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Biomedical subjects

J Hoffmann

Publications and source records attributed to J Hoffmann.

At least 109 records · Page 6Linked to original sources
PubMed1999

[Surgical therapy of basalioma of the facial skin].

The present investigation reviews the history of 673 patients having undergone surgical treatment for 1301 BCC of the face between 1977 and 1992 at our department. Based on this series the features with bearing on the surgical strategy, such as type, size and location of the lesions, will be outlined. Emphasis is put on the variants of local flap reconstruction and skin grafting techniques, particularly in the problem zones of the nose and eyelids, where no excess skin for closure of the defect is available. Throughout the whole series histologic control of the adequacy of marginal and deep tumor resection was performed. It became obvious that the required ranges for clearance to tumor edges and removal in depth cannot be predefined arbitrarily or on pure clinical judgement. Frequently a two-stage procedure of resection and repair will be necessitated. Recurrences during the mandatory follow-up were thoroughly reassessed to identify the reason for failure (e.g. accuracy of histologic category, multifocal growth, predisposition) and related to the time span from primary excision. Our series confirms that morphologically controlled surgical excision of the BCC of the face and subsequent application of reconstructive techniques produces both safe oncologic and esthetic results.

Adolescent↗
PubMed1999

[Prospective evaluation of effect of carvedilol therapy on heart rate variability in patients with dilated cardiomyopathy].

The aim of the present study was to assess the effects of carvedilol therapy in addition to conventional heart failure therapy on heart rate variability (HRV) and on left ventricular function in 14 patients with mild to moderate heart failure due to idiopathic dilated cardiomyopathy (IDC). After a 3- to 4-week titration period, carvedilol was titrated up to 50mg daily, or the highest dose tolerated (at least 25mg daily). Maintenance treatment was then continued for 8 weeks. Digital 24-hour Holter recordings were obtained at baseline and after 8 weeks of carvedilol therapy. HRV for the entire 24-hour period was computed in the time domain using the Oxford Medilog Excel 2 analysis system. Measures of HRV included the mean of all coupling intervals between normal beats (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 >50 ms (pNN50). Additional treatment with carvedilol induced a significant increase in HRV: SDNN increased from 77+/-21 ms to 110+/-22 ms (p=0.001), rMSSD from 19+/-7 ms to 26+/-7 ms (p=0.02), and mean pNN50-value increased from 1.7+/-1.3% to 5.5+/-4.5% (p<0.01) under therapy with carvedilol. Mean heart rate on carvedilol calculated over 24 hours was 13 beats less than at baseline (75 bpm versus 88 bpm, p<0.01). After 2 months of additional treatment with carvedilol, both hemodynamic and clinical parameters improved: left ventricular ejection fraction increased from 24+/-7% to 30+/-10% (p<0.05), and New York Heart Association class decreased from 2.5+/-0.8 to 1.8+/-0.7 (p<0.05). In summary, eight weeks of additional carvedilol therapy induced a significant increase in HRV parameters related to parasympathetic activity in patients with IDC. Whether increased vagal tone may contribute to the protective effect of carvedilol has to be evaluated by further studies.

Adrenergic beta-Antagonists↗
PubMed1999

Dietary fiber reduces the antioxidative effect of a carotenoid and alpha-tocopherol mixture on LDL oxidation ex vivo in humans.

