Search PubMed⌕ Search

Biomedical subjects

J Hoffmann

Publications and source records attributed to J Hoffmann.

At least 73 records · Page 4Linked to original sources
PubMed2001

Wooden foreign bodies in facial injury: a radiological pitfall.

Foreign bodies can present a diagnostic challenge to the maxillofacial surgeon. Three patients, who suffered from a penetrating injury with a wooden foreign body, were examined and treated. Their preoperative CT and MRI scans were evaluated. In an acute case, the penetrating wooden body mimicked air bubbles. In the other two patients, the wood was retained for several months and appeared with a much higher density on CT. In MRI the wooden foreign bodies gave a low signal intensity. In all injuries removal of the foreign body was delayed, because it was initially radiologically missed or misdiagnosed. In the appropriate trauma setting a penetrating wooden body must always be considered. Its attenuation value increases with time as water is absorbed from the surrounding tissues. Although the radiological appearance may show a great variety, CT imaging is the basic diagnostic technique. MRI is the method of second choice.

Adult↗
PubMed2001

pitkin(D), a novel gain-of-function enhancer of position-effect variegation, affects chromatin regulation during oogenesis and early embryogenesis in Drosophila.

The vast majority of the >100 modifier genes of position-effect variegation (PEV) in Drosophila have been identified genetically as haplo-insufficient loci. Here, we describe pitkin(Dominant) (ptn(D)), a gain-of-function enhancer mutation of PEV. Its exceptionally strong enhancer effect is evident as elevated spreading of heterochromatin-induced gene silencing along euchromatic regions in variegating rearrangements. The ptn(D) mutation causes ectopic binding of the SU(VAR)3-9 heterochromatin protein at many euchromatic sites and, unlike other modifiers of PEV, it also affects stable position effects. Specifically, it induces silencing of white+ transgenes inserted at a wide variety of euchromatic sites. ptn(D) is associated with dominant female sterility. +/+ embryos produced by ptn(D)/+ females mated with wild-type males die at the end of embryogenesis, whereas the ptn(D)/+ sibling embryos arrest development at cleavage cycle 1-3, due to a combined effect of maternally provided mutant product and an early zygotic lethal effect of ptn(D). This is the earliest zygotic effect of a mutation so far reported in Drosophila. Germ-line mosaics show that ptn+ function is required for normal development in the female germ line. These results, together with effects on PEV and white+ transgenes, are consistent with the hypothesis that the ptn gene plays an important role in chromatin regulation during development of the female germ line and in early embryogenesis.

Animals↗
PubMed2001

Pharmacodynamics and safety of lefradafiban, an oral platelet glycoprotein IIb/IIIa receptor antagonist, in patients with stable coronary artery disease undergoing elective angioplasty.

OBJECTIVE: Lefradafiban is the orally active prodrug of fradafiban, a glycoprotein IIb/IIIa receptor antagonist. The present phase II study aimed to determine the dose of lefradafiban that provides 80% blockade of the glycoprotein IIb/IIIa receptors by fradafiban, and to study the pharmacodynamics and safety of different doses in patients with stable angina undergoing angioplasty. DESIGN: A double blind, placebo controlled, dose finding study. SETTING: Four academic and community hospitals in the Netherlands. PATIENTS: 64 patients with stable coronary artery disease undergoing elective percutaneous transluminal coronary angioplasty. INTERVENTIONS: 30 mg, 45 mg, and 60 mg of lefradafiban three times daily or placebo was given for 48 hours. MAIN OUTCOME MEASURES: The primary safety end point was the occurrence of bleeding, classified as major, minor, or insignificant according to the thrombolysis in myocardial infarction (TIMI) criteria. Efficacy indices included per cent fibrinogen receptor occupancy (FRO), ex vivo platelet aggregation, and plasma concentrations of fradafiban. RESULTS: Administration of lefradafiban 30, 45, and 60 mg three times daily resulted in a dose dependent increase in median FRO levels of 71%, 85%, and 88%, respectively. Inhibition of platelet aggregation was closely related to FRO. There were no major bleeding events. The 60 mg lefradafiban group had a high (71%) incidence of minor and insignificant bleeding. The incidence of bleeding was 44% in the 30 mg and 45 mg groups, compared with 9% in placebo patients. Puncture site bleeding was the most common event. The odds of bleeding increased by 3% for every 1% increase in FRO. CONCLUSIONS: Lefradafiban is an effective oral glycoprotein IIb/IIIa receptor blocker. The clinical effectiveness of doses up to 45 mg three times daily should be investigated.

