Antibiotic prophylaxis prior to transrectal prostate biopsy in Croatia: A national survey.

OBJECTIVES: Transrectal ultrasound guided prostate biopsy (TRUSPB) is the standard of care for diagnosis of prostate cancer. Increased antibiotic resistance has led to the suspension of indication for fluoroquinolones use in prostate biopsy prophylaxis. Several classes of antibiotics have been recommended for routine use. Unequivocal consensus regarding antibiotic prophylaxis has not been made to date. The objective of the study was to assess the diversity of antimicrobial prophylaxis among Croatian urologists. MATERIALS AND METHODS: An online questionnaire was designed using Google Forms® and distributed to 19 urology public hospital's departments. Answers regarding infection risk assessment, type and duration of antimicrobial prophylaxis were accumulated. Descriptive statistical analysis was preformed using Statistica 10.0® analytics software. RESULTS: Twelve urology departments answered the questionnaire, representing 63% of urology departments in Croatia. Six different antibiotic protocols have been reported. Fluoroquinolones were the most commonly prescribed class of antibiotics (84%). Antibiotic prophylaxis started 1 day before the procedure (92%). Average duration of antibiotic prophylaxis was 5 days (75%). In case of increased risk of urinary tract infection, 42% of departments changed the type, and 8% changed the duration of antibiotic prophylaxis. Neither department performed a rectal swab prior to prostate biopsy. CONCLUSIONS: Various antimicrobial prophylaxis protocols are currently being used among Croatian urology departments. Lack of uniform guidelines contributes to protocol diverseness that inevitably leads to further increase in antibiotic resistance. New high quality studies are needed to reverse this trend and to facilitate the establishment of a uniform antimicrobial stewardship strategy.

THE COST OF KIDNEY TRANSPLANTATION AT THE MERKUR UNIVERSITY HOSPITAL, ZAGREB, CROATIA.

The aim was to determine the cost of hospitalization for a transplant procedure and identify the independent variables associated with the cost of transplantation. The investigation was designed as a retrospective single-center cohort study conducted at a tertiary university hospital transplant center in Zagreb, Croatia. The study included 219 consecutive kidney recipients transplanted during the 2007-2013 period at the Merkur University Hospital. There were 141 male and 78 female patients having undergone kidney transplantation during the study period. The majority of kidney transplants were from a deceased donor (n=179), while 40 were from a living donor. The mean cost of a transplantation was 86,140±42,240 HRK (11,460±5,600 €), ranging from 29,000 HRK (3,860 €) to 408,000 HRK (54,000 €). In the bivariate analysis, the variables associated with the cost of transplantation were the length of hospital stay, delayed graft function, death of the patient, graft loss, use of steroids, and death-censored graft loss. In the multivariate analysis, delayed graft function was the only statistically significant variable for the cost of transplantation. Since only delayed graft function had an impact on the cost of transplantation in this study, certain steps such as shortening of the cold ischemia time (better organization of organ transport), better education of family members for living donors, and higher percentage of patients on peritoneal dialysis should be taken to lower the percentage of delayed graft function.

Therapy of the rat hemorrhagic cystitis induced by cyclophosphamide. Stable gastric pentadecapeptide BPC 157, L-arginine, L-NAME.