BACKGROUND: Antioxidant concentrations in low density lipoproteins (LDL) are an important determinant for their susceptibility to oxidation and can be modulated by dietary intake. AIM OF THE STUDY: In the present study, the influence of dietary fiber on the antioxidant enrichment and the oxidation resistance of LDL after antioxidant supplementation is investigated. METHOD: An antioxidant supplement consisting of beta-carotene, lycopene, lutein, canthaxanthin and alpha-tocopherol was given to six young women together with a standard meal. Using a cross-over study design, each subject received the standard meal without additional dietary fiber and enriched with pectin, guar, or cellulose in a random order. To determine the resistance of LDL against copper ion-induced oxidation, the formation of conjugated dienes was measured. RESULTS: Eight, 10, and 24 hours after antioxidant supplementation the isolated LDL revealed significantly (p < 0.05) increased antioxidant concentrations; addition of pectin, guar, or cellulose to the meal depressed this increase. Concomitantly, the observed increase in the resistance of LDL against oxidation (measured as lag phase) was lower with dietary fiber supplementation than that found without. On average, pectin, guar, and cellulose reduced the increase of the lag phase (measured without addition of dietary fiber) by 38%, 22%, and 18%, respectively. CONCLUSIONS: These results indicate that dietary fiber supplementation decreases the antioxidative effect of a supplement consisting of carotenoids and alpha-tocopherol in LDL, an effect that is likely to be mediated by a reduced bioavailability of these antioxidants in the gut.

Adult↗
PubMed1999

Switch from antagonist to agonist of the androgen receptor bicalutamide is associated with prostate tumour progression in a new model system.

Advanced prostate cancer is treated by androgen ablation and/or androgen receptor (AR) antagonists. In order to investigate the mechanisms relevant to the development of therapy-resistant tumours, we established a new tumour model which closely resembles the situation in patients who receive androgen ablation therapy. Androgen-sensitive LNCaP cells were kept in androgen-depleted medium for 87 passages. The new LNCaP cell subline established in this manner, LNCaP-abl, displayed a hypersensitive biphasic proliferative response to androgen until passage 75. Maximal proliferation of LNCaP-abl cells was achieved at 0.001 nM of the synthetic androgen methyltrienolone (R1881), whereas 0.01 nM of this compound induced the same effect in parental cells. At later passages (> 75), androgen exerted an inhibitory effect on growth of LNCaP-abl cells. The non-steroidal anti-androgen bicalutamide stimulated proliferation of LNCaP-abl cells. AR protein expression in LNCaP-abl cells increased approximately fourfold. The basal AR transcriptional activity was 30-fold higher in LNCaP-abl than in LNCaP cells. R1881 stimulated reporter gene activity in LNCaP-abl cells even at 0.01 nM, whereas 0.1 nM of R1881 was needed for induction of the same level of reporter gene activity in LNCaP cells. Bicalutamide that acts as a pure antagonist in parental LNCaP cells showed agonistic effects on AR transactivation activity in LNCaP-abl cells and was not able to block the effects of androgen in these cells. The non-steroidal AR blocker hydroxyflutamide exerted stimulatory effects on AR activity in both LNCaP and LNCaP-abl cells; however, the induction of reporter gene activity by hydroxyflutamide was 2.4- to 4-fold higher in the LNCaP-abl subline. The changes in AR activity were associated neither with a new alteration in AR cDNA sequence nor with amplification of the AR gene. Growth of LNCaP-abl xenografts in nude mice was stimulated by bicalutamide and repressed by testosterone. In conclusion, our results show for the first time that the nonsteroidal anti-androgen bicalutamide acquires agonistic properties during long-term androgen ablation. These findings may have repercussions on the natural course of prostate cancer with androgen deprivation and on strategies of therapeutic intervention.

Androgen Antagonists↗
PubMed1999

Some dietary fibers reduce the absorption of carotenoids in women.

Dietary fiber may be partly responsible for the lower bioavailability of carotenoids from food than from purified supplements. Due to the lack of detailed information available, we investigated the effects of different kinds of dietary fiber on the absorption of carotenoids and alpha-tocopherol. Six healthy young women received an antioxidant mixture consisting of beta-carotene, lycopene, lutein, canthaxanthin and alpha-tocopherol together with a standard meal. The meal did not contain additional dietary fiber or was enriched with pectin, guar, alginate, cellulose or wheat bran (0. 15 g. kg body weight(-1)). The increases in plasma carotenoid and alpha-tocopherol concentrations were followed over 24 h, and the areas-under-curves (AUC(24h)) were calculated. The mean AUC(24h) of beta-carotene was significantly (P < 0.05) reduced by the water-soluble fibers pectin, guar and alginate with a mean decrease of 33-43%. All tested fibers significantly reduced the AUC(24h) of lycopene and lutein by 40-74% (P < 0.05). The dietary fiber effect on the AUC(24h) of canthaxanthin was almost significant (P = 0.059) and there was no effect on the AUC(24h) of alpha-tocopherol. We conclude that the bioavailability of beta-carotene, lycopene and lutein given within a mixed supplement is markedly reduced by different kinds of dietary fiber.

