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Biomedical subjects

A Franke

Publications and source records attributed to A Franke.

At least 91 records · Page 5Linked to original sources
PubMed2000

Multicenter phase II study of oral idarubicin in treated and untreated patients with B-chronic lymphocytic leukemia.

Idarubicin is the first anthracycline that can be administered orally facilitating antineoplastic chemotherapy at an improved quality of life. In different studies idarubicin has proved clinical effectiveness in patients with advanced low grade non Hodgkin's lymphoma. We performed a phase II study in 19 patients with untreated and pretreated B-CLL of Binet stage A-C. Idarubucin was administered orally at a dose of 15 mg/m2 over 3 days every 4 weeks. Of 19 evaluable patients (m:f, 16:3, median age 64 years, range 41-80 years) 7 were previously untreated while 12 patients had received prior therapy with fludarabine, chlorambucil or similar non-anthracycline containing regimens. 12 pts had Binet stage C, 5 Binet stage B and 2 Binet stage A. Five patients achieved a partial remission (26%), 5 patients had stable disease (26%) and 9 patients showed progressive disease (47%), resulting in an overall response of 26% (5/19). There was no correlation of response rate with Binet stages or previous treatment regimens. Treatment associated side effects consisted predominantly of mild nausea and vomiting (26%) as well as minor infections (21%) and diarrhoea (16%). These data demonstrate that oral idarubicin as a single agent is well tolerated but of limited effectiveness in B-CLL. Further studies are needed to assess different doses and schedules of oral idarubucin and to test it in combination with other chemotherapeutic agents.

Administration, Oral↗
PubMed2000

Transesophageal 3-dimensional echocardiography: in vivo determination of left ventricular mass in comparison with magnetic resonance imaging.

The objective of this study was to assess the accuracy and reproducibility of transesophageal 3-dimensional echocardiography (3DE) in comparison with magnetic resonance imaging (MRI) for the in vivo calculation of left ventricular mass (LVM). In addition, mass values obtained by M-mode echocardiography were compared with those calculated by MRI. Three-dimensional reconstruction of the left ventricle was performed from a transesophageal and transgastric transducer position with a multiplane transducer in 20 patients. Left ventricular mass was calculated from both transducer positions by using slices of various thicknesses, ranging from 5 to 20 mm. Reproducibility was determined by 5 repeated measurements of mass in each of 5 randomly selected left ventricles. M-mode echocardiography was performed according to the method described by Devereux. For MRI, multiple short-axis views with 10-mm slice thickness were acquired in inspiration hold. Correlation was high for mass determined by 3DE and MRI (for 10-mm slice thickness: r = 0.99; y = 0.99 x - 0.7 g; standard error of estimate = 8.5 g; P <.001). There was no statistical bias, and the limits of agreement ranged from +/-16.4 g to +/-27.2 g, depending on the slice thickness. Variability was lowest for a slice thickness of 10 mm (SD +/- 8.2 g). The reproducibility of mass determination was excellent (mean width of the 95% CI 12.8 g). Left ventricular mass values calculated from the transgastric and transesophageal transducer position were not different from each other (mean bias 0.6 +/- 9.1 g; P = ns). M-mode-based LVM calculations showed systematic overestimation and large measurement variability (bias 23.7 g; 95% CI +/- 92.8 g). Compared with MRI, transesophageal 3DE is an accurate and reproducible method for the determination of LVM and clearly superior to M-mode echocardiography.

Adult↗
PubMed1999

Transthoracic echocardiography using second harmonic imaging: diagnostic alternative to transesophageal echocardiography for the detection of atrial right to left shunt in patients with cerebral embolic events.

