Circulating microRNAs as novel biomarkers for measuring the potency of ginger extract against cyclophosphamide toxicity in rat renal tissues: molecular and histopathological study.

OBJECTIVE: This study aims to explore underlying molecular variations in the expression of miRNAs in kidney tissues of ginger-treated and non-treated cyclophosphamide (CP)-intoxicated rats. MATERIALS AND METHODS:   A total of 40 adult male Wistar rats were randomly divided into four groups of 10 each: Group I (control: received normal food and water), Group II (received ginger at a dose of 300 mg/kg), Group III (received CP 75 mg/kg, i.p.), and Group IV (received the same dose of CP and ginger extract).  Rats received a single injection of 75 mg/kg CP on days 3, 4, 5, 19, 20, and 21. In CP-intoxicated rats, the treatment with ginger extract at a dose of 300 mg/kg was received by oral gavage starting seven days before CP and continuing throughout the duration of the experiment for four weeks. Molecular variations in the expression of miRNAs, apoptotic genes, histological kidney damage, and abnormal kidney function in control, ginger, and CP-intoxicated rats were identified by using real-time RT-PCR Analysis, immunohistochemical, and colorimetric assays. In addition, HPLC analysis and liquid chromatography spectrophotometry analysis using Diphenyl-1-picrylhydrazyl (DPPH) radical, and Β-Carotene-linoleic acid reagents were applied respectively for in-vitro screening of phytoconstituents and antioxidant activity for ginger extract. RESULTS: The kidney tissues of CP-intoxicated rats displayed an increase in lipid peroxidation marker malonaldehyde (MDA), DNA damage, and fibrosis markers like hyaluronic acid (HA) and hydroxyproline Hypx) with a decrease in the superoxide dismutase (SOD) and total antioxidant capacity (TAC). In addition, molecular expressions of mRNA fibrotic genes such as collagen, type 1, alpha 1 (COL1A1), and α-smooth muscle actin (αSMA). Molecular expressions of levels of B-cell lymphoma 2 (BCl-2) mRNA gene were down-regulated, and the expression of mRNA apoptotic; BCL2 associated X gene (Bax), caspase-3, Bax/BCl-2 ratio genes were significantly up-regulated respectively. Moreover, cellular oxidative genes, erythroid 2-related factor (Nrf2), and heme oxygenase-1 (HO-1) were down-regulated, respectively. The miR-155-5p, miR-34a-5p, miR-21-5p significantly increased while the miR-193b-3p, miR-455-3p, and miR-342-3p significantly decreased. Ginger also increased the expression of Nrf2, HO-1, and BCl-2 genes in the kidneys of rats induced with CP. In addition, active phytoconstituents, particularly 6]]-shogaol and 6]]-gingerol, were significantly identified in ginger extract using HPLC analysis. Antioxidant activity of these active metabolites were shown to be higher against in vitro free radicals (DPPH and Β-Carotene-linoleic acid), suggesting the potential antioxidant and antiapoptotic properties of ginger against CP-toxicity. CONCLUSIONS: Treatment with ginger in rats induced with CP resulted in significant improvement in the expression of certain molecular miRNAs. The kidney tissues of these rats showed a marked decrease in the expression of miR-155-5p, miR-34a-5p, and miR-21-5p, while the levels of miR-193b-3p, miR-455-3p, and miR-342-3p were observed to increase significantly. In conclusion, ginger can protect rats from CP-induced nephrotoxicity.

Protective effect of Stevia on diabetic induced testicular damage: an immunohistochemical and ultrastructural study.

OBJECTIVE: Diabetes mellitus (DM) has been considered a major problem because of its related complications and growing incidence worldwide. Testicular dysfunction has become a predominant diabetic complication characterized by impaired reproductive function and testicular damage. Stevia rebaudiana Bertoni has been known for its antioxidant effect on diabetes, inflammation, and obesity. The current study investigates the protective effect of Stevia on diabetic-induced testicular injury. MATERIALS AND METHODS: Sprague Dawley adult male rats were divided into three groups: the control group, the diabetic group, and the diabetic + Stevia group, type 2 diabetes is induced by a high-fat diet (HFD) and a single dose of 35 mg/kg streptozotocin injection. The effects of Stevia were evaluated regarding biochemical, oxidative stress, histopathological and ultrastructural changes, and immunohistochemical expression of vascular endothelial growth factor (VEGF), vascular cell adhesion molecule-1 (VCAM-1), receptor-interacting serine/threonine-protein kinase 1 (RIPK 1), and caspase 3. RESULTS: Stevia extract attenuated the diabetic-induced oxidative stress, restored the testicular architecture, and decreased testicular damage, inflammation, necroptosis, and apoptosis by upregulating VEGF and downregulating VCAM 1, RIPK 1, and caspase 3. CONCLUSIONS: The current study highlights the importance of Stevia as an antioxidant anti-inflammatory that ameliorates diabetic-induced testicular injury by modulating oxidative stress, inflammation, necroptosis, and apoptosis.

