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Biomedical subjects

S Hofmann

Publications and source records attributed to S Hofmann.

At least 55 records · Page 3Linked to original sources
PubMed2000

Changes in left and right ventricular cardiac function after valve replacement for aortic stenosis determined by cine MR imaging.

The purpose of this study was to determine the changes in function of both the left and the right ventricles (LV, RV) before and after aortic valve replacement (AVR), compared with age-matched healthy volunteers using magnetic resonance (MR) imaging. Fourteen patients with aortic stenosis underwent MR imaging (1.5 T) before and 3 (n = 14) and 12 (n = 9) months after surgical valve replacement. An electrocardiographically triggered two-dimensional cine fast low-angle shot sequence was used for the evaluation of absolute values and indices related to 1 m(2) body surface area for function, mass, and LV wall thickening. Fourteen age-matched healthy volunteers served as controls. Before surgery, all patients showed significant abnormalities of LV mass and function, whereas RV mass and function were not different from those of volunteers and remained mostly unchanged. After surgery, normalization of LV ejection fraction, absolute mass, and end-systolic wall thickness was observed, whereas the LV mass index failed to normalize, and LV volumes remained elevated. Aortic stenosis combined with a significant, but not severe reduction in LV function only affects the LV, whereas the RV remains unaffected at this stage of disease. AVR leads to improved LV function and reduced hypertrophy, but without normalization of LV volumes or the LV mass index within 1 year.

Aged↗
PubMed2000

[Diagnostic imaging in femur head necrosis].

Diagnosis of avascular necrosis (AVN) of the hip has been improved by the technical progress of imaging modalities during the last decade. For a long period, only plain radiographs had been available. Scintigraphy and computed tomography contributed to differential diagnosis and early detection of bone necrosis. In the meantime, MR imaging has gained special value in the evaluation of AVN. It is now the method of choice for early detection as well as for assessment in later stage disorders. Using the ARCO system, all imaging modalities and their diagnostic viability are described. Findings regarding the different stages of AVN are correlated to tissue-specific changes.

Diagnostic Imaging↗
PubMed2000

[Pathomorphological aspects and repair mechanisms of femur head necrosis].

The pathomorphologies of non-traumatic femoral head osteonecroses (ON) are usually similar, despite various known pathogenetic factors. The size and position of the subchondral bone and marrow segment, becoming necrotic after the ischemic event(s), and the kind of repair processes determine the time course and thus the fate of this hip joint disease. Four cases of conservatively or core decompression-treated femoral head ON were selected to demonstrate differently effective repair mechanisms which are discussed in respect to existing therapeutic concepts. Diagnostic criteria from magnetic resonance imaging follow-ups were correlated with light microscopy findings on undecalcified ground and microtome sections from femoral heads retrieved at total joint replacement. Initial stage (ARCO 0) and reversible early stage ON (ARCO 1) after incomplete ischemias can apparently show spontaneous sufficient repair. After extensive and complete ischemia, however, ON progresses without detectable changes on plain radiographs into irreversible early stage ON (ARCO stage 2). Only in exceptional cases (with small, medially located necroses), a spontaneous sufficient repair seems possible. Usually, early ARCO stage 2 ON with intact articular surface shows no remodeling of the subchondral necrotic bone and fatty marrow, but only ineffective repair with fibrovascular tissue invasion and bone resorption at the vital bone border. Repeated bone appositions on partly resorbed necrotic trabeculae form the sclerotic rim in this pathognomonic reactive interface. New bone formation can also be increased underneath the necrotic area and reactive interface when surrounded by accompanying bone marrow edema. Core decompression in ARCO stage 2 ON, even if it reaches the necrotic lesion, can at best delay progression of the disease, but never leads to complete reconstruction of the necrotic area. More likely, after both conservative and operative treatment, destructive resorption without effective consecutive bone formation will lead sooner or later to collapse of the articular surface and thus to mechanical instability of transition stage ON (ARCO stage 3). On the other hand, this subchondral fracture can apparently also cause reconstructive repair which, by involving chondral and membranous ossification in this "creeping substitution", can reduce the necrotic area. However, it cannot prevent progression into late stage ON (ARCO stage 4) with secondary joint destructions. Principally, besides the rare sufficient repair in initial and certain early ON, three forms of insufficient repair in the necrotic area can be distinguished: lack of remodeling, destructive remodeling, and reconstructive remodeling. To date, no therapeutical intervention exists which leads to complete healing of irreversible ON stages by reconstructive repair. Improved understanding of pathomorphology and repair mechanisms, however, could be the basis for future therapeutical concepts which should aim at the complete regeneration of the osteonecrotic area.

