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Biomedical subjects

J Hoffmann

Publications and source records attributed to J Hoffmann.

At least 145 records · Page 8Linked to original sources
PubMed1997

A highly sensitive model for quantification of in vivo tumor angiogenesis induced by alginate-encapsulated tumor cells.

A remarkable approach to a specific tumor angiogenesis model in vivo is the use of alginate implants encapsulating tumor cells. However, this previously reported approach has often been questioned because of doubts regarding the relevance of hemoglobin at the alginate implant as a parameter of vascularization. In the present investigation, we examined whether or not the use of the blood pool agents FITC-dextran of high molecular weight would significantly improve the determination of vascularization at the alginate implant. In our experiments, we found a rapid distribution of FITC-dextran within the blood circulation of mice after i.v. bolus injection. The amount of FITC-dextran within alginate implants strongly correlated with the number of LL2 carcinoma cells or B16/F10 cells encapsulated. Even a low number of 10(3) cells per alginate implant led to a significantly increased accumulation of FITC-dextran. A more than 10-fold stimulation above that of controls was found with alginate implants containing 10(4) LL2 or B16/F10 tumor cells. Using the investigational compound AGM-1470 in different treatment schedules, we found that quantification of alginate implant anglogenesis with FITC-dextran is a sensitive method for the determination of angiogenesis inhibition. In conclusion, our results demonstrated that the use of FITC-dextran enables highly sensitive, quantitative measurement of blood vessel formation by alginate implants.

Alginates↗
PubMed1997

Effect of amiodarone on QT dispersion in the 12-lead standard electrocardiogram and its significance for subsequent arrhythmic events.

BACKGROUND AND HYPOTHESIS: QT dispersion, measured as interlead variability of QT intervals in the surface electrocardiogram, has been demonstrated to provide an indirect measurement of the inhomogeneity of myocardial repolarization. The purpose of the present study was twofold: (1) to analyze the effect of amiodarone on QT dispersion measured in the 12-lead standard ECG, and (2) to examine the association between QT dispersion on amiodarone and subsequent arrhythmic events. METHODS: To determine the effect of amiodarone on QT dispersion and its clinical significance for subsequent arrhythmic events, QT dispersion was measured in the 12-lead standard electrocardiogram (ECG) in 52 patients before and after administration of empiric amiodarone for ventricular tachyarrhythmias. RESULTS: QT intervals increased from 401 +/- 44 ms before amiodarone to 442 +/- 53 ms after amiodarone therapy, and rate corrected QT intervals (QTc) increased from 452 +/- 43 ms to 477 +/- 37 ms, respectively (p < 0.01). QT dispersion, QTc dispersion, and adjusted QTc dispersion, which take account of the number of leads measured, were not significantly different before and after initiation of amiodarone therapy (58 +/- 24 ms vs. 61 +/- 26 ms, 68 +/- 29 vs. 66 +/- 26 ms, and 22 +/- 8 vs. 22 +/- 8 ms, respectively, p = NS). During 31 +/- 25 months follow-up after initiation of amiodarone therapy, arrhythmic events defined as sustained ventricular tachycardia, ventricular fibrillation, or sudden death occurred in 11 of 52 study patients (21%). QT dispersion, QTc dispersion, and adjusted QTc dispersion on amiodarone were not different between patients with and without arrhythmic events during follow-up (65 +/- 14 vs. 59 +/- 29 ms, 73 +/- 15 vs. 64 +/- 28 ms, and 25 +/- 6 vs. 21 +/- 8 ms, respectively, p = NS). CONCLUSIONS: We conclude that (1) amiodarone increases QT intervals and QTc intervals during sinus rhythm but does not significantly change measures of QT dispersion; and (2) QT dispersion measured in the 12-lead standard ECG after initiation of amiodarone therapy does not appear to be a useful marker for subsequent arrhythmic events.

