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Biomedical subjects

C Seitz

Publications and source records attributed to C Seitz.

At least 19 recordsLinked to original sources

A novel p75TNF receptor isoform mediating NFkappa B activation.

We report the identification of a novel p75TNF receptor isoform termed icp75TNFR, which is generated by the use of an alternative transcriptional start site within the p75TNFR gene and characterized by regulated intracellular expression. The icp75TNFR protein has an apparent molecular mass of approximately 50 kDa and is recognized by antibodies generated against the transmembrane form of p75TNFR. The icp75TNFR binds the tumor necrosis factor(TNF) and mediates intracellular signaling. Overexpression of the icp75TNFR cDNA results in TNF-induced activation of NFkappaB in a TNF receptor-associated factor 2 (TRAF2)-dependent manner. Thus, our results provide an example for intracellular cytokine receptor activation.

Alternative Splicing↗

Targeted transurethral microwave thermotherapy versus alpha-blockade in benign prostatic hyperplasia: outcomes at 18 months.

OBJECTIVES: To compare directly the efficacy, safety, and durability of targeted transurethral microwave thermotherapy with that of alpha-blocker treatment for lower urinary tract symptoms of benign prostatic hyperplasia. METHODS: In a randomized, controlled clinical trial, 52 patients with lower urinary tract symptoms due to benign prostatic hyperplasia received terazosin treatment and 51 underwent microwave treatment under topical anesthesia. The patient evaluation included the International Prostate Symptom Score, peak flow rate, and quality-of-life score before microwave treatment or initiation of terazosin treatment and at periodic intervals thereafter up to 18 months. RESULTS: The mean International Prostate Symptom Score, peak flow rate, and quality-of-life score all improved significantly in both groups by 6 months. However, the magnitude of improvement was significantly greater in the microwave group than in the terazosin group. The significant between-group differences observed at 6 months in the mean International Prostate Symptom Score, peak flow rate, and quality-of-life score were fully maintained at 18 months, at which time the improvements in these three outcome measures were significantly greater (P <0.0005), by 35%, 22%, and 43%, respectively, in the microwave group than in the terazosin group. The actuarial rate of treatment failure at 18 months was significantly greater by sevenfold in the terazosin group. Adverse events were generally infrequent and readily manageable in both groups. CONCLUSIONS: Although the initial onset of terazosin action was more rapid, the longer term clinical outcomes of targeted microwave treatment were markedly superior. The more favorable results in patients who underwent microwave treatment were maintained for at least 18 months.

Adrenergic alpha-Antagonists↗

Safety and morbidity of first and repeat transrectal ultrasound guided prostate needle biopsies: results of a prospective European prostate cancer detection study.

PURPOSE: We prospectively evaluate the safety, morbidity and complication rates for first and repeat transrectal ultrasound guided prostate needle biopsies. MATERIALS AND METHODS: In this prospective European Prostate Cancer Detection Study 1,051 men, with total prostate specific antigen between 4 and 10 ng./ml., underwent transrectal ultrasound guided sextant biopsy plus 2 additional transition zone biopsies. Biopsy samples were also obtained from suspicious areas identified during transrectal ultrasound and digital rectal examination. All 820 patients with biopsy samples negative for prostate cancer underwent re-biopsy after 6 weeks. Immediate and delayed (range 1 to 7 days) morbidity, patient satisfaction and complication rates were recorded. RESULTS: Of the 1,051 subjects the initial biopsy was positive for prostate cancer in 231 and negative, including benign prostatic hyperplasia or benign tissue, in 820. Of these 820 patients prostate cancer was detected in 10% (83) on re-biopsy. Minor or no discomfort was observed in 92% and 89% of patients at first and re-biopsy, respectively (p = 0.29). Immediate morbidity was minor and included rectal bleeding (2.1% versus 2.4%, p = 0.13), mild hematuria (62% versus 57%, p = 0.06), severe hematuria (0.7% versus 0.5%, p = 0.09) and moderate to severe vasovagal episodes (2.8% versus 1.4%, respectively, p = 0.03). Delayed morbidity of first and re-biopsy was comprised of fever (2.9% versus 2.3%, p = 0.08), hematospermia (9.8% versus 10.2%, p = 0.1), recurrent mild hematuria (15.9% versus 16.6%, p = 0.06), persistent dysuria (7.2% versus 6.8%, p = 0.12) and urinary tract infection (10.9% versus 11.3%, respectively, p = 0.07). Major complications were rare and included urosepsis (0.1% versus 0%) and rectal bleeding that required intervention (0% versus 0.1%, respectively). Furthermore, an age dependent pattern of pain apprehension during biopsy was observed with the highest scores in patients younger than 60 years. CONCLUSIONS: Transrectal ultrasound guided biopsy is generally well tolerated with minor morbidity only rarely requiring treatment. Re-biopsy can be performed 6 weeks later with no significant difference in pain or morbidity. Patients younger than 60 years should be counseled in regard to a higher level of discomfort, and local and topical anesthesia if desired.