Transurethral incision of ureterocele: Does the time of presentation affect the need for further surgical interventions?

OBJECTIVES: Ureterocele management is considered to be one of the famous debates in pediatric urology. Despite some considering transurethral ureterocele incision (TUI) as a temporary line of treatment, others have reported good results in terms of being a definitive treatment. The present study evaluated the feasibility of TUI as a definitive line of management. Moreover, it studied the impact of presentation on the outcomes. PATIENTS AND METHODS: The charts of patients who had ureteroceles from 1995 to 2015 were retrospectively reviewed. Patients who had undergone initial TUI were included. The initial presentation and timing were recorded. All ultrasounds, voiding cystourethrograms (VCUG) and dimercaptosuccinic acid scans (DMSA) pre-TUI and post-TUI were reviewed. Moreover, the occurrence of febrile urinary tract infections (FUTI) and any secondary surgical intervention were recorded. RESULTS (FIG. A): A total of 51 patients with 53 ureteroceles were included. Of these, 51% presented antenatally, while others had FUTI at the time of presentation. Thirty-nine ureteroceles were associated with duplex system ureterocele (DSU), while the remaining ones had single system ureterocele (SSU). The median follow-up was 44 months. The incidence of de-novo reflux into ureterocele was 44% of SSU and 23% of DSU (P = 0.22). Reflux into ureterocele after TUI (four SSU and seven DSU) carried a high risk of surgical interventions (3/4 SSU and 6/7 DSU). Hydronephrosis was improved in 64% of both DSU and SSU patients. Secondary surgery was performed in 51% of DSU and 35.7% of SSU. Twelve patients (67%) presented postnatally with DSU and had subsequent interventions after incision in comparison with 38% (eight patients) of those who presented antenatally. The DSU had improved renal function (by DMSA) in 26%, while the remaining had stable renal function. DISCUSSION: All patients with delayed ureterocele presentation had FUTI, while 1/3 of antenatally presenting patients had FUTI during follow-up. Notably, the age at subsequent interventions was apparently the same despite different ages at presentation. Study limitations included the retrospective chart review. Additionally, the pre-operative and postoperative investigations, such as laboratory and radiological results, were present and reviewed in most, but not all, patients. CONCLUSION: Two thirds of SSU and approximately half DSU patients had no surgical intervention after TUI. However, those who presented antenatally had a lower risk of FUTI and lesser probability of being re-operated. VUR into ureterocele, regardless the system duplicity, had a high re-operation rate. After ureterocele incision, 26% of DSU patients had renal function improvement.

Comprehensive analysis of the clinical and urodynamic outcomes of primary tethered spinal cord before and after spinal cord untethering.

