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Biomedical subjects

G Bartsch

Publications and source records attributed to G Bartsch.

At least 217 records · Page 12Linked to original sources
PubMed1996

[Laparoscopic and retroperitoneoscopic kidney pyeloplasty].

The aim of this study was to evaluate laparoscopic and retroperitoneoscopic pyeloplasty and to compare the efficacy of dismembered and non-dismembered techniques. Between April 1993 and December 1995 a modified laparoscopic transperitoneal (18 patients) and a retroperitoneoscopic approach (3 patients) were used for the management of ureteropelvic junction obstruction. In 11 patients aberrant vessels were encountered; one patient had a horse-shoe kidney. Surgical repair was achieved by dismembered pyeloplasty (8 patients), non-dismembered Fenger-plasty (longitudinal incision-transverse closure: 7 patients), transection and reanastomosis of the renal pelvis (1 patient), ureterolysis and displacement of ventrally crossing vessels (4 patients). In one patient dismembered pyeloplasty could not be scheduled because of cardiovascular problems. A minimal transient lesion of the sympathetic nerve was observed postoperatively in one patient and pulmonary embolism in another. The operative time in dismembered pyeloplasty was between 240 and 360 min (mean 280); the results were good in all patients. Equally good results were obtained with non-dismembered Fenger-plasty, and the operating time was shorter (120-180 min). Ureterolysis was found to have a failure rate of 50%. Laparoscopic dismembered pyeloplasty yielded good results, but it is too complicated to become a standard procedure. Non-dismembered Fenger-plasty, which also showed good results, is more suitable for laparoscopy and retroperitoneoscopy. The indications for this technique should be defined more precisely as more experience is collected. The results of ureterolysis-when used as a single measure-were poor, and therefore this technique should be abandoned.

Adolescent↗
PubMed1996

Activation of two mutant androgen receptors from human prostatic carcinoma by adrenal androgens and metabolic derivatives of testosterone.

The androgen receptor (AR) plays a central regulatory role in prostatic carcinoma and is a target of androgen ablation therapy. Recent detection of mutant receptors in tumor specimens suggest a contribution of AR alterations to progression towards androgen independence. In a specimen derived from metastatic prostate cancer we have reported a point mutation in the AR gene that leads to a single amino acid exchange in the ligand binding domain of the receptor. Another amino acid exchange resulting from a point mutation was also identified 15 amino acids away from our mutation. This mutation was detected in the AR gene isolated from an organ-confined prostatic tumor. Here we report the functional characterization of the two mutant receptors in the presence of adrenal androgens and testosterone metabolites. These studies were performed by cotransfecting androgen-responsive reporter genes and either the wild-type or mutant AR expression vectors into receptor negative DU-145 and CV-1 cells. The indicator genes used consisted of the promoter of the androgen-inducible prostate-specific antigen gene or the C' Delta9 enhancer fragment from the promoter of the mouse sex-limited protein driving the expression of the bacterial chloramphenicol acetyl transferase gene. Cotransfection-transactivation assays revealed that the adrenal androgen androstenedione and two products of testosterone metabolism, androsterone and androstandiol, induced reporter gene activity more efficiently in the presence of the mutant receptors than in the presence of the wild-type receptor. No difference between wild-type and mutant receptors was observed in the presence of the metabolite androstandione. The interaction of receptor-hormone complexes with target DNA was studied in vitro by electrophoretic mobility shift assays (EMSA). Dihydrotestosterone and the synthetic androgen mibolerone induced a faster migrating complex with all receptors, whereas the androgen metabolite androstandione induced this complex only with the two mutant receptors. Androsterone and androstandiol were inactive in the EMSA. These aberrant properties of the mutant receptors in the presence of adrenal androgens and products of androgen metabolism may be of importance in the course of the prostate cancer, especially during androgen ablation therapy.

Androgens↗
PubMed1995

Dendritic antigen-presenting cells from the peripheral blood of renal-cell-carcinoma patients.