Absorption↗
PubMed1999

Complications of third-generation implantable cardioverter defibrillator therapy.

To determine the incidence of complications of third-generation implantable cardioverter defibrillator (ICD) therapy, 144 patients were prospectively studied who underwent first implant of third-generation devices (i.e., ICD systems with biphasic shocks, ECG storage capability, and nonthoracotomy lead systems). During 21 +/- 15 months of follow-up, 41 (28%) patients had one or more complications. No patient died perioperatively (30 days) and no ICD infection was observed during follow-up. Complications included bleeding or pocket hematoma (hemoglobin drop > 2 g/dL) in 5 (3%) patients, prolonged reversible ischemic neurological deficit in 1 (1%) patient, postoperative deep venous thrombosis of leg in 1 (1%) patient, pneumothorax in 2 (1%) patients, difficulty to defibrillate ventricular fibrillation intraoperatively in 2 (1%) patients, generator malfunction in 1 (1%) patient, arthritis of the shoulder in 3 (2%) patients, and allergic reaction to prophylactic antibiotics in 2 (1%) patients. A total of seven lead related complications were observed in six (4%) patients including endocardial lead migration in four (3%) patients. Twenty-three (16%) patients received inappropriate shocks for supraventricular tachyarrhythmias (n = 13), non-sustained ventricular tachycardia (VT) (n = 7), or myopotential oversensing (n = 3). We conclude that serious complications such as perioperative death or ICD infection are rare in patients with third-generation ICDs. Lead-related problems and inappropriate shocks during follow-up are the most frequent complications of third-generation ICD therapy. Recognition of these complications should promote advances in ICD technology and management strategies to avoid their recurrence.

Defibrillators, Implantable↗
PubMed1999

Transient QT prolongation with torsades de pointes tachycardia after ablation of permanent junctional reciprocating tachycardia.

INTRODUCTION: Catheter ablation with radiofrequency energy is a curative therapy in patients with permanent junctional reciprocating tachycardia (PJRT). METHODS AND RESULTS: For the first time, we report a case of transient QT prolongation with torsades de pointes tachycardia 18 hours after successful radiofrequency energy ablation of PJRT in a 25-year-old woman with tachycardia-induced cardiomyopathy. Of note, the torsades de pointes occurred in the absence of bradycardia, electrolyte disturbances, or QT-prolonging drugs. This patient initially was thought to have a hereditary long QT syndrome that was unmasked by PJRT ablation. Therefore, the patient received an implantable defibrillator in addition to beta-blocker therapy, which was discontinued 6 months later. Surprisingly, the QT interval completely normalized within 1 week after PJRT ablation, and the patient remained free of arrhythmias during a follow-up period of 4.5 years. CONCLUSION: Patients with incessant tachyarrhythmias should undergo ECG monitoring for at least 24 hours following successful radiofrequency catheter ablation because transient QT prolongation with torsades de pointes may occur even in the absence of bradycardia, QT-prolonging drugs, or electrolyte disturbances.

Adult↗
PubMed1999

Experimental comparative study of various mouthguards.