We focused on the cyclophosphamide-induced hemorrhagic cystitis (100 mg/kg/day intraperitoneally throughout three days) as a particular NO-system disturbance, and therapy possibilities. We demonstrated that it may be attenuated by subsequent administration of the NOS substrate L-arginine (100 mg/kg/day intraperitoneally), aggravated by NOS-blocker L-NAME (5 mg/kg/day intraperitoneally), all influenced by the stable gastric pentadecapeptide BPC 157 (10 µg/kg/day, 10 ng/kg/day, intraperitoneally or perorally, in drinking water). Regularly, cyclophosphamide dose- and time-dependently induced severe hemorrhagic cystitis lesions, gross lesions, and corresponding urothelial necrosis, vesical edema, erosion, hemorrhage, inflammation, and ulceration, microscopically. The bladder wet weight dramatically increased. Functionally, already after first cyclophosphamide administration, there is an increased leak point pressure. Until the second cyclophosphamide administration, L-arginine consistently attenuated regular cyclophosphamide-induced severe hemorrhagic cystitis lesions, grossly and microscopically, but not functionally. L-NAME aggravated these lesions and eradicated beneficial effect of L-arginine when combined. BPC 157 administration after cyclophosphamide, given in either dose or in either regimen markedly attenuated all cyclophosphamide lesions, grossly, microscopically. The increase of the bladder wet weight was consistently attenuated. Functionally, increased leak point pressure was reversed to the values noted in normal rats. The similar findings were noted in rats that received BPC 157 together with L-NAME or L-arginine, given alone or combined. Thus, the lesions are NO-related based on the administration of L-NAME as well as administration of L-arginine, and their mutual interaction, and counteraction by BPC 157 application. Likewise, we reveal new therapeutic possibilities, emphasizing stable gastric pentadecapeptide BPC 157 and L-arginine, versus L-NAME in rats underwent cyclophosphamide-induced cystitis.

Ureteritis cystica - A rare urological condition.

Ureteritis cystica is a rare benign condition. In this report, we have presented the case of a patient with a left upper back pain. The CT scan showed multiple irregular filling defects in the upper left ureter and the left renal pelvis. During the ureteroscopy, multiple yellow cystic lesions were seen in the proximal part of the left ureter and in the renal pelvis. The pathology report described cystic structures coated with single line cubic metaplastic epithelium. Ureteritis cystica should be considered in a differential diagnosis, in case of atypical radiological findings. No active treatment is required when confirmed.

POLYSEROSITIS AND SEVERE SEPSIS AFTER OPEN SUPRAPUBIC RADICAL PROSTATECTOMY: A CASE REPORT.

- Infections are well-known complications of radical prostatectomy. In the United States and Europe, the rates of surgical site infections are generally less than 1% and of other infections up to 3%. We report a case of a 62-year-old man who developed severe sepsis with renal insufficiency, paralytic ileus and polyserositis after radical prostatectomy, as a consequence of probable quinolone-resistant bacterial infection. Computed tomography of the abdomen and chest showed polyserositis with bilateral pleural and peritoneal effusions. Treatment with meropenem and other supportive measures resulted in good clinical outcome. This case suggested that severe sepsis with exudative polyserositis was probably caused by mobilization of an infective agent (bacterium) during bladder neck dissection as part of open radical prostatectomy.

BPC 157 counteracts QTc prolongation induced by haloperidol, fluphenazine, clozapine, olanzapine, quetiapine, sulpiride, and metoclopramide in rats.

AIM: Commonly, neuroleptics and prokinetics induce a prolonged QTc interval. In this study, stable gastric pentadecapeptide BPC 157 counteracts the prolongation of the QTc interval in Wistar rats that underwent daily administration of dopamine neuroleptics or prokinetics. Previously, in rats and mice, BPC 157 counteracted neuroleptic-induced catalepsy and gastric ulcers. MAIN METHODS: To counteract neuroleptic- or prokinetic-induced prolongation of the QTc interval, rats were given a BPC 157 regimen once daily over seven days (10µg, 10ng/kg ip) immediately after each administrations of haloperidol (0.625, 6.25, 12.5, and 25.0mg/kg ip), fluphenazine (0.5, 5.0mg/kg ip), clozapine (1.0, 10.0mg/kg ip), quetiapine (1.0, 10.0mg/kg ip), sulpiride (1.6, 16.0mg/kg ip), metoclopramide (2.5, 25.0mg/kg ip) or (1.0, 10.0mg/kg ip). Controls simultaneously received saline (5ml/kg ip). To assess the ECG presentation before and after neuroleptic/prokinetic medication, the assessment was at 1, 2, 3, 4, 5, 10, 15, 20 and 30min (first administration) as well as at 30min, 60min and 24h (first administration and subsequent administrations) and the ECG recording started prior to drug administration. KEY FINDINGS: Since very early, a prolonged QTc interval has been continually noted with haloperidol, fluphenazine, clozapine, olanzapine, quetiapine, sulpiride, and metoclopramide in rats as a central common effect not seen with domperidone. Consistent counteraction appears with the stable gastric pentadecapeptide BPC 157. Thus, BPC 157 rapidly and permanently counteracts the QTc prolongation induced by neuroleptics and prokinetics. SIGNIFICANCE: Pentadecapeptide BPC 157 is suited for counteracting a prolonged QT interval.