Dendritic cells are considered to be the initiators of immune responses, including those directed against tumors. Clinical research on dendritic cells was long hampered by the limited availability of these cells. The recent identification of cytokine combinations that mobilize dendritic cells with potent antigen-presenting cell function from peripheral blood represented a major progress. We show in this study that substantial numbers of dendritic cells can be obtained from the peripheral blood of patients with renal-cell carcinoma. The procedure requires a relatively small blood sample (40 ml) and avoids both priming of the patient with granulocyte-colony stimulating factor and leukapheresis. Approximately 2 to 8 million cells with the characteristics of dendritic cells could be obtained: phase-contrast microscopy revealed the typical cytoplasmic processes or veils; phenotypic analysis confirmed expression of dendritic-cell-associated molecules, including MHC class II, CD1a, CD4, ICAM-1 (CD54), LFA-3 (CD58), B7-1 (CD80) and B7-2 (CD86), and absence of T-cell, B-cell and monocyte markers; in addition, these cells rapidly attached to and migrated on collagen-type-1-coated surfaces. Interestingly, attachment was accompanied by acquisition of the CD14 antigen; functionally, cultured dendritic cells proved to be very potent co-stimulators of the phytohemagglutinin-induced proliferation of autologous tumor-infiltrating lymphocytes. The reproducible growth of functional dendritic cells from cancer patients is encouraging for the design of immunotherapy protocols.

Adult↗
PubMed1995

Mutant androgen receptors in prostatic tumors distinguish between amino-acid-sequence requirements for transactivation and ligand binding.

Mutant androgen receptors are thought to contribute to hormone resistance in prostate carcinoma. The part they play in this process, however, is ill-defined. Here we report on transactivation by 2 mutant androgen receptors from prostatic tumors with single amino-acid exchanges in their hormone-binding domains. These exchanges enhance the transactivation property of the receptors, particularly to androsterone and androstanediol, 2 metabolized derivatives of testosterone present in the prostate. Additionally, they enhance the transactivation potential of the mutant receptors to hydroxyflutamide, an anti-androgen frequently used in hormone ablation therapy. The increased transactivation by the mutant receptors did not result from altered affinity of the receptors to the inducing ligands nor from measurable changes in conformation of the liganded receptors. Thus the single amino-acid exchanges identify differences in amino-acid-sequence requirements for transactivation and ligand binding in the hormone-binding domain of the androgen receptor. These results provide new insights into ligand-dependent transactivation, and form a framework for the search for effective antagonists to be used in prostate-cancer therapy.

Amino Acid Sequence↗
PubMed1995

Tumor-infiltrating T lymphocytes from renal-cell carcinoma express B7-1 (CD80): T-cell expansion by T-T cell co-stimulation.

B7-1 (CD80) provides co-stimulation for T-cell activation by interacting with CD28 or CTLA4. Here we demonstrate the expression of B7-1 in freshly isolated and cultured lymphocytes from renal-cell carcinoma. In fresh preparations of lymphocytes infiltrating renal-cell-carcinoma tissue, B7-1 mRNA could readily be detected by reverse transcription PCR, and 2-color flow-cytometry analysis revealed substantial B7-1 expression on T cells from these isolates. As expected, tumor-derived T cells also expressed CD28, the B7 receptor. While B7-1 expression of tumor-derived T cells was maintained during culture in interleukin-2-supplemented medium, CD28 expression was further enhanced. We also show that B7-1 is functionally involved in T-cell expansion: anti-B7-1 MAb inhibited the PHA-induced proliferation of tumor-derived B7-1+ T cells (35%) in the absence of exogenous antigen-presenting cells, indicating that B7-1 mediates T-T cell co-stimulation (self-co-stimulation). Our data demonstrate that T cells infiltrating renal-cell carcinoma express B7-1, and that mutual co-stimulation via the B7-1/CD28 pathway contributes to the interleukin-2-driven expansion of tumor-derived T cells in vitro. The frequency of B7-1+ T cells in tumor lesions and the level of B7-1 on these cells may determine the time course of T-cell expansion in vivo. Self-co-stimulation, however, might also represent one mechanism leading to the state of suppression or anergy characteristic of tumor-infiltrating lymphocytes.

B7-1 Antigen↗
PubMed1995

Distant metastases from prostatic carcinoma express androgen receptor protein.

Nearly all primary prostatic carcinomas have been found to express the androgen receptor (AR) protein, which is the intracellular mediator of androgen action. To gain a better insight into the mechanisms of androgen independence of advanced prostatic carcinoma, it is important to know whether the AR is also present in metastases of androgen-independent tumors. We have assessed the status of the AR and the prostate-specific antigen in 22 metastases of 18 patients with progressive prostate cancer. In 18 cases, the metastases were localized in bone, in 3 cases in the epidural space, and in 1 case in the periosteum. All but one patient had received some kind of endocrine treatment for prostatic carcinoma. Paraffin-embedded tissue sections were stained for the AR following a streptavidinbiotin-peroxidase protocol with the polyclonal antibody PG-21, which is directed against amino acids 1 through 21 of the rat and the human AR. The percentage of AR-positive cells was evaluated on the basis of an arbitrary 4-point scale. All 22 tumor metastases displayed AR positivity. One AR-positive metastatic lesion did not stain for prostate-specific antigen, but in all other metastases, this protein was detected by means of immunohistochemistry. The present study provides evidence that, unlike androgen-independent prostatic carcinoma cell lines, distant prostatic carcinoma metastases do express the AR. These findings indicate that the AR may be involved in the progression of prostate cancer.