Administration, Oral↗
PubMed2001

Prognostic value of heart rate variability analysis in patients with carcinoid syndrome.

BACKGROUND/AIMS: Recently, a decrease in heart rate variability measures was found in patients with carcinoid syndrome suffering from carcinoid heart disease compared to those without cardiac involvement of carcinoid syndrome. The prognostic relevance of this finding, however, was not clear. PATIENTS AND METHODS: Therefore, 35 patients with carcinoid syndrome (21 men, age 56 +/- 11 years), all of them suffering from metastatic carcinoid tumors, were followed prospectively at our institution. Digital 24-hour Holter monitoring, echocardiography, and serum serotonin and urine 5-hydroxyindole acetic acid (5-HIAA) samplings were performed in all study patients at baseline. Indices of time domain heart rate variability obtained from Holter recordings included the standard deviation of all normal RR intervals (SDNN) representing overall variability, the square root of the mean of the squared differences between adjacent normal RR intervals (rMSSD), and the percentage of the number of pairs of adjacent normal RR intervals differing by >50 ms (pNN50), both indices reflecting predominantly vagal influences on heart rate. RESULTS: During a mean follow-up of 18 +/- 7 months, 15 of 35 patients with carcinoid syndrome (43%) died. Patients with cardiac manifestation of the carcinoid syndrome showed a tendency towards an increased mortality in comparison to patients without cardiac involvement (p = 0.09). Patients with the combination of decreased heart rate variability (SDNN <100 ms) and presence of carcinoid heart disease had a significant worse prognosis (p = 0.04) compared to patients without carcinoid heart disease and preserved heart rate variability (SDNN > or =100 ms). CONCLUSIONS: The presence of carcinoid heart disease in combination with decreased heart rate variability is associated with the most adverse prognosis in the setting of carcinoid syndrome.

Aged↗
PubMed2001

Aortico-pulmonary paraganglioma associated with bilateral carotid body tumors. Diagnostic presentation and clinical implications.

A case of mediastinal paraganglioma in association with bilateral carotid body tumors is presented. Characteristic radiological findings included a hypointense signal in T1-weighted, a hyperintense signal in T2-weighted magnetic resonance (MR) images and a vascular enhancement pattern in dynamic contrast enhanced MR imaging. Thus, feeding vessels could be depicted noninvasively. The importance of family screening in affected individuals is stressed, as a hereditary form of the disease exists in which multiple paragangliomas are common.

Aorta, Thoracic↗
PubMed2000

Synthesis and biological activity of a novel, highly potent progesterone receptor antagonist.

Herein we describe the chemical synthesis and pharmacological characterization of a novel, highly potent progesterone receptor (PR) antagonist, ZK 230211. The introduction of a 17alpha-pentafluorethyl side chain in the D-ring of the steroid skeleton allowed the combination of high antiprogestagenic activity with little or no other endocrinological effects. In contrast to many other antiprogestins, ZK 230211 did not convert to an agonist in the presence of protein kinase A (PKA) activators and showed high antiprogestagenic activity on both PR isoforms PR-A and PR-B. This high antiprogestagenic activity could also be demonstrated in several in vivo models. Furthermore, this compound displayed only marginal antiglucocorticoid effects. In tumor models ZK 230211 exhibited strong antiproliferative action. The pharmacological properties of ZK 230211 may prove useful in the treatment of endometriosis, leiomyomas, breast cancer, and in hormone replacement therapy.

Abortifacient Agents↗
PubMed2000

Outcome of patients with sleep apnea-associated severe bradyarrhythmias after continuous positive airway pressure therapy.

Twenty-nine patients in whom severe bradyarrhythmias occurred exclusively during obstructive sleep apnea and in whom advanced sinus node disease or atrioventricular conduction system dysfunction had been excluded by invasive electrophysiologic evaluation were prospectively followed on nasal continuous positive airway pressure. During 54 +/- 10 months follow-up, no syncope and no sudden deaths were observed, suggesting that patients with sleep apnea-associated bradyarrhythmias and a normal electrophysiologic study appear to have a favorable prognosis with continuous positive airway pressure.

Bradycardia↗
PubMed2000

Frequency of TPR-MET rearrangement in patients with gastric carcinoma and in first-degree relatives.

