Urinary transforming growth factor-beta1 excretion in renal allograft recipients during the early post-transplantation period

BACKGROUND: Transforming growth factor-beta1 (TGF-beta1), the major fibrogenic growth factor, is implicated in the pathogenesis of renal scarring in experimental and clinical nephropathies as well as in chronic allograft nephropathy. In this study we examined the pattern of changes of TGF-beta1 excretion in the urine and the sites of TGF-beta1 expression in the kidney of transplanted patients during the early post-transplantation period. METHODS: Eighteen renal allograft recipients were included in the study. In all patients urinary TGF-beta1 levels were determined by ELISA in sequential measurements during the first two postoperative months and compared to that of 14 healthy subjects. The renal expression of TGF-beta1 protein was studied in 4 patients that underwent a biopsy of the transplanted kidney at the same period. All patients were treated with prednisolone, cyclosporin, and mycophenolate mofetil. RESULTS: Urinary TGF-beta1 levels were increased during the first postoperative days. Although they were gradually reduced during the first two post-operative months, they remained significantly higher compared to those of normal subjects (580 +/- 148 ng/24 h vs. 310 +/- 140 ng/ 24 h p < 0.01). The decline of urinary TGF-beta1 excretion followed that of serum creatinine. TGF-beta1 protein expression was identified within the cytoplasm of tubular epithelial cells of transplanted patients. CONCLUSIONS: Elevated urinary TGF-beta1 levels are observed during the early post-transplantation period in renal allograft recipients and are maintained high even after restoration of renal function to normal.     

Selective hepatic arterial infusion of In-111-DTPA-Phe<Superscript>1</Superscript>-octreotide in neuroendocrine liver metastases

Purpose  The aim of this study is to evaluate the effectiveness of ¹¹¹In-DTPA-Phe¹-octreotide infusions after selective catheterization of the hepatic artery in inoperable metastasised liver, sst₂ receptor-positive neuroendocrine tumours due to the effect of ¹¹¹In Auger electron emission, minimising in parallel the toxicity of non-target tissue. Methods  The average dose per session administered monthly to each patient (17 cases in total) was 6.3 ± 2.3 GBq. Repetitions did not exceed 12-fold, except in one case (15 sessions). Response assessment was classified according to the Response Evaluating Criteria in Solid Tumours. CT/MRI scans were performed as baseline before, during and after the end of treatment, and monthly ultrasound images for follow-up measurements. Toxicity (World Health Organization criteria) was measured using blood and urine tests of renal, hepatic and bone marrow function. Results  Complete response was achieved in one (5.9%) patient and partial in eight (47.0%), and disease stabilization in 3 (17.7%) patients; five (29.4%) did not respond. A 32-month median survival time was estimated in 12 (70.5%). Nine of these 12 surviving had a mean target diameter shrinkage from 144 ± 81 to 60 ± 59 mm. Grade 1 erythro-, leuko- and thrombo-cytopenia occurred in three (17.6%) cases. Conclusion  In unresectable metastatic liver lesions positive for somatostatin receptors repeated, transhepatic high doses of ¹¹¹In-DTPA-Phe¹-octreotide show an effective therapeutic outcome. Given the locoregional modality character of the administration technique plus the extremely short range of ¹¹¹In Auger and internal conversion electrons emission, no nephro-, liver- or myelo-toxicity has so far been observed.     

Occult acetabulum fracture. A case report

Acetabular fractures that are radiographically occult are associated with insufficiency fractures, stress fractures, and fractures secondary to steroid-induced osteoporosis, usually affecting older patients after low-energy trauma. Occult acetabulum fractures in young patients are extremely rare. We discuss herein a case of an occult acetabulum fracture after high-energy trauma, in a young patient. This case illustrates the need for further diagnostic studies such as computed tomography, magnetic resonance imaging, or bone scanning when, despite negative radiographic findings, groin pain is persistent.     

Management strategy for arterial priapism: therapeutic dilemmas

PURPOSE: We present 7 cases of arterial high flow priapism and propose management algorithms for the condition. MATERIALS AND METHODS: We studied 2 children and 5 adults with posttraumatic arterial priapism. Blood gas analysis and color Doppler ultrasonography of the corpora cavernosa confirmed the diagnosis in 4 adults, while 1 patient had already undergone cavernous artery ligation in elsewhere. In the children perineal compression resulted in detumescence, a sign that is proposed to be indicative of the diagnosis of arterial priapism (piesis sign) complementing physical examination. Mechanical compressive force was applied to the perineum of 1 boy, while the other received a watchful waiting program. All adults participated in an observation regimen except 1, who decided to undergo immediate embolization of the internal pudendal artery. RESULTS: Perineal compression led to the resolution of priapism in 1 child, while spontaneous resolution was noted in the other. An adult noticed spontaneous penile detumescence 3 to 4 months after trauma, which was attributable to site specific venous leakage and decreased, inflow in the contralateral cavernous artery. The patient underwent venous surgery and is on an intracavernous injection regimen. Successful embolization of the internal pudendal artery was performed immediately in 1 man and in the other 4 months after trauma due to social inconvenience. Adult patient 3 is still on the watchful waiting protocol (42 months), while the one who underwent cavernous artery ligation is receiving treatment for erectile dysfunction. CONCLUSIONS: Absent of long-term damaging effects of arterial priapism on erectile tissue combined with the possibility of spontaneous resolution or progressive concomitant hemodynamic abnormalities associated with blunt perineal trauma are suggestive of the introduction of an observation period in the management algorithm of high flow priapism. Such a period may help avoid unnecessary intervention and determine the impact of priapism on patient personal life. Perineal compression may be also added as part of the physical examination as a sign specifically indicative of arterial priapism.     