The aim of this study was to evaluate the mechanical and physical properties of several standard size commercially available mouthguards. For the purpose of objective testing, a special study model, which the various gum shield devices could be fitted onto, was developed to record tooth deflection caused by impact forces induced by a pendulum ram impact testing machine. The data measured on teeth provided with various gum shield devices were correlated with those of unprotected teeth; this enabled the individual cushioning effects of the respective devices and their specific force conduction to be evaluated. Using mouthguards considerably diminishes the deflection of the teeth subjected to stress in comparison with the row of unprotected teeth. In addition, force is transmitted to the adjacent teeth all the way to the distal regions of the row of teeth. The individual cushioning effects are directly correlated to the thickness of the material; the force distribution is determined by the rigidity of the gum shield device. The devices examined showed considerable differences with regard to force distribution and dimensioning. The study showed that this was due to the thickness of the materials, the manufacturing process and the composition of the materials of the devices examined. In comparison to laboratory-produced devices of similar material thickness, the devices that were designed to be fitted by the user achieved significantly poorer results as regards both cushioning properties and dissipation of exerted forces.

Athletic Injuries↗
PubMed1999

Induction of TFF1 gene expression in pancreas overexpressing transforming growth factor alpha.

BACKGROUND/AIMS: Chronic pancreatitis is an inflammatory disease of the exocrine pancreas associated with extensive fibrosis, enlarged pancreatic ducts, acinar cell degeneration, and the formation of tubular complexes. The molecular and biochemical alterations associated with these histological changes are not kown. Generally, the new family of TFF peptides (formerly known as P-domain peptides or trefoil factors) is aberrantly expressed during chronic inflammatory diseases of the gastrointestinal tract. METHODS: Using human pancreatic tissues obtained from patients with chronic pancreatitis and murine pancreatic tissues obtained from transgenic mice overexpressing transforming growth factor alpha (TGF-alpha), the expression and cellular distribution of TFF1 was analysed using northern blot analysis, polymerase chain reaction (PCR), and immunohistochemistry. RESULTS: In the normal human pancreas, TFF1 was scarce, with only a few ducts exhibiting cytoplasmic TFF1 immunoreactivity. In contrast, human chronic pancreatitis tissue specimens exhibited strong TFF1 immunoreactivity in ductal cells, areas of ductal hyperplasia, and tubular complexes. Semiquantitative PCR analysis of TFF1 mRNA levels showed enhanced expression of TFF1 in the pancreas of patients with chronic pancreatitis. Furthermore, TFF1 mRNA levels were detectable in the pancreas in four of five transgenic mice overexpressing TGF-alpha. In contrast, four of five wild type mice did not exhibit a TFF1 mRNA transcript. In addition, while no specific TFF1 immunoreactivity was present in the pancreas of the wild type mice, ductal epithelial cells and duct-like tubular complexes in the pancreas of the transgenic mice overexpressing TGF-alpha exhibited pronounced TFF1 immunoreactivity. CONCLUSIONS: Ductal cells and tubular complexes in pancreatic fibrosis express TFF1. As the 5'-flanking region of TFF1 contains an epidermal growth factor responsive enhancer region and the expression of epidermal growth factor and TGF-alpha is enhanced in pancreatic fibrosis, the enhanced expression of TFF1 in pancreatic fibrosis may be mediated by TGF-alpha.

Adolescent↗
PubMed1999

Binding and selective detection of the secretory N-terminal domain of the alzheimer amyloid precursor protein on cell surfaces.

The secretory N-terminal domain of the Alzheimer amyloid precursor protein (sAPP) evokes specific responses in cells on binding to their surfaces. Because APP is expressed in a large variety of cell types, the localization of sAPP binding requires detection techniques that selectively recognize sAPP as a ligand. For this purpose, we prepared antibodies against recombinant sAPP695 (sAPPrec) previously expressed in E. coli. Such antibodies were found to distinguish between sAPPrec and cellular APP or sAPP, as shown by immunocytochemistry and by immunoblot. In addition, they allowed the selective localization of bound sAPPrec on cell surfaces without any signal from cellular APP or sAPP. Saturation of sAPPrec binding to cell surfaces, as determined radiometrically, was reached at 10 nM [125I]-sAPPrec. Binding was specific because it was almost completely inhibited by a 100-fold excess of unlabeled sAPPrec. This specificity of binding was confirmed by surface plasmon resonance spectroscopy. Binding of sAPPrec to cell surfaces occurred in patches and was dependent on the state of cell differentiation. The sAPPrec used in this study contains heparin binding sites, but enzymatic removal of cell surface associated heparin did not affect sAPPrec binding. Aldehyde fixation of cells strongly inhibited their ability to bind sAPPrec. The data point to a fixation-sensitive sAPPrec binding protein which is detectable in the form of patches and therefore is part of assembled cell surface microdomains.

