Biomedical subjects

Jürgen Berger

Publications and source records attributed to Jürgen Berger.

At least 19 recordsLinked to original sources

PubMed2005

Oxypurinol improves coronary and peripheral endothelial function in patients with coronary artery disease.

Coronary endothelial dysfunction is a powerful prognostic marker in patients with coronary artery disease (CAD) that is centrally related to oxidative inhibition of nitric oxide (NO)-dependent vascular cell signaling. Xanthine oxidase (XO), which both binds to and is expressed by endothelial cells, generates superoxide and hydrogen peroxide upon oxidation of purines. Whether inhibition of xanthine oxidase activity results in improved coronary vasomotor function in patients with CAD, however, remains unknown. We assessed coronary and peripheral (brachial artery) endothelial function in 18 patients (pts; 65+/-8 years, 86% male) with angiographically documented CAD, preserved left ventricular function, and non-elevated uric acid levels (233+/-10 microM). Patients received incremental doses of intracoronary acetylcholine (ACh; 10(-7) to 10(-5) microM), and minimal lumen diameter (MLD) and coronary blood flow (CBF) were assessed before and after intravenous administration of oxypurinol (200 mg). Oxypurinol inhibited plasma XO activity 63% (0.051+/- 0.001 vs 0.019+/- 0.005 microU/mg protein; p<0.01). In pts who displayed endothelial dysfunction as evidenced by coronary vasoconstriction in response to ACh (n=13), oxypurinol markedly attenuated ACh-induced vasoconstriction (-23+/- 4 vs -15+/- 4% at ACh 10(-5) microM, p<0.05) and significantly increased CBF (16+/-17 vs 62+/-18% at ACh 10(-5) microM, p<0.05), whereas in patients with preserved coronary endothelial function, oxypurinol had no effect on ACh-dependent changes in MLD (+2.8+/- 4.2 vs 5.2+/- 0.7%, p>0.05) or CBF (135+/-75 vs 154+/-61%, p>0.05). Flow-mediated dilation of the brachial artery, assessed in eight consecutive patients, increased from 5.1+/-1.5 before to 7.6+/-1.5% after oxypurinol administration (p < 0.05). Oxypurinol inhibition of XO improves coronary vascular endothelial dysfunction, a hallmark of patients with CAD. These observations reveal that XO-derived reactive oxygen species significantly contribute to impaired coronary NO bioavailability in CAD and that XO inhibition represents an additional treatment concept for inflammatory vascular diseases that deserves further investigation.

Aged↗

PubMed2005

Morbidity and Mortality After Stroke, Eprosartan Compared with Nitrendipine for Secondary Prevention: principal results of a prospective randomized controlled study (MOSES).

BACKGROUND AND PURPOSE: In hypertensive stroke patients, for the same level of blood pressure control, eprosartan will be more effective than nitrendipine in reducing cerebrovascular and cardiovascular morbidity and mortality. METHODS: A total of 1405 well-defined, high-risk hypertensives with cerebral event during the last 24 months (proven by cerebral computed tomography scan or nuclear magnetic resonance) were randomized to eprosartan or nitrendipine (mean follow-up 2.5 years). Primary end point was the composite of total mortality and all cardiovascular and cerebrovascular events, including all recurrent events. RESULTS: Randomization was successful without significant differences in the baseline characteristics. Blood pressure was reduced to a comparable extent without any significant differences between the 2 groups during the whole study period (150.7/84 mm Hg and 152.0/87.2 mm Hg with eprosartan and nitrendipine therapy to 137.5/80.8 mm Hg and 136.0/80.2 mm Hg, respectively, confirmed by ambulatory blood pressure monitoring). Moreover, already after 3 months, normotensive mean values were achieved, and 75.5% reached values <140/90 mm Hg with the eprosartan regimen and 77.7% with the nitrendipine regimen. During follow-up, in total, 461 primary events occurred: 206 eprosartan and 255 nitrendipine (incidence density ratio [IDR], 0.79; 95% CI, 0.66 to 0.96; P=0.014). Cardiovascular events were: 77 eprosartan and 101 nitrendipine (IDR, 0.75; 95% CI, 0.55 to 1.02; P=0.06); cerebrovascular events: 102 eprosartan and134 nitrendipine (IDR, 0.75; 95% CI, 0.58 to 0.97; P=0.03). CONCLUSIONS: The Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention (MOSES) study was the first to compare an angiotensin II type 1 receptor antagonist with a calcium antagonist in secondary stroke prevention. In these high-risk hypertensive stroke patients, an early normotensive and comparable blood pressure was achieved. The combined primary end point was significantly lower in the eprosartan group.