Aged↗

Genotypic and phenotypic spectrum in tricho-rhino-phalangeal syndrome types I and III.

Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Three subtypes have been described: TRPS I, caused by mutations in the TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. To investigate whether TRPS III is caused by TRPS1 mutations and to establish a genotype-phenotype correlation in TRPS, we performed extensive mutation analysis and evaluated the height and degree of brachydactyly in patients with TRPS I or TRPS III. We found 35 different mutations in 44 of 51 unrelated patients. The detection rate (86%) indicates that TRPS1 is the major locus for TRPS I and TRPS III. We did not find any mutation in the parents of sporadic patients or in apparently healthy relatives of familial patients, indicating complete penetrance of TRPS1 mutations. Evaluation of skeletal abnormalities of patients with TRPS1 mutations revealed a wide clinical spectrum. The phenotype was variable in unrelated, age- and sex-matched patients with identical mutations, as well as in families. Four of the five missense mutations alter the GATA DNA-binding zinc finger, and six of the seven unrelated patients with these mutations may be classified as having TRPS III. Our data indicate that TRPS III is at the severe end of the TRPS spectrum and that it is most often caused by a specific class of mutations in the TRPS1 gene.

Adolescent↗

Pretreatment prostate-specific antigen as an outcome predictor of targeted transurethral microwave thermotherapy.

OBJECTIVES: To evaluate pretreatment serum prostate-specific antigen (PSA) as an outcome predictor of targeted microwave thermotherapy. METHODS: Seventy-one patients with lower urinary tract symptoms of benign prostatic hyperplasia underwent targeted transurethral microwave thermotherapy using the Targis system. Outcomes 12 months after treatment were evaluated by the International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), and quality-of-life (QOL) score. The ability of PSA to predict outcomes was evaluated by linear and logistic regression and receiver operating characteristic curve analysis. RESULTS: Higher pretreatment PSA levels were significantly predictive of an absolute IPSS change of -7.5 or less for patients with moderate baseline symptoms or - 15 or less for those with severe baseline symptoms; an absolute Qmax change of 5 mL/s or greater; an absolute QOL score change of -3 or less; an IPSS at 12 months of 7 or less; a Qmax at 12 months of greater than 12 mL/s; and a QOL score at 12 months of 1 or less. Nevertheless, even without taking pretreatment PSA into account, most patients benefitted substantially from targeted microwave thermotherapy. Thus, 74%, 71%, and 79% of all eligible patients improved 50% or more in IPSS, Qmax, and QOL score, respectively, at 12 months compared with baseline. No significant association between PSA and either prostate or transition zone volume could be demonstrated. CONCLUSIONS: Most patients benefit substantially from targeted microwave thermotherapy. However, higher PSA levels are significantly predictive of more favorable outcomes. This association may reflect patient-to-patient differences in the relative abundance of PSA-producing epithelial cells in the transition zone of the prostate.

Aged↗

Structurally diverse forms of HLA-B27 molecules are displayed in vivo in a cell type-dependent manner.

