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Biomedical subjects

M P Wirth

Publications and source records attributed to M P Wirth.

At least 37 records · Page 2Linked to original sources
PubMed2001

Identification of a novel gene on chromosome 13 between BRCA-2 and RB-1.

METHODS AND RESULTS: By differential display we isolated a new cDNA-fragment, named C13, that is downregulated in malignant prostate tissues. Northern hybridization revealed the fragment to be part of 3.0 and 4.4 kb mRNAs. Fluorescence in situ hybridization, Southern blotting and radiation hybrid mapping demonstrated a chromosomal localization of C13 on 13q12-14 closest to the SHGC-34125 marker. In the 5% chromosomal environment of C13 we detected changes of the allelic status in 13 of 21 prostate cancers. A downregulation was detected at the mRNA level in patients with advanced carcinoma. The 3.0 kb full length cDNA clone encodes a protein with an open reading frame of 2,202 bp or 733 amino acids. The corresponding protein contains a putative nuclear localization signal, several glutamine clusters and an alpha-helix-rich domain. By in situ RNA hybridization we could demonstrate the mainly epithelial expression of the C13 mRNA in prostatic tissue. CONCLUSIONS: The localization of C13 between the tumor suppressor genes BRCA-2 and RB-1, the detected allelic imbalances, the downregulation of its mRNA in some prostatic cancer tissues, the epithelial expression and the described protein structure suggest that this gene encodes a protein that may have tumor or metastasis suppressing function in prostate tissue.

BRCA2 Protein↗
PubMed2001

[Gene therapy and immunotherapy in prostatic carcinoma].

Although local prostate cancer (PC) can be cured in most cases by radical prostatectomy, therapies for metastatic and androgen-independent PC are limited and rather unsatisfactory. Gene and immunotherapy based on progress in molecular biology are novel treatment options especially for these PC stages. In the field of passive immunotherapy, chimeric/recombinant antibodies and derivatives thereof show promising results in early clinical trails (phase I/II). Before treatment, a careful selection of patients who could profit from this therapy is important (theranostics). Concerning active immunotherapy, administration of dendritic cells loaded with PC-specific tumor antigens seems to be an interesting therapy option. Promising gene therapeutic approaches include antisense and suicide gene therapy. Antisense therapy studies revealed the advantage that even systemic treatment does not lead to strong toxic side effects if the target gene is not involved in important cell functions. Improvement of the gene therapy vectors and identification of new therapeutic genes for PC are essential prerequisites for successful application in humans. Present developments of alternative approaches show that future treatments will be very patient specific.

Clinical Trials as Topic↗
PubMed2001

Malignant fibrous histiocytoma of the ileum at a site of previous surgery: report of a case.

Sarcomas rarely arise in the intestinum, and leiomyosarcoma represents the majority of cases. With only seven cases reported in the available English literature up to now, malignant fibrous histiocytoma of the small intestine is exceedingly rare. Moreover, follow-up data are almost completely unavailable. We present herein the unique case of a malignant fibrous histiocytoma arising in a postoperatively adherent intestinal loop. To the best of our knowledge, this is the first such case ever to be described. The clinical history and the intraoperative findings suggested that chronic postoperative repair processes might have been a promoting factor in the tumorigenesis of this neoplasm, on the analogy of malignant fibrous histiocytoma arising at different sites. The patient recovered well but 9.5 years after surgical removal, a solitary recurrent tumor developed in the urinary bladder and progressed rapidly, highlighting the need for long-term, possibly life-long, surveillance of patients with this rare type of intestinal cancer.

Female↗
PubMed2001

Spontaneous late rupture of orthotopic detubularized ileal neobladders: report of five cases.

