Kidney stone nano-structure - Is there an opportunity for nanomedicine development?

BACKGROUND: Kidney stone analysis techniques are well-established in the field of materials characterization and provide information for the chemical composition and structure of a sample. Nanomedicine, on the other hand, is a field with an increasing rate of scientific research, a big budget and increasingly developing market. The key scientific question is if there is a possibility for the development of a nanomedicine to treat kidney stones. MAJOR CONCLUSIONS: The main calculi characterization techniques such as X-ray Diffraction and Fourier Transform Infrared Spectroscopy can provide information about the composition of a kidney stone but not for its nanostructure. On the other hand, Small Angle X-ray Scattering and Nitrogen Porosimetry can show the nanostructural parameters of the calculi. The combination of the previously described parameters can be used for the development of nano-drugs for the treatment of urolithiasis, while no such nano-drugs exist yet. GENERAL SIGNIFICANCE: In this study, we focus on the most well-known techniques for kidney stone analysis, the urolithiasis management and the search for possible nanomedicine for the treatment of kidney stone disease. We combine the results from five different analysis techniques in order to represent a three dimensional model and we propose a hypothetical nano-drug with gold nanoparticles. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editor: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader.

Predictive values of urinary bladder tumor markers survivin and soluble-Fas comparison with cystoscopy and bladder tumor antigen.

AIM: The aim of the study was to evaluate the predictive values of two novel urinary markers for bladder cancer: survivin and soluble-Fas (s-Fas). METHODS: The study included 84 individuals divided in two groups. The first group contained 47 patients, who underwent transurethral bladder tumor resection and the second, control, group 20 patients with non-malignant conditions, who underwent cystoscopy and 17 health volunteers. Fresh, second morning voided urine was collected for measurement of s-Fas, survivin, BTA and for cytology. Sensitivity, specificity, positive and negative predictive values and accuracy were calculated. RESULTS: Bladder tumor patients had significantly higher survivin urine levels in comparison to the controls. Survivin correlated also with the tumor stage. Combination of survivin with BTA had a sensitivity of 86.4% but still lower than that of cystoscopy (97.8%). Only the specificity of the combination between survivin and BTA was higher than that of cystoscopy (86.4% and 75.6%, respectively). CONCLUSION: Survivin was a better marker for tumor detection than s-Fas and was better enough to discriminate cancer stage. Combination of survivin and BTA had a specificity of 86.4% to exclude bladder malignancy and the combination of s-Fas with survivin and BTA had a sensitivity of 93.6% to detect bladder cancer.

Sodium sensitivity and its role in the maintenance of high blood pressure in two-kidney, one-clip renovascular hypertension after removal of the clipped kidney in rats.

AIM: The aim of the present study was to define the role of sodium balance and sodium sensitivity in the maintenance of two-kidney, one-clip renovascular hypertension in rats. METHODS: Six months after induction of hypertension, systolic blood pressure, sodium balance, water intake and urine excretion were measured under normal conditions, after nephrectomy of the clipped kidney, and under conditions of sodium load. RESULTS: No difference between control rats and rats with or without post-Goldblatt hypertension emerged during the development of renovascular hypertension and after nephrectomy of the clipped kidney. Under conditions of high sodium intake, the contalateral kidney of the post-Goldblatt hypertensive rats was unable to excrete surplus sodium. Sodium retention was not correlated with water retention. In contrast to the controls, systolic blood pressure increased in the animals with post-Goldblatt hypertension and those with post-Goldblatt normotension during the sodium load period. No correlation was found between blood pressure increase and sodium retention. The animals were considered sodium sensitive in relation to blood pressure. CONCLUSION: In the chronic phase of two kidney-one clip renovascular hypertension, the post-Goldblatt hypertensive and the post-Goldblatt normotensive animals showed sodium sensitivity of blood pressure. The contralateral kidney of the post-Goldblatt hypertensive animals was unable to excrete surplus sodium under conditions of high sodium intake. But this inability and the sodium sensitivity of blood pressure cannot be thought responsible for the maintenance of renovascular hypertension in this model.

Lithotomy by empirical doctors in the 19th century: a traditional surgical technique that lasted through the centuries.