Inhaled iloprost controls pulmonary hypertension after cardiopulmonary bypass

PURPOSE: Severe pulmonary hypertension (PH) is a major cause of right ventricular (RV) dysfunction. Various iv vasodilator modalities have been used with limited results because of lack of pulmonary selectivity. The aim of the present controlled study was to evaluate the efficacy of inhaled iloprost, a synthetic prostacyclin analogue, in patients with elevated pulmonary vascular resistance (PVR) immediately after separation from cardiopulmonary bypass (CPB). METHODS: Twelve patients with persistent PH after discontinuation of CPB were included in the study. In all patients standard hemodynamic monitoring was used. Inhaled iloprost was administered via nebulized aerosol at a cumulative dose of 0.2 micro g*kg(-1) for a total duration of 20 min. Complete sets of hemodynamic measurements were performed before inhalation (baseline), during and after cessation of the inhalation period. Echocardiographic monitoring of RV function was also used. RESULTS: Inhaled iloprost induced a reduction in the transpulmonary gradient at the end of the inhalation period in comparison to baseline (9.33 +/- 3.83 mmHg vs 17.09 +/- 6.41 mmHg, P < 0.05). The mean pulmonary artery pressure to systemic artery pressure ratio decreased over this period (0.28 +/- 0.08 vs 0.45 +/- 0.17, P < 0.05). A statistically significant decrease of the PVR to systemic vascular resistance ratio was also observed (0.15 +/- 0.05 vs 0.21 +/- 0.05, P < 0.05). Improved indices of RV function were observed in echocardiographic monitoring. CONCLUSION: Inhaled iloprost appears to be a selective pulmonary vasodilator and may be effective in the initial treatment of PH and the improvement of RV performance in the perioperative setting.     

Transforming growth factor-beta(1) in the kidney and urine of patients with glomerular disease and proteinuria.

BACKGROUND: Transforming growth factor-beta(1) (TGF-beta(1)) is the major fibrogenic growth factor implicated in the pathogenesis of renal scarring. Proteinuria is a poor prognostic feature for various types of glomerular disease and its toxic action may be related to the activation of tubular epithelial cells towards increased production of cytokines and chemoattractant peptides. In this work we studied the site of synthesis and expression profile of TGF-beta(1) in the renal tissue of patients with heavy proteinuria and examined the relation of this expression with the urinary excretion of TGF-beta(1). METHODS: Twenty-five patients with heavy proteinuria (8.4+/-3.0 g/24 h) were included in the study. All patients underwent a diagnostic kidney biopsy and were commenced on immunosuppressive therapy with corticosteroids and cyclosporin. The sites of synthesis and expression profile of TGF-beta(1) mRNA and protein in the kidney were examined by in situ hybridization and immunohistochemistry. Urinary and plasma TGF-beta(1) levels were determined by ELISA before the initiation of treatment and 6 months later and compared with those of normal subjects and of patients with IgA nephropathy and normal urinary protein excretion. RESULTS: The site of synthesis and expression of TGF-beta(1) in the renal tissue of patients with heavy proteinuria was mainly localized within the cytoplasm of tubular epithelial cells. Interstitial expression was also present but glomerular TGF-beta(1) expression was found only in patients with mesangial proliferation. Urinary TGF-beta(1) excretion was significantly higher in nephrotic patients compared with normal subjects and with patients with IgA nephropathy and normal urinary protein excretion (783+/-280 vs 310+/-140 and 375+/-90 ng/24 h, respectively; P<0.01). In patients with remission of proteinuria after immunosuppressive therapy, urinary TGF-beta(1) excretion was significantly reduced (from 749+/-290 to 495+/-130 ng/24 h; P<0.01), while in patients with persistent nephrotic syndrome, it remained elevated. CONCLUSIONS: The localization of TGF-beta(1) mRNA and protein within tubular epithelial cells, along with its increased urinary excretion in patients with nephrotic syndrome, suggest the activation of these cells by filtered protein towards increased TGF-beta(1) production.     

