A New Promising Pathway in Aggressive Prostate Cancer: Treg/mir-let8c/lin28b

Purpose: The progress of prostate cancer entails complex contemporaneous tumor developmental events in diverse stages that they are still yet to be clarified. miRNAs might accompany to balance between regulatory and cytotoxic T cells in tumors. Here, we investigated miRNAs and Regulatory T cell (Treg) marker FOXP3 expressions within prostate cancer spectrum. Methods: Thirty-eight prostate cancer patients enrolled within two groups to the study as having Gleason Score ≤ 7 (Group-1) and ≥ 8 (Group-2) that compared to 19 benign prostate hyperplasia controls. Twelve miRNAs expressions were analyzed by real time PCR from paraffin-embedded prostate tissue samples. Correlations between serum PSA levels, immunohistochemical staining of CD3, CD4, FOXP3 and miRNA expressions were analyzed. Results: In our study, hsa-let7c-3p significantly 1,52 (p=0.018) and 1,84 (p=0.0095) fold down- regulated whereas, miR-141-3p was significantly 2,36 (p=0.0006) and 2,24 (p=0.001) fold upregulated in the prostate cancer patients compared to benign prostate hyperplasia in group 1 and 2, respectively. Only CD4 (p=0.004) and PSA (p<0.001) have statistically significant differences among groups when compared to benign prostate hyperplasia. miR-143-p, miR-221-3p, hsa-let7c-3p and miR-17-3p expressions were significantly correlated with regulatory T cell marker FOXP3 expression. Conclusions: For the first time, we reported significantly altered expression levels of miRNAs (miR-let7c, miR221, miR-146a, miR-141, miR-143, miR17) and correlations between Treg marker FOXP3 in the aggressive prostate cancer patients suggesting that prostate cancer progression might be under the regulation of crosstalk between Tregs and miRNAs (AU)

Propósito: El progreso del cáncer de próstata implicaeventos complejos de desarrollo tumoral contemporáneo endiversas etapas que aún no se han aclarado. Aquí, investigamos los MIRNAs y el marcador de células T reguladoras(Treg) FOXP3 expresiones dentro del espectro de cáncer depróstata.Métodos: Treinta y ocho pacientes con cáncer depróstata inscritos dentro de dos grupos para el estudio unapuntuación de Gleason ≤ 7 (Grupo-1) y ≥ 8(Grupo-2)que en comparación con 19 controles benignos de hiperplasia de próstata. Doce expresiones miRNAs fueron analizadas por PCR en tiempo real a partir demuestras detejidoprostático incrustado en parafina. Se analizaronlos nivelesde PSA séricos de correlaciónsetween, la tinción inmunohistoquímica de expresiones CD3, CD4, FOXP3 y miRNA.Resultados: En nuestro estudio, has-let7c-3p significativamente 1,52 (p-0.018) y 1,84 (p-0. 0095) plegarsehacia abajo, mientras que, miR-141-3p fue significativamente 2,36 (p-0.0006) y 2,24 (p-0. 001) plegarse reguladoen los pacientes con cáncer de próstata en comparación conla hiperplasia benigna de próstata en los grupos 1 y 2, respectivamente. Sólo CD4 (p-0.004) y PSA (p<0. 001)tienen diferencias estadísticamente significativas entre losgrupos en comparación con la hiperplasia benigna de próstata. las expresiones miR-143-p, miR-221-3p, has-let7c-3py miR-17-3p se correlacionaron significativamente conlaexpresión FOXP3 del marcador de celda T egulatorio r.Conclusiones: Fo laprimera vez,informamos denivelde expresión significativamente alterado demiRNAs (miR-let7c, miR221, miR-146a, miR-141, miR-143,miR17) y correlaciones entre el marcador Treg DE Treg33en los pacientes agresivos de cáncer de próstata sugiriendoque la progresión del cáncer de próstata podría estar bajo laregulación de la cruz entre Tregtalks y miR. (AU)

Changes in antimicrobial resistance and demographics of UTIs in pediatric patients in a single institution over a 6-year period.

