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Biomedical subjects

E Winter

Publications and source records attributed to E Winter.

At least 19 recordsLinked to original sources
PubMed2005

Regulation of insulin-like growth factor binding protein-5, four and a half lim-2, and a disintegrin and metalloprotease-9 expression in osteoblasts.

The roles of insulin-like growth factors (IGFs) in regulating growth and their modulation by six IGF binding proteins (IGFBP) are well established. IGFBP-5, the most abundant IGFBP stored in bone, is an important regulator of bone formation via IGF-dependent and -independent mechanisms. Two new proteins, four and a half lim (FHL)-2, a transcription modulator that interacts with IGFBP-5, and a disintegrin and metalloprotease (ADAM)-9, an IGFBP-5 protease, have been identified as potential regulators of IGFBP-5 action in bone. We tested the hypothesis that agents which modulate bone formation by regulating IGFBP-5 expression would also regulate FHL-2 and ADAM-9 expression in a coordinated manner. We evaluated the expression of IGFBP-5, FHL-2, and ADAM-9 by real-time reverse transcriptase (RT)-PCR during differentiation of mouse bone marrow stromal cells into osteoblasts and in response to treatment with bone formation modulators in the LSaOS human osteosarcoma cell line. IGFBP-5 and FHL-2 increased 4.3- and 3.0-fold (P < or = 0.01), respectively, during osteoblast differentiation. Dexamethasone (Dex), an inhibitor of bone formation, decreased IGFBP-5 and FHL-2 and increased ADAM-9 in LSaOS cells (P < or = 0.05). Bone morphogenic protein (BMP)-7, a stimulator of bone formation, increased IGFBP-5 and decreased ADAM-9 (P<0.01). To determine if BMP-7 would eliminate Dex inhibition of IGFBP-5, cells were treated with Dex+BMP-7. The BMP-7-induced increase in IGFBP-5 was reduced, but not eliminated, in the presence of Dex (P < or = 0.01), indicating that BMP-7 and Dex may regulate IGFBP-5 via different mechanisms. Transforming growth factor (TGF)-beta, a stimulator of bone formation, increased IGFBP-5 and FHL-2 expression (P < or = 0.01). IGF-I and TNF-alpha decreased expression of ADAM-9 (P<0.05). In conclusion, our findings are consistent with the hypothesis that FHL-2 and ADAM-9 are important modulators of IGFBP-5 actions and are, in part, regulated in a coordinated manner in bone.

ADAM Proteins↗
PubMed2004

[Treatment of pain in cancer patients].

Patients experiencing constant pain continue to receive less than optimal treatment. In the case of cancer pain in particular, adequate therapy is a must. On the basis of the WHO analgesic ladder, nonopioids and opioids of varying potency must be applied as required, together with antiemetics, laxatives, gastric-protective preparations and bisphosphonates to ameliorate side effects. A particular problem in the treatment of cancer pain is the suddenly occurring stress and perforation pain. This can be reduced with fast-acting opioids such as the fentanyl stick. If the patient does not respond adequately to any of the noninvasive methods, local anesthetics and opiates applied via an i.v. pump system that permits bolus application and spinal and epidural methods have proven useful.

Analgesics↗
PubMed2004

Personality pathology and outcome in recurrently depressed women over 2 years of maintenance interpersonal psychotherapy.