INTRODUCTION: Primary tethered spinal cord (TSC) refers to a group of abnormalities associated with a posterior bony spinal defect that develops beneath an intact dermis and epidermis. There is relative agreement that patients with symptomatic TSC will require surgical intervention. However, it is still debatable as to how to approach asymptomatic patients with primary TSC. OBJECTIVE: To study the clinical and urodynamic (UDS) outcomes of patients with primary TSC after spinal cord untethering (SCU). STUDY DESIGN: Charts of patients with primary TSC between 1998 and 2010 were retrospectively reviewed. Patients that underwent before and after SCU clinical and UDS evaluation with minimum of 5-years follow-up were included. Continence status was assessed in children ≥5 years. Patients with dry intervals of ≥4 h were considered continent. Urologic and neuro-orthopedic manifestations, as well as UDS parameters, were compared before and after SCU. Categorical data were compared using Fisher-Exact test and continuous variables were compared using Wilcoxon-Signed-Rank test. A P-value <0.05 was considered significant. RESULTS: Twenty-two patients met the inclusion criteria. The median age at time of SCU was 11.5 months (range 3-211). The median age at time of follow-up UDS after SCU was 22 months (range 9-218). The median age at time of last follow-up was 153.5 months (range 65-228). The median follow-up time was 71 months (range 60-192). A total of 14/22 patients had clinical manifestation before SCU, while 8/22 were asymptomatic and diagnosed based on magnetic resonance imaging/UDS findings. Of the symptomatic patients, 86% had symptom improvement after SCU. The UDS parameters showed statistically significant improvement in the median percentage of change of actual bladder capacity (P = 0.01), median intravesical pressure for patients with pre-operative pressure ≥40 cm/H2O at total cystometric bladder capacity (P = 0.012), and median bladder compliance at 75% bladder capacity (P = 0.01) (Table). DISCUSSION: Tethered spinal cord syndrome (TSCS) is a clinical entity that presents with neurological, urological, and/or orthopedic symptoms caused by primary or secondary tethering of the spinal cord, which may result in ischemic damage of the neural tissue and symptom development. While some authors believe that surgical management should be reserved for symptomatic patients, others prefer prophylactic surgery to avoid possible irreversible neurological damage. The present study provides detailed discussion of the clinical and UDS outcomes for patients with primary TSC that underwent SCU. CONCLUSION: For patients with primary TSC, spinal cord untethering is beneficial in terms of clinical and UDS outcomes. A prospective long-term study with large numbers could further highlight outcomes for this particular group of patients.

Testicular hypertrophy as a predictor for contralateral monorchism: Retrospective review of prospectively recorded data.

OBJECTIVES: Testicular hypertrophy has previously been evaluated as a predictor of monorchism. However, its implication in clinical practice is not well evaluated. The aim of the present study was to examine its value in planning the operative time. PATIENTS AND METHODS: Medical charts of prospectively recorded data of 76 consecutive patients with unilateral impalpable testis from 2011 to 2014 were reviewed at the present institute. Inclusion criteria included prepubertal patients with non-palpable testes by examination under anesthesia. Contralateral testes were prospectively measured using a Takihara orchidometer. Orchiectomy or orchiopexy was performed according to the viability of the undescended testis (UDT). Collected data included age of surgery, contralateral testicular size, surgical time and laparoscopic findings. A ROC curve was used to define the best cut-off volume of the contralateral testis that can predict ipsilateral testicular viability. The Student's t-test was used to examine if this cut-off volume would be useful in allocating the operative time. RESULTS: Of 76 patients, four palpable testes by examination under anesthesia were excluded. The remaining 72 patients were included in the study. Ipsilateral normal viable testes were found in 26 (36.1%) patients, while 46 (63.9%) had non-viable testes (testicular nubbins or vanishing testes) (Figure). A contralateral testicular volume > 2 ml was significantly predictive for monorchism with 71.7% sensitivity and 100% specificity (P < 0.001). The mean operative time for management of UDT with a contralateral size >2 ml was 50 min, which was significantly shorter than that for UDT with a contralateral size ≤ 2 ml, which was 88 min (P < 0.001). DISCUSSION: In previously published reports, the cut-off value for testicular hypertrophy that predicts monorchism greatly varied. This is likely due to the different methods used for testicular measurements that make it impractical to make a direct comparison. The usefulness of predicting monorchism before surgery has not previously been used as a guide for allocating operative time in the management of a unilateral non-palpable testicle. This study had some limitations, including a relatively small sample size and involvement of different surgeons, which may have affected the operative time. CONCLUSION: Using the cut-off volume of a contralateral testis >2 ml as a predictor for monorchism can reduce the allocated operative time by approximately one third.

Short communication: A nanoemulsified form of oil blends positively affects the fatty acid proportion in ruminal batch cultures.

