients. For years, the clinical sciences have been stagnating due to a lack of basic science knowledge. Investigations into neuroanatomy and neurophysiology are urgently needed. Therefore, the neuroanatomy of the prostate gland in an experimental setup was explored. Recent progress in neuroscience methodology allows a transneuronal tracing by using a self-amplifying virus tracer, pseudorabies virus (PRV). METHODS: Sixty-two individual adult male Sprague-Dawley rats were used for retrograde transneuronal mapping of the spinal cord and brain stem after PRV-injection and control experiments. A PRV-tracer (5 microl, 1 x 10(8) pfu/ml) was injected into the prostate gland. After a survival time of 72, 96, or 120 hr, the animals were sacrificed. Brain and spinal cord were harvested via a dorsal laminectomy. After cutting on a freezing microtome, the tissue was immunostained for PRV. RESULTS: PRV-positive cells were found within the sacral (S1-S2) and the thoracolumbar (T13-L2) spinal cord. At the supraspinal level, positive cells were found within the following regions: nucleus raphe, lateral reticular formation, nucleus gigantocellularis, A5 noradrenergic cell region, locus coeruleus, pontine micturition center, hypothalamus, medial preoptic region, and periaquaductal gray. CONCLUSIONS: This is the first investigation on the central innervation of the prostate gland showing a broad central representation of neurons involved in the control of the prostate gland. It is obvious, comparing data from the literature, that there is a broad overlap in the innervation of pelvic visceral organs (bladder, rectum, and urethra). The appreciation of these neuroanatomical circumstances allows a growing understanding of common urological pathologies within the pelvis (pelvic pain, lower urinary tract, and bowel dysfunction).

Specificity of detection of Chlamydia pneumoniae in cardiovascular atheroma.

Chlamydia pneumoniae is commonly detected in atherosclerotic plaque but the frequency of detection in non-cardiovascular (CV) tissues has not been well determined. In this study, archival autopsy tissue specimens from both CV and non-CV sites from 38 patients were tested by polymerase chain reaction and immunocytochemistry to detect C. pneumoniae. In addition, 33 surgical granuloma biopsy specimens were also tested. C. pneumoniae was detected most frequently in coronary artery tissue (34%) but was also detected in specimens from lung (13%), liver (10%), spleen (5%), bone marrow (10%), and lymph node (8%). The organism was detected in 3 of 33 granuloma specimens. These findings suggest that C. pneumoniae demonstrates a tropism for CV tissues and is either not widely distributed to non-CV tissues or does not persist chronically in those tissues after initial infection.

Sacral neuromodulation in the treatment of urgency-frequency symptoms: a multicenter study on efficacy and safety.

PURPOSE: Neuromodulation of sacral nerves has shown promising results in correcting voiding dysfunction. We report the results of a multicenter trial designed to assess the efficacy of sacral nerve neuromodulation in patients presenting with refractory urinary urgency-frequency. MATERIALS AND METHODS: A total of 51 patients from 12 centers underwent baseline assessment, including a detailed voiding diary, urodynamic evaluation and percutaneous test stimulation of the sacral nerves at S3 and/or S4. All patients enrolled in the study had undergone prior conventional treatment, such as pharmacotherapy, hydrodistention and surgical intervention, which failed. All patients demonstrated a satisfactory response to trial stimulation and were randomly divided into a stimulation group (25 patients) and a control group (26). A sacral nerve stimulation device was implanted after 6 months in the control group. Patients were followed at 1, 3 and 6 months, and at 6-month intervals for up to 2 years after implantation of a neuroprosthetic InterStim* system. dagger The study variables included the number of voids daily, volume voided per void and degree of urgency before void. RESULTS: Compared to the control group, 6-month voiding diary results demonstrated statistically significant improvements (p <0.0001) in the stimulation group with respect to the number voids daily (16.9 +/- 9.7 to 9.3 +/- 5.1), volume per void (118 +/- 74 to 226 +/- 124 ml.) and degree of urgency (rank 2.2 +/- 0.6 to 1.6 +/- 0.9). Patients in the control group showed no significant changes in voiding parameters at 6 months. Significant improvements in favor of the stimulation group were noted in various parameters with respect to water cystometry and quality of life (SF-36). At 6 months after implant, neurostimulators were turned off in the stimulation group and urinary symptoms returned to baseline values. After reactivation of stimulation sustained efficacy was documented at 12 and 24 months. CONCLUSIONS: Neuromodulation of the sacral nerves is an effective, safe therapy that successfully treats significant symptoms of refractory urgency-frequency.

Retinoblastoma expression in thyroid neoplasms.

Retinoblastoma (Rb) mutation in thyroid neoplasia has been identified in a few molecular studies; however, the utility of Rb immunohistochemistry in distinguishing benign and malignant thyroid lesions has not been documented in formalin-fixed, paraffin-embedded tissues. The present study investigated Rb immunohistochemistry in a series of 111 formalin-fixed, paraffin-embedded benign and malignant thyroid lesions. All of the major histologic subtypes were included to detect any heterogeneity in Rb-1 expression that might influence the diagnostic utility of this technique or further elucidate the pathogenesis of thyroid neoplasia among the categories. Altogether, 34 follicular adenomas, 9 follicular carcinomas, 7 Hürthle cell adenomas, 5 Hürthle cell carcinomas, 23 papillary carcinomas (8 of which were follicular variants), 4 insular carcinomas, 4 anaplastic carcinomas, 6 medullary carcinomas, and 19 nodular goiters were analyzed. Avidinbiotin immunohistochemistry was performed using the Dako Rb-1 clone. Pronase digestion was introduced into the epitope retrieval protocol to eliminate false-positive cytoplasmic stainig. Nuclear immunoreactivity was assessed as positive if 10% or more of thyroid epithelial nuclei stained positively, and conversely as negative. The majority of benign non-Hürthle thyroid lesions, whether hyperplastic or neoplastic, retained Rb nuclear immunopositivity in most cells (51 of 53 cases [96%]). Conversely, malignant thyroid neoplasms lacked Rb immunoreactivity in the majority (42 of 51 cases [82%]), including all papillary carcinomas (23 of 23) and almost all follicular carcinomas (8 of 9 [89%]). Virtually all Hürthle cell neoplasms were negative (11 of 12 [92%]), whether benign or malignant. In conclusion, Rb immunohistochemistry can aid in the distinction between benign and malignant thyroid lesions in conjunction with morphology. This seems to be most applicable to the often problematic differentiation between follicular adenoma and the follicular variant of papillary carcinoma (P < .0001; sensitivity and specificity, 100%) or minimally invasive follicular carcinoma (P = .0007; sensitivity, 89%; specificity, 100%).