BACKGROUND: Empirical data on the impact of personality pathology on acute treatment outcome for depression are mixed, in part because of challenges posed by assessing trait-like personality patterns while patients are in an active mood episode. To our knowledge, no previous study has examined the effect of personality pathology on maintenance treatment outcome. By maintenance treatment we refer to long-term treatment provided to prevent depression recurrence among remitted patients. METHOD: Structured Clinical Interviews for the DSM-III-R Personality Disorders (SCID-II) were obtained on a sample of 125 recurrently depressed women following sustained remission of the acute mood episode and prior to entering maintenance treatment. SCID-II interviews were then repeated following 1 and 2 years of maintenance interpersonal psychotherapy. RESULTS: At the pre-maintenance assessment, 21.6% of the sample met SCID-II personality disorder criteria. Co-morbid personality pathology was related to an earlier age of onset, more previous depressive episodes, and a greater need for adjunctive pharmacotherapy to achieve remission of the acute mood episode. Co-morbid personality pathology predicted both higher rates of depression recurrence and a shorter time to recurrence over the 2-year course of maintenance treatment. Notably, among those patients who remained depression-free, continuous levels of personality pathology steadily declined over the 2-year course of maintenance therapy. CONCLUSIONS: Results highlight the need for early and effective intervention of both episodic mood disorder and inter-episode interpersonal dysfunction inherent to the personality disorders. Future maintenance treatment trials are needed to clarify the relationship between episodic mood disorder and personality function over time.

Adult↗
PubMed2004

European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG).

Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based chemotherapy, together with radiation and surgical measures, leads to the high cure rate of > or = 99% in early stages and 90%, 75-80% and 50% in advanced disease with 'good', 'intermediate' and 'poor' prognostic criteria (IGCCCG classification), respectively. The high cure rate in patients with limited metastatic disease allows the reduction of overall treatment load, and therefore less acute and long-term toxicity, e.g. organ sparing surgery for specific cases, reduced dose and treatment volume of irradiation or substitution of node dissection by surveillance or adjuvant chemotherapy according to the presence or absence of vascular invasion. Thus, different treatment options according to prognostic factors including histology, stage and patient factors and possibilities of the treating centre as well may be used to define the treatment strategy which is definitively chosen for an individual patient. However, this strategy of reduction of treatment load as well as the treatment itself require very high expertise of the treating physician with careful management and follow-up and thorough cooperation by the patient as well to maintain the high rate for cure. Treatment decisions must be based on the available evidence which has been the basis for this consensus guideline delivering a clear proposal for diagnostic and treatment measures in each stage of gonadal and extragonadal germ cell tumour and individual clinical situations. Since this guideline is based on the highest evidence level available today, a deviation from these proposals should be a rare and justified exception.

Europe↗
PubMed2003

[Gemcitabine/cisplatin vs. MVAC. 5 year survival outcome of the phase III study of chemotherapy of advanced urothelial carcinoma in Germany].

Of 405 patients with stage IV transitional cell carcinoma from an international multicenter phase III trial, 70 were randomized in Germany to receive either gemcitabine/cisplatin or standard MVAC systemic chemotherapy for locally advanced or metastatic urothelial cancer. Overall survival as the primary endpoint of the study was similar in both arms (median survival GC 15.4 months vs MVAC 16.1 months), as were tumor-specific survival and time to progressive disease. In the intent-to-treat analysis, the 5-year overall survival rate was 10% for patients randomized to GC and 18% randomized to MVAC. Tumor overall response rates (GC 54%, MVAC 53%) were similar. The toxic death rate was 0% in the GC arm and 3% (one patient) in the MVAC arm. Significantly more GC than MVAC patients experienced grade 3/4 anemia (GC 52%, MVAC 20%) with significantly more red blood cell transfusions in the GC arm.Significantly more GC than MVAC patients had grade 3/4 thrombocytopenia (GC 54%, MVAC 17%) without grade 3/4 hemorrhage or hematuria in either arm. More MVAC patients experienced grade 3/4 neutropenia (GC 56%, MVAC 61%, p=1.000), neutropenic or leukopenic fever (GC 0%, MVAC 10%, p=0.237), mucositis (GC 0%, MVAC 7%, p=0.495), and alopecia (GC 6%, MVAC 36%, p=0.004). GC represents a reasonable alternative for the palliative treatment of patients with locally advanced and metastatic transitional cell carcinoma. Sustained long-term survival was only found for patients with locally advanced cancer, lymphatic metastases, or solitary distant metastasis but not for visceral metastatic disease.

Adult↗
PubMed2003

[Distinctive features of the os naviculare pseudarthrosis vs the os naviculare accessorius].