PURPOSE: To determine changes in antimicrobial resistance and demographics of UTIs in pediatric patients in a single institution over a 6-year period. MATERIALS AND METHODS: The current study examined outpatient urinary isolates from patients aged <18 years. A retrospective cross-sectional analysis of bacteria isolated from children with UTI was performed between 2009 and 2014. The most common bacterial pathogens were determined in the following four age groups: <2 years; 2-5 years; 6-12 years; and 13-17 years. The study analyzed the prevalence and antibiotic resistance patterns for the six most common uropathogens: Escherichia coli, Proteus, Klebsiella, Enterobacter, Pseudomonas and Enterococcus (Summary table). The antibiotic resistance pattern for UTI during 2009-2014 was also examined. RESULTS: A total of 6515 urinary cultures was examined. The majority of these isolates were from female patients (66.8%). E. coli was the most common uropathogen overall, but the prevalence of E. coli was higher among females (79.5%) than males (54.9%). The biggest percentage of isolates in males was from children aged <2 years (46.1%). Conversely, the majority of isolates in females were from children aged >6 years (46.8%). Results of antimicrobial resistance for E. coli were the highest for ampicillin (70%) and lowest for meropenem (0.19%). Comparing the hospital network data from 2009 to 2014, E. coli resistance increased for ampicillin (from 47.1% to 89%), trimethoprim-sulfamethoxazole (TMP-SMX) (from 44.8% to 56%) and nitrofurantoin (from 5.3% to 15.1%). In contrast, cephalosporins have maintained low antibiotic resistance. CONCLUSION: UTI in females was nearly twice as common than in males. E. coli remained the most common pediatric uropathogen. Although widely used in other tract infections, ampicillin was a poor empiric choice for pediatric UTIs. Cephalosporins were appropriate alternatives given their low resistance rates. A successful empirical treatment protocol should be based on local epidemiology and susceptibility rates.

Complete upper urinary tract obstruction caused by penetrating pellet injury of the ureterintroduction.

Ureteral injuries due to gunshots are tend to be misdiagnosed because of concomitant vascular and intraabdominal organ wounds. Our case is a 23-year-old man who was admitted to the hospital with multiple abdominal gunshot wounds. Laboratory findings showed worsening anemia, and the computed tomography (CT) scan showed multiple lead bullets inside the abdomen and retroperitoneum. Patient was then taken to the operation room for laparatomy. There were many intestinal injuries and also a stable retroperitoneal hematoma. There was no ureteral injury mentioned in the operation note or the initial CT report. Two weeks after this operation, the patient developed significant urine leakage from the abdominal wounds. Ureteral J stent placement was our first choice of treatment. This was complicated with a late ureteral obstruction. The final treatment was an ureteroureterostomy. Diagnosing ureteral injuries due to traumatic causes can be hard in most of the cases. Physicians should consider early evaluation of the patient for ureteral leakage if there is suspicion about ureteral injury.

Comparison of combined antioxidants and thymoquinone in the prevention of testis ischemia - reperfusion injury.

We aimed to compare the preventive effects of combined antioxidants (CA1, 2) with a single antioxidant drug (thymoquinone; TQ) on experimental testis Ischemia/Reperfusion (I/R) injury. Thirty-five adult male Wistar rats were divided into five groups of seven rats each: control, testis I/R, testis I/R + CA1, testis I/R + CA2, and testis I/R + TQ. After 1 h of testicular ischemia, reperfusion was achieved by detorsion for 4 h. Antioxidants were intraperitoneally administered for 30 min prior to reperfusion. All rats were sacrificed 4 h after reperfusion to evaluate the tissue levels of malondialdehyde (MDA) and total antioxidant status (TAS) and the immunohistochemical evaluation of tissue inducible and endothelial nitric acid synthase (iNOS, eNOS) and apoptosis protease-activating factor 1 (APAF-1). MDA levels were lower and TAS values were higher in the I/R + antioxidant groups than in the I/R group (p < 0.05). iNOS and eNOS levels in the I/R + antioxidant groups were also lower than those in the I/R group (p < 0.05). There were no significant differences between the CA groups and the TQ group according to aforementioned parameters. In addition, tissue APAF-1 values were significantly higher in the I/R group than in the other groups. However, there was a significant difference between the TQ and CA groups in APAF-1 levels, which were highest in the TQ group (p < 0.05). Although TQ alone increased TAS values and reduced tissue iNOS and eNOS levels, combined antioxidant treatment may more effectively reduce apoptosis and increase preventive effects in testis I/R injury.