OBJECTIVES: We sought to evaluate whether transthoracic contrast echocardiography using second harmonic imaging (SHI) is a diagnostic alternative to transesophageal contrast echocardiography (TEE) for the detection of atrial right to left shunt. BACKGROUND: Paradoxic embolism is considered to be the major cause of cerebral ischemic events in young patients. Contrast echocardiography using TEE has proven to be superior to transthoracic echocardiography (TTE) for the detection of atrial shunting, SHI is a new imaging modality that enhances the visualization of echocardiographic contrast agents. METHODS: We evaluated 111 patients with an ischemic cerebral embolic event for the presence of atrial right to left shunt using an intravenous (IV) contrast agent in combination with three different echocardiographic imaging modalities: 1) TTE using fundamental imaging (FI); 2) TTE using SHI; and 3) TEE. The severity of atrial shunting and the duration of contrast visibility within the left heart chambers were evaluated for each imaging modality. Image quality was assessed separately for each modality by semiquantitative scoring (0 = poor to 3 = excellent). Presence of atrial right to left shunt was defined as detection of contrast bubbles in the left atrium within the first three cardiac cycles after contrast appearance in the right atrium either spontaneously or after the Valsalva maneuver. RESULTS: A total of 57 patients showed evidence of atrial right to left shunt with either imaging modality. Fifty-one studies were positive with TEE, 52 studies were positive with SHI, and 32 were positive with FI (p<0.001 for FI vs. SHI and TEE). The severity of contrast passage was significantly larger using SHI (61.6+/-80.2 bubbles) compared to FI (53.7+/-69.6 bubbles; p<0.005 vs. SHI) but was not different compared to TEE (43.9+/-54.3 bubbles; p = NS vs. SHI). The duration of contrast visibility was significantly longer for SHI (17.4+/-12.4 s) compared to FI (13.1+/-9.7 s; p<0.001) and TEE (11.9+/-9.6 s; p<0.02). Mean image quality improved significantly from FI (1.5+/-0.8) to SHI (2.0+/-0.8; p<0.001 vs. FI) and TEE (2.5+/-0.7; p<0.001 vs. SHI). CONCLUSIONS: In combination with IV contrast injections, TEE and SHI have a comparable yield for the detection of atrial right to left shunt. Both modalities may miss patients with atrial shunting. In young patients with an unexplained cerebrovascular event and no clinical evidence of cardiac disease, a positive SHI study may obviate the need to perform a TEE study to search for cardiac sources of emboli.

Adult↗
PubMed1999

Characterization of glycosylphosphatidylinositol-linked molecule CD55/decay-accelerating factor as the receptor for antibody SC-1-induced apoptosis.

The human monoclonal antibody SC-1 induces apoptosis of stomach carcinoma cells and is currently used in a clinical Phase II trial. The antibody binds to a target molecule that is preferentially expressed on diffuse- and intestinal-type stomach cancer cells and shows a very restricted expression on other normal and malignant tissues. In this paper, we show that the SC-1 receptor is a stomach carcinoma-associated isoform of CD55 [membrane-bound decay-accelerating factor (DAF)-B] with a relative molecular mass of approximately 82 kDa. The antigenic site of SC-1 is an N-linked carbohydrate residue. Cross-linking of the DAF receptor increases apoptotic activity. SC-1 binding induces tyrosine phosphorylation of three proteins of approximately 60, 75, and 110 kDa, whereas a serine residue of an approximately 35-kDa protein is dephosphorylated. Expression of caspase-3 (CPP32) and caspase-8 (FLICE) is elevated, and activation of these caspases occurs. These data show that a tumor-specific variant form DAF is involved in apoptosis and can be used for adjuvant therapeutical purposes on gastric carcinoma.

Antibodies, Monoclonal↗
PubMed1999

Anatomically positioned aorta ascending-descending bypass grafting via left posterolateral thoracotomy for reoperation of aortic coarctation.

OBJECTIVE: Operation for aortic recoarctation and/or residual hypoplastic arch represents a surgical challenge because of surrounding scar tissue in the coarctation area, hazard of spinal cord ischemia due to aortic cross-clamping, laceration of the recurrent nerve, and the choice of the best approach. We demonstrate the first results of an anatomically guided technique via the prior left thoracotomy approach without establishment of cardiopulmonary bypass. METHODS: Since 1989, five patients underwent anatomically positioned ascending-descending bypass grafting for treatment of recoarctation. Indication was a non-dilatable hypoplastic aortic arch segment; in two cases an additional isthmic restenosis was present. Inclusion criteria for our technique was an aorta ascending diameter large enough to allow partial clamping. Primary repair of aortic coarctation was end-to-end anastomosis in four patients and patch angioplasty in one. Mean age at primary repair was 5.5 years and at reoperation 16.1 years. Systolic pressure gradients at rest ranged from 35 to 70 mmHg; upper extremity hypertension was present in all patients. Operative technique consisted of performing a dacron or PTFE aorta ascending-descending bypass graft parallel to the aortic arch, size 18 or 20 mm in diameter, via the prior left thoracotomy. RESULTS: There were no intraoperative complications and all patients survived. Postoperative complications were left lung atelectasis with necessity of reintubation, pericardial effusion, and transient left diaphragm elevation, each in one patient. After 7-90 months all patients are free of symptoms, have normal blood pressure (with two patients being under anti-hypertensive medication), and have no echocardiographically measurable pressure gradients. CONCLUSIONS: Anatomically positioned aorta ascending-descending bypass grafting via the prior left posterolateral thoracotomy without cardiopulmonary bypass is a safe and efficient method for operation of complex recoarctation in patients with an acceptable size of the aorta ascendens.

