Optical and thermal modeling of an optrode microdevice for infrared neural stimulation.

Infrared neural stimulation is a promising medical technique using pulsed infrared light for generating temperature-controlled firing of neurons. A combined optical and thermal model of a stimulating microtool-or so-called optrode-has been developed to investigate the amount, the spatial distribution, and the temporal behavior of the thermal excitation. Ray tracing and Fourier optics were used to describe the propagation and scattering of light in the optrode, and the finite element method was applied to model heat transfer. The scattered intensity distribution profiles were calculated based on measured surface roughness of the device and were integrated into the ray optics model. As a validation of the optical model, the simulated and measured values of the light efficiency of the microoptical system are compared. The temperature rise of the brain tissue during the infrared stimulation was estimated using the combined model. Using 30 mW total power and a single 100 ms pulse, the excitation resulted in a temperature rise of 3°C of the brain tissue. The spatial and temporal distributions of the tissue temperature are discussed in the paper. The proposed combined model is an efficient tool for the investigation and optimization of the stimulation process and for further development of the optrode configuration.

Simulation of small- and wide-angle scattering properties of glass-bead retroreflectors.

Retroreflective materials are extensively used as traffic signs and security patterns. These goods are often realized by spherical glass-beads attached to some reflective substrate. New applications, especially 3D projection, require the precise evaluation and design of the characteristics of light backscattered from retroreflective screens. Simulation of such materials is not straightforward due to the different optical processes taking place: direct retroreflection involving small-angle diffraction effects, and multiple scattering resulting in wide-angle diffuse light. We propose a new complex method to describe the backscattering properties of glass-bead retroreflectors that uniquely combines diffraction calculations with ray tracing based on the microscopic properties of the screen. We validated our simulation method by measurements performed on commercial retroreflective samples.

[Genitourinary tuberculosis in Germany: diagnosis and treatment]. / Urogenitaltuberkulose in Deutschland : Diagnose und Behandlung.

Genitourinary tuberculosis (GUTB) usually results from the reactivation of old, dormant tuberculous diseases by pathogens of the Mycobacterium tuberculosis complex. The diagnosis of tuberculosis of the urinary tract is based on the case history, the finding of pyuria in the absence of infection as judged by culture on routine media and by radiological imaging. A positive yellow egg culture and/or histological analysis of biopsy specimens possibly combined with the polymerase chain reaction (PCR) is still required in most patients to establish a definitive diagnosis of GUTB. Antituberculous drug treatment is based on an initial 2 month intensive phase with three or four drugs daily followed by a 4 month continuation phase with only two drugs. Surgery as a treatment option in GUTB might be indicated in complicated urinary tuberculosis. After antituberculous treatment of GUTB a follow-up surveillance over 5 years is recommended. Although the incidence of GUTB in Germany is relatively low, it is still necessary to impart and deepen scientific knowledge of the diagnosis and therapy of GUTB.

[Testicular adrenal rest tumors (TART) in adult men with classic congenital adrenal hyperplasia (CAH)]. / Testikuläre adrenale Resttumoren (TART) bei erwachsenen Männern mit klassischem adrenogenitalen Syndrom (AGS).

BACKGROUND: Information about treatment of adult male patients with congenital adrenal hyperplasia (CAH) and testicular adrenal rest tumors (TART) is scarce. Diagnostic and therapeutic guidelines do not exist. The aim of this review is to evaluate the current state of therapeutic options in adult male patients with CAH. METHODS: We performed an extensive search of the literature of the last 10 years by using PubMed/MEDLINE. RESULTS: The aims of treatment in adult male patients with CAH are prevention of adrenal crisis and TART, improvement of general well-being, good quality of life and sexual well-being, fertility, and prevention of side effects of gluco- and mineralocorticoid therapy. However, fertility is impaired in these patients and correlates with TART. The current therapeutic concepts are discussed. CONCLUSIONS: A future system of regular follow-up visits and standards in therapeutic concepts is needed to guarantee an improved fertility and lifelong good quality of life in adult male patients with CAH.

High-resolution magnetic resonance imaging of trabecular bone in the wrist at 3 tesla: initial results.