Efficacy of cyclosporin in difficult-to-treat idiopathic membranous nephropathy

SUMMARY: Poor tolerance and the potential long-term toxicity have limited the widespread use of corticosteroids and cytotoxic drugs in the treatment of idiopathic membranous nephropathy (IMN). Cyclosporin A (CyA) has been proven to be a less toxic alternative, but its efficacy needs further confirmation. Cyclosporin A (2–3mg/kg per day) in combination with low-dose methylprednisolone (4mg/day) was given to 28 nephrotic patients with IMN who had failed to respond, or tolerate, or to complete treatments with steroids and/or cytotoxic drugs. the mean duration of treatment was 11 ± 7 months. Seven patients (25%) showed a complete remission of proteinuria, 17 (60%) a partial one, and four (15%) did not respond at all. the average time to achieve optimal remission was 4.2 ± 1.4 weeks following the initiation of therapy. In those who responded completely or partially, plasma creatinine (Per) did not change significantly from pre CyA levels during follow up (1.0 ± 0.3 vs 1.2 ± 0.3mg/dL, P =NS). the remaining four patients who had renal insufficiency already before CyA (mean Per: 2.1 ± 0.8mg/dL), showed a rapid deterioration of renal function after the initiation of CyA (mean Per: 3.1 ± 1.5 mg/dL, P <0.01), and as a consequence, the drug was discontinued. A mul-tivariate analysis on the clinical and histological features demonstrated that the degree of renal function impairment ( P <0.02), the percentage of obsolete glomeruli ( P <0.01), and the severity of interstitial fibrosis ( P <0.005) independently predicted the response to therapy. Low dose CyA is an effective and safe alternative treatment for patients with IMN and normal renal function. However, the drug should be given with caution to patients with established renal insufficiency.     

Mycophenolate mofetil impairs the integrity of colonic anastomosis

BACKGROUND: The aim of this experimental study was to investigate the effect of mycophenolate mofetil (MMF) during the three phases of colonic anastomosis healing and specifically to check the effect of MMF on the expression of transforming growth factor-beta1 (TGF-beta1), one of the most important growth factors contributing to mechanical stability of colonic anastomosis. MATERIALS AND METHODS: Sixty male Wistar rats underwent colonic resection and end-to-end anastomosis. The animals were divided into two groups, a study group given MMF 40 mg/kg, intraduodenally and a control group given vehicle. The rats were sacrificed at 3, 7, and 14 days (10 animals in each group). The anastomoses were tested by measuring bursting pressure and hydroxyproline content. Histological examination and immunohistochemical expression of TGF-beta1 also were assessed. RESULTS: The mean bursting pressure in the study group was significantly lower on day 3 and 7, but there was no statistical significance on day 14. The mean hydroxyproline content was lower in the study group on days 3, 7, and 14. Histology showed decreased number of macrophages and fibroblasts on days 3 and 7 but no difference on day 14. The expression of TGF-beta1 was significantly reduced in the study group, with the difference being more pronounced on days 3 and 7. CONCLUSION: MMF weakens the integrity of colonic anastomosis, and this effect is more significant during the inflammatory phase of healing. MMF has a negative effect on macrophages and TGF-beta1 expression, resulting in decreased collagen accumulation at the anastomosis.     

Multifocal Versus Solitary Papillary Thyroid Carcinoma

Background

Papillary Thyroid Carcinoma (PTC) which accounts for >85 % of all thyroid cancers in iodine-rich areas, appears either as a single tumor or as two or more, neoplastic foci within the thyroid gland (Multifocal PTC). We present the comparative results between solitary and MFC PTC.

Materials and methods

Demographics, tumor characteristics (size, laterality, foci number, histologic subtype) and TNM staging were compared between solitary and MFPTC patients. The presence of lymphocytic or Hashimoto’s thyroditis was also recorded.

Results

From January 2008 to December 2012, among 647 PTC patients, 241(37.2 %) had MFPTC 177 females (73.4 %) and 64 males (26.6 %), mean age 48.5 years (range 12–87). Mean number of tumor foci was 3.3 (range 2–26). MFPTC patients presented with more advanced T stage (28.2 vs. 18.7 %, p = 0.01) and more LN metastases (28.6 vs. 15.5 %, p < 0.001). Foci number correlates with male gender and LN metastases (p = 0.014 and p = 0.019, respectively). Central (N1a) or lateral (N1b) LN involvement correlates strongly with male gender (p  = 0.024) and younger age (p < 0.001). The follicular variant was the next most frequent histologic subtype associated with extremely rare LN metastases.

Conclusion

MFPTC comprises a more aggressive form of papillary thyroid cancer since it is associated with more frequent N1a/ N1b disease and occurs more frequently in T3/T4 patients. MFPTC foci number correlates with male gender and LN metastases.

     

Fibroepithelial polyp of distal ureter with periodic prolapse into bladder

Ureteric fibroepithelial polyp is a rare disease; it is of mesodermal origin and exhibits benign characteristics. Hydronephrosis occurs in rare cases, and it is generally accepted that it may result in an obstruction without causing alterations of renal function. In many cases it is difficult to differentiate from transitional cell carcinomas. Nowadays, endoscopic evaluation is the means of treatment and management. In our case study we report a patient with a long fibroepithelial polyp of the distal ureter prolapsing into the bladder in a periodic pattern. Cystoscopy revealed that movement of the polyp was moving forward and backward in the right ureteric orifice. Cold-cut biopsy established the diagnosis. The patient underwent ureteroscopic excision and remains asymptomatic a year later.