Acrylates↗

PubMed2005

Angiographic and clinical outcomes at 8 months of cutting balloon angioplasty and beta-brachytherapy for native vessel in-stent restenosis (BETACUT): results from a stopped randomized controlled trial.

The objective of this study was to assess angiographic and clinical outcomes of cutting balloon (CB) angioplasty and concomitant Sr/Y-90 beta-brachytherapy as a treatment modality for patients with native vessel in-stent restenosis (ISR). Procedural advantages over the standard balloon (SB) have been claimed for the CB. Intracoronary brachytherapy preceded by SB angioplasty is regarded as the treatment of choice in patients with ISR. In an interim analysis of a prospective randomized trial designed for 652 patients, 100 consecutive patients with ISR were assigned to treatment with SB angioplasty (n = 51) or CB angioplasty (n = 49), followed in either case by Sr/Y-90 beta-brachytherapy. Quantitative coronary angiography at baseline, postintervention, and at 8 months was performed by an independent central laboratory. More than 90% of target lesions in the overall patient population were diffuse, with 14% of stents totally occluded. Procedural parameters and immediate angiographic outcomes were essentially the same in either study arm. At 8 months, no statistically significant differences were observed in recurrent angiographic restenosis (SB = 26.1%; CB = 29.5%; P = 0.82), target lesion revascularizations (SB = 13.7%; CB = 8.2%; P = 0.53), and major adverse cardiac events (SB = 15.7%; CB = 8.2%; P = 0.36). In this interim analysis, there was no indication of a beneficial effect of CB use over SB use in terms of angiographic or clinical outcomes at 8-month follow-up. CB angioplasty appears to be as safe and efficacious as SB angioplasty in beta-radiation treatment of patients with predominantly diffuse native vessel ISR. It was decided to discontinue the trial.

Aged↗

PubMed2005

A retrospective comparison of costs for regional and general anesthesia techniques.

In this retrospective study, we compared the costs for three different regional anesthesia techniques with the costs of general anesthesia (GA). A total of 1587 anesthesia cases which were performed for orthopedic and trauma patients over a 1-yr period in a tertiary level, university hospital setting were analyzed. The anesthesia technique-related costs were determined calculating case-specific costs for personnel, supplies, and drugs. The techniques were compared on the basis of anesthesia costs and surgical procedure duration. As a result, we found that the costs per surgical minute largely depend on the surgical procedure duration. Based on the regression function, the cost advantage of spinal anesthesia over GA can be estimated to be 13% for a 50-min case, 9% for a 100-min case, and 5% for a 200-min case. The cost disadvantage of brachial plexus anesthesia over GA can be estimated to be 19% for a 50-min case, 8% in a 100-min case, and 1% for a 200-min case. We found no difference in costs between epidural and GA. We concluded that cost comparisons of anesthesia techniques largely depend on the surgical duration of the cases studied. Even in a teaching hospital setting, spinal anesthesia has economic advantages over GA. Especially for short cases, brachial plexus block is more expensive in this setting.

Adult↗

PubMed2004

Myeloperoxidase enhances nitric oxide catabolism during myocardial ischemia and reperfusion.

Impaired microvascular function during myocardial ischemia and reperfusion is associated with recruitment of polymorphonuclear neutrophils (PMN) and has been attributed to decreased bioavailability of nitric oxide (NO). Whereas myeloperoxidase (MPO), a highly abundant, PMN-derived heme protein facilitates oxidative NO consumption and impairs vascular function in animal models of acute inflammation, its capacity to function in this regard during human myocardial ischemia and reperfusion remains unknown. Plasma samples from 30 consecutive patients (61 +/- 14 years, 80% male) presenting with acute myocardial infarction were collected 9 +/- 4 h after vessel recanalization and compared to plasma from healthy control subjects (n = 12). Plasma levels of MPO were higher in patients than in control subjects (1.4 +/- 0.9 vs 0.3 +/- 0.2 ng/mg protein, respectively, p < 0.0001). The addition of hydrogen peroxide to patient plasma resulted in accelerated rates of NO consumption compared to control subjects (0.53 +/- 0.25 vs 0.068 +/- 0.039 nM/s/mg protein, respectively, p < 0.0001). Myocardial tissue from patients with the same pathology revealed intense recruitment of MPO-positive PMN localized along infarct-related vessels as well as diffuse endothelial distribution of non-PMN-associated MPO immunoreactivity. Endothelium-dependent microvascular function, as assessed by an acetylcholine-dependent increase in forearm blood flow in 75 patients with symptomatic coronary artery disease, inversely correlated with MPO plasma levels (r = -0.75, p < 0.005). Plasma from patients undergoing myocardial reperfusion contained increased levels of MPO, which catalytically consumed NO in the presence of H(2)O(2). Given the correlation between intravascular MPO levels and forearm vasomotor function in patients with coronary artery disease, MPO appears to be an important modulator of vasomotor function in inflammatory vascular disease and a potential therapeutic target for treatment.