Bone Neoplasms↗
PubMed1995

Activation of the androgen receptor by polypeptide growth factors and cellular regulators.

The polypeptide growth factors insulin-like growth factor I (IGF-I), epidermal growth factor (EGF), and transforming growth factor-alpha (TGF-alpha); second-messenger cyclic adenosine monophosphate (cAMP): protein kinase activators; and neurotransmitters were found to activate the estrogen (ER), progesterone (PR), and glucocorticoid receptor (GR) either in the absence of their natural ligands or synergistically with the respective hormone. There is now evidence of coupling of signaling pathways involving the androgen receptor (AR). Three polypeptide growth factor, IGF-I, keratinocyte growth factor (KGF), and EGF, stimulated AR-mediated reporter-gene transcription in the absence of androgen in DU-145 cells, which were cotransfected with the reporter gene and an AR expression vector. IGF-I effects were observed irrespective of the promoter driving the reporter gene. This growth factor increased the prostate-specific antigen (PSA) level in LNCaP cells, which contain endogenous AR. In CV-1 cells, which transiently express the AR, second-messenger cAMP potentiated effects of testosterone in stimulation of AR-mediated reporter-gene activity. Inhibition of androgen-stimulated chloramphenicol acetyltransferase (CAT) activity in the LNCaP cell line was achieved with retinoic acid. Stimulation and inhibition of prostatic carcinoma cell growth by polypeptide growth factors and cellular regulators may depend on the presence of the AR in an androgen-depleted environment.

Animals↗
PubMed1995

Comparison of different prostate-specific antigen cutpoints for early detection of prostate cancer: results of a large screening study.

OBJECTIVES: This study was designed to compare the usefulness of the normal prostate-specific antigen (PSA) level and the age-referenced PSA level in a large screening study for early detection of prostate cancer. METHODS: A total of 21,078 subjects (aged 45 to 75 years) were participants in a 1-year prostate cancer screening project with PSA as the initial test. Of the volunteers, 1618 (8%) showed an elevated PSA level according to age-specific reference ranges, and using the normal PSA cutoff point (4.0 ng/mL), 1872 (9%) had elevated PSA levels between 4.0 and 6.5 ng/mL. RESULTS: Biopsies in both groups were performed if the PSA level was elevated. We evaluated the effect on biopsy rate and cancer detection. A PSA cutoff point of 2.5 ng/mL in men 45 to 49 years old and a PSA cutoff point of 3.5 ng/mL in men 50 to 59 years old with normal digital rectal examination findings resulted in an 8% increase in the number of biopsies (66 of 778) and an 8% increase in organ-confined cancer detection. An increasing cutoff of 4.5 ng/mL in men 60 to 69 years old and 6.5 ng/mL in men 70 to 75 years old resulted in 21% fewer biopsies (205 of 983) and would have missed 4% of organ-confined tumors (8 of 220). CONCLUSIONS: We conclude that the use of PSA age-specific reference ranges increases the detection of clinically important and organ-confined cancers in young men and decreases the number of biopsies in older men.

Aged↗
PubMed1995

Three-dimensional sonographic guidance for interstitial laser therapy in benign prostatic hyperplasia.

In recent years, interstitial laser therapy was introduced to provide a new treatment of benign prostatic hyperplasia (BPH). However, the precise positioning of the laser fibers has remained a major unsettled issue. Three-dimensional (3-D) transrectal ultrasound scanning permits precise differentiation of the prostatic zones, in particular the transition zone, which is enlarged in BPH. Initially, a volume scan of the prostate is obtained. On the monitor, three sections of the prostate in the coronal, sagittal, and horizontal planes are displayed simultaneously. This new 3-D technology enables precise and reproducible positioning of the laser fibers at any selected site in the adenoma under sonographic guidance, thus providing the basis for complete laser prostatectomy. Placement of the laser fibers proved to be precise, quick, and uncomplicated.

Humans↗
PubMed1995

Renal cell carcinoma extending into the vena cava: surgical approach, technique and results.

