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R Casella

Publications and source records attributed to R Casella.

At least 19 recordsLinked to original sources
PubMed2003

Microsatellite instability and defects in mismatch repair proteins: a new aetiology for Sertoli cell-only syndrome.

Microsatellite instability is characteristic of certain types of cancer, and is present in rodents lacking specific DNA mismatch repair proteins. These azoospermic mice exhibit spermatogenic defects similar to some human testicular failure patients. Therefore, we hypothesized that microsatellite instability due to deficiencies in mismatch repair genes might be an unrecognized aetiology of human testicular failure. Because these azoospermic patients are candidates for testicular sperm extraction and ICSI, transmission of mismatch repair defects to the offspring is possible. Seven microsatellite loci were analysed for instability in specimens from 41 testicular failure patients and 20 controls. Blood and testicular DNA were extracted from patient and control specimens, and amplified by PCR targeting seven microsatellite loci. DNA fragment length was analysed with an ABI Prism 310 Genotyping Machine and GeneScan software. Immunohistochemistry was performed on paraffinized testis biopsy sections and cultured testicular fibroblasts from each patient to determine if expression of the mismatch repair proteins hMSH2 and hMLH1 was normal in both somatic and germline cells. Results demonstrate that microsatellite instability and DNA mismatch repair protein defects are present in some azoospermic men, predominantly in Sertoli cell-only patients (P < 0.01 and P < 0.05 respectively). This provides evidence of a previously unrecognized aetiology of testicular failure that may be associated with cancer predisposition.

Animals↗
PubMed2001

Metastatic primitive neuroectodermal tumor of the kidney in adults.

OBJECTIVE: Primitive neuroectodermal tumors (PNET) of the kidney are rare and highly aggressive malignancies. The purpose of our study was to present information about the management of patients with metastatic disease. METHODS: The records of 2 patients (30-year-old female and 32-year-old male) with metastatic PNET of the kidney were reviewed and our data compared with the literature. RESULTS: Neither clinical evaluation nor radiological methods allowed to distinguish PNET from renal cell carcinoma. Immunohistochemistry revealed strong positivity for CD99 in tumor 1 and weak positivity for NSE and vimentin in both tumors. In tumor 2, EWS/FLI1 translocation was detected by RT-PCR. Patient 1 underwent nephrectomy, seven cycles of polychemotherapy, two cycles of high-dose chemotherapy, autologous bone marrow rescue, radiotherapy of suspicious skeletal foci and is without evidence of recurrent disease 28 months after therapy. Patient 2 underwent six cycles of polychemotherapy, nephrectomy, high-dose chemotherapy with cyclophosphamide and abdominal radiotherapy. Because of relapse high-dose chemotherapy with stem cell rescue was not performed. He underwent three further cycles of polychemotherapy and died one year after diagnosis due to cerebral metastasis. CONCLUSIONS: The diagnosis of renal PNET must be considered in young patients with renal neoplasm, particularly those with advanced disease at presentation. Achieving exact diagnosis has important clinical consequences because polychemotherapy and high-dose chemotherapy may lead to dramatic tumor reduction or even complete remission.

12E7 Antigen↗
PubMed2000

Direct compression tablets containing a series of four beta-cyclodextrin complexes formed by neutralizing an acidic drug.

A series of four beta-cyclodextrin complexes (called products) was formed by neutralizing an acidic drug to study the effect of drug solubility on complex formation and the dissolution performance from direct compression tablets. Four solid products were prepared by neutralizing the drug in 0.05, 0.10, 0.20, and 0.30 M tromethamine solutions with a constant 0.09 M beta-cyclodextrin concentration, filtering the solutions, and removing the water through evaporation with heat and vacuum. The four products contained drug and water in a distinct relationship, thus suggesting a complex formation that was dependent on the tromethamine concentration. Infrared, powder X-ray diffraction, differential scanning calorimetry (DSC), phase solubility, and scanning electron microscopy (SEM) techniques revealed distinct differences among the four products, suggesting three of the four products were complexes, and one product was either a weak complex or a physical mixture. Ultraviolet (UV) analysis showed no evidence of complex formation. Phase solubility results showed one product had a slight increase in drug solubility, and three products had no increase in drug solubility with increasing beta-cyclodextrin concentration. The lack of a solubility increase suggests insoluble complex formation. Drug dissolution in water was improved significantly in all tablets containing either a product or a physical mixture when compared to the pure drug. The products prepared with the two highest concentrations of tromethamine showed a dissolution performance that was superior to all other formulations. Enthalpy measurements by DSC were a good indicator of dissolution performance for tablets containing the four products. Drug dissolution through salt formation in the absence of beta-cyclodextrin showed the drug-salt dissolution varied from better to worse when compared to the dissolution profiles of the four products. The varying dissolution performance was attributed to the formation of distinct beta-cyclodextrin complexes with varing solubilities.