Aged↗

PubMed2004

Explaining computation of predictive values: 2 x 2 table versus frequency tree. A randomized controlled trial [ISRCTN74278823].

BACKGROUND: Involving patients in decision making on diagnostic procedures requires a basic level of statistical thinking. However, innumeracy is prevalent even among physicians. In medical teaching the 2 x 2 table is widely used as a visual help for computations whereas in psychology the frequency tree is favoured. We assumed that the 2 x 2 table is more suitable to support computations of predictive values. METHODS: 184 students without prior statistical training were randomised either to a step-by-step self-learning tutorial using the 2 x 2 table (n = 94) or the frequency tree (n = 90). During the training session students were instructed by two sample tasks and a total of five positive predictive values had to be computed. During a follow-up session 4 weeks later participants had to compute 5 different tasks of comparable degree of difficulty without having the tutorial instructions at their disposal. The primary outcome was the correct solution of the tasks. RESULTS: There were no statistically significant differences between the two groups. About 58% achieved correct solutions in 4-5 tasks following the training session and 26% in the follow-up examination. CONCLUSIONS: These findings do not support the hypothesis that the 2 x 2 table is more valuable to facilitate the calculation of positive predictive values than the frequency tree.

Adult↗

PubMed2004

Expression of extracellular matrix metalloproteases inducer on micrometastatic and primary mammary carcinoma cells.

PURPOSE: EMMPRIN (extracellular matrix metalloprotease inducer) is a glycosylated member of the immunoglobulin superfamily known to stimulate the production of matrix metalloproteases (MMPs) 1, 2, and 3 and MT1-MMP in peritumoral fibroblasts. We here evaluated whether EMMPRIN expression is related to tumor progression in human breast cancer. EXPERIMENTAL DESIGN: An immunohistochemical study using high-density tissue microarrays (n = 2222 breast cancer samples) and EMMPRIN-specific antibodies HIM6 and MEM-M6/1 was performed, and staining results were statistically correlated with various clinicopathological parameters. To analyze the putative association between EMMPRIN expression and bone marrow (BM) micrometastasis, an additional set of 55 breast tumors from patients with or without micrometastatic cells as determined with anti-cytokeratin antibody A45-B/B3 were included in our study. Cytokeratin-positive cells in BM were costained with EMMPRIN-specific antibody 1G6.2. RESULTS: Positive EMMPRIN staining correlated significantly with various histopathological risk factors (higher tumor grade, increased tumor size, negative estrogen receptor status and progesterone receptor status, and higher mitotic index) as well as decreased tumor-specific survival (log-rank, P = 0.0027). In particular, in patients > 50 years (i.e., postmenopausal women), EMMPRIN expression was an independent prognosticator as shown by Cox regression analysis (relative risk = 1.7, 95% confidence interval 1.4-4.3, P = 0.036). An involvement of EMMPRIN in tumor progression was also supported by the fact that it was expressed on approximately 90% of micrometastatic cells in BM. CONCLUSIONS: EMMPRIN expression in primary tumor predicts an unfavorable prognosis in breast cancer, suggesting a crucial role of EMMPRIN in progression of human mammary carcinomas.

Antigens, CD↗

PubMed2004

Extracapsular spread of nodal metastasis as a prognostic factor in rectal cancer.

