Dynamic gadolinium-enhanced MRI evaluation of porcine femoral head ischemia and reperfusion.

OBJECTIVE: To examine the potential of gadolinium (Gd)-enhanced dynamic MRI in the detection of early femoral head ischemia. Furthermore, to apply a three-compartment model to achieve a clinically applicable MR index for femoral head perfusion during the steady state and arterial hip joint tamponade. DESIGN AND MATERIALS: In a porcine model femoral head perfusion was measured by radioactive tracer microspheres and by using a dynamic Gd-enhanced MRI protocol. Femoral head perfusion measurements and MRI tests were performed unilaterally before, during and after the experimentally induced ischemia of one of the hip joints. Ischemia was induced by increasing intra-articular pressure to 250 mmHg. RESULTS: All pigs showed ischemia of the femoral head epiphysis under hip joint tamponade followed by reperfusion to the same level as before joint tamponade. In two cases perfusion after removal of tamponade continued to be low. In dynamic MRI measurements increases in signal intensity were seen after intravenous infusion of Gd-DTPA, followed by a slow decrease in signal intensity. The signal-intensity curve during femoral head ischemia had a minor increase. Also the coefficient determined was a helpful indicator of femoral head ischemia. CONCLUSIONS: Femoral head blood flow as measured by microspheres fell significantly under joint tamponade. Early detection of this disturbed regional blood flow was possible using a dynamic MRI procedure. A biomathematical model resulted from the evaluation of the intervals of signal intensity over time which allows detection of bone blood flow changes at a very early stage. Using this new method earlier detection of femoral head necrosis may be possible.

Expression of different survivin variants in gastric carcinomas: first clues to a role of survivin-2B in tumour progression.

Survivin is a novel member of the inhibitor of apoptosis family and determines the susceptibility of tumour cells to pro-apoptotic stimuli. Recently, we identified two novel alternative splice variants of survivin, differing in their anti-apoptotic properties: whereas the anti-apoptotic potential of survivin-DeltaEx3 is preserved, survivin-2B has lost its anti-apoptotic potential and may act as a naturally occurring antagonist of survivin. Because the in vivo expression of these alternative splice variants has not been explored so far, we analysed gastric carcinomas of different histological subtypes, grades and stages. Since no antibodies are currently available to determine the novel splice variants, quantitative reverse transcriptase polymerase chain reaction was performed, using RNA samples obtained from 30 different gastric carcinomas. Polymerase chain reactions products were quantified by densitometric evaluation. We found that all gastric carcinomas, irrespective of their histological types, grades or stages, express survivin-DeltaEx3, survivin-2B and survivin, the latter being the dominant transcript. Comparing the disease stages I+II with III+IV, expression of survivin and survivin-DeltaEx3 remained unchanged. In contrast, a significant (P=0.033) stage-dependent decrease in the expression of survivin-2B became evident. Our study demonstrates for the first time the expression of alternative splice variants in gastric carcinomas and provides a first clue to a role of survivin-2B in tumour progression.

p53 immunohistochemistry in bladder cancer. Combined analysis: a way to go?

Seven years after the initial reports of the potential prognostic value of p53 immunohistochemistry in bladder cancer, key questions remain unanswered. This is mainly due to conflicting results obtained through multiple retrospective trials mostly performed with small numbers of poorly defined patients. The aim of this article was to investigate the feasibility of a combined analysis of previously published data. Based on a MEDLINE search in 1997, papers reporting on the prognostic role of p53 alterations were identified and the respective groups were invited to participate. Twenty-six of 38 study centers approached contributed patient data sets according to the protocol requirements. Acceptance of the initiative was similar in Europe, North America, and Australasia. A total of 3,421 patients with bladder cancer from 25 centers are included in the further analysis. With regard to gender, age distribution, and tumor stage the patients contributed are comparable with a normal bladder cancer population. Considering tumor grade, G2 tumors appear to be over- represented while the amount of G1 tumors is smaller than expected. The reason for this is probably related to the low rate of p53 accumulation in G1 tumors. No significant differences between those groups initially approached and those that finally cooperated were noted. Therefore, it is concluded that a combined study is feasible, and the patient data collected are representative for the population presented in the published literature. The final analysis of the data is the subject of current investigation.

[14-year experience with implantable cardioverter/defibrillators: determination of prognosis and discharge behavior]. / 14 Jahre Erfahrung mit implantierbaren Cardioverter/Defibrillatoren: Determinanten der Prognose und des Auslöseverhaltens.