Amiodarone↗
PubMed1997

Solution structure of drosomycin, the first inducible antifungal protein from insects.

Drosomycin is the first antifungal protein characterized recently among the broad family of inducible peptides and proteins produced by insects to respond to bacterial or septic injuries. It is a small protein of 44 amino acid residues extracted from Drosophila melanogaster that exhibits a potent activity against filamentous fungi. Its three-dimensional structure in aqueous solution was determined using 1H 2D NMR. This structure, involving an alpha-helix and a twisted three-stranded beta-sheet, is stabilized by three disulfide bridges. The corresponding Cysteine Stabilized alpha beta (CS alpha beta) motif, which was found in other defense proteins such as the antibacterial insect defensin A, short- and long-chain scorpion toxins, as well as in plant thionins and potent antifungal plant defensins, appears as remarkably persistent along evolution.

Amino Acid Sequence↗
PubMed1997

Lack of interaction between meloxicam and warfarin in healthy volunteers.

OBJECTIVE: The effect of multiple oral doses of meloxicam 15 mg on the pharmacodynamics and pharmacokinetics of warfarin was investigated in healthy male volunteers. Warfarin was administered in an individualized dose to achieve a stable reduction in prothrombin times calculated as International Normalized Ratio (INR) values. Then INR- and a drug concentration-time profile was determined. For the interaction phase, meloxicam was added for 7 days and then INR measurements and the warfarin drug profiles were repeated for comparison. Overall, warfarin treatment lasted for 30 days. RESULTS: Warfarin and meloxicam were well tolerated by healthy volunteers in this study. Thirteen healthy volunteers with stable INR values entered the interaction phase. Prothrombin times, expressed as mean INR values, were not significantly altered by concomitant meloxicam treatment, being 1.20 for warfarin alone and 1.27 for warfarin with meloxicam cotreatment. R- and S-warfarin pharmacokinetics were similar for both treatments. Geometric mean (% gCV) AUCss values for the more potent S-enantiomer were 5.07 mg.h.l-1 (27.5%) for warfarin alone and 5.64 mg.h.l-1 (28.1%) during the interaction phase. Respective AUCss values for R-warfarin were 7.31 mg.h.l-1 (43.8%) and 7.58 mg.h.l-1 (39.1%). CONCLUSION: The concomitant administration of the new non-steroidal anti-inflammatory drug (NSAID) meloxicam affected neither the pharmacodynamics nor the pharmacokinetics of a titrated warfarin dose. A combination of both drugs should nevertheless be avoided and, if necessary, INR monitoring is considered mandatory.

Administration, Oral↗
PubMed1997

Efficacy of 24-week monotherapy with acarbose, metformin, or placebo in dietary-treated NIDDM patients: the Essen-II Study.