PURPOSE: Lithotomy is an ancient surgical procedure, well-known in the history of urology. We describe the method as it was performed by empirical doctors in Greece during the 19th century and compare it to older techniques. MATERIALS AND METHODS: The original Greek text of a doctor's autobiography includes a description of a lateral perineal cystotomy performed by empirical doctors in 1818. The technique is compared with that described by Celsus and Byzantine medical writers. RESULTS: A study of the sources revealed that the 2 itinerant doctors who specialized in lithotomy used a lateral perineal cystotomy to remove stones from the bladder. Consent was obtained from the parents of the patient. The patient adopted the standard lithotomy position, the surgeon located the stone with his finger via the anus and immobilized it, and made a lateral perineal incision to remove it. A newly killed fowl was then placed on the wound. CONCLUSIONS: The ancient surgical lithotomy technique seems to have been passed on almost unchanged from father to son and has influenced urology in Europe since the time of Celsus (1st century AD) and the Byzantine surgeon Paul of Aegina (7th century AD). Postoperative therapy is similar to that of other Byzantine techniques, and it is interesting that written informed consent was obtained, signed in the presence of witnesses.

Urological management of indinavir-associated acute renal failure in HIV-positive patients.

INTRODUCTION: Indinavir, a protease inhibitor that is commonly used to treat HIV infection, may cause crystal formation within the renal tubules when urine pH is above 3.5. Crystallization in the urine may lead to intrarenal crystal deposition and acute renal failure (ARF). AIM: To establish the beneficial urological management of acute renal failure caused by indinavir treatment of HIV/AIDS patients. PATIENTS--METHODS: Five HIV positive patients (four men, one woman) with a mean age of 32 years (range 28-36 years) were referred to our Department of Urology from an AIDS outpatient Clinic, because of the development of postrenal acute renal failure with continuously elevated creatinine and urea plasma levels after indinavir therapy. Among the initial therapeutic maneuvers, indinavir administration was interrupted for 1 week while bilateral double-J ureteral stents were inserted in all the HIV/AIDS patients, during the first 24-72 h to secure upper-tract drainage. Concurrently urine has been acidified by oral administration of the amino acid L: -methionine and oral fluid intake was increased. RESULTS: All the patients responded well to the treatment and their renal function was effortlessly restored to normal within a few days. CONCLUSION: HIV-positive patients receiving indinavir therapy might be complicated by acute renal failure, mainly due to intrarenal crystal deposition (tubules) or urolithiasis (postrenal obstruction). This adverse effect may simply manage by the discontinuation of indinavir administration, urine acidification, as well as the possible early insertion of bilateral double-J ureteral stents.

Acid-induced phase separation of anionic surfactants for the extraction of 1,4-dichlorobenzene from honey prior to liquid chromatography.

The acid-induced liquid-liquid phase separation of anionic surfactants in aqueous solutions and its applicability to cloud point extraction methodology were applied as a tool for the extraction of 1,4-dichlorobenzene (p-DCB) from aqueous samples. p-DCB is extracted into the micelles of sodium dodecane sulfonate (SDSA) in a 4.2 M HCl solution. The micellar phase is separated from the bulk aqueous solution after centrifugation and collected from the surface of the suspension. The micellar extracts are injected into a high-performance liquid chromatographic apparatus and quantified at 225 nm with a reference wavelength of 280 nm. Following the proposed methodology, a preconcentration factor of ca. 160 is achieved (starting from 50 mL solutions) allowing for detection limits at the low microg/L level. Application to honey samples produced detection limits of 2.5 microg/kg with quantification limits of 7.5 microg/kg, while the recoveries of the method ranged from 85% at high concentrations to 95% at lower concentrations of p-DCB. The combined uncertainty of the entire analytical procedure was 4.5% at the concentration level of 30 microg/kg allowing for reliable and reproducible results for the determination of p-DCB at the concentration levels considered as thresholds for EU and U.S. legislation (10 microg/kg).

Malakoplakia of the testis.

Malakoplakia of the testis presenting as painless enlargement of the testis in an 80-year-old man is described. The literature is reviewed.

Malakoplakia of the testis. Case report.

Malakoplakia of the testis presenting as painless enlargement of the testis in an 80-year-old man is described. The literature is reviewed.

Leiomyoma of the bladder: a case report.

A case of leiomyoma of the urinary bladder in a 20-year-old man is reported. The patient presented with severe frequency and perineal burning at the end of urination along with microscopic haematuria. Enucleation of the tumour was performed because transurethral biopsy revealed leiomyoma. The prognosis of these tumours is excellent.

Influence of preoperative vesicle biopsy on the decision for radical prostatectomy.