Adult↗
PubMed2000

[Osteonecrosis: natural course and conservative therapy].

The natural course of Osteonecrosis (ON) of the femoral head has yet not been evaluated sufficiently. Especially in the early forms of the disease (ARCO 0 to II) without collapse of the femoral head, useful information on the natural course could only be collected since the routine use of MR-imaging. The unspecific findings in ARCO stage I with negative radiographs are potential reversible. The "point of no return" already lies in the irreversible ARCO stage II in almost all cases. Prognosis for further progression for both early stages depends primarily on the extension and location of the lesion. Only the rare, small to medium sized lesions in the medial or central location may have a good prognostic course over a period of more than five years. The much more common large sized and lateral located lesions will have a probability of about 80% to progress to femoral head collapse within two years. Conservative therapy with single protected weight bearing has shown bad results not significantly different from the natural course of the disease. Pulsed electromagnetic fields are still discussed controversially. Until now there is no MRI controlled study available in early ON, showing superior results compared to the easy and cost-effective core decompression therapy. The extra corporal shock wave therapy has shown spontaneous pain relief in early ON. Midterm results of this new therapeutical concept are not available yet. Hyperbaric oxygen therapy has shown to stimulate the repair process in an animal experiment. The preliminary clinical results of this time and cost consuming therapy are not convincing. Vasoactive drugs in combination with limited weight bearing may play a role in the conservative management of early ON (ARCO I and part of ARCO II) in the future. For the conservative therapy in ON several other substance are currently in clinical testing. The benefit of conservative therapeutical concepts in ON in the future can only be evaluated with prospective MRI controlled clinical studies. The use of cytokines in combination with surgical debridement and bone grafting of the necrotic area may be a possible therapeutical concept for the future.

Disease Progression↗
PubMed2000

["Transient osteoporosis" as a special reversible form of femur head necrosis].

There is still controversy whether transient osteoporosis of the hip joint represents a distinct self-limiting disease, or reflects only an early, reversible subtype of non-traumatic osteonecrosis (ON). Transient osteoporosis has several synonyms: algodystrophy of the hip; transient marrow oedema; or bone marrow oedema syndrome--BMOES. Clinical presentation of BMOES shows mechanical hip joint pain, ON risk factors, and a diffuse bone marrow oedema in MR imaging. Histomorphological changes resemble early ON, but with diffuse sufficient repair in BMOES and focal and insufficient repair only at the border of the necrotic lesion in ON. Therefore the clinical course and outcome are significant different, with restitution occurring in BMOES, while progressive destruction of the joint takes place in ON. So far, the preferred treatment strategies are protected weight bearing for BMOES, but operative treatment for ON. In a prospective study of patients with BMOES, the clinical, radiographic, and MRI course of 43 hip joints after core decompression treatment were investigated. All patients showed immediate relief of pain after surgery and the average duration of symptoms with conservative treatment could be dramatically reduced by core decompression from 6 months down to 2 months. There were no perioperative complications. Based on our experience with over 100 BMOES patients, we are convinced that this syndrome represents not a distinct disease but an early reversible subtype of non-traumatic ON. Due to the excellent clinical results of core decompression, we recommend this operative therapeutical concept in patients with painful BMOES.

Adult↗
PubMed2000

[The value of core decompression in treatment of femur head necrosis].