Two consecutive rumen batch cultures were used to study the effect of nanoemulsified oils as a new type of supplement, on the in vitro fatty acid proportion and vaccenic acid formation. Three levels (3, 5, and 7%) of 2 different oil blends [soybean:fish oil (SF) or rapeseed-fish oil (RF)] were used. Both oil blends were used either in the raw form (SF or RF, respectively) or in the nanoemulsified form (NSF or NRF, respectively). The diets were the control (0%), which consisted of a dry total mixed ration without any supplements, the control plus 3, 5, or 7% of the SF or RF oil blend in appropriate form (raw or nanoemulsified). For each treatment, 6 incubation vessels were used. Each batch culture was incubated for 24h and conducted twice in 2 consecutive days. All supplements were calculated as a percentage of the substrate dry matter (400mg). Nanoemulsified supplements were recalculated to make sure the oil amount was equal to the raw oil supplementation levels. The results from both experiments indicated that the proportions of vaccenic acid and cis-9,trans-11 C18:2 increased when a raw oil blend was supplemented; on the other hand, no influence of nanoemulsified form of oil blend was observed on the proportion cis-9,trans-11 C18:2. Generally, supplementation with the nanoemulsified oil blends had less effect on biohydrogenation intermediates than the raw form of oil blends. However, the nanoemulsified form had a greater effect on the increase of n-3 and n-6 fatty acids. Nanoemulsified oil blends had a positive effect on decreasing the transformation rate of polyunsaturated fatty acids to saturated fatty acids in the biohydrogenation environment. Supplements of nanoemulsified oil blends tended to be more effective than supplements of raw oils in preserving a greater proportion of polyunsaturated fatty acids in the fermentation culture.

Evaluating the photo-catalytic application of Fenton's reagent augmented with TiO(2) and ZnO for the mineralization of an oil-water emulsion.

In the present study, homogenous (photo-Fenton) and heterogeneous photo-assisted systems (Fenton/TiO(2)/UV, Fenton/ZnO/UV and Fenton/TiO(2)/UV/Air) were investigated for the treatment of a diesel-oil wastewater emulsion. The augmentation of the photo-Fenton process by heterogeneous TiO(2) increased the reaction rate, in terms of COD reduction efficiency from 61% to 71%. Furthermore, the COD removal efficiency was increased to 84% when air was bubbled through the reactants. However, if the Fenton/TiO(2) /UV/Air process is to be utilized as a treatment for this wastewater, the separation of the TiO(2) from the treated effluent would need further consideration.

Photo-catalytic degradation of an oil-water emulsion using the photo-fenton treatment process: effects and statistical optimization.

The application of advanced oxidation processes (AOPs) to the treatment of an effluent contaminated with hydrocarbon oils was investigated. The AOPs conducted were Fe2+/H2O2 (Fenton's reagent), Fe2+/H2O2/UV (Photo-Fenton's reagent) and UV-photolysis. These technologies utilize the very strong oxidizing power of hydroxyl radicals to oxidize organic compounds to harmless end products such as CO2 and H2O. A synthetic wastewater generated by emulsifying diesel oil and water was used. This wastewater might simulate, for example, a waste resulting from a hydrocarbon oil spill, onto which detergent was sprayed. The experiments utilising the Photo-Fenton treatment method with an artificial UV source, coupled with Fenton's reagent, suggest that the hydrocarbon oil is readily degradable, but that the emulsifying agent is much more resistant to degradation. The results showed that the COD (chemical oxygen demand) removal rate was affected by the Photo-Fenton parameters (Fe2+, H2O2 concentrations and the initial pH) of the aqueous solution. In addition, the applicability of the treatment method to a 'real' wastewater contaminated with hydrocarbon oil is demonstrated. The 'real' wastewater was sourced at a nearby car-wash facility located at a petroleum filling station and the experimental results demonstrate the effectiveness of the treatment method in this case. A statistical analysis of the experimental data using the Statistical Analysis System (SAS) and the response surface methodology (RSM) based on the experimental design was applied to optimize the Photo-Fenton parameters (concentrations of Fe2+, H2O2 and initial pH) and to maximize the COD removal rate (more than 70%).

Elevated serum endostatin levels are associated with favorable outcome in acute myeloid leukemia.

