Surgical ultrasonography of the seminal vesicles in andrologic pathology. Research in progress

The authors describe their experience with percutaneous transperineal puncture (PTP) of the seminal vesicles in andrologic pathologic conditions, using transrectal US guidance. Three cases are reported: 2 anomalies of the genital ducts and one prostatic-vesicular abscess. In the first two cases PTP allowed a diagnosis to be reached on the basis of the analysis of vesicular fluid. Moreover, the examination allowed the selection of the patients to be submitted to surgery for seminal duct anomaly (endoscopic resection of the colliculus seminalis). In cases 1 and 3 PTP allowed the aspiration of the fluid from a cyst in the left ejaculatory duct and from a prostatic-vesicular abscess, respectively. These procedures were facilitated using US guidance. The clinical possibilities and utility of PTP have not yet been completely defined. The authors suggest a diagnostic protocol to be used in the presence of azoocytospermia, where US must be performed only in patients with excretory infertility. The present paper must be considered a work in progress. Further study is required to identify the clinical indications of interventional US of the seminal vesicles in patients with andrologic pathologic conditions.     

Glucocorticoid resistance in dialysis patients may impair the kidney allograft outcome.

This study examines in vitro steroid sensitivity in chronic renal failure (CRF) patients and its influence on the allograft outcome. We determined the inhibitory effect of dexamethasone (DEX) on concanavalin A (Con-A)-stimulated peripheral blood mononuclear cell (PBMC) proliferation, and glucocorticoid receptor' (GR) number of binding sites (B(max)) and affinity (K(d)) in 28 CRF patients and 40 normal healthy controls. Based on K(d) values >95th percentile from controls, patients were divided into two groups: glucocorticoid resistant (n = 11) and glucocorticoid sensitive (n = 17). Patients were followed during 18 months post-transplantation observing acute rejection episodes (ARE), chronic allograft nephropathy (CAN), allograft failure and death. The DEX concentration that caused 50% inhibition of Con-A-stimulated PBMC proliferation (IC(50)) was higher in CRF than in healthy controls (2.2 x 10(-5) +/- 1.0 x 10(-5) versus 8.3 x 10(-6) +/- 4.2 x 10(-6) mol/L, P = 0.02). Values of K(d) (12.4 +/- 1.8 versus 7.2 +/- 0.9 nM) and B(max) (7.7 +/- 1.1 versus 4.1 +/- 0.3 fmol/mg protein) were higher in CRF patients (P = 0.02 and P = 0.001, respectively). There were higher incidences of ARE (P = 0.02) and CAN (P = 0.002) in the glucocorticoid-resistant group. Univariate and multivariate logistic regression showed that K(d) was an independent predictor of ARE (OR 8.8, P = 0.03) as well as of CAN (OR 16.5, P = 0.01). In conclusion, we observed glucocorticoid resistance in a subgroup of CRF patients undergoing dialysis, which led to a higher morbidity due to ARE and CAN in an 18-month follow-up period.     

US-guided prostatic biopsy in 63 cases

Over a 20-months period, 63 patients with prostatic lesions less than or equal to 2 cm in size, detected at palpation or at ultrasonography (US), were followed-up with US-guided transperineal biopsy. Within the nodules located in the peripheral parts of the gland, and still confined within the capsule, focal cancer, chronic prostatitis and benign atypical hyperplasia were detected, but typical echo patterns were not seen. All nodules located in the periurethral gland were benign hyperplasia. US-guided biopsy in all patients presenting with small, suspicious nodules or focal echo pattern changes, localized within the peripheral gland, is recommended.     

Papillary nephrocarcinoma: radiographic and echographic aspects

Between 1976 and 1987, 395 patients with kidney tumors were studied with radiological techniques and sonography. In 37 cases (9.4%) histopathology diagnosed pure papillary renal cell carcinoma. Analyzing the radiographic patterns of these neoplasms, the authors observed constantly diminished vascularity (100%), frequent calcifications (35.1%) and necrotic areas (51.3%). Such X-ray features are not specific: nevertheless, their coexistence is strongly suggestive of papillary renal cell cancer. No consistent US pattern was found; however, necrotic areas were easily demonstrated in most cases. It must be stressed how patients with papillary carcinoma experienced a longer postoperative survival; it has not yet been established whether such favorable behavior is due to low biological aggressiveness or to earlier diagnosis.     

Metabolic genotypes as modulators of asbestos-related pleural malignant mesothelioma risk: a comparison of Finnish and Italian populations

The role of CYP1A1, GSTM1, GSTT1, EPHX1, and NAT2 genotypes in susceptibility to malignant mesothelioma (MM) was compared in two case-control studies, previously conducted in two countries where different types of asbestos fibers have been used [Hirvonen et al., 1995. Inherited GSTM1 and NAT2 defects as concurrent risk modifiers in asbestos-related human malignant mesothelioma. Cancer Res. 55, 2981-2983; Hirvonen et al., 1996. Glutathione S-Transferase and N-Acetyltransferase genotypes and asbestos-associated pulmonary disorders. J. Natl. Cancer Inst.88, 1853-1856; Neri et al., 2005. Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure. Mutat. Res. 592, 36-44]. Fifty-seven asbestos-exposed MM patients and 255 controls were recruited in Italy, 48 cases and 121 controls in Finland. In order to make the two studies comparable, they have been updated and new genotyping analyses have been performed. The NAT2 fast acetylator and EPHX1 low-activity genotypes were positively associated with MM in the Italian study, while they were negatively associated with this malignancy in the Finnish one. A combined significant effect was also observed in the Italian study for the NAT2 fast acetylator and EPHX1 low-activity genotypes, while this combination was protective in the Finnish study. Combination of NAT2 fast acetylator and GSTM1 null genotype posed a significantly increased risk of MM in the Italian, but not in the Finnish study. The opposite results obtained in Finland and Italy may be ascribed to random chance, but a role may be hypothesized for the fact that different types of asbestos have been used in the two countries.     