The formation of a trimeric complex, composed of heavy chain (HC), beta(2)-microglobulin (beta(2)m) and antigenic peptide, is generally believed to be a prerequisite for the expression of HLA class I molecules at the cell surface in vivo. Therefore, a possible role in immunological processes for HC/beta(2)m complexes devoid of peptide has not been seriously considered. Using a novel HLA-B*2705-transgenic rat model and monoclonal antibodies that distinguish between structurally different forms of HLA-B27 molecules, we demonstrate here that class I molecules which appear to lack antigenic peptides are expressed in abundance on a variety of cell types in lymphoid organs. These results imply a role for structurally diverse, possibly empty, MHC molecules in physiological T cell selection which has so far not been sufficiently appreciated.

Amino Acid Sequence↗

Elastin gene expression in benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is mainly a stromal process, showing an increased ratio of stromal to epithelial elements, a collagen type III downregulation, and a collagen types I and IV upregulation. Little is known about elastin gene expression in BPH tissues due to difficulties related to extensive alternative splicing of the elastin gene. Therefore, we analyzed and quantified elastin gene expression in BPH. METHODS: A competitive reverse transcriptase-polymerase chain reaction (competitive RT-PCR) quantitative technique was used, and a quantitative elastin mRNA analysis with normal (n = 10) and BPH (n = 12) tissues was performed with two newly designed elastin primers. Small tissue samples (4-8 mg) were homogenized and sonicated, and cDNA was synthesized from mRNA using a RT reaction. Various target (wild-type) elastin cDNAs with unknown concentrations were competitively coamplified with known serial dilutions of the control mutant template, differing from the target cDNA by a short deletion. Gel fractions and computerized densitometry, were performed and cDNA concentration was calculated by linear regression. RESULTS: The primers identified in our study (BOB-1 and BOB-2) accurately amplified a consistent length of the elastin cDNA, avoiding areas of alternative splicing. The average elastin mRNA concentration in BPH tissues was 53 attomole/mg +/- 11.6 vs. 140.6 attomole/mg +/- 19.6 in normal prostatic tissue (P = 0.019). The variation within every sample was less than 10%. CONCLUSIONS: Our observations suggest a significant downregulation (70%) of the elastin mRNA gene in the transition zone of BPH patients.

Aged↗

Neoadjuvant and adjuvant alpha-blockade improves early results of high-energy transurethral microwave thermotherapy for lower urinary tract symptoms of benign prostatic hyperplasia: a randomized, prospective clinical trial.

OBJECTIVES: Improved long-term results with respect to symptoms, voiding function, and quality of life (QOL) in patients with lower urinary tract symptoms (LUTS) of benign prostatic hyperplasia (BPH) are achieved with targeted high-energy transurethral microwave thermotherapy (TUMT) compared with alpha-blocker treatment alone. However, maximal improvement after TUMT is not attained until 3 to 6 months after treatment. Measures to provide earlier symptom relief and improved voiding function and QOL would add to the clinical utility of TUMT. The objective of the present study was to determine whether neoadjuvant and adjuvant alpha-blockade is capable of accelerating a post-TUMT decrease in LUTS of patients with BPH. METHODS: In this randomized, prospective study of 81 patients with LUTS of BPH, 41 underwent TUMT with neoadjuvant and adjuvant tamsulosin (0.4 mg daily) treatment, and 40 had TUMT alone. International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), and QOL score were determined before treatment and at periodic intervals thereafter up to 12 weeks after TUMT. RESULTS: Mean IPSS values in the TUMT plus tamsulosin group at 2 weeks (14.0, 95% confidence interval [CI] 13.1 to 14.9) and 6 weeks (8.6; 95% CI 7.7 to 9.5) were 15% and 24% lower, respectively, than those at 2 weeks (16.5, 95% CI 15.6 to 17.4) and 6 weeks (11.3, 95% CI 10.4 to 12.2) in the TUMT-alone group (P<0.0005). However, by the final evaluation at 12 weeks, no significant difference between the groups in mean IPSS was evident. A similar temporal pattern of difference between the two study groups was also observed in QOL score. No significant between-group difference in mean Qmax was evident after TUMT. Urinary retention 1 week or more in duration occurred in 5 (12%) of 40 TUMT-alone group patients compared with 1 (2%) of 41 TUMT plus tamsulosin group patients. CONCLUSIONS: Neoadjuvant and adjuvant alpha-blocker treatment results in significantly greater early symptom reduction and QOL score improvement after TUMT, adding to the clinical utility of this minimally invasive treatment modality. In addition, post-TUMT complications such as urinary retention may be reduced.