We report on two cases in which the differential diagnosis between an os tibiale externum (os naviculare accessorius) and a post-traumatic pseudarthrosis of the os naviculare was subject to discussion.Both patients had suffered an acute trauma in the region of the middle foot and showed identical clinical symptoms. Conventional X-ray did not allow a definite classification of the diagnosis either.However, this was possible in both cases by virtue of typical signs evidenced by computed tomography and magnetic resonance imaging.

Adult↗
PubMed2003

[Cemented versus uncemented hip replacement--rational decision making using the BiCONTACT total hip system].

The BiCONTACT femoral stem has been developed as a modular system which is suitable for both cemented and uncemented implantation. A highly standardized procedure using an identical set of instruments for both modes of fixation ensures bone preservation. Primary stability is achieved by special design parameters. The cementless implants are coated proximally, thus facilitating osteointegration and proximal load transfer. Cemented stems provide an identical design but a smooth surface and are anchored by a homogenous cement mantle. The BiCONTACT stem is in use in the BG Trauma Center Tuebingen since 14 years and a consecutive series of 250 cases (series A) with uncemented implantation and of 250 cases (series B) with cemented implantation has been analyzed in two different prospective follow-up studies. Long-term survival after 11 years was 97.1 % (95 % confidence limits: 93.8 %-98.7 %) for series A, the follow-up rate was 99.2 %. For series B, the follow up-rate was also 99.2 %, survival estimate after 11 years was 97.5 % (95 % CI: 94.2 %-99.0 %).

Adult↗
PubMed2003

Long-term results with the BiCONTACT system--aspects to investigate and to learn from.

The BiCONTACT femoral stem for cementless fixation is being used without any technical modification after 15 years. The long-term results should be evaluated in this study. A consecutive series was continuously monitored in a prospective follow-up study. A survival analysis was performed, clinical results were rated according to the Harris score. There were 236 patients with 250 total hip replacements (THR); mean age at time of implantation was 58.2 years. Indications for THR included osteoarthritis (62.4%), dysplasia (16.8%), trauma (8.4%) and femoral-head necrosis (16.8%). Average time of follow-up evaluation was 8.9 years (range 7.4-10.7 years). At follow-up, 27 patients had died and two could not be located. Seven patients were revised--two for infection, one for recurrent dislocation, two for component undersizing with rapid subsidence, and one for aseptic loosening of a varus-malaligned stem; one radiologically well-fixed stem had been revised during acetabular revision. Survival estimate showed an overall survival rate of 97.1% after 11 years (confidence limits: 98.7% upper and 93.6% lower). Radiologically, tiny reactive lines (< 2 mm) were present in the distal zones of the femoral shaft, but no radiolucencies could be found in the proximal anchoring zone. Migration analysis with Ein-Bild-Röntgen-analyse/femoral component analysis (EBRA/FCA) demonstrated a very small amount of migration: in 31.0%, the overall migration was between 0.5 and 1 mm after 120 months; 8.5% had an absolute amount of subsidence exceeding 2 mm after 120 months (one case more than 3 mm). Mean subsidence was 0.2 mm after 3 months and 6 months, 0.3 mm after 12 months, and reached 0.5 mm after 10 years. An initial small amount of subsidence could be detected in 45.1%, and 15.5% had a late onset of subsidence. Continuous sinking could be found in 12.7%, while 26.8% had irregular patterns of migration. Clinical results were somewhat compromised by a higher-than-average rate of cup loosening (uncoated threaded cup). The average Harris hip score at follow-up was 84.3 points. Interestingly, no femoral osteolysis could be detected, even in cases with severe acetabular osteolyses, indicating sealing of the stem interface by tight osseointegration of the proximally-coated stem.

Arthroplasty, Replacement, Hip↗
PubMed2002

Testicular germ cell cancer despite previous local radiotherapy to the testis.