BACKGROUND: The treatment of life threatening ventricular arrhythmias with implantable cardioverter/defibrillators (ICD) has become the therapy of choice; the survival benefit of ICD treatment compared to drug therapy in patients with aborted sudden cardiac death (SCD) and hemodynamically unstable ventricular tachycardia has been proven. In addition for the primary prevention of SCD in high risk patients, ICD therapy is gaining growing acceptance. PATIENTS AND METHODS: We analyzed the long-term follow-up of 274 consecutive patients (211 male, 63 female, age 59 +/- 12 years, left ventricular ejection fraction 39 +/- 15%) provided with an ICD between 1984 and 1998. The aim of the study was to ascertain the survival rate in different subgroups and to discover determining factors of ICD discharge and prognosis. RESULTS: Long-term survival probability at 10 resp. 14 years was 84 resp. 65% for the total collective, and the freedom of event probability (neither shocks nor antitachycardiac pacing from the ICD) to 28% each. The risk to die from SCD was below 3% over time. The most pronounced differences regarding prognosis ensued from dividing the collective into heart insufficiency stages. Thus in NYHA class I and II versus III and IV, the cumulative event rate was 61% vs 82% at 5 years, and survival rate amounted to 94 vs 63% at 5 years and 87% vs 30% at 14 years (p < 0.001). Calculating the relative benefit of ICD therapy survival benefit provided by the ICD was shown to decrease significantly after 5 years for patients in NYHA class III/IV, while it increased progressively for patients in NYHA class I/II up to 10 years. Additional determinants of prognosis and ICD discharge rate were identified left ventricular ejection fraction, age and tendency for the basic cardiac disease, however neither the result of electrophysiological testing nor the results of non-invasive risk stratification. In patients with ischemic heart disease, revascularization procedures improved prognosis only in tendency, while the effect of ICD therapy was significant. In patients with the non-obstructive form of hypertrophic cardiomyopathy ICD, discharges occurred in about 50% of patients; in contrast patients with surgical myectomy for obstructive cardiomyopathy showed no events during follow-up. In patients with chronic inflammatory heart disease and normal left ventricular function (LVF), a very low event rate was expected if patients were treated by immunosuppressive drugs. Patients with dilated cardiomyopathy did not differ from patients with ischemic heart disease with respect to prognosis and ICD discharge rate. CONCLUSION: Significant determinants of prognosis and ICD discharge rate are left ventricular function, age and with limitations the basic cardiac disease. In contrast to patients with better LVF relative survival benefit decreases significantly after 5 years in patients with a worse LVF. Patients with aborted SCD and preserved LVF experience half the ICD discharges compared to patients with poor LVF and gain at the same time a normalization of life expectancy. Causative treatment of the basic disease has an impact on the overall prognosis and event rate, but should in general not influence the decision for IDC implantation in high risk patients.

[Reperfusion capacity of the femur head after ischemia--an experimental study]. / Die Reperfusionsfähigkeit des Femurkopfes nach Ischämie--Eine experimentelle Studie.

PURPOSE OF THE STUDY: The aim of this study was to evaluate bone blood flow of the proximal femur during experimentally induced ischemia and to document the ability of epiphyseal and metaphyseal reperfusion. METHODS: 11 pigs (danish landrace) were used to investigate the effect of tamponade by increased joint pressure (Dextran 70) on the perfusion of the femoral head. Additional 8 pigs were used as control. The blood flow in the hip joint was studied by means of the microsphere technique. The flow was determined before, during and after intraarticular pressure increase. With the "radioactive tracer microsphere"-method the blood flow of the epiphysis, metaphysis and proximal femoral corticalis could be measured. RESULTS: In the epiphyseal femoral head the initial blood flow rate, 11.7 ml/min/100 g, was not significant different from that of the control side (11.1 ml/min/100 g). The blood flow decreased in the ischemic phase to 1.8 ml/min/100 g followed by reperfusion to 13.5 ml/min/100 g (p < 0.01). The bone blood flow of reperfusion was not significant different from that of the initial blood flow rate but in 2 cases a "blow out" of the epiphyseal bone blood flow was seen. The proximal femoral metaphysis showed the highest of the measured intraosseous flow rates (17.9 resp. 23.3 ml/min/100 g). During ischemia and reperfusion of the epiphysis bone blood flow of the metaphysis remained the same. The proximal femoral corticalis showed the lowest of the measured intraosseous flow rates. The operated (10.1 ml/min/100 g) and contralateral hip side (11.7 ml/min/100 g) showed no significant differences in the initial blood flow rate. During ischemia and reperfusion the blood flow of the proximal corticalis showed no significant difference to the initial blood flow corresponding to the metaphysis. CONCLUSIONS: Our study demonstrates disturbances of the circulation of different regions of the femoral head during intraarticular pressure increase and following pressure decrease of the growing pig. 2 "blow outs" document a vulnerable proximal epiphysis already after a 6-hour ischemia. Additional minor "bone quality" in cases of certain diseases (kidney transplantation, leukemia) and special administration of drugs (corticosteroids) seem to create an additional vulnerability of the proximal femoral head. The experiment proves to be a reliable model for decreasing the blood flow of the growing epiphysis temporarily and to document the beginning of normal reperfusion. With this model it is possible to examine the vulnerability of the epiphyseal perfusion after different diseases and under the influence of different medication.