PURPOSE: To evaluate the prognostic value of lymph node metastasis with extracapsular extension (ECE) for local control and metastasis-free survival in rectal cancer. METHODS AND MATERIALS: A total of 145 rectal cancer patients were treated with surgery and postoperative radiochemotherapy. Patients were grouped according to nodal status (node negative, n = 49; node positive without ECE, n = 64; node positive with ECE, n = 32). In addition, well-known prognostic factors such as International Union Against Cancer (UICC) stage, T and N stage, presence of lymphangiosis, and grade were assessed. The end points were analyzed by the Kaplan-Meier method, and prognostic factors were compared in a Cox regression model. RESULTS: Of the entire group, the actuarial 5-year local control and distant metastasis-free survival rate was 85% and 66%, respectively, after a median follow-up of 47 months (range, 14-104). Patients with ECE of lymph node metastasis had an impaired 5-year local control rate (58%) compared with node-negative (83%) and node-positive without extracapsular involvement patients (87%, p = 0.041). Metastasis-free survival also differed for the three groups, with a rate of 40% for those with extracapsular involvement, 54% for those without ECE, and 78% for node-negative patients (p <0.0001). The impact of ECE on local control was confirmed in the regression model (risk ratio [RR] 1.6, 95% confidence interval [CI] 1.01-2.7, p = 0.044). T stage was only of borderline significance (RR 2.4, 95% CI 1.0-5.7, p = 0.052). However, only UICC stage (RR 5.1, 95% CI 2.0-13.1, p <0.001) and the presence of lymphangiosis (RR 2.8, 95% CI 1.4-5.3, p = 0.002) were of independent prognostic value for distant metastasis. CONCLUSION: ECE of node metastasis is connected with a substantial decline in local control. The frequency of distant metastasis is increased in this patient group as well, but stage and lymphangiosis are the independent factors for assessment of a patient's risk of systemic spread.

Actuarial Analysis↗

PubMed2004

Combined intrinsic and extrinsic influences pattern cranial neural crest migration and pharyngeal arch morphogenesis in axolotl.

Cranial neural crest cells migrate in a precisely segmented manner to form cranial ganglia, facial skeleton and other derivatives. Here, we investigate the mechanisms underlying this patterning in the axolotl embryo using a combination of tissue culture, molecular markers, scanning electron microscopy and vital dye analysis. In vitro experiments reveal an intrinsic component to segmental migration; neural crest cells from the hindbrain segregate into distinct streams even in the absence of neighboring tissue. In vivo, separation between neural crest streams is further reinforced by tight juxtapositions that arise during early migration between epidermis and neural tube, mesoderm and endoderm. The neural crest streams are dense and compact, with the cells migrating under the epidermis and outside the paraxial and branchial arch mesoderm with which they do not mix. After entering the branchial arches, neural crest cells conduct an "outside-in" movement, which subsequently brings them medially around the arch core such that they gradually ensheath the arch mesoderm in a manner that has been hypothesized but not proven in zebrafish. This study, which represents the most comprehensive analysis of cranial neural crest migratory pathways in any vertebrate, suggests a dual process for patterning the cranial neural crest. Together with an intrinsic tendency to form separate streams, neural crest cells are further constrained into channels by close tissue apposition and sorting out from neighboring tissues.

Ambystoma mexicanum↗

PubMed2004

Urinary 8-iso-prostaglandin F2alpha as a risk marker in patients with coronary heart disease: a matched case-control study.

BACKGROUND: Oxidative stress is involved in the pathophysiology of atherosclerosis, diabetes mellitus, hypertension, obesity, and cigarette smoking, all of these being risk factors for coronary heart disease (CHD). We tested the hypothesis that risk factors of CHD are associated with abundant systemic oxidative stress. METHODS AND RESULTS: We conducted a case-control study with 93 CHD patients and 93 control subjects frequency-matched by age and sex. Urinary excretion of the F2-isoprostane 8-iso-prostaglandin (PG) F2alpha and its major urinary metabolite, 2,3-dinor-5,6-dihydro-8-iso-PGF2alpha, were measured by gas chromatography-tandem mass spectrometry. Body mass index, systolic blood pressure, and C-reactive protein were elevated in CHD patients (P<0.01). Urinary 8-iso-PGF2alpha and 2,3-dinor-5,6-dihydro-8-iso-PGF2alpha also differed, from 77 (interquartile range, 61-101) to 139 (93-231) pmol/mmol creatinine and from 120 (91-151) to 193 (140-275) pmol/mmol in control subjects and case subjects, respectively (P<0.001). 8-iso-PGF2alpha and its metabolite were highly correlated (Spearman's rho=0.664, P<0.001). HDL cholesterol was diminished in CHD patients (P<0.001). All of these characteristics predicted CHD in univariate analysis. In a multivariate model, the odds ratios were increased only for 8-iso-PGF2alpha (> or =131 pmol/mmol, P<0.001) and C-reactive protein (>3 mg/L, P<0.01), ie, by 30.8 (95% CI, 7.7-124) and 7.2 (1.9-27.6), respectively. 8-iso-PGF2alpha was found to be a novel marker in addition to known risk factors of CHD, ie, diabetes mellitus, hypercholesterolemia, hypertension, and smoking. Urinary excretion of 8-iso-PGF2alpha correlated with the number of risk factors for all subjects (P<0.001 for trend). CONCLUSIONS: 8-iso-PGF2alpha is a sensitive and independent risk marker of CHD.

