Color Doppler provides a reliable and rapid means of monitoring luteolysis in female donkeys.

When artificial reproduction technologies designed for use with horses are used with donkeys, success is dependent on awareness of the physiological differences between these species, yet little information is available on many aspects of donkey reproduction. The present work examines the activity of the CL in Catalonian jennies after induced luteolysis. Plasma progesterone concentration, luteal blood flow (determined by color Doppler), and CL cross-sectional area (CL-CSA; determined by B-mode ultrasound examination) were assessed after a single dose (5 mg intramuscular) of dinoprost thromethamine (DT, a PGF2α analog) on Day 10 after ovulation in two experiments. In experiment 1, a preliminary experiment, data were collected daily for 4 days after DT administration. Values for all the measured variables decreased over this period. In experiment 2, data were collected during the first 24 hours after DT administration because in experiment 1, most luteolytic activity occurred during this time. An increase in luteal blood flow was seen between 0 and 3 hours, followed by a progressive reduction, whereas the values for plasma progesterone and CL-CSA gradually decreased from 0 hours onward. In both studies, negative correlations were seen between all variables and the time of sampling. In contrast, positive correlations were seen between plasma progesterone, CL-CSA, uterine tone, and luteal blood flow. Indeed, a strong correlation was recorded between plasma progesterone and luteal blood flow (r = 0.70; P < 0.0001). In conclusion, plasma progesterone and CL-CSA both become reduced after induced luteolysis in Catalonian jennies. Unlike in mares, an increase in luteal blood flow occurs soon after induced luteolysis, rather like that seen in the cow. The luteal blood flow, as evaluated here by color Doppler, was also closely related to the plasma progesterone concentration. Color Doppler would appear therefore to offer a rapid and easy means of examining the state of luteolysis.

Embryo quality and transcervical technique are not the limiting factors in donkey embryo transfer outcome.

Embryo transfer (ET) in the donkey resulted in a very low recipient pregnancy rates. The aim of these studies was to investigate if nonsurgical transfer techniques or donkey embryo quality affect donkey recipient pregnancy failure. In Study 1, the impact of transfer technique was investigated by evaluating if cervical catheterization is associated with prostaglandin release and suppression of luteal function and if donkey recipients would become pregnant after nonsurgical transfer of horse embryos. Four jennies, from 5 to 8 d after ovulation, were submitted to a sham transcervical ET and to evaluation of PGFM and progesterone plasma concentrations. Five 8 d horse embryos were nonsurgically transferred into synchronized donkey recipients (HD). Cervical stimulation caused a transient PGF(2α) release in two of four jennies in the absence of a significant decrease in progesterone plasma concentration. All transferred horse embryos resulted in pregnancies in the jenny recipients. In Study 2, donkey embryo viability was investigated by 1.2 meters, 6-diamidino-2-phenylindole (DAPI) staining of 10 embryos and by the transfer of 6 and 12 donkey embryos in synchronized mare (DH) and donkey (DD) recipients, respectively, of known fertility. The estimated proportion of dead cells in DAPI stained embryos was 0.9% (range 0-3.9%) and below what is considered normal (20%) for horse embryos. Three of six and six of 12 of the DH and DD ETs, respectively resulted in pregnancies at 14 and 25 d (50%), a higher pregnancy rate than previously reported after DD ET. The overall results of this study suggest that the transcervical technique for ET and donkey embryo viability are not the reasons for the low pregnancy rates that have previously been described in donkey recipients, and that nonsurgical ET in donkeys can result in acceptable results.

Clinical use of dopamine antagonist sulpiride to advance first ovulation in transitional mares.