PURPOSE: To compare the therapeutic potential of acarbose, metformin, or placebo as first line treatment in patients with non-insulin-dependent diabetes mellitus (NIDDM). PATIENTS AND METHODS: Ninety-six patients with NIDDM (35-70 years of age, body mass index (BMI) < or = 35 kg/m2, insufficiently treated with diet alone, glycated hemoglobin (HbA1c; 7% to 11%) were randomized into 3 groups and treated for 24 weeks with acarbose, 3 x 100 mg/day, or metformin, 2 x 850 mg/day, or placebo. Efficacy, based on HbA1c (primary efficacy criterion), fasting blood glucose (BG) and insulin, 1 hour postprandial BG and insulin (after standard meal test), postprandial insulin increase, plasma lipid profile, and tolerability, based on subjective symptoms and laboratory values were determined every 6 weeks. Analysis of covariance was performed for endvalues with adjustment on baseline values. Ninety-four patients were valid for efficacy evaluation. RESULTS: Both active drugs showed the same improvement of efficacy criteria compared with placebo. Baseline adjusted means at endpoint were as follows: BG, fasting and 1 hour postprandial, 9.2 mM and 10.9 mM with placebo, 7.6 mM and 8.7 mM with acarbose, and 7.8 mM and 9.0 mM with metformin; HbA1c was 9.8% with placebo, 8.5% with acarbose, and 8.7% with metformin. Comparisons: acarbose versus placebo and metformin versus placebo were statistically significant, but not acarbose versus metformin. No effect on fasting insulin could be observed. Relative postprandial insulin increase was 1.90 with placebo, 1.09 with acarbose, and 1.03 with metformin. Comparisons: acarbose versus placebo and metformin versus placebo were statistically significant, but not acarbose versus metformin. With respect to lipid profile, acarbose was superior to metformin. Low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratio increased by 14.4% with placebo, was unchanged with metformin, but decreased by 26.7% with acarbose. Comparisons: acarbose versus placebo and acarbose versus metformin were statistically significant, but not metformin versus placebo. Slight body weight changes were observed with acarbose (-0.8 kg) and metformin (-0.5 kg), but not with placebo. Acarbose led to mild or moderate intestinal symptoms in 50% of the patients within the first 4 weeks, but in only 13.8% of the patients within the last 4 weeks. CONCLUSIONS: Acarbose and metformin are effective drugs for the first line monotherapy of patients with NIDDM. With respect to plasma lipid profile, especially HDL cholesterol, LDL cholesterol and LDL/HDL cholesterol ratio acarbose may be superior to metformin.

Acarbose↗
PubMed1997

Lower frequency (5 MHZ) intracardiac echocardiography in a large swine model: imaging views and research applications.

Our previous investigation indicated that, in the 50-114-kg weight range, the swine model provides transeosophageal echocardiographic normal values for cardiac structures comparable to those found in human adults. Intracardiac echocardiographic imaging using a 12.5-MHz ultrasound catheter is limited, due to ultrasonic attenuation. Transesophageal echocardiographic imaging of the right heart is also limited with its anterior anatomic location. To further study the utility of intracardiac imaging, we placed a 5-MHz (30 Fr) multiplane transducer at the junction of the superior vena cava and right atrium, in the right atrium and right ventricle in 8 closed-chest swine (weight 129 +/- 61 kg). In each animal, complete whole heart imaging was obtained, with tomographic views including the cardiac 4-chamber, right atrium, right ventricle and outflow, left atrium and ventricle, and basal great vessels. Major intracardiac anatomic landmarks (i.e., crista terminalis, right atrial appendage, coronary sinus orifice, interatrial septum, tricuspid valve, right ventricular outflow, pulmonary veins, mitral valve and left ventricular papillary muscles) were visualized in every swine. Thus, this 5-MHz multiplane transducer, as a prototype for a steerable low-frequency intracardiac ultrasound catheter, improved both whole heart and individual cardiac structure imaging from a single intracardiac location. Further technological development and refinement is needed for routine use in research and clinical imaging practice.

Animals↗
PubMed1997

Magnetic resonance imaging and signal-averaged electrocardiography in patients with repetitive monomorphic ventricular tachycardia and otherwise normal electrocardiogram.

Early or localized forms of arrhythmogenic right ventricular dysplasia (ARVD) have been proposed as the arrhythmogenic substrate of repetitive monomorphic ventricular tachycardia (RMVT) originating in the right ventricular outflow tract in patients without any underlying cardiac abnormality on clinical examination and echocardiography. To further examine this hypothesis, magnetic resonance imaging (MRI) and signal-averaged electrocardiography (SAECG) were performed on 23 patients with RMVT and normal 12-lead standard ECG of conducted sinus beats. MRI was performed using ECG-gated turbo spin-echo images of the heart in order to detect signs of early or localized forms of ARVD, such as localized wall thickness reductions, signal intensity increase indicating adipose tissue infiltrates, and regional bulgings or aneurysms. MRI was normal in 22 (96%) of 23 study patients. In the remaining patient (4%), MRI demonstrated signal intensity increase in the intraventricular septum but not in the right ventricular outflow tract. Time-domain analysis of the SAECG was normal in 21 (91%) of 23 patients and revealed ventricular late potentials in 2 study patients (9%). Frequency-domain analysis of the SAECG was normal in 22 (96%) of 23 patients and revealed ventricular late potentials in one study patient (4%). We conclude that normal MRI findings of the heart and absence of ventricular late potentials in the SAECG in most patients with RMVT and otherwise normal ECG do not support the hypothesis that early or localized forms of ARVD create the arrhythmogenic substrate in the majority of these patients.