BACKGROUND: Endostatin is the C-terminal antiangiogenic fragment of the extracellular matrix protein collagen XVIII, and is generated by tumor-derived proteases. The levels and the prognostic relevance of serum endostatin in acute myeloid leukaemia (AML) patient are not fully clear. OBJECTIVE: The aim of this study was to evaluate serum levels of endostatin in acute myeloid leukemia patients before chemotherapy and after achieving complete remission and to correlate endostatin levels with patient outcome. MATERIALS AND METHODS: Serum samples from 30 adult patients (22 males and eight females, median age 37, range 19-66 years) with AML had been taken before chemotherapy was administered. In addition 25 out of 30 patients were reinvestigated again at complete remission (CR). Ten samples from healthy normal persons of matched age and sex were evaluated as a reference control group. Serum endostatin levels were determined using enzyme linked immune sorbent assay (ELISA). Endostatin serum levels were not significantly different in the pre-treatment AML patients as compared to that in normal controls (p>0.05). In AML patients the baseline endostatin levels were significantly lower than at CR (p=0.001). RESULTS: No significant relation were detected between pre-treatment serum endostatin levels and age, peripheral blood white cell counts, platelet counts, bone marrow blast cell counts, blast cell distribution ratio or cytogenetic findings. The prognostic value of serum endostatin (sE) was also evaluated by dividing AML patients into high and low sE groups using the 75 percentile sE levels of the patients group as cutoff. The authors found that patients group in the high sE group survived for significantly longer time than those patients in the low sE group. CONCLUSION: Elevated endostatin levels at AML diagnosis is a good prognostic marker for patients' outcome. Wide scale study is recommended in order to establish the clinical value of this study.

Elevated serum endostatin levels is associated with favorable outcome in acute myeloid leukemia.

INTRODUCTION: Endostatin is the C-terminal antiangiogenic fragment of the extracellular matrix protein collagen XVIII, and is generated by tumor-derived proteases. The levels and the prognostic relevance of serum endostatin in AML patient is not fully clear. AIM: To evaluate serum levels of endostatin in acute myeloid leukemia patients before chemotherapy and after achieving complete remission and to correlate endostatin levels with patients outcome. MATERIALS AND METHODS: Serum samples from 30 adult patients (22 males and 8 females, median age 37, range 19-66 years) with AML had been taken before chemotherapy was administered. In addition 20 out of 30 patients were reinvestigated again at complete remission (CR). Ten samples from healthy normal persons of matched age and sex were evaluated as a reference control group. Serum endostatin levels were determined using enzyme linked immune sorbent assay (ELISA). RESULTS: Endostatin serum levels were not significantly different in the pretreatment AML patients as compared to that in normal controls (P>0.05). In AML patients the baseline endostatin levels were significantly lower than at CR (P=0.001). No significant correlation were detected between pretreatment serum endostatin levels and age, peripheral blood white cell counts, platelet counts, bone marrow blast cell counts, blast cell distribution ratio. The prognostic value of sE was also evaluated by dividing AML patients into high and low sE groups using the 75 percentile sE levels of the patients group as cutoff. The authors found that patients group in the high sE group survived for significantly longer time than those patients in the low sE group. CONCLUSIONS: Elevated endostatin levels at AML diagnosis is a good prognostic marker for patients' outcome. Wide scale study is recommended in order to establish the clinical value of this study.

Prognostic relevance of circulating matrix metalloproteinase-2 in acute myeloid leukaemia patients.

Matrix metalloproteinases (MMPs) were postulated to have important implication in progression and invasiveness of many malignant disorders. On the other hand the biological role of MMP-2 in acute myeloid leukaemia (AML) is not fully clear. Serum samples from 37 adult patients with AML had been taken before chemotherapy was administered. In addition 20 out of the 37 patients were analysed again after achieving complete remission (CR). Ten samples from healthy volunteers were evaluated as the control. Total MMP-2 levels were measured using ELISA Kit obtained from R&D system. MMP-2 serum levels were significantly lower in pretreatment AML patients than that in the normal controls (p = 0.000) and in CR (p = 0.007). No significant correlations were detected between pretreatment sMMP-2 levels and FAB subtypes, peripheral blood blast cell counts, peripheral blood WBCs, bone marrow blast cell counts or blast cell distribution ratio. The prognostic value of MMP-2 was evaluated by dividing AML patients into high and low MMP-2 groups using the pretreatment median MMP-2 level of the AML group as the cut-off. The authors found that patients in the high group survived for a significantly shorter time than those patients in the lower MMP-2 group. High pretreatment levels of sMMP-2 among AML patients were associated with poor survival. Prospective studies are recommended to establish the clinical value of longitudinal sMMP-2 measurement.

Vaginal reconstruction with a greater omentum-pedicled graft combined with a vicryl mesh after anterior pelvic exenteration. Surgical approach with long-term follow-up.