Adolescent↗
PubMed1999

The rox1 and rox2 RNAs are essential components of the compensasome, which mediates dosage compensation in Drosophila.

The rox1 and rox2 RNAs have been suggested to be components of the dosage compensation machinery in Drosophila. We show that both rox RNAs colocalize with the male-specific lethal proteins at hundreds of specific bands along the male X chromosome. The rox RNAs and MSL proteins also colocalize with the X chromosome in all somatic cells and are expressed in the same temporal pattern throughout development. Genetic analysis shows that the functions of the rox genes are redundant and required for the association of the MSL proteins with the male X chromosome. These data provide compelling evidence for a direct function of the rox RNAs in dosage compensation.

Animals↗
PubMed1999

[Changes in psychophysiologic status during inpatient rehabilitation in the orthopedics service--a preliminary study].

OBJECTIVES: Assessment of non-operative treatment of orthopaedic diseases is sometimes considered difficult. The purpose of this retrospective longitudinal study on the one hand is to evaluate the formal quality of questionnaire data under routine conditions in an in-patient rehabilitation hospital and on the other hand to study the impact of additional psychologic treatment on the outcome of patients who received conservative treatment for chronic orthopaedic diseases. PATIENTS AND METHODS: During a 7-month period, a total of 900 patients received a standardized questionnaire at the beginning and the end of a 4-week inhouse treatment for chronic orthopaedic diseases. A questionnaire handed out to the patients at arrival includes 33 items of psychophysiologic interest. At discharge, a modified questionnaire was used, focussing on the course of complaints during the treatment period, and including additional control-questions for consistency. Return of the questionnaires was voluntary, no pressure was applied, no effort was made to correct inconsistent or missing data. The results presented here are based on 105 orthopaedic patients who returned both questionnaires complete with consistent data. Of these, 44 received additional psychologic treatment by a psychologist, while 61 did not. Participation or non-participation in the psychologic treatment was the grouping variable in this study. RESULTS: For only 189/900 (21%) of the patients taking part in the study complete and consistent questionnaires were available for analysis. For the 105 orthopaedic patients, no significant score differences at arrival between the groups were detected (p = 0.38) using the Mann-Whitney U-test. At discharge, the mean rank sums for the psychological intervention group was 45.7, while it amounted to 58.3 in the control group, indicating significantly stronger improvement of symptoms in the intervention group (p = 0.04). CONCLUSIONS: Under routine conditions without any arrangements to ensure data quality a great amount of incomplete and/or inconsistent data has to be expected. For subsequent studies, this fact has to be taken into account. Irrespective of this aspect, complementary psychologic treatment of certain orthopaedic diseases seems to lead to significantly better results of treatment, as assessed by a psychophysiological questionnaire.

Adult↗
PubMed1998

[Is homeopathy more than a placebo?].

Homeopathy can be characterized by three axioms "treating like with like" (law of similars), "increasing effects with increasing potency" (potentization) and "effects on the basis of ultra-high dilutions" (beyond-molecular effects), where it is unlikely that the dilutions contain a single molecule of the original substance. On the basis of these tenets and the clinical evidence further research priorities are developed. Current reviews indicate small homeopathic verum effects, even after adjustment for internal validity and publication-bias. However, the results remain disputable, because reproducibility isn't assured by independent examiners. For further validation, independent replication of studies with high quality, including specially treatment with high-potencies according to law of similars, seem to be important. The prerequisites for a homeopathy-specific study methodology (inclusion of populations according to their homeopathic diagnosis) still are not fulfilled today. There is neither convincing evidence for specific drug pictures by placebo-controlled drug provings, nor is the reliability of homeopathic diagnosis proven. By reason of extensive, individual interviews, preceeding every classical homeopathic remedy finding, placebo-effects could play an important therapeutical role. The relevance of homeopathic placebo-effects should be explored against other sham treatments and an untreated group.

Clinical Trials as Topic↗
PubMed1998

Quantification of the initial decline of serum hepatitis C virus RNA and response to interferon alfa.