Manganese superoxide dismutase polymorphism in chronic pelvic pain syndrome patients.

Chronic pelvic pain syndrome (CPPS) is a common and serious health problem affecting the quality of life in men. In this study, we aim to investigate the manganese superoxide dismutase (MnSOD) polymorphism at nucleotide 47 as a result of the change of Ala to Val on the protein sequence in CPPS patients. The frequencies were 0.45 and 0.38 for the Ala and 0.55 and 0.62 for Val in National Institutes of Health category 3a and 3b groups. The differences between control and CPPS patients were statistically significant (P<0.05). However, frequencies recorded in 3a and 3b groups were not statistically different (P>0.05). Same results were obtained for enzyme analysis of MnSOD and glutathione peroxidase. Control group antioxidant enzyme levels were higher than patients' samples. The low antioxidant status of CPPS patients might be the clue for pathophysiological problems, and highly distributed Val allele frequency can be a mediator point of the illness. Our findings lead to the suggestion that oxidative disorder-linked medical health problems can be associated with genetic risk factors such as polymorphisms.

Color doppler ultrasonography and spectral analysis of venous flow in diagnosis of varicocele.

OBJECTIVE: The standardization of diagnostic criteria for varicocele has not yet been established. This causes difficulty in evaluating both the incidence and clinical studies. Our aim was to establish diagnostic criteria for varicocele in Doppler procedures. METHODS: The characteristics of blood flow in the internal spermatic vein were investigated with color Doppler ultrasonography (CDU) and venous flow spectral analysis in 100 infertile men without clinical varicocele (group I), 100 infertile men with clinical left varicocele (group II), and 50 fertile men without clinical varicocele served as controls (group III). RESULTS: Three types of flow pattern were found in the spectral analysis of venous flow. If the venous flow was directed to the heart and did not change direction with an intra-abdominal pressure increase, it was classified as type I; venous flow directed to the heart, but changing direction with an intra-abdominal pressure increase, was classified as type II, and blood flow directed to the testicles and augmenting with an intra-abdominal pressure increase, was classified as type III. In group I, flow patterns were 39, 56 and 5% on the left side and 55, 42 and 3% on the right side for types I, II and III, respectively. In group II, flow patterns were 0, 35 and 65% on the left side and 61, 38 and 1% on the right side for type I, II and III patterns, respectively. In group III, the figures were 44, 54 and 2% for the left and 54, 46 and 0% for the right. Type II and III flow patterns were seen more frequently than type I in patients with clinical left varicocele (p<0.001). Whereas type I and II flow patterns were more common than type III in subjects without clinical varicocele (p<0.05). A type II flow pattern during normal breathing was seen at a lower rate in the control group than in the other groups (p<0.05). CONCLUSION: Spectral analysis of Doppler waves should be used in combination with CDU for the diagnosis of varicocele. Varicocele should not only be diagnosed with a type II flow pattern which occurs during valsalva. For the diagnosis of varicocele, the main criterion must be a type III pattern flow, as well as a type II pattern during normal breathing.

Serum PSA and age-specific reference ranges in patients with prostatism symptoms.

Prostatic specific antigen (PSA), a tumour marker helpful in the diagnosis and follow-up of prostate cancer, may rise due to causes other than prostate cancer (i.e. BPH, acute prostatitis, etc.). Investigations in order to increase the sensitivity and specificity of PSA in prostate carcinoma are being carried out. Serum PSA levels of patients with prostatism with regard to age as well as these levels in the male population at risk but without clinical prostatic disease (those above the age of 40) should be well documented. The aim of this study is to find age-specific values and ranges of PSA in patients with prostatism symptoms.

Echo-colour doppler ultrasonography in the diagnosis of varicocele.