PURPOSE: To evaluate the feasibility of high-resolution magnetic resonance imaging (MRI) of trabecular bone of the wrist at 3 Tesla (3T) in vivo and to assess the potential benefit of the increased resolution for clinical assessment of structural changes in spongy bone. MATERIAL AND METHODS: High-resolution MRI of the wrist was performed with a whole-body 3T MR scanner using a dedicated circularly polarized transmit-receive wrist-coil. Two 3D-FISP sequences with a spatial resolution of 300 x 300 x 300 microm3 in a measuring time of TA = 7:51 min, and 200 x 200 x 200 microm3 in TA = 9:33 min were applied. Seven young healthy volunteers and three elderly subjects with suspected osteoporosis were examined. The signal-to-noise ratio (SNR) in the optimized setup at 3T was compared to measurements at 1.5T. RESULTS: The images at 3T allow microscopic analysis of the bone structure at an isotropic spatial resolution of 200 microm in examination times of <10 min. Differences in the structure of the spongy bone between normal and markedly osteoporotic subjects are well depicted. The SNR at 3T was found up to 16 times higher than at 1.5T applying unchanged imaging parameters. CONCLUSION: The proposed high-resolution MRI technique offers high potential in the diagnosis and follow-up of diseases with impaired bone structure of hand and/or wrist in clinical applications.

[Possibilities of whole-body MRI for investigating musculoskeletal diseases]. / Möglichkeiten der Ganzkörper-MRT zur Diagnostik muskuloskelettaler Erkrankungen.

This contribution outlines possibilities and limitations of whole-body MRI for investigating musculoskeletal diseases. Benefits and drawbacks of the novel whole-body MRI technology are discussed and a possible whole-body MRI sequence protocol for musculoskeletal examinations is proposed. Muscle, joint and bone diseases are discussed in which the application of whole-body MRI may be of advantage. Particularly, polymyositis, muscledystrophy, rheumatoid arthritis, spondylitis ancylosans, multiple trauma, skeletal metastases, multiple myeloma and malignant lymphoma are mentioned. Whole-body MRI opens new advantages for the examination of multifocal musculoskeletal diseases. The clinical benefit of this method for particular diseases has to be evaluated in further studies, however.

3.0 T high-resolution MR imaging of carpal ligaments and TFCC.

PURPOSE: To determine the diagnostic value of 3.0 Tesla MRI for imaging carpal ligaments and triangular fibrocartilage complex (TFCC). Image quality of different optimized MRI sequences is evaluated for high resolution wrist anatomy. MATERIALS AND METHODS: Ten healthy volunteers were examined at 3.0 T and 1.5 T using following sequences: T1 SE, fat-saturated PD-/T2-TSE, TIRM, 3D T1/T2* DESS, 3D-CISS, 2D and 3D T2* MEDIC. Voxel size varied from 0.2 x 0.2 x 1.5 mm (2D sequences) to 0.33 mm (3) and 0.26 mm (3) (3D sequences). Image quality (signal-to-noise-ratio, contrast-to-noise-ratio, artifacts) and carpal ligament/TFCC detection rate were judged by a score. The results obtained from the 3.0 T and 1.5 T devices were compared. RESULTS: With identical voxel size, image matrix and FOV, 3.0 T MRI provided significantly better image quality and ligament detection rates for all sequences in comparison with 1.5 T. The 2D and 3D MEDIC sequences yielded best image quality and detection rates. Excellent image quality and visualization of ligament structures by the fat-suppressed PD-TSE sequence were compromised by a relatively high susceptibility to pulsation and motion artifacts. T1 SE and 3D DESS sequences gave moderate image quality and allowed only partial differentiation between ligament structures. TIRM, T2-TSE and 3D-CISS sequence proved to be unsuitable for examining ligaments at 3.0 T due to their poor image quality and detection rate. CONCLUSION: 3.0 T MRI of the wrist proved to be superior to 1.5 T MRI for high-resolution imaging of carpal ligaments and TFCC using 2D and 3D T2* MEDIC sequences. Clinical studies investigating ligament injuries or carpal instability are recommended for evaluating clinical relevance of high-resolution MRI of the wrist.

[European Association of Urology guidelines on urinary and male genital tract infections]. / Synoptische Leitlinie der sexuell übertragbaren Erkrankungen (STD) mit Primärsymptomen im männlichen Genitale (S1). Leitinien der Deutschen Gesellschaft für Urologie.