OBJECTIVE: To describe the technique and results of a thoraco-abdominal approach to removing the caval thombi in patients with renal cell carcinoma extending into the vena cava. PATIENTS AND METHODS: Between 1970 and 1990 35 patients presenting with renal cell carcinoma extending into the vena cava were treated at the Department of Urology, Innsbruck. Twenty-three of these patients underwent radical tumour nephrectomy including cavotomy and thrombectomy or caval resection. A transabdominal approach had been used in this department for radical tumour nephrectomy including cavotomy and thrombectomy or caval resection until 1987. Since 1988, a thoraco-abdominal approach has been employed. In group I patients the approach was via the seventh intercostal space, whereas in group II and III patients the thoraco-abdominal incision was made through the fifth intercostal space. In the present study the anatomy of the thoraco-abdominal approach is described. RESULTS: Tumour staging and grading yielded stage T3b in 15 patients (grade I, 1; grade II, 6; grade III, 8); another eight patients with stage T3b were found to have metastatic disease (N1, 6; N2, 2; M1, 3). On the basis of the extension of the caval thrombus the patients were classified as follows: group I, 16; group II, 3; group III, 4. In T3b N0 M0 patients the 5-year-survival rate was 62.5%, while in patients with positive lymph nodes the mean survival rate was 15.5 months. CONCLUSION: Our results suggest that the thoracoa-abdominal approach is the method of choice for the safe removal of renal cell carcinomas associated with caval thombi. If resection of the caval tumour is complete, prognosis is dependent on known factors, such as tumour invasion, nodal involvement and distant metastases rather than the extension of the tumour thrombus. An aggressive approach is not warranted in patients with nodal involvement and/or distant metastases, as it does not improve survival.

Carcinoma, Renal Cell↗
PubMed1995

Variability of Doppler parameters in the healthy kidney: an anatomic-physiologic correlation.

Contradictory results have been obtained in classifying various renal diseases when trying to use the resistive index measured by duplex Doppler technique in renoparenchymal arteries. These measurements may have been influenced by the lack of standardization of the anatomic site at which the renoparenchymal artery is sampled. To elucidate this influence, we measured the resistive index, peak systolic velocity, end diastolic velocity, and pulsatility index in 120 healthy kidneys at three different positions of the renal vasculature. The resistive index at the level of the interlobar-arcuate arteries proved to be the parameter with the most consistent results and should be preferred in clinical applications.

Adult↗
PubMed1995

Rationale and technique of nerve sparing radical cystectomy before an orthotopic neobladder procedure in women.

PURPOSE: We developed refinements in the technique of cystectomy and subsequent intestine to urethra anastomosis to improve postoperative results in women undergoing anterior exenteration and creation of an orthotopic neobladder to the urethra. MATERIALS AND METHODS: Anatomical dissection and microdissection studies were performed on formalin-carbol fixed adult cadavers and correlated with previous anatomical and clinical findings. The resulting surgical variations were performed in 5 carefully selected women undergoing lower urinary tract reconstruction. RESULTS: Optimal postoperative results in regard to continence and voiding without compromising oncological outcome may be obtained by preserving the entire lateral vaginal walls, performing nerve sparing dissection of the bladder neck and proximal urethra, removing 1 cm. proximal urethra en bloc with the cystectomy specimen and using additional attachments of the anastomosed intestinal pouch to surrounding pelvic structures. Patients achieved day and night continence after 6 months, mean pouch volume was 580 cc (range 450 to 750) and residual volumes ranged from 0 to 150 cc. No tumor recurred after 6 to 17 months. CONCLUSIONS: Refinements in the technique of radical cystectomy and orthotopic neobladder to the urethra in women may improve continence and spontaneous voiding without compromising surgical oncological outcome, and they further justify orthotopic diversion in select women with bladder cancer.

Aged↗
PubMed1995

[Hormonal therapy of benign prostatic hyperplasia].

In the last 30 years transurethral prostatectomy (TURP) has been the standard treatment for benign prostatic hyperplasia. While the mortality rate of TURP has been reduced to zero, the postoperative morbidity rate has remained unchanged at 15-18% for several decades. Increasing costs and the preference of many patients for non-surgical treatment have now led to the development of new pharmacological treatment options. All hormone therapeutic modalities known to date, such as GnRH-agonists, cyproteronacetate and flutamide, have acted on the male hypothalamic-pituitary-gonadal system. Because of their side effects they are rarely used for the treatment of symptomatic benign prostatic hyperplasia. The 5-alpha-reductase inhibitor finasteride is a new endocrinological treatment option. It can be used to reduce the volume of enlarged prostates and to improve flow rates without severe side effects. According to the available data, finasteride is a safe treatment option for symptomatic patients with benign prostatic hyperplasia if surgery is not yet indicated. It should not, however, be regarded as an alternative to surgical treatment of benign prostatic hyperplasia.