Class side effects: decreased pressure in the lower oesophageal and the pyloric sphincters after the administration of dopamine antagonists, neuroleptics, anti-emetics, L-NAME, pentadecapeptide BPC 157 and L-arginine.

The ulcerogenic potential of dopamine antagonists and L-NAME in rats provides unresolved issues of anti-emetic neuroleptic application in both patients and experimental studies. Therefore, in a 1-week study, we examined the pressures within the lower oesophageal and the pyloric sphincters in rats [assessed manometrically (cm H2O)] after dopamine neuroleptics/prokinetics, L-NAME, L-arginine and stable gastric pentadecapeptide BPC 157 were administered alone and/or in combination. Medication (/kg) was given once daily intraperitoneally throughout the 7 days, with the last dose at 24 h before pressure assessment. Given as individual agents to healthy rats, all dopamine antagonists (central [haloperidol (6.25 mg, 16 mg, 25 mg), fluphenazine (5 mg), levomepromazine (50 mg), chlorpromazine (10 mg), quetiapine (10 mg), olanzapine (5 mg), clozapine (100 mg), sulpiride (160 mg), metoclopramide (25 mg)) and peripheral(domperidone (10 mg)], L-NAME (5 mg) and L-arginine (100 mg) decreased the pressure within both sphincters. As a common effect, this decreased pressure was rescued, dose-dependently, by BPC 157 (10 µg, 10 ng) (also note that L-arginine and L-NAME given together antagonized each other's responses). With haloperidol, L-NAME worsened both the lower oesophageal and the pyloric sphincter pressure, while L-arginine ameliorated lower oesophageal sphincter but not pyloric sphincter pressure, and antagonized L-NAME effect. With domperidone, L-arginine originally had no effect, while L-NAME worsened pyloric sphincter pressure. This effect was opposed by L-arginine. All these effects were further reversed towards a stronger beneficial effect, close to normal pressure values, by the addition of BPC 157. In addition, NO level was determined in plasma, sphincters and brain tissue. Thiobarbituric acid reactive substances (TBARS) were also assessed. Haloperidol increased NO levels (in both sphincters, the plasma and brain), consistently producing increased TBARS levels in the plasma, sphincters and brain tissues. These effects were all counteracted by BPC 157 administration. In conclusion, we revealed that BPC 157 counteracts the anti-emetic neuroleptic class side effect of decreased pressure in sphincters and the dopamine/NO-system/BPC 157 relationship.

Cyclophosphamide induced stomach and duodenal lesions as a NO-system disturbance in rats: L-NAME, L-arginine, stable gastric pentadecapeptide BPC 157.