Cyclodextrins↗
PubMed2000

Urinary level of nuclear matrix protein 22 in the diagnosis of bladder cancer: experience with 130 patients with biopsy confirmed tumor.

PURPOSE: We prospectively evaluated the value of nuclear matrix protein 22 (NMP22dagger) and cytology in the diagnosis of bladder cancer. MATERIALS AND METHODS: We analyzed NMP22 in voided urine from 235 patients before cystoscopy. Of the patients 130 had transitional cell carcinoma of the bladder and subsequently underwent surgery. In a subset of 200 patients bladder washout samples for cytology were collected during cystoscopy. The cutoff for NMP22 was 10.0 units per ml. For cytology only high grade atypia was considered positive. RESULTS: Histology showed 77 superficial (pTa, pTis) and 53 invasive (pT1 or greater) tumors. Sensitivity of NMP22 was 51% and specificity was 83%. NMP22 sensitivity was 36% for superficial tumors and 73% for invasive transitional cell carcinoma. Overall sensitivity of cytology was 52% and specificity was 89%. Cytology sensitivity was 38% for superficial tumors and 83% for invasive transitional cell carcinoma. NMP22 sensitivity for grades 1, 2 and 3 tumors was 30%, 56% and 68%, respectively. Cytology sensitivity for grades 1, 2 and 3 tumors was 30%, 50% and 91%, respectively. Combined NMP22 and cytology had a sensitivity of 70%. CONCLUSIONS: NMP22 has sensitivity and specificity similar to those of cytology from bladder washout samples. Particularly in low stage and low grade tumors both tests show the same disappointing sensitivity. Because of a false-negative rate of 49%, NMP22 cannot replace cystoscopy in clinical practice, as the danger of missing NMP22 negative tumors is too high to rely on its results in an individual patient.

Biomarkers, Tumor↗
PubMed1999

["Burned out" testicular tumor: a rare form of germ cell neoplasias].

Burned-out tumour of the testis is a rare form of a germ-cell malignancy of testicular localisation which can regress or disappear. This is a rare form of germ-cell neoplasm. We report on 2 patients with such a tumour. The histological findings, on clinical manifestations, on difficult differential diagnosis from primary retroperitoneal germ-cell tumour, therapy, and outcome of this malignancy are discussed. In the absence of palpable testicular tumour the symptomatology is due to metastasis. Burned-out tumour of the testis must be considered in a patient with retroperitoneal lymph node involvement and histology of "germ-cell tumour". In these patients sonography of scrotal contents may be useful to identify intratesticular abnormalities. These are often the site of the primary tumour. If burned-out tumour of the testis is suspected, the indication for surgery is given. If the frozen section is not "normal testicular tissue", orchiectomy should be performed. The metastasis is treated according to the histology and clinical stage of the tumour. It is important to distinguish burned-out tumour of the testis from true extragonadal germ-cell tumours. Primary removal of the testicular tumour is necessary because of the high rate of persistent testicular malignancy, which may be as much as 50% despite systemic chemotherapy.

Adult↗
PubMed1999

[Sexually and drug-stimulated erections are proportional].

Even complex diagnostic tests may not establish aetiology and degree of erectile dysfunction (ED) in many patients. Therefore, we evaluated a self-report method with a restrictive focus to quality of erections which may yield information sufficient to make an aetiologic diagnosis. We studied 74 patients 25 to 75 years of age with untreated ED. Sexually stimulated erections were quantified and compared to duplexsonographically and clinically evaluated data from pharmacostimulated erections. Patients reported that there was a marked decrease in ability to penetrate the partner, to sustain an erection and of penile rigidity (p < 0.001). Parameters from duplexsonography and clinically assessed response to pharmacostimulation correlated (r = 0.72). Direct comparison of these data with quantified history showed no relation (r = 0.05). Using change in penile volume due to erection as a basis to compare with, showed significant correlation with quantified data from history (r = 0.26-0.34; p < 0.03) and measured parameters from pharmacostimulated erections (r = 0.44-0.55; p < 0.0001). Sexually- and pharmacostimulated erections are proportional to change in penile volume. Although there is a relation between erections emerging from both stimulations, quantifying history on sexually stimulated erections does not qualify to make an aetiologic diagnosis without using complex tests.