BACKGROUND: The activation of the c-met protooncogene through a rearrangement has been detected previously in gastric carcinoma tissue and precancerous lesions. In the current study the authors analyzed the rearrangement of TPR-MET in gastric carcinoma patients and in first-degree relatives to evaluate the potential role and timepoint of this genetic alteration in the process of gastric carcinogenesis and its potential value in identifying those individuals with an increased risk of developing gastric carcinoma. METHODS: The presence of TPR-MET mRNA was determined in gastric tissue from 19 patients with gastric carcinoma and in the gastric mucosa of 18 first-degree relatives without gastric carcinoma and in the gastric mucosa of 18 first-degree relatives without gastric carcinoma using a nested reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis. A 205-base pair (bp) cDNA fragment and a 70-bp cDNA fragment spanning the breakpoint were amplified by nested PCR. Amplification products were hybridized with an oligonucleotide labeled at the 3'-end with DIG-11-dUTP spanning the breakpoint using Southern blot analysis. The MNNG-HOS cell line served as a positive control. RESULTS: TPR-MET mRNA was detected in nine gastric carcinoma patients (47%). Among these patients, TPR-MET mRNA was present in the both tumor and tumor free tissues in 5 patients (26%), in the tumor tissue only in 2 patients (11%), and in the tumor free gastric mucosa only in 2 patients (11%). It is interesting to note that TPR-MET rearrangement also was detected in the gastric corpus mucosa of 1 first-degree relative (6%), but in none of the control subjects. CONCLUSIONS: The data from the current study indicate that TPR-MET activation may be an early event in gastric carcinogenesis and may be useful for the identification of individuals with an increased risk of developing gastric carcinoma.

Adult↗
PubMed2000

Significance of accelerated idioventricular rhythm in idiopathic dilated cardiomyopathy.

Holter monitoring was performed in 202 patients with idiopathic dilated cardiomyopathy, which revealed accelerated idioventricular rhythm in 16 patients (8%) and nonsustained ventricular tachycardia in 70 patients (35%). During 32 +/- 15-month prospective follow-up, no significant difference was observed for major arrhythmic events and transplant-free survival between patients with and without accelerated idioventricular rhythm, whereas patients with nonsustained ventricular tachycardia had a significantly higher incidence of major arrhythmic events and a lower transplant-free survival rate.

Accelerated Idioventricular Rhythm↗
PubMed2000

Expression of metallothionein II in intestinal metaplasia, dysplasia, and gastric cancer.

Differential display is a valuable tool for the identification of differentially expressed genes in human carcinogenesis and development. The search for differentially expressed genes in gastric cancer and its premalignant lesions may help to define molecular alterations in the gastric mucosa that may precede the development of gastric cancer. Using the differential display technique, we identified a cDNA fragment, encoding metallothionein (MT) IIa mRNA. We performed immunohistochemical analysis using a monoclonal antibody directed against human MT and tissues obtained from 34 patients with gastric cancer and 20 healthy individuals to determine the expression and localization of MT in gastric cancer and its associated premalignant lesions and to correlate our findings with histomorphological features and Helicobacter pylori status. In addition, MT expression was assessed in gastric tissues obtained from patients with gastric cancer and first-degree relatives of patients with gastric cancers and healthy individuals using reverse transcription-PCR analysis. Northern blot analysis confirmed the overexpression of MT IIa in gastric cancer. In the normal gastric tissues, no MT immunoreactivity was observed at the superficial gastric epithelium toward the top of gastric glands. However, MT immunoreactivity was detected at the foveolar neck of the gastric glands. Immunohistochemical analysis revealed an intense MT immunoreactivity in gastric cancer cells, independent of tumor stage, grade of differentiation, or tumor type. Furthermore, areas of dysplasia and intestinal metaplasia also exhibited intense MT immunoreactivity. Reverse transcription-PCR analysis of gastric biopsies obtained from first-degree relatives of patients with gastric cancer revealed the frequent expression of MT Ia in this high-risk group as compared with healthy subjects (P < 0.01). The overexpression of MT in gastric cancer and the expression of MT in intestinal metaplasia and dysplasia, as well as the expression of MT in the gastric mucosa of first-degree relatives of patients with gastric cancer, point to a role for MT in the early process of malignant transformation of the gastric mucosa.

Adult↗
PubMed2000

Cardiac autonomic tone and its relation to nonsustained ventricular tachyarrhythmias in idiopathic dilated cardiomyopathy.