Core decompression of the necrotic area for treatment of idiopathic osteonecrosis of the femoral head was developed and published by Ficat and Arlet in 1962 within the scope of their "Functional exploration of bone". The mode of action is attributed to a reduction of the intramedullary pressure in the bony compartment of the femoral head. The possibilities of repair and bone regeneration following core decompression are still discussed controversially. Core decompression is a common but not generally accepted procedure in the treatment of idiopathic osteonecrosis of the femoral head. After first publications of positive mid- and long-term effects, some subsequent studies judged it as an ineffective and high-risk method. Analysis of the literature shows that the effectiveness of core decompression depends on the stage of osteonecrosis at the time of surgical intervention. Prognosis is influenced by the extent and location of the necrotic area, the presence and amount of head depression, and continued risk factors--mainly corticoid medication. The best prognosis can be given for patients with a small, medial-centrally located necrosis without head depression. The classification according to Ficat appears to be insufficient, as the extent and localization of the necrotic area are not assessed. Magnetic resonance imaging has become a diagnostic gold standard, as radiographic diagnosis showed poor sensitivity and specificity, especially in the early stages of the disease. As an essential part, MRI was integrated into the new classification of the "Association Internationale de Recherche sur la Circulation Osseuse" (ARCO). On account of the literature and our own experience, treatment by core decompression can be recommended in cases of reversible early stages of osteonecrosis (ARCO 1), as well as in those cases of irreversible early stages (ARCO 2) that show a medial or central location of the necrosis with an extent of less than 30% of the femoral head. Once the disease reaches the irreversible early stage, complete recovery cannot be expected. In these cases only reduction of pain and retardation of the natural course of the osteonecrosis are possible to gain time until total hip replacement is unavoidable.

Decompression, Surgical↗
PubMed2000

Age- and gender-specific differences in left and right ventricular cardiac function and mass determined by cine magnetic resonance imaging.

We examined possible age- and gender-specific differences in the function and mass of left (LV) and right (RV) ventricles in 36 healthy volunteers using cine gradient-recalled echo magnetic resonance imaging. Subjects were divided into four groups (nine men and nine women in each): men aged under 45 years (32 +/- 7), women aged under 45 (27 +/- 6), men aged over 45 (59 +/- 8), and women aged over 45 (57 +/- 9). Functional analysis of cardiac volume and mass and of LV wall motion was performed by manual segmentation of the endocardial and epicardial borders of the end-diastolic and end-systolic frame; both absolute and normalized (per square meter body surface area) values were evaluated. With age there was a significant decrease in both absolute and normalized LV and RV chamber volumes (EDV, ESV), while LV and RV masses remained unchanged. Gender-specific differences were found in cardiac mass and volume (for men and women, respectively: LV mass, 155 +/- 18 and 110 +/- 16 g; LV EDV, 118 +/- 27 and 96 +/- 21 ml; LV ESV, 40 +/- 13 and 29 +/- 9 ml; RV mass, 52 +/- 10 and 39 +/- 5 g; RV EDV, 131 +/- 28 and 100 +/- 23 ml; RV ESV, 53 +/- 17 and 33 +/- 15 ml). Normalization to body surface area eliminated differences in LV volumes but not those in LV mass, RV mass, or RV function. Functional parameters such as cardiac output and LV ejection fraction showed nonsignificant or only slight differences and were thus largely independent of age and gender. Intra- and interobserver variability ranged between 1.4% and 5.9% for all parameters. Cine magnetic resonance imaging thus shows age- and gender-specific differences in cardiac function, and therefore the evaluation of cardiac function in patients should consider age- and gender-matched normative values.

Adult↗
PubMed2000

Protein translocation into mitochondria: the role of TIM complexes.

