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Biomedical subjects

K Renner

Publications and source records attributed to K Renner.

At least 19 recordsLinked to original sources

[Are there indications for organ-preserving tumor resection in urothelial cancers of the upper urinary tract?].

PURPOSE: Identification of prognostic factors for tumor recurrence in nephronsparing surgery and tumor progression after organ-preserving surgery. MATERIAL AND METHODS: From June 1989 to February 2003, 43 patients (47 nephron units) underwent organ-preserving surgery or the upper urinary tract because of urothelial carcinoma, with 26 (60.5 %) having an elective indication (healthy contralateral kidney). RESULTS: The mean follow-up was 39.2 months with a range of 10.6 to 168.3 months. Ipsilateral recurrences occurred in 13 (27.6 %) of reno-ureteral units. Recurrences were significantly more common for tumors located in the renal pelvis or opposite the ureteral origin (p = 0.018). Tumor progression occurred in 8 of 43 patients (18.6 %) and significantly correlated with the T- and G-stage of the primary tumor (p = 0.006 and p = 0.002). Of the 47 conservatively treated reno-ureteral units, 38 (80.8 %) could be preserved. CONCLUSION: Organ-preserving resection of the urothelial carcinoma of the upper urinary tract is an alternative in some patients with well-differentiated superficial tumors. A follow-up for life and a good patient compliance are necessary. Tumors of the renal pelvis have a significantly higher recurrence rate than ureteral tumors. Poorly differentiated tumors should undergo organ-preserving surgery only if the goal is palliation and in patients with solitary kidney after intensive consultation about the high risk of invasive recurrences and the development of metastases.

Aged↗

[Collateral circulation of the left colon: historic considerations and actual clinical significance].

INTRODUCTION: The arterial communication between the superior and inferior mesenteric arteries is important in surgery of the colon and aorta. METHODS: The anastomosis between the median colic artery (ACM) and the superior colic artery (AMS) was studied on 52 cadavers (32 female, 20 male). The length of the artery was measured using a flexible scale, and its diameter was determined at three different locations (origin, middle, end). RESULTS: The median lengths of the arteries were: 6.8 cm (range 3.9-9.7) for ACM, 12.2 cm (range 7-17.4) for ACS, and 23 cm (range 13.6-34.2) for margin artery. The median diameters were: 3.4 mm (range 2.7-4.1) for ACM, 3.1 mm (range 2.1-4.1) for ACS, and 2.7 mm (range 2-3.4) for margin artery. In 9.6% of the cadavers ( n=5), additional anastomoses between the AMS and inferior mesenteric arteries were proven. In 90.4% ( n=47), only margin arteries were found. SUMMARY: The low incidence of an additional communication (Riolan's arch) and possible additional impairment of the blood supply should be taken into account during operation.

Angiography↗

A conceptual view on glucocorticoid-lnduced apoptosis, cell cycle arrest and glucocorticoid resistance in lymphoblastic leukemia.

Glucocorticoids (GC) control cell cycle progression and induce apoptosis in cells of the lymphoid lineage. Physiologically, these phenomena have been implicated in regulating immune functions and repertoire generation. Clinically, they form the basis of inclusion of GC in essentially all chemotherapy protocols for lymphoid malignancies. In spite of their significance, the molecular mechanisms underlying the anti-leukemic GC effects and the clinically important phenomenon of GC resistance are still unknown. This review summarizes recent findings related to GC-induced apoptosis, cell cycle arrest, and GC resistance with particular emphasis on acute lymphoblastic leukemia (ALL). We hypothesize that under conditions of physiological Bcl-2 expression, GC might induce classical programmed cell death by directly perturbing the Bcl-2 rheostat. In the presence of anti-apoptotic Bcl-2 proteins, cell death might result from accumulating catabolic and/or other detrimental GC effects driven by, and critically dependent on, GC receptor (GR) autoinduction. Although still controversial, there is increasing evidence for release of apoptogenic factors through pores in the outer mitochondrial membrane, rather than deltapsiloss-dependent membrane rupture, with maintenance of mitochondrial function at least in the early phase of the death response. GC-induced cell cycle arrest in ALL cells appears to be independent of apoptosis induction and vice versa, and critically depends on repression of both cyclin-D3 and c-myc followed by increased expression of the cyclin-dependent kinase inhibitor, p27Kip1. Since development of GC-resistant clones requires both cell cycle progression and survival, GC resistance might frequently result from structural or regulatory defects in GR expression, perhaps the most efficient means to target both pathways concurrently.