OBJECTIVES: To report five spontaneous ruptures in 4 patients. Spontaneous late rupture of orthotopic ileal bladder replacements is a rare complication of continent urinary diversion. METHODS: Four recurrence-free patients aged 36 to 68 years experienced apparently spontaneous rupture of continent orthotopic ileal bladder replacement 3 months to 3 years after curative radical cystectomy and urinary diversion for invasive bladder cancer. Ileal bladder rupture occurred twice in 1 patient with an interval of 9 months. RESULTS: All 4 patients had had a good result from their diversion procedure and had reported complete day and nighttime continence before the spontaneous rupture. The spontaneous rupture was evidently caused by overdistension of the ileal neobladder in four of five instances. In addition to overdistension, a second factor such as minor blunt abdominal trauma or urethral occlusion was identifiable in two instances. The rupture occurred in the right upper corner of the ileal bladder in four of five instances and led to acute and severe abdominal pain. Cystography was done in three instances, but was diagnostic in only 2 cases. The histologic examination of the excised bladder wall margins revealed nonspecific inflammatory changes in 3 cases. Open surgical drainage and repair was successfully undertaken in all cases. CONCLUSIONS: The circumstances of the cases described suggest that late spontaneous rupture of an orthotopic ileal bladder replacement is not related to the surgical technique but rather to factors of patient compliance and medical management.

Abdominal Pain↗
PubMed2001

Application of the Mitrofanoff principle for intermittent self-catheterization in quadriplegic patients.

OBJECTIVES: Patients with cervical spinal cord lesions have impaired hand function, which often prohibits clean intermittent self-catheterization (CIC), especially in female patients. Enabling these patients to perform CIC gives them control of their bladder management and can improve their quality of life considerably. We have used an appendicovesicostomy to provide easy access for CIC in such patients. METHODS: Five patients (4 women, 1 man) with a mean age of 31 years (range 20 to 52) and a mean duration of the cervical cord lesion of 22 months (range 7 to 37) underwent appendicovesicostomy. Three patients were young victims of motor vehicle accidents, 1 patient had a progressive rheumatoid arthritic disorder, and 1 patient had a complex functional paraplegia syndrome and underwent bladder augmentation at the same time. RESULTS: The surgical procedure with the creation of a catheterizable stoma in the right lower abdominal quadrant was successful in all cases but was complicated by mechanical ileus in the patient with simultaneous bladder augmentation. All patients learned to perform independent CIC with continuing anticholinergic medication. Stomal stenosis did not occur in any of the 5 patients, and urinary tract infections occurred once in 2 patients and repeatedly in 1 patient. Three of 5 patients have been enabled by independent bladder management to achieve occupational rehabilitation. CONCLUSIONS: Appendicovesicostomy is a suitable procedure in patients with cervical spinal cord lesions who are otherwise unable to perform independent CIC. The creation of a catheterizable abdominal stoma enables these patients to gain independent control of their bladder management. However, caution in patient selection is advisable as probably the best results are achieved in highly motivated, younger patients with traumatic cervical cord lesions.

Activities of Daily Living↗
PubMed2001

Durable complete remission of metastatic sarcomatoid carcinoma of the bladder with cisplatin and gemcitabine in an 80-year-old man.

A patient with a durable, complete, local and pulmonary remission of a metastatic sarcomatoid carcinoma of the bladder treated with gemcitabine and cisplatin is presented. Sarcomatoid carcinoma arising in the bladder is a rare and notoriously aggressive variant of urothelial carcinoma for which an effective systemic treatment has not been reported up to now.

Aged↗
PubMed2001

The treatment of primary urethral carcinoma--the dilemmas of a rare condition: experience with partial urethrectomy and adjuvant chemotherapy.

BACKGROUND: Primary urethral carcinoma is a very rare condition, and no large-scale experience with such cases has been published. Treatment will therefore have to follow rules established for the treatment of similar conditions. PATIENTS: Six cases of primary urethral carcinoma (5 male, 1 female) who had been treated at our institution between 1995 and 1999 were retrospectively analyzed. In 3 male cases, a primary urothelial carcinoma of the distal urethra was treated by distal urethrectomy only. In 3 other cases with locally advanced tumors and/or lymph node metastases surgical treatment was followed by adjuvant cisplatinum-containing chemotherapy. RESULTS: In the 3 cases with distal urethral carcinoma, partial urethrectomy with preservation of the penis resulted in cure, with a follow-up of 12-71 months. In the cases with advanced disease, adjuvant chemotherapy after surgery has resulted in complete remissions in all 3 cases, with a follow-up of 4-47 months at present. CONCLUSIONS: In localized, noninvasive carcinoma of the distal male urethra, partial urethrectomy seems adequate and the avoidance of penile amputation justified. In advanced cases, after local excision and lymphadenectomy adjuvant chemotherapy which by necessity must follow the guidelines established for the treatment of other urothelial or squamous cell malignancies seems to be beneficial.