Developmental toxicity of meglumine antimoniate and transplacental transfer of antimony in the rat

Meglumine antimoniate (MA), a pentavalent antimonial (SbV) drug, has been used for the treatment of leishmaniases for over half a century but there is almost no data on its safety and kinetics during pregnancy. This study was undertaken to investigate the developmental toxicity of MA as well as the transplacental transfer of antimony (Sb) in rats. Wistar rats (approximately 20 per group) were treated subcutaneously (s.c.) with MA (0, 75, 150, 300 mg SbV/(kg BW day)) during pregnancy (days 1-20). An untreated control group was evaluated as well. Caesarean sections were performed on day 21 and implantations, living and dead fetuses, and resorptions were recorded. Fetuses were weighed and fixed in Bouin's solution and one-third of each litter was examined for soft-tissue anomalies. The remaining fetuses were cleared and stained with Alizarin red S for skeleton evaluation. No adverse effect of MA on the mothers was noted at any dose level. No embryotoxicity was observed at the lowest dose but, at the highest dose, MA increased embryolethality, reduced fetal weight and augmented the occurrence of some soft-tissue and skeleton variations. Therefore, the no-observed-adverse-effect level for MA-induced embryotoxicity was 75 mg SbV/(kg BW day). In a separate group of rats treated with 300 mg SbV/(kg BW day) s.c. during whole pregnancy, blood (0.2 mL) was taken from the tail vein 1, 2, 4, 6, 12 and 24 h after treatment on day 1 and thereafter every other day immediately before drug injection. Blood was also taken from fetuses removed on day 21, 24h after the last injection of MA. Blood levels of Sb were determined by ICP-MS and results showed that most of administered Sb was eliminated rapidly (in less than 6 h), but nadir blood concentrations increased gradually during treatment from 1 to 2 microg/g, 24h after the first dose, up to approximately 38 microg/g after the 20th dose. Levels of Sb in fetal blood were as high as 10-15 microg/g, i.e. approximately 30% their mothers' nadir levels near term. These findings indicated that repeated administration of MA during gestation led to an accumulation of Sb in mothers and fetuses.     

Moderate hyperhomocysteinemia and early-onset central retinal vein occlusion

PURPOSE: To evaluate the prevalence of moderate fasting hyperhomocysteinemia (HHcy) and postmethionine load (PML) HHcy among patients with early-onset central retinal vein occlusion (CRVO). METHODS: The prevalence of fasting HHcy and that of PML HHcy were evaluated in a consecutive series of 58 patients with CRVO who were younger than 56 years of age (mean age, 40.3 years) and in 103 controls (mean age, 39.6 years). Plasma folate, vitamin B12, and pyridoxal-5'-phosphate (PLP) levels were measured in 42 patients and 67 controls. RESULTS: Mantel-Haenszel odds ratios for CRVO patients were 3.00 (95% confidence interval [CI], 0.83-10.8) for fasting HHcy, 3.50 (95% CI, 1.07-11.4) for PML HHcy, and 3.00 (1.18-7.6) for fasting HHcy and PML HHcy in subjects with normal fasting total homocysteine (tHcy) levels. Moderate HHcy was associated with reduced plasma levels of folate and PLP (P < or = 0.04). There was no significant dependence of fasting and PML tHcy levels on any traditional risk factor evaluated. CONCLUSIONS: Moderate HHcy is an independent risk factor for early-onset CRVO.     

Incidence and evolution of soft tissues calcifications in patients in periodic hemodialysis (author's transl)

In a series of 92 patients' in hemodialysis the evolution of periarticular and vascular calcifications has been studied. A correlation exists between the incidence of arterial calcifications and the patients' age, while no direct correlation has been proved to exist with the duration of dialysis. In fact their annual average increase (8.4%) is similar to that of periarticular calcifications (12.2%).     

SV40 enhances the risk of malignant mesothelioma among people exposed to asbestos: a molecular epidemiologic case-control study

We conducted a case-control study on asbestos exposure and presence of SV40 in tumor samples of malignant mesotheliomas (MMs) and bladder urotheliomas (BUs). PCR analysis revealed the presence of SV40 DNA (SV40+) in eight (42.1%) MMs and 6 (33.3%) BUs. The odds ratio for MM Asb- and SV40+ was 0.4 [95% confidence interval (95% CI), 0.03-4.0], for Asb+ and SV40- was 3.6 (95% CI, 0.6-21.0), and for Asb+ and SV40+ was 12.6 (95% CI, 1.2-133.9). Our results suggest that SV40 increases the risk of MM among individuals exposed to asbestos.     

Thalidomide treatment reduces apoptosis levels in bone marrow cells from patients with myelodysplastic syndromes

We treated with thalidomide seven patients with primary MDS and observed reduction of the transfusion requirement in three cases and reduction of bone marrow blasts in one case. The apoptotic rate of bone marrow cells diminished significantly from a mean of 43.8% to a mean of 17.5%, whereas the proliferative activity did not change. Plasma TNF-alpha, bFGF, IL-1beta levels decreased variably, whereas VEGF levels tended to increase. Matrix metalloproteinases 2 and 9 expression decreased in bone marrow cells of responders. A reduction of CD4 cells and an increase of NK cells was observed in the peripheral blood. Thus, thalidomide may produce a fairly good hematological improvement in erythroid series in MDS, with complex biological mechanisms.