Artificial photoperiod treatment is currently the best method to hasten the first ovulation of the breeding season in winter anoestrus mares. However, this is not easy to apply in large herds of mares and, to be effective, has to be planned in the northern hemisphere in December at the latest. Pharmacological treatments have been proposed as alternatives: GnRH agonists, progesterone or its synthetic agonist Altrenogest, and dopamino-antagonists, as pherphenazine, domperidone or sulpiride. Dopamino-antagonists protocols, beginning at a given day of the year, gave controversial results in terms of hastening ovulation. The aim of this study was to evaluate the efficacy of an up-to-21-d long dopamine antagonist (sulpiride) treatment on mares at the beginning of the spring transition for its ability to hasten estrous cyclicity. In Study 1, 49 seasonally-acyclic standardbred mares, maintained in paddocks under natural photoperiod, were treated with 1 mg/kg/d sulpiride at the evidence of the first follicle with of 25 mm in diameter until ovulation for a maximum of 21 d (Group S(1); n = 34) or left untreated (Group C(1); n = 15). Group S(1) and C(1) mares showed a follicle of 35 mm in diameter after 8 and 22 d (median; P < 0.05) and ovulated after 18 and 43 d, respectively (median; P < 0.05). Twenty-two/26 and 6/15 mares of the Group S(1) and C(1) ovulated within 30 d from the beginning of the treatment, respectively (P < 0.05). All the mares of the study cycled until Autumn, unless they became pregnant. In Study 2, pregnancy rates after the first ovulation of the year of 22 acyclic standardbred mares maintained in paddocks under natural photo-period, treated following the same protocol as Study 1 (S(2)), and 47 untreated mares (C(2)) were compared. In Groups S(2) and C(2,) 63.6% and 61.7% of the mares became pregnant after the first cycle (P > 0.05) and 50.0% and 61.1% of the remaining became pregnant in the following cycles (P > 0.05), respectively. Beginning with sulpiride treatment when follicles were 25 mm in diameter resulted in a significant advancement of cyclicity in non-photo-stimulated mares. Pregnancy rates after artificial insemination of treated mares were similar to those of untreated animals.

The use of placental S100 (S100P), GATA3 and napsin A in the differential diagnosis of primary adenocarcinoma of the bladder and bladder metastasis from adenocarcinoma of the lung.

Primary bladder adenocarcinoma accounts for 0.5-2% of all malignant bladder tumours. Literature data indicate the bladder as the second most common site of metastatic genitourinary tumours, with the kidney as the most frequent location. Secondary tumours of the bladder account for about 2.3% of all bladder malignancies encountered in surgical specimens. Herein, we describe an adenocarcinoma deeply infiltrating the bladder wall, with no morphologic features of transitional cell carcinoma, in a patient with a previous diagnosis of primary lung adenocarcinoma, mixed subtype. In this case, the use of a limited immunohistochemical panel including napsin A, a recently described highly sensitive marker for lung adenocarcinoma, GATA3 and S100P, two novel markers of urothelial differentiation, was of crucial importance in differentiating between lung adenocarcinoma metastatic to the bladder and primary bladder adenocarcinoma.

Embryo recovery rate and recipients' pregnancy rate after nonsurgical embryo transfer in donkeys.

Sixty-three embryos were recovered out of 83 estrous cycles (75.9%) and 98 ovulations (64.3%) of five Pantesca jennies, 2 to 5 yr old, naturally mated or artificially inseminated with fresh semen. Embryo recovery rate was influenced by number of ovulations per cycle (133% and 63% for double and single ovulations, respectively), by the day of embryo recovery attempt (12%, 83%, and 75% at Days 7, 8, and 9 after ovulation, respectively), and by the repetition of the embryo recovery attempt on successive cycles (60%, 79%, and 100% for cycles 1 to 7, 8 to 14, and 15 to 24, respectively). All recovered embryos but three were classified as good or excellent. Of 58 nonsurgical embryo transfers to Ragusana jenny recipients, 13 (22.4%), 10 (17.2%), and 9 (15.5%) resulted in a pregnancy at Days 14, 25, and 50, respectively. Recipients' pregnancy rate was not influenced by the evaluated parameters: embryo quality and age, media employed to wash embryos, days after ovulation of the recipient, experience of the operator. Between 14 and 50 d of pregnancy, 4 of 13 (30.7%) embryos were lost with an influence of the days from ovulation of the recipient: recipients at Days 5 or 6 kept all pregnancies (N=7), whereas recipients at Days 7 or 8 lost 3 of 4 pregnancies, as one of the two recipients at Day 3. More studies are needed before embryo transfer could be considered a reliable tool to preserve endangered donkey breeds.