The relationship between varicocele and infertility has long been defined. About a third of the male patients undergoing evaluation for infertility present with a varicocele. Sixty male patients between 17 and 35 years of age (mean 25.6) were examined with a colour-doppler flow imaging system. The diameters of the veins in the pampiniform plexus were measured by gray-scale sonography. Our findings were classified with regard to venous diameter, the existence or non-existence of reflux, the circumstances under which these findings were recorded (e.g. during normal respiration and standing position or during Valsalva manoeuvre and supine position). Finally our results suggest that: (a) the clinical significance of the presence of dilated veins or reflux during increased intraabdominal pressure and under similar circumstances should be regarded with caution; (b) positive findings during normal inspirium are highly significant (grades III and IV).

Immature germ cells in semen and their correlations with other semen parameters.

PURPOSE: The significance of the presence of leukocytes and immature germ cells in semen and other parameters of semen is currently a subject of controversy. MATERIALS AND METHODS: Semen from 572 subfertile patients was analyzed according to WHO criteria and leukocytes as well as immature germ cells were assessed by identifying the round cells in semen by peroxidase staining. Microbiological investigation was carried out in cases with leukocyte counts of >1,000,000/ml. RESULTS: It was found that as the concentration of spermatozoa decreased the rate of immature germ cells increased and this increase was accompanied by a decrease in motility and in the number of spermatozoa with normal morphology. As the sperm count increased, motility, number of spermatozoa with normal morphology and of immature germ cells also increased whereas an increase in sperm motility was accompanied by an increase in the percentage of spermatozoa with normal morphology. Microbiological investigations were negative in patients with semen leukocyte counts of >l,000,000/ml. CONCLUSIONS: Although it is possible to establish that the leukocyte and immature germ cell counts correlate with other parameters of semen, these correlations are not statistically significant. The most significant finding is that as the number of sperms decreases, the ratio of immature germ cells to total germ cells increases. While assessing immature germ cells instead of giving special attention to the number of immature germ cells in semen, the ratio of immature germ cells to total germ cells should be considered. The increase of leukocyte count in the semen of oligospermic patients may not always mean leukospermia.

Prospective evaluation of prostate specific antigen (PSA), PSA density, free-to-total PSA ratio and a new formula (prostate malignancy index) for detecting prostate cancer and preventing negative biopsies in patients with normal rectal examinations and intermediate PSA levels.

OBJECTIVE: To improve the specificity and sensitivity of prostatic cancer detection, we prospectively evaluated total prostate specific antigen (PSA) level, PSA density, free-to-total PSA ratio and a new formula called prostate malignancy index (PMI) as a discriminator of prostate cancer in patients with intermediate PSA levels and normal digital rectal examinations. MATERIALS AND METHODS: Between November 1995 and October 1997, 95 patients who had serum PSA levels of 4.0 to 10.0 ng/ml with normal digital rectal examinations were prospectively evaluated. All patients underwent one or two times transrectal ultrasound guided prostate biopsies. Based on age specific reference range of PSA, PSA density and % free PSA ratio, PMI was calculated for each patient. The free and total serum PSA concentrations were determined by an Immulite assay system. (Diagnostic Product Corp., Los Angeles, California). RESULTS: Overall 20 of 95 (21%) patients had prostate cancer. There were no significant differences in patient mean age and mean total PSA between those with benign and those with malignant biopsies (p>0.05). However, there were significant differences in mean PSAD, mean free-to-total PSA ratio and mean PMI (p<0.01, p<0.05, p<0.01, respectively). Benign condition specificities for PM index, percent free PSA, PSA density and total PSA at a 90% sensitivity for prostate cancer were 48%, 10.6%, 8% and 4%, respectively. Of 95 patients, 27 (28.4%) had a PMI of equal or more than 3.1, including 12 of 75 (16%) with negative biopsy and 15 of 20 (75%) with positive biopsy. Furthermore a cutoff MI 0.86 P correctly identified 24% of benign cases without missing any prostate cancer cases. The comparison of receiver operating characteristic (ROC) curve areas showed that PMI was better than total PSA (p<0.01). Although, the area under the ROC curve of % free PSA and PSAD were higher than the area of total PSA, these differences were not statistically significant (p>0.05). CONCLUSIONS: We concluded that the prostate malignancy index could be utilized to differentiate benign conditions from prostate cancer in patients with intermediate PSA levels and normal digital rectal examination. Also significant numbers of negative biopsies can be prevented in these patients.