Adult↗

PubMed2004

Chest radiography for the diagnosis of acute aortic syndrome.

PURPOSE: We sought to assess the diagnostic accuracy of routine chest radiography for the acute aortic syndrome (dissection, intramural hematoma, penetrating ulcer, or nondissecting aneurysm). METHODS: During a 6-year period, 216 patients (143 men, 73 women; mean [+/- SD] age, 58 +/- 17 years) underwent chest radiography for suspected acute aortic syndrome. Chest films were re-evaluated blindly for aortic disease, based on an overall impression using standard criteria such as widening of the aortic contour and mediastinal shadow. Findings were matched to tomographic images, anatomical inspection, or both, as the criterion standard; aortic disease was confirmed in 109 (50%) of the patients. RESULTS: Chest radiography had a sensitivity of 64% (70/109) and a specificity of 86% (92/107) for aortic disease. Sensitivity was 67% (38/57) for overt aortic dissection, 61% (22/36) for nondissecting aneurysm, and 63% (10/16) for intramural hemorrhage or penetrating ulcer. However, sensitivity was lower for pathology confined to the proximal aorta (47% [21/45]) than for disease involving distal aortic segments (77% [49/64]). A receiver operating characteristic curve analysis of aortic diameters failed to identify a threshold for the diagnosis of aortic disease. CONCLUSION: Chest radiography is of limited value for diagnosing the acute aortic syndrome, particularly for conditions confined to the ascending aorta. Since a definitive diagnosis is required in any patient with clinically suspected acute aortic syndrome, routine chest radiography should be replaced by tomographic aortic imaging.

Acute Disease↗

PubMed2004

The developmentally regulated neural crest-associated glycotope HNK-1 predicts metastasis in cutaneous malignant melanoma.

Aberrant glycosylation is a common feature of metastatic sub-clones of malignant tumours and in uveal melanoma in particular, the HNK-1 glycotope has been positively correlated with poor prognosis. So far, no such correlation has been investigated in cutaneous melanoma. In order to do so, HNK-1 expression was evaluated immunohistochemically in 100 primary cutaneous melanomas and correlated with metastasis after up to 10-years' follow-up. Furthermore, HNK-1 expression was analysed in metastatic deposits (19 distant cutaneous metastases and six sentinel lymph node metastases), as well as in benign nevi. Kaplan-Meier analysis revealed a positive association between HNK-1 expression and metastasis (p < 0.005) and multivariate Cox regression analysis adjusted for the standard prognostic markers ulceration and vertical tumour thickness confirmed HNK-1 expression as an independent prognostic marker. HNK-1 expression was preserved in 42% of the distant cutaneous metastases, but metastatic cells in lymph nodes were devoid of HNK-1 immunoreactivity. None of the benign pigmented lesions exhibited HNK-1 immunoreactivity. Expression of the HNK-1 glycotope in cutaneous malignant melanoma is an independent prognostic marker of metastasis. Differential HNK-1 expression at the metastatic sites implies that its expression is modulated by the surrounding environment. As HNK-1 is also transiently expressed during migration of melanocyte precursor cells derived from the neural crest, recapitulation of this transient expression might occur during metastatic spread of cutaneous malignant melanoma.

Adult↗

PubMed2004

The pro-apoptotic serum activity is an independent mortality predictor of patients with heart failure.