Adrenergic alpha-Antagonists↗

High-energy transurethral microwave thermotherapy in patients with acute urinary retention due to benign prostatic hyperplasia.

OBJECTIVES: To evaluate the efficacy and safety of targeted high-energy transurethral microwave thermotherapy (HE-TUMT) in the treatment of acute urinary retention (AUR) due to benign prostatic hyperplasia (BPH). METHODS: In this prospective cohort study, 31 patients with painful AUR due to BPH underwent HE-TUMT. Patient evaluation before treatment and during a 12-week follow-up interval included determination of International Prostate Symptom Score (IPSS), quality of life (QOL) score, peak flow rate (Qmax) by uroflowmetry, and postvoid residual urine. Patients also underwent urodynamic evaluation before treatment and at 16 weeks. RESULTS: By 4 weeks after HE-TUMT, 29 (94%) of 31 patients had regained the ability to void spontaneously. The actuarial median time for restoration of spontaneous voiding was 3.0 weeks (95% confidence interval [CI] 2.2 to 3.8). At 12 weeks, the mean IPSS (9.4; 95% CI 8.3 to 10.5) was 50% below (P <0.0005) that before retention (18.9; 95% CI 18.2 to 19.6). Improvements in the mean QOL score were similar in pattern and relative magnitude to those in the mean IPSS. A 69% increase in mean Qmax (P <0.0005) determined by uroflowmetry was observed by 12 weeks versus 1 week after HE-TUMT. Complications were infrequent. CONCLUSIONS: This study provides preliminary evidence that HE-TUMT may potentially afford a novel and useful option for the patient with AUR who is not a suitable candidate for surgery.

Acute Disease↗

PSA, PSA density, PSA density of transition zone, free/total PSA ratio, and PSA velocity for early detection of prostate cancer in men with serum PSA 2.5 to 4.0 ng/mL.

OBJECTIVES: To enhance the specificity of prostate cancer (PCa) detection and reduce unnecessary biopsies in men with prostate-specific antigen (PSA) levels of 2.5 to 4.0 ng/mL, we prospectively evaluated various PSA-based diagnostic parameters. METHODS: This study included 273 consecutive men with serum PSA of 2.5 to 4.0 ng/mL referred for early PCa detection or lower urinary tract symptoms. All men underwent prostate ultrasound and sextant biopsy with two additional transition zone (TZ) biopsies. If the first biopsies were negative, repeated biopsies were performed at 6 weeks. Total PSA, PSA density (PSAD), PSA density of the transition zone (PSA-TZ), free/total PSA ratio (f/t PSA), and PSA velocity (PSAV) were determined, and the sensitivity, specificity, and predictive values of these various parameters were calculated. RESULTS: Of 273 patients, 207 had histologically confirmed benign prostatic hyperplasia (BPH) and 66 had PCa. f/t PSA and PSA-TZ were the most powerful predictors of PCa, followed by PSA, PSAD, and PSAV. Areas under the receiver operating characteristic curves for f/t PSA and PSA-TZ were 74.9% and 70.1%, respectively. With a 95% sensitivity for PCa detection, an f/t PSA cutoff of 41% and a PSA-TZ cutoff of 0.095 would result in the lowest number of unnecessary biopsies (29.3% and 17.2% specificity for f/t PSA and PSA-TZ, respectively) compared with all other PSA-related parameters evaluated. CONCLUSIONS: Compared with standard total PSA assays, f/t PSA and PSA-TZ significantly enhance the sensitivity and specificity of PCa detection in a referral patient population with a total PSA of 2.5 to 4.0 ng/mL.

Adult↗

Insulin-like growth factor 1 (IGF-1), IGF-1 density, and IGF-1/PSA ratio for prostate cancer detection.