Adult↗
PubMed2001

Etiologic factors in soft tissue sarcomas.

Soft tissue sarcomas account for about 1% of all malignancies. The increase in incidence of soft tissue sarcomas during the recent decades may predominantly be attributed to AIDS-related Kaposi's sarcoma; when this tumor is excluded, conclusive evidence for an age-adjusted increase is lacking. Beside the well investigated role of the human immunodeficiency virus 1 (HIV-1) and the human herpesvirus 8 (HHV-8) in the tumorigenesis of AIDS-related Kaposi's sarcoma and several inherited disorders, considerable evidence support a relationship between occupational chemicals as vinyl chloride, phenoxyacetic acid herbicides, chlorphenols, dioxin, medicinal measures as Thorotrast exposure and therapeutic irradiation, and the development of soft tissue sarcoma. Hormones and chronic repair processes are further probably sarcoma-promoting factors. Considering the rarity of soft tissue sarcomas despite the vast portion that soft tissues comprise in the human body, additional knowledge on the tumorigenesis of soft tissue sarcomas might considerably contribute to the understanding of the etiologic pathways of malignant tumors in humans.

Carcinogens↗
PubMed2001

Relationship of comorbidity, age and perioperative complications in patients undergoing radical prostatectomy.

OBJECTIVES: To investigate the prevalence and distribution of comorbidity and its association with perioperative complications in patients undergoing radical prostatectomy (RPE). METHODS: In 431 unselected RPE patients, the American Society of Anesthesiologists Physical Status classification (ASA-PS), the New York Heart Association classification of cardiac insufficiency (NYHA), the classification of angina pectoris of the Canadian Cardiovascular Society (CCS), height, weight, the body mass index (BMI), and the number of concomitant diseases (NCD) were assessed and related to perioperative cardiovascular complications. RESULTS: In RPE patients less than 70 years old, comorbidity rose nearly continuously with increasing age. However, after reaching an age of 70 years, the proportion of NYHA-0 patients increased (60-64 years, 86%; 65-69 years, 85%; >or=70 years, 87%). Furthermore, the severe comorbidities decreased in patients selected for RPE aged 70 or more years. There was a nonsignificant trend towards higher comorbidity in patients with perioperative cardiovascular complications. CONCLUSIONS: These data suggest that documentation of the distribution of ASA-PS, CCS, NYHA and of concomitant diseases might be helpful to characterize the general health status and the degree of selection of prostate cancer treatment populations especially in series with a high portion of patients aged 70 or more years. Concerning perioperative complications, the individual predictive value of comorbidity seems to be poor in the radical prostatectomy setting.

Age Factors↗
PubMed2001

Is there a relationship between the amount of tissue removed at transurethral resection of the prostate and clinical improvement in benign prostatic hyperplasia.

OBJECTIVE: To assess in a prospective trial the influence of the amount of tissue resected at transurethral resection of the prostate (TURP) for benign prostatic enlargement on the symptom improvement as assessed by symptom scores. METHODS: Between December 1996 and August 1998 a total of 138 men (mean age 68.2, range 53-89) with symptomatic benign prostatic enlargement who underwent TURP participated in this prospective study. Patients were assessed preoperatively with the International Prostate Symptom Score (IPSS), the American Urological Association Bother Score (AUA-BS) and the Benign Prostatic Hyperplasia Impact Index (BPH-II) as well as urinary flow rate measurements (Qmax) and prostate volume (PV) and residual urine determination by ultrasound. The amount of tissue resected was weighed. Patients were followed with reevaluation of Q(max), residual urine and the symptom and bother scores at 3 and 6 months. RESULTS: A close correlation between preoperative PV (mean 49.0 ml, SD 22.0, range 13-140) and the resected tissue weight (RTW, mean 24.7 g, SD 18.0, range 6-128) was seen (r = 0.75, p < 0.001). Age was correlated with preoperative PV (r = 0.23, p < 0.05). While significant mean improvements in Q(max), residual volume and IPSS, AUA-BS and BPH-II were found 3 and 6 months postoperatively, a negative correlation was seen between the RTW and the IPSS, the AUA-BS and the BPH-II 3 months after TURP (r = -0.23, p < 0.024; r = -0.23, p < 0.025; r = -0.20, p = 0.05). No statistically significant correlation was seen between symptom change and the percentage of PV removed or the residual prostatic weight. Classification of the patients into groups depending on preoperative PV (< 30, 31-50, 51-70 and >70 ml) showed a tendency for patients with larger PV to gain more symptom improvement postoperatively. CONCLUSIONS: Early symptom improvement after TURP will depend on the amount of tissue removed but the relationship is weak and affected by several other confounding factors. Apparently, the symptomatic improvement after TURP is not primarily dependent on the relative completeness of the resection. Patients with larger prostates and larger RTW tend to gain more symptomatic benefit from TURP than do patients with smaller prostates.