PURPOSE: The presence of seminal vesicle invasion (SVI) by prostate cancer is difficult to detect clinically and is associated with poor prognosis. The aim of our study was to identify the efficacy of transrectal ultrasound-guided seminal vesicle biopsies in the detection of seminal vesicle invasion (SVI) in patients with prostate cancer. MATERIALS AND METHODS: One hundred transrectal ultrasound-guided seminal vesicle biopsies were performed in 50 patients with clinically localized prostate cancer. Every patient underwent two biopsies, one for each seminal vesicle. Radical retropubic prostatectomy was performed in all cases and the specimens with the attached seminal vesicles were examined for the presence of prostate cancer invasion. RESULTS: Of a total of 100 seminal vesical biopsies 87 were identified as seminal vesicle by characteristic epithelium. Cancer was found in 7 (8%) biopsies, confirmed in all cases by pathology in the surgical specimen. Eighty biopsies (40 patients) were normal. Pathological analysis of these 40 radical prostatectomy specimens revealed that 6 seminal vesicles (5 patients) were invaded by prostate cancer (6 false negative biopsies, 7.5%). Transrectal ultrasound images of 15 seminal vesicles were suspicious for invasion while 85 were normal. Of the 15 suspicious cases 11 were invaded by cancer (73.3%). Of the sonographically benign seminal vesicles 5 (5.88%) were invaded by cancer. Our data were analyzed by the ARCUS PRO-STAT statistical package. CONCLUSIONS: We suggest that transrectal ultrasound-guided seminal vesicle biopsy is useful and reliable for a more exact preoperative staging of prostate cancer, therefore helpful in correct decision making for radical prostatectomy.

Participation rates in cervical cancer screening: experience in rural Northern Greece.

BACKGROUND AND AIM: Cervical cancer is one of the most common causes of cancer mortality among women worldwide but it is one of the most preventable cancers due to the Pap smear test. The aim of this study was to estimate the participation rate of females in screening of cervical cancer with Pap smear test. METHODS: The study took place in a hospital in Rural Northern Greece during April and May 2007. Convenience sampling was performed and questionnaires were completed by 214 eligible females aged 20-64 years. RESULTS: One hundred and twenty four (57.9%) of the participants had had a Pap-test at some point in their lifetime. 72 of them (33.65%) had the test performed for the first time according to current guidelines. 13.6% were unaware about the recommended onset age of the test, 16.4% did not know the proper intervals, while 22.4% did not know the recommended upper age limit. 32.6% were informed by mass media, family members and friends. The take-up rates, the source of information and the setting where the examination was performed were related to age, origin, income, educational status, type of occupation and place of residence. Disparities in participation rates were detected. CONCLUSIONS: Special efforts should be made by National Health Services towards enhancing secondary prevention of cervical cancer by increasing participation rates of older women, those with lower educational background, females with low income, Roma, retired or unemployed and residents of rural areas.

Transvaginal vs transobturator approach for synthetic sling placement in patients with stress urinary incontinence.

We present comparative short-term experience with the transvaginal (TVT) and the transobturator (TVT-O) approaches for the treatment of stress urinary incontinence (SUI). We studied 315 women with SUI, treated with a tension-free tape placement. The TVT approach was applied in 265 women, while 50 women were treated by the TVT-O approach. The mean operation time was 25 and 17 min in the TVT and TVT-O group, respectively (p<0.001). In the TVT group, continence rates were 87% after 1 year, while in the TVT-O group, the continence rate was 94%. Postoperative pain was reported in 14.4 and 28% of the TVT and TVT-O patients, respectively (p=0.02). Complications such as bladder perforation, retropubic hematoma, and urinary retention took place only in the TVT group. Urinary tract infections were recorded in 20 and 8% of the TVT and TVT-O patients, respectively (p=0.04), while vaginal erosion took place in 1.5 and 2% and de novo urgency in 14 and 8%. Both approaches show high rates of cure at the first postoperative year, while complications are less with the TVT-O procedure.

Semen and the diagnosis of infertility in Aristotle.

Aristotle (384-322bc) was one of the leading intellectual figures of all time. In his work he systematised a massive amount of knowledge on a diverse range of subjects, including medicine. This article discusses the observations and hypotheses of this great philosopher on semen and infertility, as they are presented in his work Generation of Animals. This is combined with an evaluation of his positions in relation to those of the Hippocratic Corpus on the same subject. An extensive review of Aristotle's work Generation of Animals was performed with particular focus on his perspectives about semen and infertility. Publications referring to this work were also reviewed. According to Aristotle, semen is that which contains the principles that come from both parents when they unite. He believed that semen was formed by the secretion of nutriments by the body, developing his theories of sterility on this basic principle. A lack of fertility is attributed to genetic or acquired causes. He proposed methods for diagnosing sterility, primarily the 'water test' for men and the 'pessary' method for women. Even if his observations contain clear mistakes, such as attributing only secondary functions to male testicles and the identification of menses as women's 'seed', Aristotle's views also contain keen observations and exceptional thinking, both on the characteristics of semen and the causes of sterility (infertility).