OBJECTIVES: Recent studies suggest an association between increased serum levels of insulin-like growth factor 1 (IGF-1) and an increased risk of prostate cancer (PCa). We prospectively analyzed the value of IGF-1, IGF-density (IGFD), and IGF-1/prostate-specific antigen (PSA) ratio for early detection of prostate cancer. METHODS: IGF-1, IGFD, and IGF-1/PSA ratio were determined prospectively during an 11-month period in the serum from 245 consecutive white men with PSA levels between 2.5 and 15 ng/mL. Octant biopsy (including transition zone biopsy) was performed. A second biopsy was performed 6 weeks later if the first biopsy was negative. Prostate volume was measured using transrectal ultrasound and the prolate ellipsoid method. Receiver operating characteristic curves were performed to compare tests. RESULTS: No evidence of malignancy was found in 174 patients (71%), and PCa was found in 71 (29%). The mean age for patients with no evidence of malignancy and those with PCa was 67.7+/-9 and 65.7+/-6 years, respectively (P = 0.17). IGF-1, IGFD, IGF-1/PSA ratio, and PSA were significantly higher in patients with PCa than in those with benign disease (P = 0.03, P = 0.045, P = 0.001, and P = 0.018, respectively). The area under the curve value derived from the receiver operating characteristic curves for IGF-1/PSA ratio, PSA, IGFD, and IGF-1 was 71%, 61%, 60%, and 58%, respectively. At 95% sensitivity, the specificity of the IGF-1/PSA ratio was significantly greater than that of all other parameters (P<0.0001 ). An IGF-1/PSA cutoff value of 25 afforded a 95% sensitivity for detecting PCa and would have avoided unnecessary biopsies in 24.1% of patients. CONCLUSIONS: Although IGF-1 and IGFD were unable to enhance the performance of PSA in our study, the IGF-1/PSA ratio significantly improved PCa detection over the use of PSA alone. Thus, increased IGF-1 levels (i.e., the IGF-1/PSA ratio) may not only be associated with an increased PCa risk but may also be a useful tool for early detection.

Aged↗

Evaluation of the in vitro and in vivo performance of two sustained-release lithium carbonate matrix tablets. Effect of different diets on the bioavailability.

Two sustained-release (SR) lithium carbonate (Li) matrix tablets, which use a hydrophilic (HP) matrix of hydroxypropylmethylcellulose (Methocel 4K MP) and a lipid (L) matrix of hydrogenated castor oil (Cutina HR) as sustaining agents, have been studied. In vitro performance through dissolution tests in different media was established. The L and HP formulations were affected by the composition of the dissolution media, and liberation was complete in 8 hr using a variable-pH medium that simulates the gastrointestinal (Gl) pH. Liberation was better described by the diffusional model of the square root of time for the L matrix and by zero-order kinetics for the HP matrix. Absolute bioavailability (BA) and food-induced changes on BA of both formulations were studied. The in vivo study design was a 4 x 4 Latin square involving 12 subjects who received two tablets of a 300-mg dose of SR formulations while fasting or with a standardized normal, high-fat, or high-fat/high-protein meal. The results for both formulations showed no differences in the disposition parameters and mean residence time when the tablets were administered with any type of diet. Changes in rate of absorption were found when both types of tablets were administered with any class of diet. The analysis of the ratio Cmax/AUC (area under the curve) evidenced that changes in Cmax were attributable to a higher rate of absorption for the HP matrix and to a higher amount absorbed for the L matrix. In the last, high-fat and high-fat/high-protein diets produced higher AUCs than under fasting condition. The SR Li tablets formulated with hydrogenated castor oil were affected more by high-fat food, probably because of the increase of pancreatic and biliary secretions promoted by the meal, which would affect the matrix itself. The HP matrix was also affected, but to a lesser extent. The magnitude of the change in Cmax observed with this matrix probably is not important from a clinical point of view. Absolute BA was very low for the lipid matrix; in addition, since it is more seriously affected by food, probably it is not a good choice for a drug such as lithium. The in vivo behavior of the HP matrix makes it advisable to invest in efforts to achieve increased BA. Comparing in vitro and in vivo results, the focus should be achieving sustained, but complete, in vitro liberation in not more than 3 hr, with simulation of the transit time through the stomach and small bowel since lithium ion is only absorbed to this point.

Analysis of Variance↗

In vitro conditions for the study of the in vivo performance of sustained-release theophylline matrix tablets administered in fasted conditions and with a high-fat diet.