Aged↗
PubMed2001

Is transurethral vaporesection of the prostate better than standard transurethral resection?

OBJECTIVE: The aim of this study was to undertake an evaluation of the comparative efficacy and morbidity of transurethral vaporesection (TUVRP) and standard transurethral resection (TURP), two resection techniques using loops of different thickness and power settings. METHODS: In a prospective study, 185 patients with lower urinary tract symptoms suggestive of bladder outlet obstruction and benign prostatic enlargement were randomized to undergo either TUVRP or standard TURP. Inclusion criteria were benign prostatic enlargement, moderate or severe lower urinary tract symptoms and/or a significant urinary residual (>60 ml), while patients with previous prostatic surgery, prostate cancer or neurogenic bladder disorders were excluded. Prostate size, residual urine, urinary flow rate and symptoms as well as associated bother (using the International Prostate Symptom Score (IPSS) and the American Urological Association Bother Score (AUA-BS)) were assessed preoperatively. Intraoperative blood loss and fluid absorption were evaluated by measuring serum hemoglobin and respiratory alcohol concentration. Patients were followed for 1 year with the evaluation of flow rates, residual urine volumes, symptom scores and complications at 3, 6 and 12 months. RESULTS: A significant difference was seen in the weight of the resected tissue (TURP 30.3 g vs. TUVRP 21.9 g, p<0.003). There were no significant differences in blood loss, intraoperative fluid absorption or procedure time between TUVRP and TURP, although more patients in the TURP group required blood transfusions (13 vs. 7) and mean procedure time was longer for TUVRP (71.0 vs. 65.9 min). The postoperative improvements in IPSS, AUA-BS, residual and Q(max) were significant in both groups (p<0.01 for each) but without difference between the two groups. The rate of complications (urinary tract infections, urethral stricture, reintervention rate) during follow-up was the same in both groups. CONCLUSIONS: In this prospective randomized comparison of the clinical outcome and morbidity of standard TURP versus TUVRP, there were no significant differences in any of the parameters evaluated except for the weight of the resected tissue.

Aged↗
PubMed2001

Morbidity and discomfort of ten-core biopsy of the prostate evaluated by questionnaire.

Transition zone biopsies have been found to increase the detection rates of cancer of the prostate in patients with negative digital rectal examination. There are however no data available whether the higher biopsy rate is associated with greater morbidity. The present study was therefore designed to evaluate the complication rate of extended sextant biopsy. In this prospective study, 162 consecutive patients who presented for prostatic evaluation were included. After starting prophylactic antibiotic treatment 48 h prior to the procedure, transrectal ultrasound-guided core biopsies were obtained from each lobe: three each from the peripheral zone (apex, mid-zone and base) and two from the transition zone of each prostatic lobe. In all patients a questionnaire was obtained 10-12 days after the procedure. Major complications occurred in 3 patients. In 2 of the 3 cases major macroscopic hematuria was treated by an indwelling catheter for 1 or 2 days and 1 patient developed fever >38.5 degrees C for 1 day. Minor macroscopic hematuria was present in 68.5% of the patients. In 17.9% of these cases, the hematuria lasted for more than 3 days. Hematospermia was observed in 19.8% and minor rectal bleeding occurred in 4.9%. Ten-core biopsies did not lead to an increase in adverse effects or complications when compared to the results of sextant biopsies reported in the literature.

Adult↗
PubMed2001

Human telomerase reverse transcriptase antisense treatment downregulates the viability of prostate cancer cells in vitro.