Apoptosis↗

Needle perforation of the appendix.

BACKGROUND/AIMS: Needles are among the most frequently swallowed foreign bodies. In most cases they are excreted per vias naturales, but in some cases needles can lead to perforation of the stomach or duodenum in adults. METHODS: We report a case of acute appendicitis after perforation of the appendix by a swallowed needle. An appendectomy was performed without any knowledge of the reason for perforation. RESULTS: Inspection of the resected appendix demonstrated a needle of 1.5 cm length inside the lumen of the appendix, which had caused a perforation of the distal end of the appendix. CONCLUSION: As seen in this case a longer-lasting nondiagnosed perforation can lead to extensive local inflammation which could have been avoided by early surgical treatment which should also be considered if the patient has very few symptoms, as in this case.

Adult↗

Quality of life after surgery for rectal cancer: do we still need a permanent colostomy?

INTRODUCTION: A permanent colostomy is a serious limitation of the quality of life. Besides cure of cancer, preservation of sphincter function is an important goal of surgery for rectal cancer. METHODS: In a prospective study a concept offering every patient with rectal cancer either sphincter salvage or a "neosphincter" was investigated, and the impact of this strategy on oncologic results, sphincter function, and quality of life was analyzed. RESULTS: From 1992 to 1997, 276 patients were accepted for the study. Two hundred sixty-one patients had elective surgery, and 15 patients had emergency surgery for their rectal tumors. The postoperative mortality rate was 4 percent. A radical resection (R0) was possible in 197 patients (75 percent). Anterior resection was the most common procedure (n = 87), and intersphincteric resection with coloanal anastomosis was the preferred method for low tumors (n = 65). Abdominoperineal resection was necessary in 15 cases. Thirteen patients had an immediate restoration of sphincter function by means of a dynamic graciloplasty, and 2 patients needed emergency abdominoperineal resection for bleeding. The follow-up was relatively short (median, 36.4 months) at the time of data analysis and showed a local recurrence rate of 8 percent. Although postoperative continence according to the Williams score revealed satisfactory results, subjective quality of life and the scale for specific symptoms showed a significantly worse outcome in patients with ultralow (coloanal) anastomoses compared with those with anterior resection. CONCLUSIONS: We conclude that for elective curative surgery of rectal cancer, a permanent colostomy is not necessary provided all presently available techniques of sphincter salvage and restoration are applied. However, the patient has to be informed about possible side effects associated with surgical procedures such as coloanal anastomosis or neosphincter reconstruction, to avoid severe psychological difficulties.

Aged↗

Activated lymphocytes from breast cancer patients express the characteristics of type 2 helper cells--a possible role for breast cancer-associated p43.

P43, a breast cancer-associated antigen, has been repeatedly described as an immunosuppressive factor. The objective of the present study was to investigate whether immune dysregulation induced by p43 affects the profile of cytokines secreted by mitogen-stimulated lymphocytes in breast cancer patients as compared with stimulated lymphocytes in women with benign tumors. The study consisted of 32 women undergoing surgical excision for a suspicious lesion in their breast. Histology revealed malignant breast disease in 20 patients and benign lesions in 10 patients. Lymphocytes isolated from peripheral blood were activated by Conconavalin A (Con A) with and without the addition of p43 and the concentrations of cytokines (IL-2, TNF-alpha, IFN-gamma, IL-4, IL-10 and IL-6) secreted into the culture medium were determined. Lymphocytes of patients with malignant breast disease stimulated with Con A secreted a significantly higher concentration of IL-10 compared with lymphocytes of patients with benign tumors. No significant differences were found between the two groups regarding the levels of IL-2, TNF-alpha, IFN-gamma and IL-4. Cytokine concentrations were analyzed according to the type 1/type 2 cytokine profile (IL-2, TNF and IFN-gamma and IL-4, IL-6 and IL-10, respectively). This analysis revealed no significant differences in IL-2, TNF or IFN-gamma between benign and malignant tumors. However, in the type 2 cytokines, lymphocytes from cancer patients secreted significantly higher levels of IL-4 (27.3 +/- 7.2 U/ml) and IL-10 (44.1 +/- 22.3 U/ml) than did the lymphocytes from patients with benign disease (21.4 +/- 7.3 and 1.8 +/- 0.3 U/ml, respectively). The addition of p43 to the culture medium significantly enhanced the levels of IL-4 secreted by lymphocytes in both groups of patients (malignant disease, from 27.3 +/- 9.2 to 40.7 +/- 6.3 U/ml; benign disease, from 21.4 +/- 7.3 to 28.4 +/- 2.1 U/ml). P43 antigen significantly enhanced the low levels of IL-10 in the benign lymphocytes (from 1.8 +/- 0.4 to 8.4 +/- 1.5 U/ml) while the high levels of IL-10 secreted by the PBL in patients with malignant tumors were not significantly increased (44.1 +/- 22.3 versus 50.1 +/- 12.6 U/ml). The study showed a difference in the immune response of lymphocytes between malignant and benign tumors. When the current results were analyzed according to the type of response, i.e. in terms of whether at least two cytokines of either type 1 or type 2 were elevated, a significant type 2 response was observed in the PBL of patients with malignant breast cancer (IL-10 and IL-4). These results may explain why antitumor response is impaired in patients with breast cancer.