Action Potentials↗
PubMed1997

Does the initial presentation of patients with implantable defibrillator influence the outcome?

The influence of the clinical presentation on the long-term outcome in 213 consecutive patients with ICDs, ECG storage capability, and nonthoracotomy leads, was analyzed. Sixty-six patients presented with cardiac arrest (CA), 81 patients with hemodynamically stable VT, and 66 patients with syncope (SY). Patient characteristics were: mean age CA 62, VT 61, SY 61 years; mean ejection fraction CA 31%, VT 29%, SY 30%; coronary artery disease CA 71%, VT 71%, SY 64% (all P > 0.05 Fisher's exact test); female gender CA 40%, VT 14%, SY 19% (CA vs VT and SY, P < 0.005); inducibility by programmed stimulation CA 50%, VT 84%, SY 61% (VT vs CA and SY, P < 0.001, CA vs SY, P > 0.05). During a mean follow-up of 14.5 months, 29 patients died: CA 12%, VT 14%, SY 9% (P > 0.05). Comparing Kaplan-Meier curves, no difference in the time course of overall mortality was found (log-rank P > 0.05). In the CA, VT, and SY groups, 543, 1,630, and 189 ICD therapies (including antitachycardia pacing, low energy cardioversion, and defibrillation) were observed, respectively. Actuarial analysis showed a shorter interval between implantation and first ICD therapy for VT versus CA and SY (log-rank P < 0.005). Patients presenting with VT experienced earlier and more frequent ICD therapies than patients with CA or SY independent of age, ejection fraction, and heart disease. No difference in overall mortality and time course of fatal events was observed among the three groups.

Actuarial Analysis↗
PubMed1997

Postoperative infection in a double-occupancy operating room. A prospective study of two thousand four hundred and fifty-eight procedures on the extremities.

The purposes of this study were to determine the rate of infection associated with elective outpatient operations on an extremity, performed in a double-occupancy operating room (one operating room designed to accommodate two separate operating teams), and to determine which factors influenced this rate. We evaluated the records of 2458 consecutive patients who had had such a procedure, performed by one of nine surgeons during a two and one-half-year period, and in whom the operative wound had been classified as clean (without a drain) or clean-contaminated (with a drain). The information regarding the factors associated with the operation and the operating-room environment was recorded for each patient at the time of the operation. Each wound was inspected periodically in the attending surgeon's office for at least thirty days postoperatively. Using definitions established by the Centers for Disease Control, the attending surgeon determined the presence of infection primarily by judging whether there was purulent drainage or whether erythema or swelling at the operative site was beyond that expected from the procedure. Of the 2458 patients, thirty-seven (1.5 per cent; 95 per cent confidence interval, 1.1 to 2.1 per cent) had infection of the operative wound. Only eight patients (0.3 per cent) had deep infection, with seven of the infections necessitating a reoperation. Infection developed in thirty of the 2311 clean wounds, a rate of 1.3 per cent (95 per cent confidence interval, 0.9 to 1.8 per cent), and in seven of the 147 clean-contaminated wounds, a rate of 4.8 per cent (95 per cent confidence interval, 2.3 to 9.5 per cent) (p = 0.001). No cross-contamination occurred between patients who had infection. The rate of infection was not related to the number of patients who were operated on in the same room at the same time. Logistic regression analysis, used to account for confounding factors, demonstrated a significant association between the classification of the wound (use of a drain) and a higher rate of infection (p = 0.006) as well as between the instillation of a topical steroid solution and a lower rate of infection (p = 0.04). It also demonstrated a significant difference, with respect to the rate of infection, among individual surgeons (p = 0.02).