Weekly administration of docetaxel and epirubicin as first-line treatment for hormone-refractory prostate carcinoma.

Androgen-independent prostate carcinoma (AICP) is one of the tumors that continue to respond poorly to chemotherapy. Recently, protocols based on the use of docetaxel have significantly improved survival for patients in this disease. In other types of neoplastic disease, combined therapy with taxanes and anthracycline derivatives has been shown to produce additive effects in terms of growth inhibition, and superior tolerability when associated with weekly administration schedules. These findings prompted us to examine the tolerability and efficacy of weekly treatment of AICP with docetaxel (DOX) plus epirubicin (EPI). We enrolled 35 chemotherapy-naive men with AICP (mean age 72 years, range 68-77) and normal hepatic, renal, and cardiac function. The chemotherapy protocol provided for the IV administration of DOX (30 mg/m2) and EPI (30 mg/m2) on days 1, 8, and 15 every 28 days. Treatment was continued for 6 months or until disease progression and/or unacceptable toxicity was observed. Serum levels of prostate-specific antigen (PSA) were monitored in all patients, and reductions from baseline values of >50% were considered indicative of positive responses to treatment. Thirty-four patients were included in the analysis of toxicity, and objective responses to treatment were assessed in the 28 patients with measurable lesions. Nineteen patients (56%) experienced PSA reductions of >50% that persisted for more than 4 weeks. The response to therapy was classified as complete in 1 of the 28 patients (4%) with measurable disease (at the lymph node level). Thirteen others (13/28, 46%) had partial responses, in nine (32%) the disease remained unchanged, and progression was observed in the remaining five (18%); overall response rate was 50% (CR + PR). Of the 27 patients with pain at the time of enrollment, 16 (59%) experienced pain reduction during treatment. The median time to disease progression was 11.7 months (95% CI: 7.7-15.7) while the median survival time was 18.7 months (95% CI: 12.3-25.1). During the study, four patients developed grade 3 anemia and leukopenia, which was reversible in all cases. Lower grades of asthenia, nausea, vomiting, diarrhea, and peripheral edema were also observed. There were no cases of cardiotoxic effects. Alopecia was frequent but reversible in all cases. The results of this preliminary study indicate that the combined administration of DOX and EPI for treatment of AIPC is effective and well tolerated. The weekly administration of the drug combination appears to be a promising approach to the treatment of these tumors.

[Spontaneous regression of lung metastases from renal cell carcinoma: the importance of immunogenetic factors and a review of the literature]. / Regressione spontanea delle metastasi polmonari da carcinoma renale. Ipotesi immunogenetiche e revisione della letteratura.

Spontaneous regression of renal cell cancer (RCC) metastases most frequently occurs after nephrectomy, since reducing target size makes possible a more effective immune response. RCC is immunotherapy-sensitive, as are RCC metastases, especially metastases to the lungs (organs are rich in immune cells and continually exposed to antigens), which have an antigenic effect. Immunotherapy could be perfected if a renal antigen that could be incorporated into a vaccine were identified. This would have played an important role in treatment and follow-up. Vaccine therapy for RCC is no longer far out of reach. The characteristics of RCC make it a fertile field for the study of prometastatic and endogenous antiangiogenic factors.

Surgical management of isolated bilateral adrenal metastases from colon carcinoma causing adrenal insufficiency.

Adrenal insufficiency due to histologically proven bilateral metastatic adrenal involvement from colon cancer has been clinically reported only twice. Surgical treatment of bilateral adrenal metastases is seldom performed, since other metastatic localizations are usually concomitant. To the best of our knowledge, we report the first case of relatively long-term disease-free survival after bilateral adrenalectomy in a patient with adrenal insufficiency due to bilateral metastases from colon carcinoma.

Transurethral radiofrequency thermal ablation of prostatic tissue: a feasibility study in humans.