Resection of anterior vaginal wall that occurs with some cases of anterior pelvic exenteration leaves the patient with a small and narrow vagina. This affects their sexual life leading to major psychologic problems, especially in young women. The aim of this study is to evaluate a new technique of vaginal reconstruction following anterior pelvic exenteration with clinical and cytohistologic follow-up. Between March 2002 and November 2004, ten sexually active female patients underwent vaginal reconstruction after radical cystectomy that required en bloc removal of the anterior vaginal wall, with a pedicle graft of greater omentum combined with a vicryl mesh. The mean age of the patients was 38 years. The mean operative time of the reconstructive procedure was 50 min. There were no complications regarding the reconstructive procedure. On follow-up, the neovagina accepted two fingers easily and showed a pink-colored smooth lining. Seven patients reported successful attempts of sexual intercourse. It was concluded that reconstruction of vagina after anterior pelvic exenteration in sexually active women can be done safely with the use of vicryl mesh combined with a pedicled omental graft. It is a simple, reliable, and not time-consuming technique. The long-term follow-up was very beneficial in detection of complete healing, postoperative infections, and hormonal activity of the graft and recurrence of malignancy.

Cyclin D1 expression in acute leukemia.

BACKGROUND: Disorders of the cell cycle regulatory machinery play a key role in the pathogenesis of cancer. Over expression of cyclin D1 protein has been reported in several solid tumors and certain lymphoid malignancies, but little is known about the involvement of cyclin D1 in acute leukemia. PATIENTS AND METHODS: In this study, we analyzed the expression of cyclin D1 at protein level in, 40 newly diagnosed patients with acute myeloid leukemia (AML), 10 patients with acute lymphoblastic leukemia (ALL), and 11 normal controls using flow cytometry. RESULTS: The expression of cyclin D1 was not significantly different in AML group as compared to normal controls. On the other hand, over expression of cyclin D1 was evident in ALL group (4/10) as compared to that in healthy control. The ALL cases with cyclin D1 over expression were significantly correlated to blast cell counts in the peripheral blood and bone marrow (BM) but not with hemoglobin level, WBC, and platelets count. The ALL group with lymphadenopathy and organomegaly express significantly higher cyclin D1 over expression as compared to those without. CONCLUSION: The biological value of cyclin D1 over expression might be different in AML and ALL.

Comprehensive analysis of tubularized incised-plate urethroplasty in primary and re-operative hypospadias.

OBJECTIVE: To retrospectively review our experience of the tubularized incised-plate (TIP) urethroplasty over the last 4 years. PATIENTS AND METHODS: From 1998 to December 2001, 133 patients (mean age 7 years, sd 4, range 1-22), had a TIP urethroplasty by one surgeon for primary (103) and re-operative (30) hypospadias; the defects included 106 (79%) distal and mid-shaft, and 27 (21%) posterior shaft. The neourethra was covered by a subcutaneous flap in 66 (50%) patients or by corpus spongiosa (spongioplasty) in 31 (23%), with no cover in the remaining 36 (27%). In the last 20 patients (15%) a modified meatoplasty was used; the site and size of the new meatus was predetermined on the glans around a suitable catheter before any incision. Urethral stents were not used after repair in 39 (29%) patients, and regular meatal dilation was used only in patients with voiding difficulty and obvious tendency to stenosis. The presence of complications requiring re-operation and overall general appearance were recorded. RESULTS: The mean (sd) follow-up was 10 (5) months; there were 24 complications in 20 patients (15%), including a small fistula in 12 (9%), complete disruption of the repair in 4 (3%), meatal stenosis in seven (5%) and neourethral stricture in one (0.8%). Complications were not significantly different between primary and re-operative cases, and unaffected by the use of the stents. On univariate analysis complications were significantly higher with running than interrupted sutures, in repairs in the first 2 years of the study, in patients with posterior hypospadias, and in those with no neourethral coverage. However, the last two factors were the only significant independent risk factors in a multivariate analysis. Regular urethral dilatation was indicated in 43 patients (32%). Modified meatoplasty was associated with a significantly lower requirement for regular dilatation (P < 0.05) and no meatal stenosis. In the 113 complication-free patients the operation gave an excellent cosmetic appearance with a vertical slit meatus on the tip of conical glans in 110 (97%); there was slight meatal retraction in the remaining three patients. CONCLUSION: The TIP repair is a reliable method for treating both distal and proximal penile shaft hypospadias, is suitable for both primary and re-operative cases, and is more versatile than other repairs. Covering the neourethra with a flap or spongioplasty significantly improves the results. Regular urethral dilatation is required in a third of patients but modified meatoplasty obviates the need for regular dilatation and eliminates the risk of meatal stenosis.