Holmium laser lithothripsy of ureteral calculi: our initial experience.

AIM: To evaluate effectiveness and safety of intracorporeal holmium:YAG (Ho:YAG) laser lithotripsy of ureteral calculi. PATIENTS AND METHODS: Between October 2003 and September 2005, 45 patients (age range 27-74, mean age 51.5 years) with 49 ureteral stones (measuring 4-28 mm in size) were treated with Ho:YAG laser lithotripsy. The locations of the stones in the ureter were: 6 in the upper third, 7 in the middle third, and 36 in the lower third. Under general anaesthesia, we used semirigid 9- to 11-Fr ureteroscopes and a flexible 7.5-Fr ureteroscope. The Ho:YAG laser had a maximum power of 1.8 J at 8 Hz, and a 365-mum flexible quartz fibre was used. One month postoperatively the patients were followed up with imaging tests. RESULTS: Stone disintegration was feasible in all cases. The mean hospital stay was 2.8 days. One month postoperatively, stone-free status was revealed in 93.3% of the cases. Only minor complications were noted in 4 patients (8.8%). No long-term complications were recorded. CONCLUSION: Ho:YAG laser lithotripsy of ureteral calculi is a feasible, safe, and effective procedure.

Tension-free vaginal tape for the treatment of stress urinary incontinence in geriatric patients.

OBJECTIVE: To evaluate the safety and efficacy of tension-free vaginal tape (TVT) for the treatment of stress urinary incontinence (SUI) in geriatric patients. PATIENTS AND METHODS: Fifty-one women, aged 65-80 (mean 72.3) years, underwent a TVT procedure for genuine SUI from 2001 to 2004. A urodynamic test together with uroflowmetry were performed. The patients' SUI bother score was assessed using a visual analog scale (VAS). RESULTS: The mean operative time was 25 (range 14-29) min and mean hospitalization time was 1.2 (range 1-2) days. Bladder perforation occurred in 3 cases (5.8%) and was managed conservatively. Pre- and postoperative maximum flow rate were not significantly different (p > 0.05). The patients' SUI bother score estimated by the VAS was statistically significantly improved (p < 0.0001). After a mean follow-up of 35.6 (range 14-60) months, 49 patients (96%) had no SUI, while 2 patients (3.9%) had persistent SUI. Also, during the follow-up 5 patients (9.8%) were diagnosed with de novo urgency due to detrusor overactivity and 1 patient (1.9%) had persistent dysuria that was resolved with urethrolysis. CONCLUSIONS: SUI in elderly women can be safely treated with the TVT procedure in the vast majority of the patients. However, bladder perforation during surgery and de novo urgency postoperatively should be taken into account.

Double-pigtail stents for distal ureteral calculi: an alternative form of definitive treatment.

In this study, we treated patients with a solitary distal ureteral stone of less than 10 mm in maximum diameter by placing a double-pigtail stent and subsequently removing it allowing the calculus to pass spontaneously. A total of 40 patients were enrolled in the study with a mean stone size of 5.1 x 3.5 mm (range 2-8 mm in length and 2-7 mm in width). The indication for intervention was intractable pain in 5 patients, infection due to obstruction in 2, highly obstructed urinary tract in 10, absence of progression for 30 days in 21 and desire of the patient to be free of stone in 2. A double-pigtail stent was inserted in the involved ureter under local anesthesia and left in place for 2 weeks. After stent removal, 34 patients succeeded in passing the stone within an average time of 5.8 days. The overall success rate was 85%. We suggest this method as an alternative form of treatment for distal ureteral calculi to extracorporeal shockwave lithotripsy of ureterolithotripsy under selected clinical circumstances.

Efficacy of escalating doses of intravesical interferon alpha-2b in reducing recurrence rate and progression in superficial transitional cell carcinoma.