AIM: Systemic inflammation with elevated serum levels of circulating pro-inflammatory cytokines is a major determinant of prognosis in heart failure (HF). Since serum of patients with HF induces apoptosis of endothelial cells (EC), we aimed to determine whether the pro-apoptotic activity in the serum may predict prognosis of patients with HF. METHODS AND RESULTS: We measured the pro-apoptotic activity in the serum of 48 patients with HF of different aetiology by an ex vivo cell culture assay and subsequently monitored these patients for the single endpoint all-cause mortality. During follow-up, 16 patients died and 11 patients received a heart transplant. Survivors had a lower pro-apoptotic serum activity (P=0.007). By univariate analysis, pro-apoptotic serum activity, NYHA class, pro-BNP, low blood pressure, and creatinine levels were significantly associated with mortality. In a multivariable stepwise Cox-regression model, the pro-apoptotic serum activity (adjusted hazard ratio, HR=1.85 per %, P=0.008), elevated pro-BNP levels (HR=9.35 per log[pro-BNP], P=0.001), and low blood pressure (HR=0.96 per mmHg, P=0.041) remained as independent predictors of death. CONCLUSION: In this exploratory study, the pro-apoptotic serum capacity is independently associated with a worse prognosis in patients with HF, suggesting that the assessment of serum-induced EC apoptosis could provide an integrative estimate of the deleterious effects of various pro-inflammatory cytokines and other cytotoxic factors in HF.

Apoptosis↗

PubMed2004

Effect of different cost drivers on cost per anesthesia minute in different anesthesia subspecialties.

BACKGROUND: Little is known about differences in costs to provide anesthesia care for different surgical subspecialties and which factors influence the subspecialty-specific costs. METHODS: In this retrospective study, the authors determined main cost components (preoperative visit, intraoperative personnel costs, material and pharmaceutical costs, and others) for 10,843 consecutive anesthesia cases from a 6-month period in the 10 largest anesthesia subspecialties in their university hospital: ophthalmology; general surgery; obstetrics and gynecology; ear, nose, and throat surgery; oral and facial surgery; neurosurgery; orthopedics; cardiovascular surgery; traumatology; and urology. Using regression analysis, the effect of five presumed cost drivers (anesthesia duration, emergency status, American Society of Anesthesiologists physical status of III or higher, patient age younger 6 yr, and placement of invasive monitoring) on subspecialty-specific costs per anesthesia minute were analyzed. RESULTS: Both personnel costs for anesthesiologists and total costs calculated per anesthesia minute were inversely correlated with the duration of anesthesia (adjusted R2 = 0.75 and 0.69, respectively), i.e., they were higher for subspecialties with short cases and lower for subspecialties with longer cases. The multiple regression model showed that differences in anesthesia duration alone accounted for the majority of the cost differences, whereas the other presumed cost drivers added only little to explain subspecialty-specific cost differences. CONCLUSIONS: Different anesthesia subspecialties show significant and financially important differences regarding their specific costs. Personnel costs and total costs are highest for subspecialties with the shortest cases. Other analyzed cost drivers had little effect on subspecialty-specific costs. In the light of these cost differences, a detailed cost analysis seems necessary before the profitability of an anesthesia subspecialty can be assessed.

Adult↗

PubMed2003

Comparative evaluation of urokinase-type plasminogen activator receptor expression in primary breast carcinomas and on metastatic tumor cells.

The urokinase-type plasminogen activator receptor (uPAR, CD87) plays a central role in the plasminogen activation cascade, which participates in extracellular matrix degradation, cell migration and invasion. Here we performed a comprehensive immmunohistochemical evaluation of uPAR expression in primary tumor cells, tumor-surrounding fibroblasts, lymph node metastases and micrometastatic cells in bone marrow of patients with breast carcinomas at the time of primary diagnosis. Variable degrees of uPAR staining of tumor cells were observed in 84 of 93 (90%) carcinomas, whereas intratumoral fibroblasts were uPAR-positive in 70 (75%) carcinomas. The fraction of uPAR-positive primary tumor cells but not fibroblasts was positively correlated with the presence of tumor cells in bone marrow (p = 0.037), whereas no correlation with lymph node metastasis was found. Immunophenotyping of bone marrow and lymph node specimens revealed expression of uPAR on metastatic tumor cells in 10 of 13 and 22 of 23 cases, respectively. Direct comparison to the autologous primary tumor cells showed different uPAR staining scores in most patients with evidence for both up- and downregulation of uPAR on metastatic cells. Our results indicate that uPAR plays an active role in breast cancer metastasis and may therefore be a promising target for new biologic therapies.