BACKGROUND: Testicular intraepithelial neoplasia (TIN, also carcinoma in situ of the testis) is the uniform precursor of testicular germ cell cancer. Local radiotherapy to the testis with dosages of 18-20 Gy has been found to safely eradicate TIN and germ cells, too. Thus, the general assumption is that the development of invasive germ cell tumours can be prevented by this radiotherapy. PATIENTS AND METHODS: Herein, we report two patients with one-sided testicular tumour and biopsy-proven contralateral TIN. Both of them developed germ cell neoplasms in the remaining testis although local radiotherapy with 20 Gy had been applied to the testis. RESULTS: One patient developed pure seminoma 7 years after completion of radiotherapy, the other developed a combined tumour consisting of embryonal carcinoma and seminoma after 5 years. Treatment consisted of orchiectomy in each of the cases. Histologically, both had TIN in the testicular tissue surrounding the new growths. CONCLUSIONS: Pathogenetically, a small fraction of radioresistent TIN cells overcoming irradiation and progressing to full-blown germ cell cancer in the later course may be the histogenetic clue to explain these unexpected events. Other explanations, though less probable, could be technical radiotherapeutic failure due to targeting problems and a pre-existing radioresistent germ cell tumour in the irradiated testicle.

Adolescent↗
PubMed2001

Arabidopsis eIF3e (INT-6) associates with both eIF3c and the COP9 signalosome subunit CSN7.

The Arabidopsis COP9 signalosome is a multisubunit repressor of photomorphogenesis that is conserved among eukaryotes. This complex may have a general role in development. As a step in dissecting the biochemical mode of action of the COP9 signalosome, we determined the sequence of proteins that copurify with this complex. Here we describe the association between components of the COP9 signalosome (CSN1, CSN7, and CSN8) and two subunits of eukaryotic translation initiation factor 3 (eIF3), eIF3e (p48, known also as INT-6) and eIF3c (p105). To obtain a biochemical marker for Arabidopsis eIF3, we cloned the Arabidopsis ortholog of the eIF3 subunit eIF3b (PRT1). eIF3e coimmunoprecipitated with CSN7, and eIF3c coimmunoprecipitated with eIF3e, eIF3b, CSN8, and CSN1. eIF3e directly interacted with CSN7 and eIF3c. However, eIF3e and eIF3b cofractionated by gel filtration chromatography in a complex that was larger than the COP9 signalosome. Whereas eIF3, as detected through eIF3b, localized solely to the cytoplasm, eIF3e, like CSN7, was also found in the nucleus. This suggests that eIF3e and eIF3c are probably components of multiple complexes and that eIF3e and eIF3c associate with subunits of the COP9 signalosome, even though they are not components of the COP9 signalosome core complex. This interaction may allow for translational control by the COP9 signalosome.

Animals↗
PubMed2001

Results of a cemented titanium alloy straight femoral shaft prosthesis after 10 years of follow-up.

Two-hundred fifty implantations of a cemented femoral stem made of titanium alloy in 239 patients were followed for 9.7 years (range 8.7-10.3 years). Eighty-nine patients with 93 hips have died and two could not be located. Five hips have been revised, two for infection, one for aseptic loosening and two during revision of the cup. Three stems showed radiological loosening but have not been revised. The average hip score was 85. The results are encouraging and comparable to other cemented femoral stems.

Adult↗
PubMed2001

Allogeneic cancellous bone graft and a Burch-Schneider ring for acetabular reconstruction in revision hip arthroplasty.

BACKGROUND: There is an ever-increasing number of failed hip arthroplasties associated with massive deficiency of acetabular bone stock consisting of a segmental or cavitary defect. This study was undertaken to evaluate the long-term results after use of morselized cryopreserved allogeneic bone graft and an antiprotrusio cage to treat such a deficiency. METHODS: From January 1, 1988, to January 1, 1994, forty-one patients (forty-one hips) with an acetabular defect classified as type IIl or IV according to the American Academy of Orthopaedic Surgeons system were operated on with use of a Burch-Schneider ring and morselized cryopreserved allogeneic cancellous bone graft. Thirty-eight patients (thirty-eight hips) were available for clinical and radiographic follow-up examinations at an average of 7.3 years (range, 4.2 to 9.4 years) after surgery. RESULTS: All measured clinical parameters had improved significantly by the time of the follow-up examination (p < 0.0001). Radiographs confirmed that none of the thirty-eight hips had any measurable migration or displacement of the acetabular component and that osseous consolidation occurred only within the grafted area in all patients. CONCLUSION: Acetabular reconstruction with use of morselized cryopreserved allogeneic cancellous bone graft and the Burch-Schneider ring can be highly successful in managing massive acetabular deficiencies in revision hip arthroplasty.