Antigens, Neoplasm↗

[Therapy studies of the Austrian Breast Cancer Group (ABC)].

The Austrian Breast Cancer Group (ABC) consisting of more than 60 participating centers in Austria has randomized more than 5800 patients in 11 randomized trials since 1984. At present, roughly 30% of all patients with the diagnosis primary breast cancer are accrued in protocols throughout the country. Due to specific activities, the breast conservation rate raised from an initial 20% to more than 60% in the last years. Multicenter trials are not only the basis for progress in medicine but also tools for quality control and quality improvement.

Antineoplastic Agents, Hormonal↗

Muscle transformation of the sartorius muscle in a canine model: clinical impact for electrodynamic graciloplasty as a "neosphincter".

PURPOSE: Transformation of fast-twitching skeletal muscles to slow-twitching, slowly fatigable muscles has become of clinical interest in the recent past. Transposition and transformation of the gracilis muscle to use it as a substitute for a resected or defected anal sphincter (graciloplasty) have been reported as achieving promising results in the treatment of fecal incontinence caused by sphincter defects or following abdominoperineal anorectal excision for cancer. METHOD: This experimental study used a canine model and the sartorius muscle to evaluate the functional efficiency of two different configurations of the muscle loop to compare the presently applied transformation program (8 weeks) with a shorter (5 weeks) protocol. In six beagle dogs, both sartorius muscles were wrapped around two stomas, either in an alpha fashion or in the so-called split-sling technique. Muscle transformation was achieved by controlled neuromuscular stimulation either during eight (Program A) or five weeks (Program B). After completion of the transformation period, the function of the muscle slings was evaluated by manometry, and histomorphologic evaluation of the sartorius muscles was performed. RESULTS: It was shown that muscle transformation led to a slowly fatigable muscle that made it possible to perform continuos (tetanic) contraction, regardless of the configuration or the duration of the transformation. Median pressures created by these muscles also did not differ significantly. In accordance with these functional findings, the histologic evaluation showed the typical, significant increase of Type I fibers in both muscle slings and following both transformation protocols. Although the decrease of fast-twitching Type II fibers was more pronounced following the conventional (8 weeks) program, this finding did not influence the functional results. CONCLUSIONS: Results of our experiment indicate the possibility for using a shorter transformation protocol for transformation of the gracilis muscle during graciloplasty in the clinical setting. Furthermore, the efficacy and safety of the modified (split-sling) wrap technique was demonstrated.

Anal Canal↗

Expression of the gene for the POU domain transcription factor Tst-1/Oct6 is regulated by an estrogen-dependent enhancer.

Expression of the POU domain protein Tst-1/Oct6 during development of glia and neurons is subject to a tight multifactorial control. Here we show that 17beta-estradiol increases the level of endogenous Tst-1/Oct6 in glial cells. This effect was mediated at the level of gene expression by an enhancer present in the 5' flanking region of the mouse gene for Tst-1/Oct6, approximately 5 kb upstream of the transcriptional start site. The enhancer contained as the functional element a sequence motif that closely resembled a classical estrogen response element. It consisted of an imperfect palindrome with a spacing of 3 bp, and was bound in vitro by activated estrogen receptor. Furthermore, this element was able to confer estrogen responsiveness when introduced into a heterologous promoter. In the Tst-1/Oct6 gene enhancer, a TPA response element was found in close proximity to the estrogen receptor binding site. As a consequence, TPA and estrogen activated transcription of the Tst-1/Oct6 gene in a synergistic manner.