Breast Neoplasms↗

PubMed2003

High migration rate of two types of threaded acetabular cups.

INTRODUCTION: Survivorship analysis was performed on 479 Link V-type threaded cups and on 110 modified V-type Bad Bramstedt cups (a modification of the Link V-type cup since 1993 with a smaller primary coil) to evaluate the effect of the modifications. MATERIALS AND METHODS: Indication for hip arthroplasty with a Link V-type cup was an inflammatory arthritis in 310 patients, osteoarthritis in 138 patients and dysplastic hip joints in 31 patients. The average follow-up was 8.6+/-3.2 (range 3.0-15.2) years. The 110 modified V-type Bad Bramstedt cups had a mean follow-up period of 4.5+/-0.7 (range 3.0-5.9) years, including 49 with inflammatory arthritis, 49 with osteoarthritis and 12 with dysplastic hip joints. To evaluate the migration rate and radiolucent lines, radiographical examination according to the method of Nunn et al. and Delee and Charnley was performed on 264 Link V-type cups with a mean follow-up period of 8.2+/-2.7 years and 59 modified V-type Bad Bramstedt cups with a mean follow-up period of 4.6+/-0.7 years. Relevant parameters influencing cup migration were analysed. RESULTS: The cumulative survival rate of the former Link V-type acetabular cup was 94.5% after 5 years, 88.1% after 10 years and 70.2% after 15 years. The Bad Bramstedt cup showed a 5-year survivorship rate of 97.9%. Migration of more than 3 mm or tilting of the cup greater than 5 degrees was found in 73% of the former type and in 39% of the modified cup. Radiolucent lines greater than 2 mm and detectable in two zones appeared in 6.4% of the former Link V-type and in 1.7% of the Bad Bramstedt cup design. Among the influencing factors analysed, length of follow-up and primary cup positioning showed a significant correlation to cup migration. CONCLUSION: The modification of the Link V-type cup showed no satisfactory improvement in cup migration. Therefore, both threaded cups were abandoned in favour of cementless press-fit cups.

Acetabulum↗

PubMed2003

Control of crystal size and lattice formation by starmaker in otolith biomineralization.

The stone-like otoliths from the ears of teleost fishes are involved in balance and hearing and consist of calcium carbonate crystallites embedded in a protein framework. We report that a previously unknown gene, starmaker, is required in zebrafish for otolith morphogenesis. Reduction of starmaker activity by injection of modified antisense oligonucleotides causes a change in the crystal lattice structure and thus a change in otolith morphology. The expression pattern of starmaker, along with the presence of the protein on the growing otolith, suggest that the expression levels of starmaker control the shape of the otoliths.

Amino Acid Sequence↗

PubMed2003

The ACCESS Study: evaluation of Acute Candesartan Cilexetil Therapy in Stroke Survivors.

BACKGROUND AND PURPOSE: The Acute Candesartan Cilexetil Therapy in Stroke Survivors (ACCESS) study was designed to assess the safety of modest blood pressure reduction by candesartan cilexetil in the early treatment of stroke. The study was also designed to provide an estimate of the number of cases required to perform a larger phase III efficacy study. METHODS: Five hundred patients were recruited in a prospective, double-blind, placebo-controlled, randomized, multicenter phase II study. RESULTS: This safety trial was stopped prematurely when 342 patients (339 valid) had been randomized because of an imbalance in end points. Demographic data, cardiovascular risk factors, and blood pressure on admission, on study onset, and within the whole study period were not significantly different between the 2 groups. However, the cumulative 12-month mortality and the number of vascular events differed significantly in favor of the candesartan cilexetil group (odds ratio, 0.475; 95% CI, 0.252 to 0.895). There were no significant differences in concomitant medication and in number or type of side effects. CONCLUSIONS: Although the mechanisms by which angiotensin type 1 (AT1) receptor blockade affects cardiovascular morbidity and mortality are still unresolved, the present study shows that early neurohumoral inhibition has similar beneficial effects in cerebral and in myocardial ischemia. The fact that no cardiovascular or cerebrovascular event occurred as a result of hypotension is of significant clinical importance. When there is need for or no contraindication against early antihypertensive therapy, candesartan cilexetil is a safe therapeutic option according to the ACCESS results.

Acute Disease↗