Acetabulum↗
PubMed2001

Novel chemokine functions in lymphocyte migration through vascular endothelium under shear flow.

The recruitment of circulating leukocytes at vascular sites in target tissue has been linked to activation of Gi-protein signaling in leukocytes by endothelial chemokines. The mechanisms by which apical and subendothelial chemokines regulate leukocyte adhesion to and migration across endothelial barriers have been elusive. We recently found that endothelial chemokines not only stimulate integrin-mediated arrest on vascular endothelial ligands but also trigger earlier very late antigen (VLA)-4 integrin-mediated capture (tethering) of lymphocytes to vascular cell adhesion molecule 1 (VCAM-1)-bearing surfaces by extremely rapid modulation of integrin clustering at adhesive contact zones. This rapid modulation of integrin avidity requires chemokine immobilization in juxtaposition with the VLA-4 ligand VCAM-1. We also observed that endothelial-bound chemokines promote massive lymphocyte transendothelial migration (TEM). It is interesting that chemokine-promoted lymphocyte TEM requires continuous exposure of lymphocytes but not of the endothelial barrier to fluid shear. It is noteworthy that lymphocyte stimulation by soluble chemokines did not promote lymphocyte TEM. Our results suggest new roles for apical endothelial chemokines both in triggering lymphocyte capture to the endothelial surface and in driving post-arrest events that promote lymphocyte transmigration across endothelial barriers under shear flow.

Animals↗
PubMed2000

The Src kinase p56(lck) up-regulates VLA-4 integrin affinity. Implications for rapid spontaneous and chemokine-triggered T cell adhesion to VCAM-1 and fibronectin.

In circulating lymphocytes, the VLA-4 integrin preexists in multiple affinity states that mediate spontaneous tethering, rolling, and arrest on its endothelial ligand, vascular cell adhesion molecule-1 (VCAM-1). The regulation and function of VLA-4 affinity in lymphocytes has never been elucidated. We show here that p56(lck), the major Src kinase in T cells, is a key regulator of high affinity VLA-4. This high affinity is essential for the rapid development of firm adhesion of resting T cells to VCAM-1 and to their extracellular matrix ligand, fibronectin. Lck-regulated VLA-4 function does not require intact TCR nor several key components of the TCR signaling pathway, including ZAP-70 and SLP-76. Furthermore, stimulation of p56(lck) by the phosphatase inhibitor, pervanadate, triggers firm VLA-4-dependent adhesion to VCAM-1. Although Lck is not required for chemokine receptor signaling to mitogen-activated protein kinase, the presence of Lck-regulated high affinity VLA-4 also facilitates firm adhesion triggered by the chemokine, SDF-1, at short-lived contacts. Surprisingly, bond formation rates, ability to tether cells to VLA-4 ligand, and VLA-4 tether bond stability under shear flow are not affected by VLA-4 affinity or Lck activity. Thus, the ability of high affinity VLA-4 to arrest cells on VCAM-1 under flow arises from instantaneous post-ligand strengthening rather than from increased kinetic stability of individual VLA-4 bonds. These results suggest that p56(lck) maintains high affinity VLA-4 on circulating lymphocytes, which determines their ability to strengthen VLA-4 adhesion and rapidly respond to proadhesive chemokine signals at endothelial sites.

Blotting, Western↗
PubMed2000

The pachytene checkpoint in Saccharomyces cerevisiae requires the Sum1 transcriptional repressor.