[The role of trans-rectal echography (TRE) in the evaluation and staging of bladder tumors: comparison with suprapubic echography and computerized axial tomography (CAT)]. / Il ruolo dell'ecografia trans-rettale (ETR) nella valutazione e stadiazione dei tumori vescicali: confronto con ecografia sovrapubica e tomografia assiale computerizzata (TAC).

TAU and CT are, after cystoscopy, the two most largely used methods in the diagnosis and the staging of the bladder tumors. TRUS is mostly used in the pathologies of the prostate and the seminal vesicles. 38 patients (34 M and 4 F) suffering from bladder cancer are included in this study in the period from July 1995 to January 1997. They are evaluated with TAU, TRUS and CT in order to evaluate the sensitivity and the specificity of TRUS in the diagnosis and the stadiation of bladder tumors. The patients included in this study are divided in two subgroups as patients having superficial and infiltrating tumors according to pathologic stage after TURB or radical cystoprostatectomy. Specificity and sensitivity values, overstaging and undestaging rates are calculated for each group. In the superficial tumors, TAU had a sensitivity and specificity of 72.2%, while with CT these values were respectively 70% and 75%; in the infiltrating tumors, TAU presented sensitivity of 65% and specificity of 70% while CT presented respectively 72.2% and 77.5%. With TRUS these values were 88.8% and 94.4% in the superficial tumors and 90% and 95% in the infiltrating tumors. The method with the highest overstaging rate was CT with 33.3% while the ones with the highest understaging rates were TAU and CT with 22.2%. The sensitivity with TRUS was 100% in a total of 29 infiltrating and superficial tumors of the trigone while it was only 55.5% in the tumors of the lateral walls and the dome. With TAU these values were respectively 82.7% and 22.2%, with CT respectively 79.3% and 44.4%. The specificity with TRUS was 100% for the tumors of the lateral walls and 77.7% of the dome; with TAU these values were respectively 75.8% and 55.5% with CT 75.8% and 77.7%. In conclusion, TRUS may be used with a high sensitivity and specificity in the diagnosis and the stadiation of infiltrating and superficial bladder tumors situated at the peritrigonal zone and in the diagnosis of tumors situated in other regions of the bladder.

Fracture of the penis.

Fracture of the penis is a rare condition. The fracture is easy to recognize but treatment remains controversial. Between December 1991 and January 1997, eleven patients underwent emergency operation on the first day after penile fracture. Our operative plan consisted of immediate exploration, identification, debridement and primary repair of the tear in the tunica albuginea. The patients' mean age was 27 years (range 21-38 yrs.). Penile fracture was due to sexual manoeuvres in 8, manipulation in 2 and fall onto erect penis in one of 11 patients. The mean hospitalization time was 2.2 days (range 1 to 3 days). There was no significant early postoperative complication except wound infection in one patient. In the first postoperative month, there was a residual fibrosis due to nonabsorbable sutures in one patient and mild pain during coitus in the other one. All patients had full erection and no patient needed additional treatment. To avoid serious complications and preserve penile functions immediate surgical intervention is recommended.

Urinary tuberculosis in a two-year-old boy.

The authors describe a case of genitourinary tuberculosis hitherto unobserved in early childhood.

Acupuncture and hypnotic suggestions in the treatment of non-organic male sexual dysfunction.

We have examined the effects of acupuncture and hypnotic suggestions, and compared them with placebo in the treatment of male sexual dysfunction with no detectable organic cause. The study comprised 15 men (mean age 36.7 +/- 10.43 years) who received acupuncture treatment, 16 men (mean age 38.4 +/- 10.75 years) who underwent hypnosis (mean age 35.3 +/- 11.52 years) and 29 men (mean age 36.2 +/- 11.38 years) who served as controls. They were interviewed periodically; the patients' reports were verified by interviewing their partners. Men who received placebo had a 43-47% improvement in sexual function, while the rates of improvement in the treated groups were higher, but not significantly so. The success rates of acupuncture and hypnotic suggestions were 60% and 75% respectively. Although the improvement was not statistically significant, treatment with acupuncture could be used as an adjuvant therapy in non-organic male sexual dysfunction. The only treatment superior to placebo seemed to be hypnosis. A more effective treatment may be obtained by combining these therapeutic modalities, but this needs further study.