Adult↗
PubMed1999

Reasons for discontinuing intracavernous injection therapy with prostaglandin E1 (alprostadil).

OBJECTIVES: To clarify the reasons why experience with self-injection therapy for erectile dysfunction shows high dropout rates. METHODS: We studied 86 patients 36 to 76 years old who had been on home treatment for at least 3 months. Sixty-nine patients (80%) were continuing to use injections, and 17 (20%) had discontinued the treatment. Patients were evaluated by interview and clinical examination. RESULTS: Patients still in the program used one injection every 2 weeks, and those who had given up treatment had used one injection in 3 weeks (P = 0.31). They were in the program for 39+/-27 and 16+/-22 months (P = 0.002), respectively, and had used 50 (95% confidence interval [CI] 21 to 91) versus 12 (95% CI 4 to 20) injections, respectively (P<0.0001). Injections producing unsatisfactory penile rigidity, prolonged erections, hematoma at injection site, corporal fibrosis, secondary penile deviation, and mean estimated duration of a pharmacoinduced erection showed no significant differences. Patient satisfaction (P = 0.02), estimated partner satisfaction (P = 0.02), increase in self-esteem (P = 0.01), and negligible effort in performing injections (P = 0.001) all showed significantly better results for those still in the program. CONCLUSIONS: Reasons for dropout from self-injection therapy are not based on objective side effects and discomfort. Patients leaving the program are less motivated, less satisfied with the quality of pharmacoinduced sexuality, consider the effort to perform injections to be substantial, and have not achieved improved self-esteem.

Adult↗
PubMed1999

Life-threatening spontaneous retroperitoneal bleeding: a rare complication of oral anticoagulation.

In a patient on oral anticogulation with sudden onset of loin pain, the possibility of spontaneous bleeding in the retroperitoneum must be considered in the differential diagnosis of renal colic. This rare pathology can be life-threatening, and rapid diagnosis with ultrasound and computerized tomography of the abdomen must be made. If the patient is hemodynamically stable, a conservative approach is justified. Otherwise, emergency nephrectomy may be needed. As patients become older and indications for anticoagulant therapy become more common, we will probably have to face more of these rare bleeding complications in the future. We report such a case.

Administration, Oral↗
PubMed1998

Ki67 labeling index in core needle biopsies independently predicts tumor-specific survival in prostate cancer.

A better knowledge of the biological aggressiveness of individual tumors could facilitate the selection of treatment in prostate cancer patients. This study assesses the influence of histological and molecular features in core needle biopsy specimens of prostate cancer on tumor-specific survival. Formalin-fixed core needle biopsy specimens from 111 consecutive patients (mean follow-up, 5.0 years) were immunohistochemically examined for their proliferative activity (Ki67 labeling index [LI]) and expression of p53 and Bcl-2. Overexpression of p53 was found in 16% of the biopsy specimens and was mainly restricted to poorly differentiated tumors. Bcl-2 positivity was found in 20% of tumors. The median Ki67 LI was 7.5%. There was a strong relationship between Ki67 LI and Gleason grade, with a continuous increase in the proliferative activity from low-grade to high-grade tumors (P = .0006). Univariate tumor-specific survival analysis showed that high Gleason score (P = .0018), high percentage of biopsy tumor involvement (P = .0227), high Ki67 LI (P = .0007), and p53 positivity (P = .0024) were predictors of tumor-related death. A high Ki67 LI emerged as the only independent predictor of tumor-specific survival in multiparametric analysis. These results indicate that core needle biopsy specimens of the prostate not only are useful for diagnosis of malignancy but also can provide valuable prognostic information. Immunohistochemical examinations of molecular features may be a helpful adjunct for a better pretherapeutic assessment of prostate cancer aggressiveness and therefore contribute to an improved initial patient management.

Aged↗
PubMed1998

Focal neuroendocrine differentiation lacks prognostic significance in prostate core needle biopsies.