Today, the classical bacteria that cause venereal diseases, e.g. gonorrhea, syphilis, chancroid and inguinal granuloma, only account for a small proportion of all known sexually transmitted diseases (STDs). Other bacteria and viruses as well as yeasts, protozoa and epizoa must also be regarded as causative organisms of STD. Taken together, all sexually transmitted infections comprise more than 30 relevant STD pathogens. However, not all pathogens that can be sexually transmitted manifest diseases in the genitals and not all infections of the genitals are exclusively sexually transmitted. Concise information and tables summarising the diagnostic and therapeutic management of STDs in the field of urology allow a synoptic overview, and are in agreement with the recent international guidelines of other specialist areas. Special considerations (i.e. HIV infection, pregnancy, infants, allergy) and recommended regimens are presented.

Tissue inhibitors of metalloproteinases 1 and 2 in human seminal plasma and their association with spermatozoa.

A 24-kDa heparin binding protein recently identified as tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in bovine seminal fluid was suggested to play an important role in bull fertility. As no data are present for men, the concentrations of tissue inhibitors of metalloproteinases 1 (TIMP-1) and TIMP-2 were quantified in human seminal plasma of normozoospermic and azoospermic men using enzyme-linked immunosorbent assay methods. TIMP-1 and 2 were not significantly different in both groups and there were no relationships between the concentrations of both TIMPs and other sperm characteristics. It is assumed that TIMPs are released from accessory sex glands.

Quantitative differences in matrix metalloproteinase (MMP)-2, but not in MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 or TIMP-2, in seminal plasma of normozoospermic and azoospermic patients.

BACKGROUND: Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), have been detected in reproductive tissues and seminal plasma. The purpose of this study was to quantify MMP-2, MMP-9, TIMP-1 and TIMP-2 in human seminal plasma and to evaluate their association with sperm. METHODS: Seminal plasma was analysed using ELISA assays for all four analytes in 12 normozoospermic and 12 azoospermic patients and then for MMP-2 only in another 114 men with azoospermia (n = 16), after vasectomy (n = 20) and with sperm counts within the following ranges: 0.3-19 x 10(6)/ml (n = 20), 20-23 x 10(6)/ml (n = 11), 49-57 x 10(6)/ml (n = 12), 96-110 x 10(6)/ml (n = 12), 139-161 x 10(6)/ml (n = 12) and 215-346 x 10(6)/ml (n = 11). Additional zymographic analyses using SDS-PAGE were performed. RESULTS: All investigated MMPs and TIMPs were detected. MMP-9, TIMP-1 and TIMP-2 were not significantly different in normozoospermia and azoospermia. Only the MMP-2 concentration was significantly decreased in azoospermic compared with normozoospermic patients (mean +/- SD: 650.6 +/- 288.9 versus 1677 +/- 910.4 ng/ml respectively; P = 0.0002) and significantly correlated with the number of sperm (r = 0.54; P < 0.0001). CONCLUSION: MMP-2 in seminal plasma was strongly correlated to the sperm count in a linear fashion. Its origin and potential function remain to be elucidated.

[Diagnosis of chronic prostatitis]. / Diagnostik der chronischen Prostatitis.

The new classification of prostatitis syndromes by the National Institutes of Health clearly defines the diagnostic criteria for categorization according to the clinical symptoms. In addition to the validated symptom scores, the four-glass test demonstrating increased numbers of leukocytes and/or bacteria serves for differentiating between the symptoms. Increased levels of leukocytes and/or increased bacterial count in expressed prostatic excretion (EPS) are typical of prostatitis, although there is a high degree of correspondence with the VB3 fraction (urine voided after prostatic massage). The detection of peroxidase cells (granulocytes) and of an increased concentration of polymorphonuclear (PMN) leukocyte elastase in the ejaculate are indicative of uroadnexitis. Nonbacterial forms of prostatitis (NIH III) and increased PSA levels require intensive clinical diagnosis.

Genitourinary tuberculosis.