OBJECTIVES: To evaluate the feasibility and efficacy of ablating prostatic tissue by inducing thermal lesions using radiofrequency (RF) energy delivered transurethrally through electrodes mounted on a Foley-like catheter. METHODS: Twenty male patients, candidates for radical cystoprostatectomy to treat bladder carcinoma, underwent RF prostate ablation 1 to 8 days before surgery (mean 2.8). Stainless steel, internally cooled, 2-cm-long electrodes mounted on a Foley-like catheter were used to deliver RF energy to the prostatic tissue. Semicircular electrodes were used in 10 patients (group A) and circular electrodes were used in the remaining 10 patients (group B). The urethral, rectal, and prostatic tissue temperatures were recorded. Histologic step sections were performed on whole mounts of the prostates to define the volume of the thermal lesions. RESULTS: The mean RF energy delivered was 36.5 kJ (range 26.4 to 53.1) in group A and 82.3 kJ (range 38 to 149) in group B. The intraprostatic temperatures were between 44 degrees C and 80 degrees C in group A and between 60 degrees C and 119 degrees C in group B. The urethral and rectal temperatures never exceeded 42 degrees C. No major complications occurred. After the RF procedure, 5 patients who received more than 75 kJ of energy could not void and required catheterization. The mean prostate volume was 11.54 cm(3) for group A and 24.02 cm(3) for group B. The mean volumes of the thermal lesions and their relative percentages in relation to the whole prostate in groups A and B were, respectively, 1.69 cm(3) and 15% and 6.91 cm(3) and 29% (P = 0.049). Analysis of variance showed a significant correlation between the thermal lesion volume and the energy delivered, regardless of the electrode shape (P = 0.001). CONCLUSIONS: Satisfactory thermal ablation of prostatic tissue can be achieved using RF electrodes mounted on a Foley-like catheter. The procedure is effective, simple, and safe and, therefore, can be used in pilot clinical studies on patients with benign prostatic hyperplasia.

Evidence for elevated telomerase activity in small cell carcinoma of the bladder.

Telomerase activity was found to be elevated using a quantitative assay on snap-frozen protein extracts of exfoliated cells in urine and bladder washings and tumor tissue obtained from a male patient with small cell carcinoma of the bladder. To the best of our knowledge, this is the first demonstration of elevated values of telomerase activity in genitourinary small cell carcinoma and is in keeping with the findings in primary lung locations.

Comparison of telomerase activity in bladder carcinoma and exfoliated cells collected in urine and bladder washings, using a quantitative assay.

Telomerase activity was measured with a quantitative assay, based on a modification of telomeric repeat amplification protocol method, in bladder cancers and apparently normal mucosa in 33 patients. In the same patients, the enzyme was also measured in exfoliated cells collected both with voided urine and bladder washings. Results obtained in urine were compared with those from 20 healthy subjects. Telomerase activity was present in 31 (94%) bladder cancer tissues and in 23 (72%) apparently normal mucosa samples. However, the levels of enzyme activity were significantly higher in cancer tissues in comparison with normal mucosa (mean +/- SD, 47.3 +/- 23.2 and 14.9 +/- 6.1 ng DNA/microg protein, respectively; P < 0.0001). Telomerase activity in bladder cancer tissues was not related to tumor stage and grade. Enzyme activity was present in 27 urine samples and in 27 (82%) bladder washings collected from cancer patients. We did not find correlation between the activity in urine and washings, and their mean levels were not different (22.2 +/- 10.1 and 20.7 +/- 8.0, respectively). Telomerase activity in bladder cancer tissues was correlated to its activity in urine (r = 0.650, P < 0.001) and in bladder washings (r = 0.410, P < 0.05). Only 2 of 20 urine samples from control subjects were found to express telomerase activity at a very low level. This was the first attempt to correlate telomerase activity in exfoliated cells from urine and bladder washings with the activity in corresponding bladder cancers. According to these results we postulate that telomerase activity in urine sediment reflects the activity in bladder cancers better than bladder washings and, for its easy collection, is to be preferred as diagnostic marker in this tumor.

Ureteral obstruction after kidney transplantation secondary to bone metaplasia.