Dissolution profiles of theophylline (TP) from three types of sustained-release (SR) matrix tablets (plastic [PL], lipid [LP], and hydrophilic [HP]) in different dissolution media, with and without enzymes, were established. Also investigated was the influence of a treatment of the tablets with peanut oil prior to the dissolution test. The in vivo behavior of the tablets under the fasted state and with the concomitant administration with a high-fat diet was previously evaluated; the diet produced changes in the absorption profiles for the three matrix tablets in comparison with fasted administration. Level A correlations were obtained between cumulative percentage dissolved (CPD) and cumulative percentage absorbed (CPA). For the fasted condition, better correlations were obtained with water as the dissolution medium for the HP and LP matrix; for PL matrix, the best correlation was obtained with a medium with gradual change of pH. The pretreatment with peanut oil showed better correlations for the fed state.

Animals↗

[Prevention of temporary prostatic obstruction after high-energy microwave thermothery by placement of prostatic bridge catheter].

OBJECTIVES: The clinical utility of a novel intraurethral prostatic bridge-catheter (PBC) was evaluated for prevention of temporary prostate obstruction following targeted high-energy transurethral microwave thermotherapy (TUMT) in patients with benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: High-energy TUMT was administered to 54 BPH patients under topical urethral anesthesia followed by placement of a PBC, which remained indwelling up to 1 month. Patient evaluation included determination of peak urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), and quality of life (QOL) score at baseline, immediately following TUMT and PBC placement, and at periodic intervals thereafter up to 1 month. Results were compared retrospectively with those of 51 patients who underwent TUMT followed by standard temporary urinary catheterization, generally for 24 h. RESULTS: Immediately following TUMT and PBC placement significant improvements (p < 0.0005) were observed in mean Qmax, IPSS and QOL score of 59.3%, 33.5% and 23.6% respectively, compared with baseline values. Further improvements were demonstrable up to 1 month, at which time mean Qmax, IPSS and QOL score had improved 79.0%, 54.9% and 56.5%, respectively, vs baseline means (p < 0.0005). In a retrospective comparison at baseline and 14 days between PBC recipients (PBC group) and a cohort of TUMT patients who had undergone temporary standard catheterization and subsequent catheter removal (standard catheterization group), mean baseline Qmax, IPSS and QOL score were similar between the two groups. However, at the 14 day follow-up evaluation in the PBC group mean Qmax was 101.8% higher, and IPSS and QOL score were 47.9% and 51.1% lower, respectively, than the corresponding values in the standard catheterization group (p 0.0005). The PBC was well tolerated and remained in situ throughout the entire 1 month follow-up period in 48/54 (88.9%) patients. Early PBC removal was performed in 3/54 patients (5.6%) because of urinary retention and in 3/54 patients (5.6%) due to PBC migration. During the acute post-TUMT recovery period, PBC recipients experienced impairment in sexual function which, though statistically significant, was comparatively small in magnitude. CONCLUSION: PBC provides an efficacious and well-tolerated option for preventing prostatic obstruction in the acute post-TUMT period. This approach avoids the inconvenience and infection risk of standard indwelling catheters or intermittent self-catheterization. PBC insertion and removal are rapid, facile and non-traumatic. PBC placement may prove useful in improving the early results of TUMT.

Aged↗

Outcome analysis of minimally invasive treatments for benign prostatic hyperplasia.

The armamentarium of minimally invasive treatment modalities for patients with benign prostatic hyperplasia has increased steadily during the past decade. The energy sources used range from microwaves and radiofrequency waves to high-intensity focused ultrasound, with laser vaporization/coagulation/resection and electrosurgical techniques. The large amount of data available allow some conclusions to be drawn concerning the present role of the "gold standard" TURP among the minimally invasive procedures. Although the subjective response after TURP and other minimally invasive procedures is comparable, improvements of flow and urodynamic parameters usually are more pronounced after TURP. Failure rates requiring reintervention (usually TURP) are considerable. Minimally invasive procedures lead to a shift of morbidity from the intraoperative phase, which is reduced (risk of bleeding, TUR syndrome, transfusion) to the postoperative phase. This period is characterized by prolonged urinary retention (ILC, VLAP), significant dysuria (VLAP, TUVP), and nycturia. Recent advances in electrosurgical techniques, such as band TURP loops that facilitate coagulation due to the longer contact time between the electrode and the tissue, have the potential to convert TURP into a less invasive procedure. Finally, high-energy TUMT seems to offer a truly minimally invasive treatment combining efficacy and the need for topical anesthesia only. However, due to a lack of homogeneity of criteria for patient recruitment, parameters of evaluation, and adequate follow-up; accurate guidelines for appropriate patient management have not been established yet.