Telomerase, a ribonucleoprotein complex is activated in the vast majority of human malignancies, including prostate cancer. Its inhibition is a putative way to affect cancer proliferation and might be used in the therapy of tumors. We analysed the influence of antisense phosphorothioate oligonucleotides (PTO) against the reverse transcriptase subunit of telomerase on prostate cancer cell viability, telomerase activity and telomere length. DU145 prostate cancer cells were cultivated in PTO containing medium. The PTO-incorporation was confirmed by confocal laser scanning microscopy. Cell viability was measured by a WST-1 tetrazolium assay. After 15 days of antisense PTO treatment, a significant inhibition of cell viability occurred. Telomerase activity was determined by a telomeric repeat amplification protocol (TRAP) assay and telomere length by Southern blot analysis. Since the long-term telomerase antisense treatment reduces the viability of prostate cancer cells significantly, this antisense approach could be a new therapeutic strategy to treat patients with advanced prostate cancer.

Blotting, Southern↗
PubMed2000

Favorable long-term outcome in adult genitourinary low-grade sarcoma.

OBJECTIVES: To report our experience treating sarcomas in 20 consecutive patients. METHODS: Pretreatment and follow-up data were obtained from 20 adult patients consecutively treated between 1992 and 1998 for primary or locally recurrent genitourinary sarcoma. RESULTS: Eight patients (40%) were classified as having high-grade and 12 (60%) low-grade disease. Except for 3 patients, the primary treatment was surgery alone. The median follow-up was 52 months. The actuarial disease-specific 5-year survival rate was 84% in all patients and was 100% for patients with Memorial Sloan Kettering Cancer Center (MSKCC) Stages 1-2 and 54% in MSKCC Stages 3-4. The disease-specific survival was significantly better in low-grade tumors (log-rank test, P = 0.0063) and inguinal-scrotal tumors (P = 0.019), tumors 5 cm or less (P = 0.039), and MSKCC Stages 1-2 tumors (P = 0.0035). CONCLUSIONS: The results of this study with a high proportion of low-grade, low-stage, and inguinal-scrotal sarcomas demonstrate the favorable prognosis of these subgroups.

Adolescent↗
PubMed2000

Mucoepidermoid penile carcinoma: clinical, histologic, and immunohistochemical characterization of an uncommon neoplasm.

We report a case of a mucoepidermoid penile carcinoma. The specimen was studied by immunohistochemistry and DNA cytometry. Mucoepidermoid and adenosquamous penile carcinoma are exceedingly rare variants of penile cancer, with very little follow-up data available. To evaluate the possible prognostic significance of these differentiation patterns, it is necessary to document more cases of this unusual tumor entity.

Aged↗
PubMed2000

Bladder wall thickness in normal adults and men with mild lower urinary tract symptoms and benign prostatic enlargement.

There is evidence that increased bladder wall thickness can be a useful parameter in the evaluation of men with clinical benign prostatic hyperplasia (BPH). However, normal values for bladder wall thickness (BWT) in adults have not been established. BWT was measured by suprapubic ultrasonography. Bladder volume was calculated as the product of the ultrasonographic measurements of bladder height, width and depth, and a correction factor (0.6). Three groups were assessed: men with normal lower urinary tracts (n = 172; mean age, 39.9), women with normal lower urinary tracts (n = 166; mean age, 37.8), and men with mild lower urinary tract symptoms (LUTS) and clinical benign prostatic enlargement (BPE) (n = 150; mean age, 66.4). For the whole group of men and women with normal bladders, mean BWT was 3.35 mm, and BWT appeared normally distributed. There were a weak negative correlation with bladder volume (r = -0.12, P < 0.003) and a weak positive correlation for BWT and age for both men (r = 0.12, P < 0.014) and women (r = 0.17, P < 0.013). Mean BWT was 3.04 mm in healthy women, 3.33 mm in healthy men, and 3.67 mm in men with LUTS and BPE. Sub-dividing normal men into different age groups showed an increasing mean BWT of 3.08 mm (<20 years, n = 27), 3.25 mm (21-40 years, n = 75), 3.42 mm (41-60 years, n = 39), and 3.57 mm (>60 years, n = 31) for those sub-groups. BWT in normal adult women is 3.0 +/- 1 mm and 3.3 +/- 1. 1 mm in normal adult men. A small increase in BWT with age is seen for both genders, and BWT tends to be greater in men than in women. Men with LUTS and BPE show a moderate increase in BWT. Adjustments for bladder volume are for practical purposes negligible, although there is a small decrease in BWT with increasing volume.

Adult↗