Although several virus- and host-related predictive factors for the response to interferon alfa (IFN-alpha) have been defined in patients with chronic hepatitis C, no pretreatment parameter can definitely predict the response to antiviral treatment. Assessment of the initial response by quantification of serum hepatitis C virus RNA before and 4 weeks after initiation of therapy may be a clinically applicable and reliable parameter to predict long-term response. Therefore, the aims of the present study were to test the predictive value of a decline in HCV RNA of at least 3 log in the first 4 weeks of treatment (deltaHCV RNA) in patients treated with 3 x 10(6) units of recombinant IFN-alpha2a (rIFN-alpha2a) three times per week subcutaneously and to compare deltaHCV RNA with other established predictive factors, such as HCV genotype and pretreatment viremia. Serum HCV RNA was measured by a validated quantitative reverse transcription-polymerase chain reaction (RT-PCR). Geno/subtyping of HCV was performed by direct sequencing of the nonstructural (NS) 5B region of PCR-amplified isolates and subsequent phylogenetic analysis. Stable HCV RNA levels (deltaHCV RNA < or = 1 log) within the first 4 weeks of IFN-alpha treatment were present in 42 of 70 patients. A decline in HCV RNA levels between 1 to 3 log and more than 3 log was observed in 9 (13%) and 19 patients (27%), respectively. In 21 of 70 patients (30%), HCV RNA was not detectable at the end of 12 months' treatment. Three of 26 patients (11%) with a pretreatment viremia of < or = 10(6) copies/mL (all HCV subtype 3a) and 6 of 44 patients (14%) with a pretreatment viremia of > 10(6) copies/mL (HCV subtypes 1b, 2a, 2c, 3a [two patients], and 4) achieved a virological sustained response to interferon-alpha2a treatment. All patients with a virological sustained response had an initial deltaHCV RNA of more than 3 log. In a stepwise discriminant-function analysis, the initial deltaHCV RNA was confirmed as the strongest predictor of virological sustained response (P < .0001). In conclusion, the data of the present study suggest that IFN-alpha treatment can be terminated after 4 weeks in patients with a decrease in HCV RNA levels of less than 3 log, when apparent HCV eradication is considered the therapeutic target. The predictive value of deltaHCV RNA clearly exceeds the significance of HCV genotype and pretreatment viremia as predictors of successful IFN-alpha treatment.

Adult↗
PubMed1998

Quantitative assessment of the operative results after extended myectomy and surgical reconstruction of the subvalvular mitral apparatus in hypertrophic obstructive cardiomyopathy using dynamic three-dimensional transesophageal echocardiography.

OBJECTIVES: The aim of this study was to examine the value of dynamic three-dimensional (3D) transesophageal echocardiography (TEE) for the postoperative evaluation after extended myectomy and surgical reconstruction of the subvalvular mitral valve apparatus in patients with hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND: Two-dimensional imaging techniques such as echocardiography, computed tomography and magnetic resonance imaging have not been able to precisely quantify the effects of surgical therapy on the morphology of the left ventricular outflow tract (LVOT). METHODS: Multiplane TEE with 3D reconstruction was performed in 11 patients before and after the operation and in 16 normal control subjects for comparison. The preoperative maximal systolic pressure gradient in the LVOT was 69 +/- 59 mm Hg. The following variables were measured within the dynamic 3D data set: depth, width, length and cross-sectional area (CSA) gain caused by the myectomy trough, minimal CSA of the LVOT at each time point and its cyclic changes and maximal mitral leaflet deviation during systole. RESULTS: Functional class improved from 3.0 +/- 0.2 before the operation to 1.5 +/- 0.6 after it. The maximal systolic pressure gradient in the outflow tract decreased to 26 +/- 21 mm Hg postoperatively (p < 0.001). Minimal CSA of the outflow tract increased from 1.1 +/- 1.2 to 3.8 +/- 1.9 cm2 postoperatively (p < 0.001), similar to the value of the control group (4.2 +/- 1.5 cm2, p = NS). The area gain due to the myectomy trough was 1.3 +/- 1.0 cm2, corresponding to 48 +/- 12% of the total operative area difference. Maximal systolic depth of the myectomy was 7 +/- 2 mm, maximal width was 20 +/- 8 mm and length was 28 +/- 7 mm. Maximal deviation of the mitral leaflets fell from 15 +/- 7 to 6 +/- 7 mm postoperatively (p < 0.01). In five patients mass measurements of the intracavitary portion of the papillary muscle (PM) revealed an increase from 7.3 +/- 1.0 to 12.1 +/- 2.5 g due to surgical mobilization of PMs (p < 0.01). CONCLUSIONS: 3D TEE quantifies the differences in outflow tract morphology before and after surgery for HOCM. This technique may have an impact on the planning of operative interventions and allow for the evaluation of its results.