Adolescent↗
PubMed1997

[Differential diagnosis of cystic adnexa processes. A comparison of the value of sonography, puncture cytology and color and biochemical biopsy analysis with histology].

The histological diagnoses of 109 cystic adnexal masses were compared with the results of ultrasound examination, color, cytology and biochemical analyses of cystic fluid. In cases with suspicious results by ultrasound examination most of the malignant tumors but only a small number of benign cystic masses were found. Macroscopic and cytologic examinations gave no further informations. By biochemical analyses functional cysts could be detected with 86% of sensitivity and 100% of specificity by a combination of estradiol, progesterone and Ca 12-5. Endometrioma and malignant tumors could be separated from other adnexal masses (specificity 95%, sensitivity 100%) with a combination of Tag 72-4 and CASA.

Adenofibroma↗
PubMed1997

[Possibilities for correcting the neck profile in pterygium colli].

Pterygium colli is characterized by bilateral webbing of the neck extending from the mastoid to the acromion. There is a broad variation in aetiology, very often chromosomal and congenital diseases are included, and most of the known cases present in association with Turner's syndrome. In one case we applied a posterior approach for correction of the webbed neck defect, which involved wide anterolateral skin undermining and skin resections from the nape of the neck. The redundant tissue and underlying defect are corrected and the resultant scar is hidden in the scalp. In two other cases a Z-plasty procedure was used to reduce the hypertrophic tissue, leaving the hairline in the original course. On the long-term follow-up all cases presented with improved aesthetic results, but showed hypertrophic scars.

Adolescent↗
PubMed1996

Electrophysiologic evaluation of sinus node function and atrioventricular conduction in patients with prolonged ventricular asystole during obstructive sleep apnea.

In 15 patients with ventricular asystole of 8.5 +/- 3.5 seconds (range 5.0 to 16.8) occurring exclusively during obstructive sleep apnea, electrophysiologic study of sinus node function and atrioventricular conduction before and after administration of intravenous atropine (0.02 mg/kg) was performed. Electrophysiologic parameters of sinus node function were normal in 12 of 15 patients (80%) and atrioventricular (AV) nodal function was normal in 7 patients (47%). Almost all abnormal findings of sinus node function and AV nodal function were reversible by administration of atropine. The HisPurkinje system function was normal in 6 patients (40%). Prolonged HV intervals (57 to 73 ms) were found in 9 patients (60%). Intra- or infra-His block was not observed in any patient. In summary, electrophysiologic parameters of sinus node function and AV conduction were normal or only slightly abnormal in all 15 study patients, which suggests that prolonged ventricular asystole during obstructive sleep apnea is not due to fixed or anatomic disease of the sinus node or the AV conduction system.

Atrioventricular Node↗
PubMed1996

Croquemort, a novel Drosophila hemocyte/macrophage receptor that recognizes apoptotic cells.

Programmed cell death is first observed at stage 11 of embryogenesis in Drosophila. The systematic removal of apoptotic cells is mediated by cells that are derived from the procephalic mesoderm and differentiate into macrophages. We describe a macrophage receptor for apoptotic cells. This receptor, croquemort (catcher of death), is a member of the CD36 superfamily. Croquemort-mediated phagocytosis represents the concept that phagocytosis evolved primarily as a cellular process for the removal of effete cells. Our findings support the idea that the primordial function of macrophages may have been in tissue modeling and that their adapted role is in host defense.

Amino Acid Sequence↗
PubMed1996

Heart rate variability and major arrhythmic events in patients with idiopathic dilated cardiomyopathy.