BACKGROUND: In contrast to postinfarct patients, little is known about cardiac autonomic tone and its relation to spontaneous ventricular tachyarrhythmias in idiopathic dilated cardiomyopathy (IDC). Both heart rate variability (HRV) and baroreflex sensitivity (BRS) are indices of autonomic innervation of the heart. HYPOTHESIS: The aim of the present study was to determine the relation between cardiac autonomic tone assessed by HRV and BRS and spontaneous nonsustained ventricular tachycardia (NSVT) on Holter in a large patient population with IDC. METHODS: 24-h digital Holter recordings including HRV analysis and BRS testing were prospectively performed in 137 patients with IDC and preserved sinus rhythm. Mean age was 48 +/- 12 years, and mean left ventricular (LV) ejection fraction was 32 +/- 9%. The HRV analysis on Holter included the mean RR interval (RRm), the standard deviation of all normal RR intervals (SDNN), the square root of the mean of the squared differences between adjacent normal RR intervals (rMSSD), and the proportion of adjacent normal RR intervals differing more than 50 ms (pNN50). Testing for BRS was performed noninvasively using the phenylephrine method. RESULTS: Of 137 study patients, 42 (31%) had spontaneous NSVT on 24-h Holter. Compared with patients without NSVT, patients with NSVT on Holter had a higher New York Heart Association (NYHA) functional class (NYHA III: 40 vs. 18%, p < 0.01), a lower ejection fraction (29 +/- 9 vs. 34 +/- 9%, p = 0.01), and an increased LV end-diastolic diameter (69 +/- 8 mm vs. 66 +/- 7 mm, p = 0.03). The HRV variables rMSSD, pNN50, RRm, and BRS did not differ significantly between patients with and without spontaneous NSVT. Only SDNN on Holter was slightly lower in patients with versus without NSVT (106 +/- 45 vs. 121 +/- 46 ms, p = 0.08). CONCLUSIONS: Patients with IDC and spontaneous NSVT on Holter are characterized by a higher NYHA functional class, a lower LV ejection fraction, an increased LV end-diastolic diameter, and a tendency toward a lower SDNN value compared with patients without NSVT. The remaining measures of HRV including rMSSD and pNN50 reflecting primarily tonic vagal activity, as well as BRS reflecting predominantly reflex vagal activity, were similar in patients with and without NSVT. The prognostic significance of these findings in patients with IDC is currently under investigation in the Marburg Cardiomyopathy Study (MACAS) at our institution.

Adolescent↗
PubMed2000

Patterns, chunks, and hierarchies in serial reaction-time tasks.

The impact of relational structures (i.e., the systematicity of relations between successive items) on incidental sequence learning was investigated in a serial reaction-time (SRT) task while keeping constant the statistical structure. In order to assess the influence of relational structures in stimulus and response sequences separately, the strength of relational patterns in sequences of digits as stimuli and of keystrokes as responses was orthogonally varied. In Exps. 1 and 2, the variation of relational patterns was mainly effective in the keystroke sequence. In Exp. 2, in addition to the variation of relational patterns, the presentation of stimuli was delayed at serial positions that were incongruent with the relational structure. The results show that these incongruent pauses reduced the learning of strongly structured sequences of keystrokes but improved the learning of weakly structured sequences. Experiment 3 suggests that even higher-order relations between elementary patterns are utilized to accelerate responses. The data are interpreted as evidence for the impact of relational patterns, in addition to statistical redundancies, on the formation of chunks. Reasons are discussed for the finding that relational chunking was more pronounced in the keystroke than in the digit sequences.

Adolescent↗
PubMed2000

Prediction of major arrhythmic events and sudden cardiac death in dilated cardiomyopathy. The Marburg Cardiomyopathy Study design and description of baseline clinical characteristics.

The Marburg Cardiomyopathy Study (MACAS) is a prospective observational study designed to determine the value of the following potential non-invasive arrhythmia risk predictors in more than 200 patients with idiopathic dilated cardiomyopathy (IDC) over a 5-year follow-up period: New York Heart Association functional class, left ventricular end-diastolic diameter and ejection fraction, left bundle branch block and atrial fibrillation on ECG, QTc and JTc-dispersion on 12-lead ECG, abnormal time-domain analysis and spectral turbulence analysis of the signal-averaged ECG, ventricular arrhythmias and heart-rate variability on 24-hour Holter ECG, baroreflex sensitivity, and microvolt T wave alternans during exercise. This report describes the rationale of MACAS as well as the clinical characteristics of the first 236 patients enrolled between March 1996 and October 1999. The prognostic significance of the potential arrhythmia risk predictors in MACAS will be determined by multivariate Cox analysis at the end of 5-year follow-up. Primary endpoints are total mortality and major arrhythmic events defined as sustained ventricular tachycardia, ventricular fibrillation or sudden cardiac death. The results of MACAS will have important implications for the design of future studies evaluating the role of prophylactic defibrillator therapy in idiopathic dilated cardiomyopathy.