Animals↗

T antigen of human papovavirus JC stimulates transcription of the POU domain factor Tst-1/Oct6/SCIP.

Human papovavirus JC exhibits a strong tropism for glial cells in vivo. To a large extent, this effect is due to the pronounced glia specificity of viral gene expression, which is mediated by the specific interaction of glial transcription factors such as Tst-1/Oct6/SCIP with viral promoter sequences. Here we show that, in return, expression of the glial transcription factor Tst-1/Oct6/SCIP can be strongly activated by T antigen, the early gene product of JC virus, in a dose-dependent manner. In transient transfection experiments, stimulation by T antigen was entirely dependent on a 335-bp segment of the Tst-1/Oct6/SCIP gene promoter that included the transcriptional start site. The same fragment was also bound by purified T antigen in immunoprecipitation assays due to the presence of three closely spaced and tandemly oriented GAGGC pentamers. However, when this array of pentamers was mutated so that binding of T antigen was strongly reduced, T-antigen-dependent transcriptional activation remained unaffected. Thus, similar to viral late gene expression, transcriptional stimulation of the Tst-1/Oct6/SCIP gene by T antigen was not dependent on binding to GAGGC pentamers present within the promoter. Nevertheless, our data provide strong support for a model in which JC virus influences gene expression of its host cell via its early gene product in a manner favourable for its own propagation.

Animals↗

Functional comparison of PML-type and archetype strains of JC virus.

Isolates of the human polyomavirus JC can be grouped as either PML-type or archetype strains primarily on the basis of divergence in their regulatory regions. Only PML-type viruses have so far been found to be associated with the human demyelinating disease progressive multifocal leukoencephalopathy. Here we have compared the functional properties of archetype and PML-type regulatory regions with regard to DNA replication and viral gene expression. No significant differences could be detected between archetype and PML-type regions in their ability to direct episomal DNA replication in the presence of JC virus T antigen. When viral gene expression was examined, early- and late-gene promoters from all PML-type strains exhibited a significantly higher activity in glial than in nonglial cells. Surprisingly, archetype strain promoters were also preferentially active in glial cells, although this effect was less pronounced than in PML-type strains. Furthermore, all promoters from archetype strains reacted to the presence of viral T antigen or the glial transcription factor Tst-1/Oct6 in a manner similar to the promoters of the PML-type viral strain Mad-1. Interestingly, T antigen and Tst-1/Oct6 were found to function in a species-specific and cell-type-specific manner, respectively. We concluded from our experiments that the differences in the regulatory regions cannot account for the different biology of archetype and PML-type viral strains.

Antigens, Polyomavirus Transforming↗

Cost-justifying electronic medical records.

As interest in electronic medical record systems increases, the need to cost-justify these systems is becoming more important. But determining the cost-benefit ratio of such systems is difficult. The cost of implementing a system includes more than the price of hardware and software. It can be difficult to quantify the qualitative benefits associated with computerizing clinical information. Healthcare financial managers should be aware of the uses and limitations of financial tools for assessing electronic medical records technology.

Cost-Benefit Analysis↗

Functional interaction between the POU domain protein Tst-1/Oct-6 and the high-mobility-group protein HMG-I/Y.

The POU domain protein Tst-1/Oct-6 is a transcriptional activator of human papovavirus JC virus in transient transfections. Because of its endogenous expression in myelinating glia, Tst-1/Oct-6 might also be an important determinant for the glia specificity of JC virus in vivo. Activation of viral early and late genes depends on the ability of Tst-1/Oct-6 to interact with an AT-rich element within the viral regulatory region. Here, we show that this element not only is bound by Tst-1/Oct-6 but, in addition, serves as a binding site for the high-mobility-group protein HMG-I/Y. In the presence of HMG-I/Y, Tst-1/Oct-6 exhibited an increased affinity for this AT-rich element. The specificity of this effect was evident from the fact that no stimulation of Tst-1/Oct-6 binding was observed on a site that did not allow binding of HMG-I/Y. In addition, both proteins interacted with each other in solution. Direct contacts were identified between the POU domain of Tst-1/Oct-6 and a short stretch of 10 amino acids in the central portion of HMG-I/Y. These results point to an accessory role for HMG-I/Y in the activation of JC viral gene expression by the POU domain protein Tst-1/Oct-6. In agreement with such a role, HMG-Y synergistically supported the function of Tst-1/Oct-6 in transient transfections, measured on the early promoter of JC virus or on an artificial promoter consisting of only a TATA box and the common binding element for Tst-1 and HMG-I/Y.