Adult↗
PubMed1998

Evaluation of regional systolic function in hypertrophic cardiomyopathy and hypertensive heart disease: a three-dimensional echocardiographic study.

Assessment of regional left ventricular (LV) function in patients with asymmetric LV hypertrophy is difficult with two-dimensional echocardiography mainly because of factors such as LV geometry, structure, regional wall stress, and ischemia. Multiplane transesophageal echocardiography with three-dimensional reconstruction of cross-sectional images was used for quantitative evaluation of regional wall thickness and fractional thickening. Fifteen patients (56 +/- 13 years old) with hypertrophic cardiomyopathy (LV ejection fraction 71% +/- 4%), 15 (62 +/- 13 years) with hypertensive heart disease (ejection fraction 66% +/- 8%) and 15 (53 +/- 11 years) healthy control subjects (ejection fraction 61% +/- 5%) were included in the analysis. Regional function was studied in four parallel equidistant short-axis cross sections from base to apex of the reconstructed left ventricle. In 15 degree intervals, 24 wall thickness measurements in each cross section were made at end-diastole and end-systole after endocardial and epicardial border tracing. A total of 192 measurements were obtained in each patient, and absolute wall thickening and fractional thickening were calculated. Absolute and fractional wall thickening showed a significant inverse relation to end-diastolic wall thickness in all heart conditions (r = 0.71, p < 0.0001). Regions of normal wall thickness in diseased patients were not hyperdynamic when compared with normal control subjects. Significant impairment in fractional thickening at identical end-diastolic thickness was observed in the septum compared with the lateral free wall in both hypertrophic cardiomyopathy and hypertensive heart disease. Thus regional systolic function is inversely related to end-diastolic wall thickness. The decrease in regional systolic function with increasing LV hypertrophy was similar in idiopathic and hypertensive cardiomyopathy. In both types of hypertrophy, significant differences in systolic function were observed in septal and lateral wall segments of similar wall thickness. This indicates that factors other than end-diastolic wall thickness influence myocardial thickening in patients with hypertrophy and preserved global function.

Cardiomyopathy, Hypertrophic↗
PubMed1998

Three-dimensional echocardiographic determination of left ventricular volumes and function by multiplane transesophageal transducer: dynamic in vitro validation and in vivo comparison with angiography and thermodilution.

The goal of this study was to validate 3-dimensional echocardiography by multiplane transesophageal transducer for the determination of left ventricular volumes and ejection fraction in an in vitro experiment and to compare the method in vivo with biplane angiography and the continuous thermodilution method. In the dynamic in vitro experiment, we scanned rubber balloons in a water tank by using a pulsatile flow model. Twenty-nine measurements of volumes and ejection fractions were performed at increasing heart rates. Three-dimensional echocardiography showed a very high accuracy for volume measurements and ejection fraction calculation (correlation coefficient, standard error of estimate, and mean difference for end-diastolic volume 0.998, 2.3 mL, and 0.1 mL; for end-systolic volume 0.996, 2.7 mL, and 0.5 mL; and for ejection fraction 0.995, 1.0%, and -0.4%, respectively). However, with increasing heart rate there was progressive underestimation of ejection fraction calculation (percent error for heart rate below and above 100 bpm 0.59% and -8.6%, P < .001). In the in vivo study, left ventricular volumes and ejection fraction of 24 patients with symmetric and distorted left ventricular shape were compared with angiography results. There was good agreement for the subgroup of patients with normal left ventricular shape (mean difference +/-95% confidence interval for end-diastolic volume 5.2+/-6.7 mL, P < .05; for end-systolic volume -0.5+/-8.4 mL, P = not significant; for ejection fraction 2.4%+/-7.2%, P = not significant) and significantly more variability in the patients with left ventricular aneurysms (end-diastolic volume 23.1+/-56.4 mL, P < .01; end-systolic volume 5.6+/-41.0 mL, P = not significant; ejection fraction 4.9%+/-16.0%, P < .05). Additionally, in 20 critically ill, ventilated patients, stroke volume and cardiac output measurements were compared with measurement from continuous thermodilution. Stroke volume as well as cardiac output correlated well to thermodilution (r = 0.89 and 0.84, respectively, P < .001), although both parameters were significantly underestimated by 3-dimensional echocardiography (mean difference +/-95% confidence interval = -6.4+/-16.0 mL and -0.6+/-1.6 L/min, respectively, P < .005).

Adult↗