The worldwide prevalence of tuberculosis is still high and has remained almost unchanged over the past century as a result of increasing incidence in countries of the Third World. Twenty per cent of patients with tuberculosis will develop an extrapulmonary manifestation over time, the most common site being the genitourinary tract. The patient's history can lead to the sometimes difficult diagnosis. Radiological imaging helps in depicting genitourinary tuberculosis. However, the diagnosis of genitourinary tuberculosis is made on the basis of culture studies and is supported by polymerase chain reaction. The latter has impressive sensitivity and specificity, but lacks the ability to determine biological activity. The combination of three or four anti-tuberculosis drugs over a course of 6 to 9 months remains the treatment of choice. Drug resistance is increasing and necessitates tight therapy control. Tuberculosis of the male seminal duct may be an important cause of male infertility as a result of multiple epididymidal scarring. In these cases testicular sperm extraction is the method of choice for sperm retrieval. The outcome of sperm retrieval followed by intracytoplasmatic sperm injection is not affected.

Progression in transitional cell carcinoma of the urinary bladder--analysis of Tp53 gene mutations by temperature gradients and sequence in tumor tissues and in cellular urine sediments.

The relationship between expression of p53 protein in bladder cancer and tumor progression is known. In this paper, we attempt to study this phenomenon by molecular-genetic techniques. One hundred thirty-seven bladder tumor tissues were obtained from transurethral resection (TURB). Urine sediments were collected from 72 patients suffering from transitional cell carcinoma and tumor recurrence. These patients were followed up for at least three months. Separate polymerase chain reactions (PCR) were carried out for exons 5, 6, 7, and 8 of the Tp53 gene. Temperature gradient gel electrophoresis (TGGE) was used to screen mutations in the PCR products. Sequencing from reamplified mutant and wildtype bands was excised from the TGGE. Tp53 mutation frequency is 43.1% in 137 bladder cancer specimens, but already 32.7% of Ta-tumors (16/49) were Tp53 mutated. Four of 25 patients with Tp53 wild-type tumors suffered from progression. In the group of patients with Tp53 mutated cancer, seven of 12 had a tumor progression. In 11 of 14 patients with Tp53 mutation in cancer tissue, the same mutation was also found in urine sediments. In such patients, successful tumor treatment by TURB results in loss of their Tp53 mutation in urine sediment, and tumor recurrency resulted in reappearance.

Relationship between semen quality and the seminal plasma components carnitine, alpha-glucosidase, fructose, citrate and granulocyte elastase in infertile men compared with a normal population.

The seminal plasma components neutral alpha-glucosidase, carnitine, fructose, citrate, and polymorphonuclear granulocyte (PMN) elastase in 253 men were determined. The seminal plasma of 221 infertile men, a control group with proved fertility and 13 patients after vasectomy were investigated. The concentrations of free carnitine (212 versus 521 micromol/l, n = 219, P < 0.001), total carnitine (437 versus 743 micromol/l, n = 219, P < 0.001), and the activity of neutral alpha-glucosidase (15.1 versus 23.4 IU/l, n = 236, P < 0.05) were significantly reduced in the infertile patient group as compared to the fertile control group, the concentration of PMN elastase (102 versus 48 microg/l, n = 234, P < 0.05) being significantly increased in the infertile patients. In the patients after vasectomy the activity of neutral alpha-glucosidase was the only epididymal marker that was significantly reduced (4.3 versus 9. 8 IU/l, n = 35, P = 0.002) in comparison with the patients with testicular azoospermia. At a limit of 6 IU/l the sensitivity of the method was 92% and the specificity was 72%. Altogether, the epididymal markers were reduced in subfertile patients compared with the control group. For the differential diagnosis of azoospermia only the determination of the neutral alpha-glucosidase activity is useful.

Ubiquitinated aldolase B accumulates during starvation-induced lysosomal proteolysis.