Adolescent↗
PubMed2000

[Correlation between cardiac autonomic activity and compromise of left ventricular function in dilated cardiomyopathy].

In recent years, evaluation of cardiac autonomic activity by means of heart rate variability (HRV) determination and baroreflex sensitivity (BRS) testing has become readily available. The results of the ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) study showed that both diminished HRV and baro-reflex sensitivity are associated with poor outcome in patients after myocardial infarction. In contrast to patients with coronary disease little information is available concerning cardiac autonomic activity in idiopathic dilated cardiomyopathy (IDC). Therefore, HRV and BRS were assessed in 160 patients with IDC and preserved sinus rhythm in order to investigate the relationship between HRV, BRS, and left ventricular ejection fraction. Time domain indices of HRV were computed from 24-hour digital Holter recordings. BRS testing was performed using the noninvasive phenylephrine method. Mean standard deviation of all normal RR intervals (SDNN) of the whole study population was 112 +/- 46 ms. A well preserved HRV (SDNN > 105 ms) was found in 74 patients (46%), a moderately decreased HRV (SDNN 70-105 ms) in 59 patients (37%), and a severely decreased HRV (SDNN < 70 ms) in 27 patients (17%). Mean BRS was 7.5 +/- 5.0 ms/mm Hg. A well preserved BRS (> 6 ms/mm Hg) was present in 78 patients (57%), a moderately decreased BRS (3-6 ms/mm Hg) was present in 38 patients (28%), and a severely decreased BRS (< 3 ms/mm Hg) in 21 patients (15%). There was only a weak correlation between SDNN and BRS (r = 0.19; p < 0.05). A weak correlation was found for SDNN and left ventricular ejection fraction (r = 0.29; p < 0.05). There was no significant correlation between BRS and left ventricular ejection fraction (r = 0.14). In summary, there was only a weak correlation between the HRV, BRS, and left ventricular ejection fraction in patients with IDC suggesting that these 3 variables may be independent predictors of sudden death in IDC. The relative prognostic value of these variables and other potential risk predictors including the presence of arrhythmias on Holter, microvolt T wave alternans, QTc dispersion, and signal-averaged ECG is currently under investigation in a large prospective observational study (Marburg Cardiomyopathy Study (MACAS)) during 5-year follow-up at our institution.

Adolescent↗
PubMed2000

[Polytopic manifestations of paragangliomas. Diagnosis, differential diagnosis and indications for therapy].

Paragangliomas of the glomus caroticum are relatively rare, but highly vascularized neoplasmas, which develop from chemoreceptors. They can be develop at any age, but most often in the third or fourth decade of life. Paragangliomas grow very slowly and are most always of benign origin. There is a familial predisposition, and an autosomal-dominant transmission is presumed. They are commonly located in the jugular region; in rare cases a polytopic manifestation is found. We describe the case of a 47-year-old male patient who was referred to our department because of a progressive swelling of the neck on both sides. Contrast-enhanced computed tomography had displayed soft tissue tumors in the jugular regions. We performed an operative exploration, which showed a highly vascularized tumor. Histopathologic analysis revealed the diagnosis of a paraganglioma. An angiography of the neck and thoracic region, furthermore, revealed an additional paraganglioma in the anterior mediastinum. Using a surgical approach via lateral cervicotomies and thoracotomy the paragangliomas were extirpated. Our case report demonstrates the rare polytopic manifestation of paragangliomas. This perivascular neoplasms have to be removed before haemodynamic complications develop. The extent of this tumors is clearly illustrated by use of an angiography. Because of the familial predisposition, clinical and radiological examinations of relatives are mandatory.

Carotid Body↗
PubMed2000

The role of stimulus-based and response-based spatial information in sequence learning.

In 4 experiments, relational structures were independently varied in stimulus and response sequences in a serial reaction time task. Moreover, the use of spatial and symbolic stimuli and responses was varied between experiments. In Experiment 1, spatial stimuli (asterisk locations) triggered spatial responses (keystrokes); in Experiment 2, spatial stimuli triggered symbolic responses (verbal digit naming); in Experiment 3, symbolic stimuli (digits) triggered keystrokes; and in Experiment 4, digits triggered verbal responses. The results showed that there is a remarkably stronger effect of relational structures in spatial sequences than in symbolic sequences, irrespective of whether stimulus or response sequences are concerned. This suggests that learning is particularly effective for sequences of spatial locations. It is argued that spatial learning is a critical determinant for the debate on perceptual and motor learning.

Adult↗