This prospective study of 71 patients with idiopathic dilated cardiomyopathy (IDC) and preserved sinus rhythm was designed to evaluate the relation between heart rate variability (HRV) and subsequent major arrhythmic events. Standard time- and frequency-domain HRV parameters were obtained from analysis of 24-hour Holter ECG recordings. During a mean follow-up of 15 +/- 5 months, major arrhythmic events including sustained ventricular tachycardia, ventricular fibrillation, and sudden cardiac death occurred in 10 of the 71 study patients (14%). Neither time- nor frequency-domain indices of HRV differed significantly between patients with and patients without subsequent major arrhythmic events. However, there was a trend toward a lower standard deviation of the average normal RR interval for all 5-minute segments of the 24-hour recording (68 +/- 17 ms vs 80 +/- 31 ms; P = 0.06) in patients with major arrhythmic events. In addition, the percentage of adjacent normal RR intervals differing > 50 ms over the recording period tended to be lower in patients with major arrhythmic events (6% +/- 3% vs 9% +/- 6%; P = 0.08). Our results indicate a tendency toward attenuated parasympathetic activity in IDC patients with subsequent major arrhythmic events compared to arrhythmia-free patients. Larger studies with longer follow-up periods are necessary to clarify the role of HRV measurements for arrhythmia risk prediction in patients with IDC.

Adolescent↗
PubMed1996

Clinical significance of increased OT dispersion in the 12-lead standard ECG for arrhythmia risk prediction in dilated cardiomyopathy.

QT dispersion was determined from the 12-lead standard ECGs from 107 patients with idiopathic dilated cardiomyopathy (IDG) and compared to QT dispersion measurements in 100 healthy age and sex matched controls. QT dispersion, rate corrected QT dispersion and adjusted QTc dispersion were significantly greater in patients with IDC compared to controls. During a prospective follow-up of 13 +/- 7 months, arrhythmic events, defined as sustained VT, VF, or sudden death, occurred in 12 (11%) of 107 study patients with IDC. QT dispersion was increased in patients with arrhythmic events compared to patients without arrhythmic events during follow-up (76 +/- 17 vs 60 +/- 26 ms; P = 0.03). Differences in QTc dispersion and adjusted QTc dispersion between patients with and without arrhythmic events, however, failed to reach statistical significance. Thus, although QT dispersion was increased in patients with IDC and arrhythmic events during follow-up, its clinical usefulness for risk stratification appears to be very limited due to the large overlap of QT dispersion among patients with and without arrhythmic events.

Arrhythmias, Cardiac↗
PubMed1996

Value of time- and frequency-domain analysis of signal-averaged electrocardiography for arrhythmia risk prediction in idiopathic dilated cardiomyopathy.

Signal-averaged electrocardiography (SAECG) was performed in 120 consecutive patients with idiopathic dilated cardiomyopathy (IDC), and in 60 healthy controls. Time-domain analysis of SAECGs revealed ventricular late potentials in 27 of 120 patients with IDC (23%) compared to 2 of 60 controls (3%; P < 0.05). Frequency-domain analysis of SAECGs showed ventricular late potentials in 9 of 120 patients with IDC (8%) compared to none of the 60 controls (0%, P < 0.05). During a prospective follow-up of 15 +/- 7 months, serious arrhythmic events, defined as sustained ventricular tachyarrhythmias or sudden death, occurred in 17 of 120 patients with IDC (14%). The sensitivity, specificity, and positive and negative predictive values of ventricular late potentials for serious arrhythmic events were 35%, 80%, 22%, and 88% for the time-domain analysis, and 18%, 94%, 33%, and 87% for the frequency-domain analysis of SAECG, respectively. Thus, neither the time-nor the frequency-domain analysis of SAECG appears to be useful for risk stratification in the setting of IDC in view of their low sensitivity and low positive predictive value for serious arrhythmic events during follow-up.

Action Potentials↗