Saccharomyces cerevisiae mutants that fail to complete meiotic recombination are blocked by the RAD17/RAD24/MEC1 checkpoint signaling pathway in pachytene when early sporulation genes are expressed. Middle genes are not activated in checkpoint-arrested cells because the Ndt80 transcription factor is inhibited. We find that the pachytene checkpoint requires Sum1, a transcriptional repressor that recognizes a subset of Ndt80-binding sites. Mutants lacking Sum1 or Rad17 partially bypass the block to the nuclear divisions but do not form spores, while mutants lacking both Sum1 and Rad17 completely bypass the block and form morphologically normal spores. The level of Sum1 protein decreases as middle genes are expressed, and this decrease is blocked in checkpoint-arrested cells. These data suggest that Sum1 levels are regulated by the checkpoint and that progression of the meiotic divisions and spore differentiation can be differentially controlled by competition of the Sum1 repressor and Ndt80 activator for occupancy at key middle promoters.

Blotting, Northern↗
PubMed2000

[Interdisciplinary consensus on diagnosis and therapy of testicular tumors. Results of an update conference based on evidence-based medicine. German Testicular Cancer study Group (GTCSG)].

BACKGROUND: An "Interdisciplinary Consensus Statement on the Diagnosis and Therapy of Testicular Tumors" was prepared in 1996 by the "Interdisciplinary Testicular Tumor Working Group" (IAH) with input from representatives from diagnostic and therapeutic disciplines of various working groups of the German Cancer Society (Strahlenther Onkol 1997;173:397-406). In 1998 the IAH met again together with the "Testicular Tumor Working Party" of the Urooncology Working Group (AUO) and formed the "German Testicular Cancer Study Group" (GTCSG). Defined and accepted interdisciplinary standards from the initial meeting were revised based on current scientific developments and clinical results. This cooperating effort increased the quality of the initial recommendations and helped to put the recommendations for diagnosing and treating testicular tumor on a broader scientific basis. METHODS: According to the principles of "evidence-based medicine" (EBM), the Consensus from 1996 was modified, based on the current level of evidence from the published literature. The methodological process and evaluation criteria used were that of the "Cochrane Collaboration". RESULTS: An "Interdisciplinary Update Consensus Statement" summarizes and defines the diagnostic and therapeutic standards according to the current scientific practices in testicular cancer. For 21 separate areas scientifically based decision criteria are suggested. For treatment areas where more than one option exist without a consensus being reached for a preferred strategy, such as in seminoma in clinical Stage I or in non-seminoma Stages CS I or CS IIA/B, all acceptable alternative strategies with their respective advantages and disadvantages are presented. This "Interdisciplinary Update Consensus" was presented at the 24th National Congress of the German Cancer Society on March 21st and subsequently evaluated and approved by the various German scientific medical societies.

Evidence-Based Medicine↗
PubMed2000

[Functional results after suture repair in ruptures of the long biceps tendon with special consideration of subacromial impingement].

Operative treatment for ruptures of the long biceps tendon still is discussed controversially. In the present literature the keyhole-technique is recommended according to favourable biomechanical conditions. In recent years refixation to the short biceps tendon was preferred. Now it is supposed that this technique may provoke subacromial impingement considering the loss of depression function of the long biceps tendon to the humeral head. Between 1980 to 1991 83 patients with rupture of the long biceps tendon were treated operatively by refixation to the short head. 28 patients were investigated after an average follow-up of 6.5 years. Due to the criteria of the Constant-Score 85% of patients achieved very good, 15% good results. At our patients provocation of a subacromial impingement could not be observed. The subacromial space was not reduced in the postoperative x-ray control. Compared with the non-operated shoulder isokinetic determination of isometric maximal peak torque for elbow-flexion, shoulder-abduction and shoulder-flexion yield to almost identical results for the operated shoulder. Refixation to the short head can be advised for treatment of ruptures of the long biceps tendon due to the certain technique with a low complication rate and very good functional outcome.

Adult↗