Base Sequence↗

The POU domain protein Tst-1 and papovaviral large tumor antigen function synergistically to stimulate glia-specific gene expression of JC virus.

Synergism between transcriptional activators is a powerful way of potentiating their function. Here we show that the glial POU domain protein Tst-1 (also known as Oct-6 and SCIP) and large tumor antigen (T antigen) synergistically increased transcription from both the early and the late promoters of papovavirus JC in glial cells. Synergism between both proteins did not require T-antigen-mediated DNA replication or direct binding of T antigen to the promoter. The ability of T antigen to functionally cooperate with Tst-1 was contained within its N-terminal region, shown by the fact that small tumor antigen (t antigen) could substitute for T antigen in transfection experiments. In addition to this functional synergism, a direct interaction between Tst-1 and T antigen was observed in vitro. Using deletion mutants of Tst-1 and T antigen, the POU domain of Tst-1 and the N-terminal region of T antigen were found to participate in this interaction. Because of the low levels of Tst-1 present in oligodendrocytes, synergism between Tst-1 and T antigen could be an important factor in establishing the lytic infection of oligodendrocytes by JC virus during the course of the fatal demyelinating disease progressive multifocal leukoencephalopathy.

Antigens, Polyomavirus Transforming↗

Palliative radiotherapy in plasma cell myeloma.

Pain symptoms caused by bone lesions of multiple myeloma can be relieved by a local irradiation treatment. To estimate the influence of systemic treatment on the palliative effect of local radiotherapy the records of 70 myeloma patients treated with chemotherapy combined with or followed by local irradiation were reviewed. The local response rate, defined as complete pain relief at the irradiated site, was 80% in patients receiving irradiation during chemotherapy (melphalan and prednisone) and this palliative effect endured 31.8 +/- 3.6 months. If irradiation was started in the period without systemic treatment the local response rate was 39.6% and lasted 24.8 +/- 17.9 months. In sites treated with more than one radiotherapy course 94% response rate after the first treatment, 56% after the second treatment and no response after the third course was achieved. The duration of local pain control was positively related to the applied radiation dose. It is concluded that irradiation during concomitant chemotherapy is superior to radiotherapy performed in a period without systemic treatment. Local long-term palliation can only be achieved by a sufficient high radiation dose.

Adult↗

Anatomic considerations for plate-screw fixation of the cervical spine.

A cadaveric study was done to investigate the variability of interfacet distances from C3 to C7, to learn pedicle morphology at C7-T2, and to determine potential dangers of plate-screw osteosynthesis technique of the cervical spine. Twenty-two cadavers were dissected from C2 to C7 to expose the lateral masses and nerve roots. The interfacet distances from the center of the lateral mass to the next lateral mass from C3 to C7 vary widely among different individuals, ranging from 9 mm to 16 (average, 13 mm). A new plate design is necessary to better accommodate the differences in interfacet distances among different patients and different levels. The second part of the study involved 11 dissected cadaveric specimens of the cervicothoracic junction. The pedicle entry point was 1 mm inferior to the midportion of the facet joint for C7, T1, and T2. The medial angulation averaged 34 degrees at C7, 31.8 degrees at T1, and 26.5 degrees at T2. The mediolateral and superoinferior outer pedicle diameters were 6.9 mm and 7.5 mm at C7, 8.5 mm and 9.5 mm at T1, and 7.5 mm and 10.7 mm at T2, respectively. The mediolateral inner diameter averaged 5.18 mm, 6.4 mm, 5.5 mm for C7, T1 and T2, respectively. The pedicle distances (from the entry point to the posterior vertebral body line) measured 9.1 mm, 9.9 mm, and 10.4 mm for respective levels. The margins for error are small when using pedicle screws at these levels. If a pedicle screw must be used at C7, T1, and T2, one must have precise knowledge of the entrance point, diameters, and 25-30 degrees medial direction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