We have previously shown that stress-induced protein degradation requires a functional ubiquitin-activating enzyme and the autophagic-lysosomal pathway. In this study, we examined the occurrence of ubiquitin-protein conjugates that form during nutrient starvation. Kidney and liver epithelial cells respond to nutrient stress by enhancing autophagy and protein degradation. We have shown that this degradative response was more dramatic in nondividing cultures. In addition, the onset of autophagy was suppressed by pactamycin, cycloheximide, and puromycin. We observed an accumulation of ubiquitinated proteins coincident with the degradative response to amino acid starvation. The stress-induced protein ubiquitination was not affected by cycloheximide, indicating that protein synthesis was not required. The ubiquitinated proteins were localized to the cytosol and subcellular fractions enriched with autophagosomes and lysosomes. The incorporation of the ubiquitinated proteins into autolysosomes was dramatically reduced by 3-methyladenine, an inhibitor of autophagy. The evidence suggests that ubiquitinated proteins are sequestered by autophagy for degradation. We next set out to identify those primary ubiquitinated proteins at 60 kDa and 68 kDa. Polyclonal antibodies were prepared against these proteins that had been immunopurified from rat liver lysosomes. The antibodies prepared against those 68 kDa proteins also recognized a 40 kDa protein in cytosolic fractions. Internal amino acid sequences obtained from two cyanogen bromide fragments of this 40 kDa protein were shown to be identical to sequences in liver fructose1,6-bisphosphate aldolase B. Anti-Ub68 antibodies recognized purified aldolase A and aldolase B. Conversely, antibodies prepared against aldolase B recognized the 40 kDa aldolase as well as four to five high molecular weight forms, including a 68 kDa protein. Finally, we have shown that the degradation of aldolase B was enhanced during amino acid and serum starvation. This degradation was suppressed by chloroquine and 3-methyladenine, suggesting that aldolase B was being degraded within autolysosomes. We propose that aldolase B is ubiquitinated within the cytosol and then transported into autophagosomes and autolysosomes for degradation during nutrient stress.

Rapid detection of elevated prostate-specific antigen levels in blood: performance of various membrane strip tests compared.

OBJECTIVES: To compare the ability of four commercially available membrane strip tests to detect increased (4 microg/L or more) concentrations of prostate-specific antigen (PSA) in blood. METHODS: Serum samples with PSA concentrations less than 4 microg/L (n = 67) and from greater than 4 microg/L to 20 microg/L (n = 32) were independently examined by two observers using the PSA membrane strip tests from Chembio, Medpro, Seratec, and Syntron. The positive and negative results of each membrane strip test were classified as either true positive or negative and false negative or positive by comparing them with the quantitative PSA assay of Immulite DPC using the conventional threshold value of 4 microg/L. RESULTS: The interobserver variations of the tests were between 93% and 97%. The color stability of the Seratec and Chembio tests did not show significant differences between test results read within 10 to 20 minutes of the reaction time; however, the results of the other two tests were especially affected by variations in the reading time. The sensitivity and specificity of the tests in relation to the threshold of 4 microg/L were 67% to 93% and 87% to 97%, respectively. CONCLUSIONS: The Syntron test and, within certain limitations, the Seratec test fulfill the concept of a rapid and convenient PSA determination to detect PSA concentrations greater than 4 microg/L. Methodologic optimization of the tests by a grading of the PSA measuring ranges (eg, between 0 and 2, 3 and 4, 4 and 6, and 7 and 10 microg/L) should be taken into account for future development.

p53 tumour suppressor gene mutations in benign prostatic hyperplasia and prostate cancer.

OBJECTIVES: To identify and analyse point mutations in p53 tumour suppressor gene (Tp53) in benign prostatic hyperplasia (BPH) by temperature gradient gel electrophoresis (TGGE) and sequence. MATERIALS AND METHODS: 141 tissue specimens (approx. 100 mg) after transurethral resection of the prostate (TURP), 12 specimens after needle biopsy. Control samples for genetic analysis were (a) 7 prostate tissues without any sign of BPH and malignancy and (b) 103 prostate cancer (PCa) tissues. DNA of the critical Tp53 exons 5-8 was amplified and run on horizontal polyacrylamide gels under defined temperature conditions (TGGE) to yield specific gel shifts and sets of homo- and heteroduplexes in case of mutation. Sequencing with a laser-fluorescent electrophoresis unit was done from re-amplified mutant and wild-type bands. RESULTS: TGGE screening of 153 BPH samples identified 29 specimens with Tp53 mutations (5 in exon 5, 11 in exon 6, 12 in exon 7, 3 in exon 8; 1 tissue sample showed mutations in 3 exons at a time). The computed mutation frequency was 19.0%. Two patients, with mutation in BPH tissue, developed PCa 2-3 years after TURP. One patient with mutation in BPH tissue developed bladder cancer. Of 118 patients with non-mutated DNA in BPH, none is known to have a urological cancer. The Tp53 mutation frequency in 103 PCa samples was 26.2%. Significant differences of mutation frequency between BPH and PCa were detected only in lower exon 5 mutation counts in BPH. CONCLUSION: Tp53 mutation in BPH tissue may be a tumour risk factor.