We revealed a new point with cyclophosphamide (150 mg/kg/day intraperitoneally for 7 days): we counteracted both rat stomach and duodenal ulcers and increased NO- and MDA-levels in these tissues. As a NO-system effect, BPC 157 therapy (10 µg/kg, 10 ng/kg, intraperitoneally once a day or in drinking water, till the sacrifice) attenuated the increased NO- and MDA-levels and nullified, in rats, severe cyclophosphamide-ulcers and even stronger stomach and duodenal lesions after cyclophosphamide + L-NAME (5 mg/kg intraperitoneally once a day). L-arginine (100 mg/kg intraperitoneally once a day not effective alone) led L-NAME-values only to the control values (cyclophosphamide + L-NAME + L-arginine-rats). Briefly, rats were sacrificed at 24 h after last administration on days 1, 2, 3, or 7, and assessment included sum of longest lesions diameters (mm) in the stomach and duodenum, oxidative stress by quantifying thiobarbituric acid reactivity as malondialdehyde equivalents (MDA), NO in stomach and duodenal tissue samples using the Griess reaction. All these parameters were highly exaggerated in rats who underwent cyclophosphamide treatment. We identified high MDA-tissue values, high NO-tissue values, ulcerogenic and beneficial potential in cyclophosphamide-L-NAME-L-arginine-BPC 157 relationships. This suggests that in cyclophosphamide damaged rats, NO excessive release generated by the inducible isozyme, damages the vascular wall and other tissue cells, especially in combination with reactive oxygen intermediates, while failing endothelial production and resulting in further aggravation by L-NAME which was inhibited by L-arginine. Finally, BPC 157, due to its special relations with NO-system, may both lessen increased MDA- and NO-tissues values and counteract effects of both cyclophosphamide and L-NAME on stomach and duodenal lesions.

Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications.

BACKGROUND: Brain-gut interaction involves, among others, peptidergic growth factors which are native in GI tract and have strong antiulcer potency and thus could from periphery beneficially affect CNS-disorders. We focused on the stable gastric pentadecapeptide BPC 157, an antiulcer peptidergic agent, safe in inflammatory bowel disease trials and now in multiple sclerosis trial, native and stable in human gastric juice. METHODS: Review of our research on BPC 157 in terms of brain-gut axis. RESULTS: BPC 157 may serve as a novel mediator of Robert's cytoprotection, involved in maintaining of GI mucosa integrity, with no toxic effect. BPC 157 was successful in the therapy of GI tract, periodontitis, liver and pancreas lesions, and in the healing of various tissues and wounds. Stimulated Egr-1 gene, NAB2, FAK-paxillin and JAK-2 pathways are hitherto implicated. Initially corresponding beneficial central influence was seen when BPC 157 was given peripherally and a serotonin release in particular brain areas, mostly nigrostriatal, was changed. BPC 157 modulates serotonergic and dopaminergic systems, beneficially affects various behavioral disturbances that otherwise appeared due to specifically (over)stimulated/damaged neurotransmitters systems. Besides, BPC 157 has neuroprotective effects: protects somatosensory neurons; peripheral nerve regeneration appearent after transection; after traumatic brain injury counteracts the otherwise progressing course, in rat spinal cord compression with tail paralysis, axonal and neuronal necrosis, demyelination, cyst formation and rescues tail function in both short-terms and long-terms; after NSAIDs or insulin overdose or cuprizone encephalopathies were attenuated along with GI, liver and vascular injuries. CONCLUSION: BPC 157, a gastric peptide, may serve as remedy in various CNS-disorders.

Stable gastric pentadecapeptide BPC 157 heals rat colovesical fistula.

To establish the effects of BPC 157 on the healing of rat colovesical fistulas, Wistar Albino male rats were randomly assigned to different groups. BPC 157, a stable gastric pentadecapeptide, has been used in clinical applications-specifically, in ulcerative colitis-and was successful in treating both external and internal fistulas. BPC 157 was provided daily, perorally, in drinking water (10µg/kg, 12ml/rat/day) until sacrifice or, alternatively, 10µg/kg or 10ng/kg intraperitoneally, with the first application at 30min after surgery and the last at 24h before sacrifice. Controls simultaneously received an equivolume of saline (5.0ml/kg ip) or water only (12ml/rat/day). Assessment (i.e., colon and vesical defects, fistula leaking, fecaluria and defecation through the fistula, adhesions and intestinal obstruction as healing processes) took place on days 7, 14 and 28. Control colovesical fistulas regularly exhibited poor healing, with both of the defects persisting; continuous fistula leakage; fecaluria and defecation through the fistula; advanced adhesion formation; and intestinal obstruction. By contrast, BPC 157 given perorally or intraperitoneally and in µg- and ng-regimens rapidly improved the whole presentation, with both colon and vesical defects simultaneously ameliorated and eventually healed. The maximal instilled volume was continuously raised until it reached the values of healthy rats, there were no signs of fecaluria and no defecation through the fistula, there was counteraction of advanced adhesion formation or there was an intestinal obstruction. In conclusion, BPC 157 effects appear to be suited to inducing full healing of colocutaneous fistulas in rats.