Amyloid beta-Protein Precursor↗
PubMed1999

Anticancer drug sensitivity and expression of multidrug resistance markers in early passage human sarcomas.

We have established new human sarcoma lines and examined their sensitivity to common antitumor drugs and expression of putative multidrug resistance (MDR) proteins. Eighty-two sarcoma samples were transplanted in nude mice. Fourteen of these sarcomas were established as tumor cell lines. We determined a chemosensitivity profile to antitumor drugs (MDR drugs = doxorubicin, mitoxantrone, and vincristine; non-MDR drugs = cisplatin, ifosfamide, and bleomycin) for each tumor line in vivo. Response to chemotherapy with doxorubicin and ifosfamide was observed in 30-50% of these tumor lines. Our results obtained with xenotransplants are similar to the results documented in clinical trials in which doxorubicin and ifosfamide are effective in 30-50% of the patients. Furthermore, we examined expression of MDR-relevant markers like P-glycoprotein, MDR-associated protein, lung resistance protein, and mdr1 mRNA in these xenotransplants. A relationship between mdr1 mRNA expression and response to doxorubicin was demonstrated in >90% of our tumor lines. In six sarcomas with mdr1 mRNA expression, five were resistant against doxorubicin and cross-resistant against several other drugs, whereas from eight sarcomas, which lacked detectable mdr1 mRNA, seven were sensitive to doxorubicin and other drugs. We found lung resistance protein or MDR-associated protein expressed in three resistant and mdr1 mRNA-positive sarcomas. These results demonstrate that mdr1 mRNA expression is a putative marker for drug resistance in our sarcoma lines. We conclude, therefore, that inherent P-glycoprotein expression might be also responsible for drug resistance occurring in treatment of patients with sarcomas. The established tumor lines are useful for additional investigations on mechanisms of drug resistance in sarcomas and as models for preclinical screening of new antitumor drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Effect of a single oral dose of antioxidant mixture (vitamin E, carotenoids) on the formation of cholesterol oxidation products after ex vivo LDL oxidation in humans.

During oxidation of LDL not only polyunsaturated fatty acids and apolipoproteins but also cholesterol is affected. To test the preventive effect of vitamin E and carotenoids against metal ion-induced oxidative modification of the cholesterol moiety, LDL of five females (age 25-30 years) were enriched by single oral supplementation with a mixture of alpha-tocopherol, beta-carotene, lycopene, canthaxanthin, and lutein. LDL was isolated from blood samples before as well as 10 and 24 hours after supplement intake. In the 10 and 24 hours samples, total concentration of the supplemented antioxidants increased significantly to 127% and 125% of the initial value, respectively. As a consequence, the lag phase until beginning of oxidative modification of fatty acids--measured in terms of lag phase time till diene production--significantly increased by 13% (10 h and 24 h). After stopping the oxidation process in all LDL samples (0 h, 10 h, 24 h) of one person when the maximal absorbance value of diene production in the 10 h sample was reached, a statistically significant reduction in the formation of cholesterol oxidation products (COP) could be measured. In the average, 10 h and 24 h after supplementation the COP concentration reached 84% and 86% of the 0 h-value, respectively. Except for 7 beta-hydroxycholesterol, all COP measured decreased by 10-20%. The results of the in vitro-model demonstrate that an antioxidant enrichment of LDL has the potential to protect also cholesterol (besides unsaturated fatty acids) against oxidative modification.

Administration, Oral↗
PubMed1998

From differentiation to proliferation: the secretory amyloid precursor protein as a local mediator of growth in thyroid epithelial cells.