Late renal functional and morphological evaluation after non-operative treatment of high-grade renal injuries in children.

OBJECTIVE: To assess the long-term results in children with high-grade renal trauma who were managed without surgery, as such treatment was initially successful but little is known about the late ipsilateral renal function and morphology. PATIENTS AND METHODS: The study included 13 children (nine boys and four girls; mean age 8 years, sd 5) with high-grade renal injury who were managed without surgery between 1997 and 2001, and followed for a mean (sd, range) of 3 (2, 0.5-7) years. The trauma was caused by a motor-car accident in five and falling from a height in eight children, and was on the right in 10 and on the left in three. There was gross and microscopic haematuria in 10 and three patients, respectively. The trauma was graded according to the American Association for Surgery of Trauma, with grades III, IV and V renal injury in six, four and three children, respectively. All patients were treated initially by observation; one required super-selective embolization because of continuing haemorrhage. Three children with progressive urinary extravasation were treated with a percutaneous tube drain and JJ stent for 6 weeks. Patients were discharged after a mean (sd) hospital stay of 9 (6) days. Ultrasonography then showed resolving haematoma in all patients with a mean (sd) size of 7 (2) cm(2). At the last follow-up patients were re-evaluated by a clinical examination, renal scintigraphy and computed tomography angiography. RESULTS: None of the children was hypertensive nor had any abnormality on urine analysis; all had normal serum creatinine levels, and scintigraphy and angiography showed normal contralateral kidneys in all. Ipsilateral abnormalities were detected in 12 patients, and included a single scar in five, multiple scars in six and a cystic lesion with multiple septa in one. There was no vascular complication or hydronephrosis, and no significant functional loss, with all affected kidneys having a split function of 41-50% at the last follow-up. CONCLUSION: Although there is no late functional loss there are residual morphological changes in almost all children with high-grade renal injury. This study provides objective support for the non-operative management of high-grade renal injury in children, but a prolonged follow-up is warranted to assess the risk of progression of these abnormalities.

Urokinase plasminogen activator receptor and soluble matrix metalloproteinase-9 in acute myeloid leukemia patients: a possible relation to disease invasion.

Extracellular proteolytic enzymes of the urokinase-type plasminogen activator (uPA) and metalloproteinase (MMP) family play a crucial role in the matrix degradation and tissue remodeling process characteristic of malignant disorders. The receptor for urokinase plasminogen activator (uPAR) serves to localize and intensify the action of UPA and is expressed on the surface of malignant cells. Although the biological significance of MMP-9 and soluble urokinase receptor in growth and progression of lymphoid neoplasm is understood, its clinical significance in acute myeloid leukemia (AML) has not been fully elucidated. In this study, we determined the levels of soluble urokinase-type plasminogen activator receptor (suPAR), cellular uPAR and sMMP-9 in 43 newly diagnosed AML patients at diagnosis, before chemotherapy, and also studied 10 normal subjects served as a control group. After chemotherapy suPAR and MMP-9 were determined at remission and relapse. The levels of suPAR, cellular PAR were significantly higher (P= 0.001, 0.001) and MMP-9 was significantly lower (P=0.001) in AML patients at diagnosis as compared to controls. suPAR and MMP-9 levels were significantly lower in AML patients who achieved complete remission (CR) as compared to those who did not (P= 0.001 for both). Levels of suPAR and MMP-9 were significantly correlated to peripheral blood blast cells (r= 0.88, P= 0.001; r= 0.65, P= 0.001, respectively) and blast cell distribution ratio (BCDR, r= 0.84, P= 0.001; r=65, P= 0.001, respectively). suPAR, cellular PAR and MMP-9 were significantly higher in patients with extramedullary infiltration as compared with those without (P= 0.001, 0.001, <0.05). The suPAR, cellular uPAR, and MMP-9 levels were uneven in AML FAB subtypes being highest in M5(P<0.05 for all). MMP-9 and suPAR levels were correlated with the disease status. In AML survivors, MMP-9, cellular uPAR and suPAR were significantly lower as compared to non-survivors (P= 0.001 for all). In conclusion, MMP-9 and su PAR levels might be used as a marker for disease activity and may contribute to blast cell dissemination. MMP-9 and suPAR may be target molecules in the strategy of treatment of AML.