PURPOSE: The biological behavior of prostate cancer is highly variable and cannot sufficiently be predicted by histological criteria alone. New prognostic factors are needed in core needle biopsies before initial treatment decisions. We investigate the prognostic significance of focal neuroendocrine differentiation in core needle biopsies of prostate cancer. MATERIALS AND METHODS: Core needle biopsies from 105 untreated patients (mean age 71 years) were immunohistochemically examined for focal neuroendocrine differentiation using an antibody against chromogranin A. Tumor cell proliferation was assessed with Ki-67 labeling index using MIB 1 antibody. The cause of death was determined by examination of records including autopsy reports. RESULTS: Focal neuroendocrine differentiation was found in 25% of the tumors. There was no association between the presence of focal neuroendocrine differentiation and Gleason score or Ki-67 labeling index. Tumor specific survival analysis revealed that high Gleason score and high Ki-67 labeling index were predictors of tumor specific death, whereas focal neuroendocrine differentiation failed to provide prognostic information. There was a significant increase in frequency and density of neuroendocrine differentiation between initial core needle biopsies and later specimens of secondary hormone resistant prostate cancer in 15 patients. CONCLUSIONS: In contrast to high Gleason score and high Ki-67 labeling index, focal neuroendocrine differentiation is not a prognostic factor in core needle biopsies of prostate cancer. Focal neuroendocrine differentiation seems to appear more frequently and intensively in hormone resistant prostate cancer, supporting a role of neuroendocrine cells in the development of hormone refractory disease.

Aged↗
PubMed1997

[Results of microsurgical reconstruction after vasectomy].

Because of the increasing number of divorces surgical refertilisation by vasovasostomy has become increasingly important. Of 33 patients operated in the last decade, 32 could be reached for follow-up. The patency-rate was 86% and the pregnancy-rate 28%. Possible explanations for this discrepancy are discussed. The time lag between vasectomy and vasovasostomy was the most important prognostic factor. There was no difference in the results between one-layer and two-layer anastomosis. With an interdisciplinary approach the same patency rate as described in the literature was achieved.

Adult↗
PubMed1997

Mumps orchitis: report of a mini-epidemic.

PURPOSE: The incidence of mumps orchitis has declined dramatically since the introduction of vaccination. While in the past cases of mumps have only been seen occasionally at our institution, recently there has been a sharp increase in the number of confirmed cases. MATERIALS AND METHODS: Between June 1995 and April 1996, 11 patients with severe mumps orchitis were hospitalized at our clinic. Medical history, therapeutic measures and clinical outcome were recorded for each patient. RESULTS: All patients showed marked scrotal swelling with a temperature above 38.5 C. Serum C-reactive protein was significantly elevated (mean 140 mg./l.). The vaccination status of 1 of the 11 patients (9%) was unknown. Medical records from the remaining 10 patients indicated that they had not been vaccinated. Nine patients (82%) had a typical mumps parotitis preceding the orchitis. In 2 patients the clinical diagnosis of parotitis was uncertain but mumps serology was positive. None of the patients showed other manifestations of mumps. Antibodies to the mumps virus (IgG and IgM) were determined in 6 patients and positive in all cases. The average interval between parotitis and onset of orchitis was 10 days. All patients were hospitalized for an average of 6 days. Treatment included bed rest with local cooling, scrotal support and systemic treatment with nonsteroidal anti-inflammatory drugs. Ciprofloxacin or clavulanic acid/amoxicillin was administered as bacterial orchitis could not be excluded at initial presentation. The mean time to cessation of fever was 3.6 days (range 3 to 5). Antibiotics were administered for an average of 8.8 days (range 7 to 13) and anti-inflammatory drugs were given an average of 8.6 days (range 7 to 11). One patient required scrotal exploration. CONCLUSIONS: Since the introduction of a vaccine against the mumps virus there is a diminished risk for mumps and its complications. However, in case of scrotal swelling mumps orchitis should still be considered. Despite vaccination mumps has not been erradicated. Therefore, continued vaccination should be considered an important step in minimizing clinical outbreaks and working towards a possible eradication of this disease in the future.

Adolescent↗
PubMed1997

Complications of epidural infusions for analgesia in postoperative and trauma patients.

Few studies compare complications of continuous and bolus epidural analgesia. Ninety-eight postoperative and trauma patients receiving epidural infusions over 15 months were retrospectively studied. Continuous epidural analgesia was used for pain management in 60 patients (61%). Bolus epidural analgesia was administered to 38 patients (39%). Sixty patients reported 98 complications. Sixty-eight per cent of complications occurred in patients receiving continuous infusions. For the continuous infusions, motor blockade (18%), nausea/vomiting, (18%), and catheter leaks (12%) were the most common complications. For bolus infusions, nausea/vomiting (25%), mental status changes (21%), and erythema at placement site (13%) were encountered. Continuous infusions were associated with an increased incidence of complications compared with bolus infusions (P < 0.05). Patients undergoing abdominal surgery had an increased incidence of complications compared with other patients (P < 0.05). Epidural catheters are safe and effective for pain management, but they are not without risk. Hemodynamic stability and pulmonary status should be considered when evaluating patients.

Analgesia, Epidural↗