In various species, thyrotropin (TSH) is known to stimulate both differentiation and proliferation of thyroid follicle cells. This cell type has also been shown to express members of the Alzheimer amyloid precursor (APP) protein family and to release the secretory N-terminal domain of APP (sAPP) in a TSH-dependent fashion. In this study on binding to the cell surfaces, exogenously added recombinant sAPP stimulated phosphorylation mediated by mitogen-activated protein kinase and effectively evoked proliferation in the rat thyroid epithelial cell line FRTL-5. To see whether this proliverative effect of sAPP is of physiological relevance, we used antisense techniques to selectively inhibit the expression of APP and the proteolytic release of sAPP by cells grown in the presence of TSH. The antisense-induced inhibition was detected by immunoblot, immunoprecipitation, and immunocytochemical analyses. After the reduced APP expression and sAPP secretion, we observed a strong suppression of the TSH-induced cell proliferation down to 35%. Recombinant sAPP but not TSH was able to overcome this antisense effect and to completely restore cell proliferation, indicating that sAPP acts downstream of TSH, in that it is released from thyroid epithelial cells during TSH-induced differentiation. We propose that sAPP operates as an autocrine growth factor mediating the proliferative effect of TSH on neighboring thyroid epithelial cells.

Amyloid beta-Protein Precursor↗
PubMed1998

Simplified implantation of single-lead pectoral cardioverter defibrillators using device-based testing.

Device-based testing of single-lead pectoral defibrillators (defibrillation efficacy testing without an external defibrillation system after complete implantation of the device) resulted in an adequate defibrillation threshold (< or = 20 J) in 45 of 50 study patients (90%). Mean surgical implantation time (skin to skin) was 62 +/- 29 minutes without perioperative mortality and without implantable cardioverter defibrillator infection during follow-up. Thus, device-based testing appears to be a simple and safe method to test defibrillation efficacy of single-lead pectoral defibrillators.

Adolescent↗
PubMed1998

Cysteine-rich antimicrobial peptides in invertebrates.

Antimicrobial peptides are pivotal elements of the innate immune defense against bacterial and fungal infections. Within the impressive list of antimicrobial peptides available at present, more than half have been characterized in arthropods. Cysteine-rich antimicrobial peptides represent the most diverse and widely distributed family among arthropods and, to a larger extent, among invertebrates. Proeminent groups of cysteine-rich peptides are peptides with the CS alpha beta motif and peptides forming an hairpin-like beta-sheet structure. Although these substances exhibit a large structural diversity and a wide spectrum of activity, they have in common the ability to permeabilize microbial cytoplasmic membranes. Drosophila has proved a remarkable system for the analysis of the regulation of expression of gene encoding antimicrobial cysteine-rich peptides. These studies have unraveled the striking parallels that exist between insect immunity and innate immunity in mammals that point to a common ancestry of essential aspects of innate immunity.

Amino Acid Sequence↗
PubMed1998

Endocytosis and membrane turnover in the germ tube of uromyces fabae

We have used the fluorescent dye FM4-64 as a tracer to demonstrate bulk membrane internalization (endocytosis) and redistribution of the dye within the cytoplasm of the germ tube of the rust fungus Uromyces fabae. Staining of the hyphal membrane was detected 4 s after application of FM4-64 and reached a maximum after 1 min. The highest fluorescence intensity occurred in the apex. Subsequently, staining of the plasma membrane decreased and a subapical region of the fungal protoplast (5-20 &mgr;m from the tip) displayed increasing fluorescence with a maximum after 5 min. Fluorescence in the subapical region was redistributed to an area in the hyphal tip, which corresponds to the accumulation of apical vesicles, after 10-15 min and subsequently to a cytoplasmic region in front of the two nuclei (35-45 &mgr;m from the tip). We conclude from our measurements of membrane fluorescence that the turnover time from endocytosis to secretion of the dye amounts to 15 min. The uptake of the dye into the cytoplasm, but not membrane loading, could be inhibited completely with 5 mM NaN3 or by a temperature shift to 4 degreesC. This is the first evidence for endocytosis in a fungal germ tube. Copyright 1998 Academic Press.

Journal Article↗