Tubularized incised plate repair of distal hypospadias in toilet-trained children: should a stent be left?

OBJECTIVE: To evaluate the role of stenting in toilet-trained children undergoing tubularized incised plate (TIP) repair of distal hypospadias, as a stent-free TIP in boys who are not toilet-trained has been successful with no unusually prolonged discomfort. PATIENTS AND METHODS: The study included all toilet-trained children with distal penile shaft hypospadias who were not suitable candidates for meatal advancement procedures and who underwent TIP repair, by one surgeon, between March and August 2001. Patients were prospectively randomized at the end of surgery to either leaving a stent for 1 week (stented) or no stent (unstented). The study included 64 children (35 stented and 29 unstented; median age 6 years, range 2-17). In the stented group the stent was placed in the bladder for continuous bladder drainage. An adjunct penile block instead of caudal or epidural analgesia was used in all patients, to avoid drug-induced urinary retention. The early evaluation included an assessment of bladder spasms, dysuria, urinary retention and extravasation. Regular meatal dilatation was provided only to patients with voiding difficulty and an obvious tendency to stenosis. RESULTS: The median (range) follow-up was 6 (3-11) months. Voiding was painful in the first week in five (14%) and 13 (45%) of the stented and unstented patients, respectively (P < 0.01); there were bladder spasms in three (8%) and none, respectively (P > 0.05). None of stented patients developed urinary retention or extravasation, compared with seven (24%) and five (17%) in the unstented group, respectively (P < 0.05). Meatal dilatation was required in two (6%) and five (17%) of the stented and unstented patients, respectively (P > 0.05). There were complications requiring re-operation in nine boys (14%), of whom seven (10%) developed small fistulae and two (4%) had meatal stenosis. Although the re-operation rate was lower in the stented (9%) than in the unstented group (20%), the difference was not statistically significant (P > 0.05). CONCLUSIONS: The use of a stent in TIP repair in toilet-trained children is advantageous; it significantly eliminates the risk of urinary retention and extravasation, and reduces the overall patient discomfort. It is also associated with a lower re-operation rate.

Syndecan-1 in multiple myeloma: relationship to conventional prognostic factors.

Syndecan-1 (CD138) mediates myeloma cell adhesion, and loss of syndecan-1 from the cell surface may contribute to myeloma cell proliferation and dissemination and influence the prognosis in patients with multiple myeloma (MM). In order to test this hypothesis, we have evaluated syndecan-1 expression on the surface of malignant plasma cells and soluble forms of syndecan-1 in the serum of 25 newly diagnosed MM patients by flow cytometry and immunosorbent assay. Soluble syndecan-1 levels were significantly higher in MM as compared to controls (P<0.001). Cellular and soluble syndecan-1 was significantly inversely correlated (r=-0.89, P<0.001). The soluble syndecan-1 was significantly higher in non- responders to chemotherapy when compared to responders (P<0.01), and in non- survivors as compared to survivors (P<0.001). In contrast, cellular syndecan-1 expression was significantly lower in non- responders when compared to responders (P<0.01), and in non- survivors as compared to survivors (P<0.05). The levels of soluble syndecan-1 increased from stage I through stage II to stage III, whereas cellular syndecan-1 expression were decreased from high levels in stage III down to a low in stage I, with a statistically significant difference (P<0.01, P<0.05, respectively). There was a significant positive correlation between soluble syndecan-1 and plasma cell count (r=0.079, P<0.001), beta2 microglobulin (r=0.85, P<0.001), serum creatinine (r=0.84, P<0.001), C-reactive protein (r=0.082, P<0.001), alkaline phosphatase (r=0.58, P<0.05) and serum calcium (r=0.77, P<0.01) and a negative correlation with hemoglobin level (r=-0.78, P<0.01), platelets count (r=-0.82, P<0.01) and Albumin level (r=-0.64, P<0.01). Cox regression analysis using soluble syndecan-1 at mean-2SD of the controls could correctly classify patient outcome in 84.0%. The addition of beta2 microglobulin to soluble syndecan-1 increased the predictability of the patients' outcome to 96.7%. We conclude that soluble syndecan-1 levels are negatively correlated to the cellular form and that high levels of soluble syndecan-1 and lower expression of cellular syndecan-1 at diagnosis are negative prognostic factors. Assessment of soluble syndecan-1 and beta2 microglobulin at diagnosis is an independent prognostic system for MM.