We report a case of ureteral obstruction after kidney transplantation caused by localized bone metaplasia in the donor ureter. Surgical treatment consisted of removal of the involved ureteral segment, which was located 3 cm above the bladder and creation of a spatulated end-to-end anastomosis. Although bone metaplasia has been observed in the ureteral wall of some animal species secondary to experimental ischemia and microtrauma, it is exceedingly rare in humans and has never before been documented after kidney transplantation.

Focal xanthogranulomatous pyelonephritis with associated bone metaplasia.

Focal xanthogranulomatous pyelonephritis of the left lower pole was accidentally discovered in a 34-year-old woman at sonography. The patient had no history of stones and urinary tract infection and both conventional radiology and CT scan revealed radiated calcifications within a well-circumscribed mass. Surgical treatment consisted of enucleoresection of the lesion, and histopathology revealed a nucleus of bone metaplasia. To the best of our knowledge, metaplastic bone formation has never been documented before with xanthogranulomatous pyelonephritis.

Evaluation of the effects of desmopressin in acute ureteral obstruction.

OBJECTIVE: To evaluate the effects of desmopressin on pressure values inside the pelvis and ureter of the rat following acute obstruction. MATERIALS AND METHODS: By means of a microsurgical technique, 24 male Wistar rats were submitted to ureteral obstruction; pressure inside the ureter was recorded using a cannula and a micrometric glass column. In the treatment group (14 animals) 6 mg/kg of desmopressin were administered 30 min before the beginning of the experiment. RESULTS: Rats pretreated with desmopressin showed a statistically significant reduction in mean intraureteral pressure following acute obstruction (p = 0.05). CONCLUSIONS: In Wistar rats desmopressin demonstrated a powerful antidiuretic effect, reducing the intraureteral pressure. The experimental model is useful for a better understanding of physiopathology of renal colic and acute obstruction.

Squamous cell carcinoma arising at the base of the penis in a burn scar(1).

Squamous cell carcinoma developed after 32 years in a burn scar located on the ventral surface of the penis at the penoscrotal junction. The origin of squamous cell carcinoma in burn scars is a rare and not completely understood phenomenon. To the best of our knowledge, this is the first documented case of such an event in the penis because of the extreme rarity of genital burns.

Construction of synthetic signals for glycosyl-phosphatidylinositol anchor attachment. Analysis of amino acid sequence requirements for anchoring.

Many membrane proteins are anchored to the cell surface through covalent attachment to a glycosyl-phosphatidylinositol (GPI) structure. The GPI anchor is added to proteins in the endoplasmic reticulum following recognition of a signal in the COOH terminus of the protein. We show that the GPI anchoring signal can be completely recreated by the synthetic polymer Ser3-Thr8-Leu14, but not Thr11-Leu14, inserted at the COOH terminus of a protein. This is consistent with previous reports that a small amino acid such as Ser, Gly, or Ala, but not Thr, is required at the GPI attachment site. Analysis of synthetic amino acid sequences established a basic three-part signal for GPI anchoring: a cleavage/attachment domain that requires small amino acids at the first (GPI anchor attachment) and third positions but with little specificity at the middle position, a spacer domain of approximately 8-12 amino acids, and a hydrophobic domain of at least 11 amino acids. The ability to design a totally synthetic GPI anchoring signal will allow precise probing of the fine structure of this signal.

Tumor markers in uremia: carcinoembryonic antigen, neuron-specific enolase, carbohydrate antigen CA-50 and alpha-fetoprotein.

The incidence of the tumor markers was studied in 140 patients aged between 18 and 84 years who had been on dialysis for 4-188 months. Neuron-specific enolase increased in 81 cases, CA-50 carbohydrate antigen in 44, while alpha-fetoprotein was within the normal range. Carcinoembryonic antigen (CEA) with 2 monoclonal assays was increased in 7 cases. When polyclonal assays were used, CEA was found to be elevated in 12 cases with one set and in 72 cases with another kit set. The data point to the potential usefulness of these markers for the detection of malignancy and possibly neuropathy in uremia; to the importance of renal tubules in the metabolism of proteins, glycoprotein and peptides, and to the activation/inhibition in various enzyme systems in the uremic state.