Left ventricular mass is linked to cardiac noradrenaline in normotensive and hypertensive patients.

BACKGROUND: Left ventricular hypertrophy constitutes a powerful independent risk factor for heart failure, sudden death and ventricular dysrhythmia. Experimental data suggest that, apart from increased cardiac work load, noradrenaline may be one of the factors triggering myocardial hypertrophy. OBJECTIVE: To test the hypothesis that the extent of left ventricular hypertrophy is coupled to cardiac noradrenaline independently from the magnitude of arterial blood pressure. PATIENTS AND METHODS: Following exclusion of coronary artery disease by cardiac catheterization, cardiac noradrenaline release was measured in relation to left ventricular mass in 25 patients with arterial hypertension (HT), of whom five had left ventricular hypertrophy (HT + LVH) and 20 had normal left ventricular mass (HT - LVH), seven normotensive patients with hypertrophic cardiomyopathy (HCM) and a normotensive control group (n = 7). Noradrenaline was measured in arterial and coronary venous plasma using high-performance liquid chromatography. Coronary blood flow was quantified using the gas chromatographic argon method. Indices of left ventricular mass were calculated from the end-diastolic thicknesses of the interventricular septum and the posterior wall determined by echocardiography. RESULTS: The coronary venous plasma concentration of noradrenaline was significantly higher in HT - LVH, HT + LVH and HCM than it was in normotensives. Whereas in normotensives there was a net uptake of noradrenaline (17 +/- 10 pmol/min) across the coronary circulation, a net release of noradrenaline was observed in HT - LVH (69 +/- 26 pmol/min), in HT + LVH (121 +/- 55 pmol/min) and in HCM (341 +/- 96 pmol/min). In a multivariate linear regression analysis model, left ventricular mass correlated significantly with the net noradrenaline release rate (r = 0.64, P < 0.001), whereas arterial blood pressure as an additional independent variable did not correlate with left ventricular mass. CONCLUSION: The present data demonstrate that an increased left ventricular mass in normotensive and in hypertensive patients is closely coupled to an increased cardiac sympathetic activity, supporting the need for additional studies to determine whether adjunctive sympatholytic therapy is beneficial in patients with left ventricular hypertrophy and increased cardiac noradrenaline release.

Late potentials and heart rate variability in heart muscle disease.

To elucidate the incidence and clinical significance of ventricular late potentials (LP) and reduced heart rate variability (HRV) in primary and secondary heart muscle disease, 157 patients with dilated cardiomyopathy (DCM, n = 19), chronic myocarditis (MC, n = 50), hypertrophic cardiomyopathy (HCM, n = 27) and systemic hypertension (HT, n = 61) were studied. LP measured by the signal averaging technique were found in 24% of the total study group--47% of the patients with DCM, 28% with MC, 29% with HCM and 10% with HT. Complex ventricular arrhythmias were detected during Holter monitoring in 56% of patients with DCM, in 41% with MC, in 21% with HT and in 16% with HCM. An electrophysiological study was performed in a total of 75 patients. Non-sustained or sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) were inducible during programmed ventricular stimulation in 32% of patients with MC, in 30% with HT, in 20% with DCM and in 17% with HCM. The total duration of the signal-averaged, filtered QRS complex was the only independent predictive factor for severe arrhythmic events and sudden cardiac death. HRV measured in 39 patients were most reduced in patients with DCM (RR interval standard deviation (HRV-SD) 39 +/- 23 ms), followed by 44 +/- 16 ms in patients with HCM, 45 +/- 28 ms in patients with HCM and 67 +/- 51 ms in patients with HT. A significant reduction in the HRV-SD below 30 ms was recorded in 24% of patients measured.(ABSTRACT TRUNCATED AT 250 WORDS)

[A rheumatic disease register in clinical use]. / Ein Rheumaregister in der klinischen Anwendung.

A registry for the documentation of rheumatic diseases has been developed at the University of Düsseldorf. For 3 years more than 450 parameters for each patient have been documented, checked, and stored in a data bank. The registry has made a definite improvement in the diagnosis and long-term follow-up of rheumatic diseases. The use of special statistical procedures to study the frequency of various parameters in different diseases has allowed independent diagnostic criteria to be established.

Possibilities for retrieving temporal information in MEDDOK retrieval system.

This paper describes shortly some aspects of the MEDDOK retrieval language especially the methods for making vertical retrieval. In addition the question is investigated how this retrieval can be done without scanning and searching most of the data pool. Another subject of the paper is the description of the underlying data structure.

Data structures for medical documentation.

The paper describes a method to construct data base structures for patient-related documentation. The data base structures are formed over suitable classes. Functional dependences are only investigated regarding these classes. Structuring items by means of arbitrary relations are possible, too. The results are well-formed flexible data structures which can serve as a common functional basis for many documentation projects.