OBJECTIVE: To compare the efficacy of three different doses of intravesical interferon alpha-2b (IFN alpha-2b) in reducing recurrence and progression rates in superficial grade II, transitional cell carcinoma (TCC). PATIENTS AND METHODS: Eighty-nine patients with primary or recurrent TCC stage Ta/T1, grade II, were randomly allocated into four groups after transurethral resection (TUR) of the tumour. Group A (20 patients) received no further treatment, serving as the control group; group B (22 patients) received 40 MU of IFN alpha-2b, group C (24 patients) 60 MU and group D (23 patients) 80 MU. The instillations started within 48-72 h after TUR and were performed weekly for 2 months, bimonthly for the next 4 months and thereafter monthly for 6 months. The patients were followed for 36 months. The four groups were compared for the number of recurrences (simple recurrence rate), progression in stage, disease-free interval and recurrence rate per 100 patient-months. RESULTS: During the follow-up, 33 patients had recurrence (13, eight, seven and five in groups A to D, respectively). The simple recurrence rate was 65% for group A, compared with 36% (P = 0.06), 29% (P < 0.05) and 22% (P < 0.01) for groups B, C and D, respectively. The differences in simple recurrence rates between the groups treated with IFN alpha-2b were not statistically significant. Eleven patients experienced progression in stage, with six, there, one and one in groups A to D, respectively. The differences were statistically significant only between groups A and C (P < 0.05) and groups A and D (P < 0.05). The disease-free interval was 15 months for group A, compared with 21.4 (P < 0.05), 26.1 (P < 0.001) and 30 months (P < 0.001) for groups C to D, respectively. The disease-free intervals of the groups treated with IFN alpha-2b were significantly different between all patients in groups B and D (P < 0.01) and only for those with stage T1 between groups C and D (P < 0.01). Finally the recurrence rate per 100 patient-months was 2.91, 1.19, 0.88 and 0.63 for groups A to D, respectively (all P < 0.001). The results were always in favour of the patients treated with the high dose, the only exception being the difference between groups C and D (P = 0.026). No side-effects of the drug were noted, nor was any adverse reaction reported from any patient. CONCLUSION: These results show a significant advantage for adjuvant intravesical IFN alpha-2b treatment over TUR alone for the 36 months of follow up and indicate that IFN alpha-2b can modify the clinical course of superficial TCC at least in the short term. The appropriate dose was apparently 80 MU, for although 40 MU was better than TUR alone, it was less effective than 60 MU and 80 MU; the 80 MU dose was slightly better than 60 MU and thus this regimen is recommended.

Encrusted cystitis and pyelitis.

Encrusted cystitis (EC) and encrusted pyelitis (EP) are rare chronic inflammatory diseases of the bladder and renal pelvis, respectively, and are characterized by mucosal inflammation with deposits of ammonium magnesium phosphate on the urothelium. Corynebacterium urealyticum is the pathogen responsible in the vast majority of cases. We report 4 cases of EC and 1 case of EP. In 1 case of EC Ureaplasma urealyticum was isolated as the microorganism responsible. To the best of our knowledge, U. urealyticum-induced EC has never been reported previously.

Hepatitis B virus HBx protein activation of cyclin A-cyclin-dependent kinase 2 complexes and G1 transit via a Src kinase pathway.

Numerous studies have demonstrated that the hepatitis B virus HBx protein stimulates signal transduction pathways and may bind to certain transcription factors, particularly the cyclic AMP response element binding protein, CREB. HBx has also been shown to promote early cell cycle progression, possibly by functionally replacing the TATA-binding protein-associated factor 250 (TAF(II)250), a transcriptional coactivator, and/or by stimulating cytoplasmic signal transduction pathways. To understand the basis for early cell cycle progression mediated by HBx, we characterized the molecular mechanism by which HBx promotes deregulation of the G0 and G1 cell cycle checkpoints in growth-arrested cells. We demonstrate that TAF(II)250 is absolutely required for HBx activation of the cyclin A promoter and for promotion of early cell cycle transit from G0 through G1. Thus, HBx does not functionally replace TAF(II)250 for transcriptional activity or for cell cycle progression, in contrast to a previous report. Instead, HBx is shown to activate the cyclin A promoter, induce cyclin A-cyclin-dependent kinase 2 complexes, and promote cycling of growth-arrested cells into G1 through a pathway involving activation of Src tyrosine kinases. HBx stimulation of Src kinases and cyclin gene expression was found to force growth-arrested cells to transit through G1 but to stall at the junction with S phase, which may be important for viral replication.

Evaluation of needle biopsy in the diagnosis of prostatic carcinoma in men with prostatic intraepithelial neoplasia.

Prostatic intraepithelial neoplasia (PIN) is considered a premalignant lesion of the prostate. It is often encountered in prostate needle biopsy in cases where no cancer is identified. In order to evaluate its importance 25 patients with PIN in a former prostate needle biopsy underwent a second ultrasound guided needle biopsy. The first biopsy was performed in all patients as a result of positive DRE. In 13 patients (52%), prostate cancer was identified in the second specimen. All presented with high or intermediate grade PIN in the first biopsy. PSA values were compared with PIN grade and cancer presentation in the second biopsy, although no statistically significant difference was proven. In conclusion, when PIN is discovered in prostate needle biopsy in patients with positive DRE, a second biopsy has to be performed in order to exclude the possibility of a prostate carcinoma.