Catheter Ablation↗

Combination and multivariate analysis of PSA-based parameters for prostate cancer prediction.

The aim of this study was to evaluate the ability of prostate-specific antigen (PSA)-based parameters including PSA density (PSAD), PSAD of the transition zone (PSA-TZ), percent free PSA, PSA velocity, and their combination to enhance the specificity of PSA for prostate cancer detection in men with serum PSA levels between 4 and 10 ng/mL. We evaluated prospectively 559 consecutive men referred for early detection of prostate cancer who had serum PSA levels between 4 and 10 ng/mL. All men underwent prostatic ultrasonography and sextant biopsy with two additional TZ biopsies. In all cases, if first biopsies were negative an additional set of biopsies was obtained within 6 weeks. The ability of PSAD, PSA-TZ, PSA velocity, percent free PSA, and their combination to improve the detection of prostate cancer was evaluated by univariate and multivariate analysis as well as receiver operating characteristic (ROC) curves. In this prospective study of 559 patients, 217 had prostate cancer and 342 had histologically confirmed benign prostatic hyperplasia. Multivariate analysis and ROC curves showed that PSA-TZ and percent free PSA (f/t PSA) were the most powerful and highly significant predictors of prostate cancer. Areas under the ROC curve (AUC) for PSA-TZ and percent free PSA were 0.827 and 0.778, respectively (p = .01). Combination of f/t PSA with PSA-TZ (AUC = 88.1%) significantly increased AUC as compared to each of the other parameters alone as well as their combination (p = .02). The next best combinations were PSA-TZ + PSAD, PSA-TZ + PSA, and f/t PSA + PSA. PSA-TZ followed by f/t PSA and PSAD were the most powerful predictors of prostate cancer in referred patients with a serum PSA between 4 and 10 ng/mL. f/t PSA + PSA-TZ was the most effective combination. When volume-independent PSA parameters were taken into consideration, f/t PSA + PSA clearly outperformed the other options.

Aged↗

Growth inhibitory and bactericidal efficacy of sera from Lyme borreliosis patients on B. burgdorferi strains.

Two B. afzelii strains EB1 and FEM1, classified in normal human sera (NHS) as serum-resistant, and an intermediate serum-sensitive B. burgdorferi s.s. strain 297, were tested in regard of their serum sensitivity in immune sera (IS) of patients at all stages of Lyme borreliosis by a growth inhibition assay (GIA). Fifty-four per cent (13/24) of the tested IS were GIA positive, while the sera of patients in stage III disease inhibited the growth more frequently than did the patients with sera of stage II or stage I disease. Growth inhibition was predominantly directed against strain FEM1 (12/24), less against strain EB1 (4/24) and strain 297 (2/24). A growth inhibiting effect on two strains was only detectable for two IS and merely one stage III serum inhibited all three strains. Positive results in the GIA required fresh serum and resulted in the killing of the borreliae. The detection of the deposited complement components C3 and C9 on the surfaces of the inhibited strains by means of immunofluorescence assays confirmed the role of complement. In Westernblot analyses of strain FEM1, it was striking that GIA-positive IS reacted 3- to 5-fold more often with proteins of molecular masses of 48.9-, 38.6-, 27.5-, 25-, 23.1- (OspC), 21.7-, and 16-kDa, than did GIA-negative IS. Furthermore, two proteins of approximately 20- and 31.2-kDa reacted exclusively with GIA-positive IS. Antibodies reacting with these proteins could play a role in the growth inhibition of NHS-resistant borrelial strains, OspC.

Antigens, Bacterial↗