5-alpha Reductase Inhibitors↗
PubMed1995

Age-related changes in resistive index following extracorporeal shock wave lithotripsy.

PURPOSE: Changes in intrarenal vascular resistance after extracorporeal shock wave lithotripsy (ESWL*) were studied with Doppler ultrasound techniques. MATERIALS AND METHODS: In 76 patients the resistive index was measured at an interlobar artery before and after ESWL in the treated and contralateral kidneys. The resistive index levels were compared to N-acetyl-beta-D-glucosaminidase levels in 40 patients. RESULTS: We found an age-related positive linear correlation between post-therapeutic resistive index increases and patient age. N-acetyl-beta-D-glucosaminidase levels were also elevated after ESWL but these elevations were not age-related. CONCLUSIONS: Elderly patients have a higher risk of post-ESWL renal tissue damage.

Acetylglucosaminidase↗
PubMed1995

Laparoscopic ureteral anti-reflux plasty reimplantation. First clinical experience.

Several animal studies have demonstrated that antireflux surgery by means of laparoscopy is technically feasible, but clinical experience is as yet lacking. Six girls aged between 6 and 10 years underwent laparoscopic Lich-Gregoir anti-reflux surgery for vesicoureteral reflux and recurrent urinary infections. Three unilateral and three bilateral procedures were performed. No ureteral stents were used. One girl was operated on via an extraperitoneal approach. A mild unilateral stenosis was observed in one child, which, however, subsided after stenting for six weeks. A borderline compensated pyeloureteral stenosis decompensated shortly after the operation. Another child had an uncomplicated urinary tract infection. No other complications were seen. The laparoscopic Lich-Gregoir antireflux procedure is a complicated operation, which offers no advantage over the conventional procedure.

Arteries↗
PubMed1995

Diagnostic laparoscopic retroperitoneal lymph node dissection for non seminomatous testicular tumor.

Retroperitoneal lymph node dissection for nonseminomatous testicular tumor. A modified retroperitoneal lymph node dissection for stage I testicular tumor has been described by Weissbach. We have developed a two-step procedure for performing laparoscopic retroperitoneal lymph-adenectomy within these boundaries. In the first step, a ventral approach is used. The colon is dissected free, then the spermatic vein is excised, and the borders of the dissection are defined. Removal of retroaortic and retrocaval nodal tissue is technically not feasible via the ventral approach. Therefore, in the second step, a lateral approach is employed, which is the key to success since it permits easy transection of the lumbar vessels. Thus complete lymph node dissection can be achieved. Between August 1992 and March 1994 this procedure was performed in 15 patients. In nine patients, the tumor was on the right side and in six on the left. Conversion to open surgery was necessary in two patients because of uncontrollable bleeding and a large metastasis, respectively. Microscopic metastases were detected in two other patients. Apart from the above-mentioned bleeding no major complications occurred; no blood transfusion were required. The results obtained so far demonstrate that this procedure is technically feasible. Therefore, we have decided to perform laparoscopic retroperitoneal lymphadenectomy also in patients with stage II B tumors who have received chemotherapy; to date one patient with a left-sided stage II B tumor has been operated on successfully.

Adult↗
PubMed1995

The risk of urethral tumors in female bladder cancer: can the urethra be used for orthotopic reconstruction of the lower urinary tract?

We studied the risk of synchronous or secondary urethral tumors after long-term followup in women with bladder cancer. The charts of women treated for various stages of bladder cancer between 1973 and 1992 were reviewed. Of 356 evaluable patients 268 presented initially with primary and 78 with multilocular tumor involvement. There were 498 episodes of recurrent tumors in 127 patients, and a total 1,210 tumor locations in 854 primary and recurrent episodes of bladder cancer. Mean followup for these patients was 5.5 years (range 0.05 to 33.1). Overall 7 of 356 patients (2%) had urethral tumor involvement, all at initial presentation. Statistical comparison of various defined tumor localizations in the bladder revealed that the bladder neck (p < 0.000) and trigone (p < 0.035) were significantly more often the region of primary tumor occurrence in the urethral tumor group. All patients with secondary urethral tumors had tumor involvement of the bladder neck at the same time. A 1% urethral tumor involvement was seen among 104 patients with clinical stage T2 to 3b, N0, M0 transitional cell carcinoma, who could have been considered for curative radical cystectomy. No patient presenting with tumor recurrence regardless of its location was found to have urethral tumors. Subtotal urethrectomy is an option in select female patients after cystectomy for localized bladder cancer to allow orthotopic reconstruction of the lower urinary tract provided the bladder neck is free of tumor.

Adult↗