Stable gastric pentadecapeptide BPC 157 heals rectovaginal fistula in rats.

AIM: Rectovaginal fistula is a devastating condition providing more than 99% of patients for surgical treatment. We hypothesized that rectovaginal fistula may be healed by therapy with stable gastric pentadecapeptide BPC 157, in consistence with its initial clinical application and effect on external fistulas. MAIN METHODS: BPC 157 (10µg/kg or 10ng/kg) was given perorally, in drinking water (0.16µg/ml or 0.16ng/ml, 12ml/rat/day) till sacrifice, or alternatively, intraperitoneally, first application at 30min after surgery, last at 24h before sacrifice. Controls simultaneously received an equivolume of saline (5.0ml/kg ip) or water only (12ml/rat/day). The assessment (i.e., rectal and vaginal defect, fistula leakage, defecation through the fistula, adhesions and intestinal obstruction as healing processes) was at day 1, 3, 5, 7, 10, 14 and 21. KEY FINDINGS: Regularly, rectovaginal fistulas exhibited poor healing, with both of the defects persisting, continuous fistula leakage, defecation through the fistula, advanced adhesion formation and intestinal obstruction. By contrast, BPC 157 given perorally or intraperitoneally, in µg- and ng-regimens rapidly improved the whole presentation, with both rectal and vaginal defects simultaneously ameliorated and eventually healed. The maximal instilled volume was continuously raised till the values of healthy rats were achieved, there were no signs of defecation through the fistula. A counteraction of advanced adhesion formation and intestinal obstruction was achieved. Microscopic improvement was along with macroscopic findings. SIGNIFICANCE: BPC 157 effects appear to be suited to induce a full healing of rectovaginal fistulas in rats.

A giant hemorrhagic adrenal pseudocyst: case report.

OBJECTIVE: To report a rare case of a giant hemorrhagic adrenal pseudocyst and highlight the importance of this entity to clinicians. CASE PRESENTATION: A 57-year-old woman presented with a 1-year history of abdominal pain and distension. Ultrasonography and multislice computed tomography revealed a giant cystic (partially solid) mass over the left suprarenal region measuring 20 x 17 x 15 cm. A complete endocrine workup failed to detect any hormonal hypersecretion. INTERVENTION: The patient was treated with tumor excision through transabdominal pararectal approach. Histopathological examination revealed a hemorrhagic adrenal pseudocyst. CONCLUSION: To our knowledge the case presented here appears to be one of the largest hemorrhagic adrenal pseudocysts reported so far. Radiological and clinical features of the tumor are nonspecific and histopathological examination is essential to establish definitive diagnosis. An open, laparotomic adrenalectomy is the preferred surgical technique for better control of such a large mass with active bleeding inside.

Rare case of ectopic duplicated megaureter with dysplastic upper kidney moiety opening into ipsilateral ejaculatory duct.

A rare case of left mesonephric duct malformation consisting of a duplicated ectopic megaureter opening into the ejaculatory duct and ipsilateral upper moiety cystic renal dysplasia is reported to increase awareness among urologists and radiologists of this entity. Magnetic resonance imaging has been shown to be an excellent diagnostic tool for tracking of the trajectory of the ectopic ureter, thereby obviating the need for other invasive diagnostic techniques and permitting surgical correction of the anomaly. The embryology, clinical features, and diagnostic and therapeutic aspects of this rare malformation are presented.