Import of nuclear-encoded mitochondrial preproteins is mediated by a general translocase in the outer membrane, the TOM complex, and by two distinct translocases in the mitochondrial inner membrane, the TIM23 complex and the TIM22 complex. Both TIM complexes cooperate with the TOM complex but facilitate import of different classes of precursor proteins. Precursors with an N-terminal presequence are imported via the TIM23 complex, whereas mitochondrial carrier proteins require the TIM22 complex for insertion into the inner membrane. This review discusses recent advances in understanding the structure and function of the translocases of the inner membrane and the possible role of Tim proteins in the development of the Mohr-Tranebjaerg syndrome, a mitochondrial disorder leading to neurodegeneration.

Animals↗
PubMed2000

Preparative isolation of anthocyanins by high-speed countercurrent chromatography and application of the color activity concept to red wine.

Red pigments were isolated from wine and grape-skin extracts using preparative high-speed countercurrent chromatography (HSCCC) and identified by NMR and MS techniques. Four solvent systems were developed in order to separate anthocyanins with different polarities. Malvidin-3-glucoside was the major component present in young red wines, and up to 500 mg of pure malvidin-3-glucoside could be obtained from a single bottle of a red wine. Other isolated pigments were the malvidin- and peonidin-3,5-diglucosides, as well as acetyl-, coumaroyl-, and caffeoyl-derivatives of anthocyanins. Furthermore, condensed red wine pigments formed from malvidin-3-glucoside (vitisin A and acetylvitisin A) were isolated on a preparative scale. Isolated compounds were used as standards for quantification of anthocyanins in a range of red wines. The "color activity concept" was applied to red wine, and visual detection thresholds were determined for some of the isolated anthocyanins. Mono-glucosides were found to exhibit lower visual detection thresholds than di-glucosides and acylated anthocyanins.

Anthocyanins↗
PubMed2000

A combined in vivo pharmacokinetic-in vitro pharmacodynamic approach to simulate target site pharmacodynamics of antibiotics in humans.

We describe a new approach to quantify in vivo anti-infective activity by simulating effect site pharmacokinetics of antibiotics in vitro. This approach is based on (i) the in vivo measurement of interstitial drug pharmacokinetics (PK) at the target site and (ii) a subsequent pharmacodynamic (PD) simulation of the time versus drug concentration profile in an in vitro setting. To demonstrate the feasibility of this approach, individual time-concentration profiles of ciprofloxacin were measured in the interstitial space fluid of eight healthy volunteers by microdialysis following iv administration of 200 mg. Thereafter, different isolates of Pseudomonas aeruginosa were exposed in vitro to the interstitial ciprofloxacin concentration profile obtained from in vivo experiments. This led to a 1- to 3-log10 decrease in the number of viable organisms after 8 h. Significant correlations were observed between the maximal bactericidal effect and several PK surrogate parameters, notably the AUC/MIC ratio (P: = 0.0005), the C:max/MIC ratio (P: = 0.006) and the time > MIC (P: = 0.02). Furthermore, the data were analysed with an integrated PK-PD model allowing a much more detailed evaluation of the data than using MIC. The model employed an E:max relationship to link unbound ciprofloxacin concentration to bacterial kill rate. In conclusion, our experiments show that therapeutic success and failure in antimicrobial therapy may be explained by pharmacokinetic variability at the target site. Therefore, the in vivo PK-in vitro PD approach presented in our study may provide valuable guidance for drug and dose selection of antimicrobial agents.

Anti-Bacterial Agents↗
PubMed2000

Effects of transvenous regional guanethidine block in the treatment of critical finger ischemia.

The objective of this study was to determine the effects of transvenous regional guanethidine block in the treatment of patients with critical finger ischemia. Twenty-seven patients (17 collagen vascular disease, four thromboangiitis obliterans, three embolism, three atherothrombosis) presenting with ischemic rest pain and/or ulcerations of the fingers received a single block with 5 mg guanethidine injected in 60 mL into the clinically more affected hand under 30 minutes of arterial arrest. Marked hyperemia was induced in the treated upper limb, increases (p < 0.01) in finger blood flow, finger skin temperature, and laser Doppler flux were higher and longer lasting than in forearm blood flow, persisting for a whole month. Effects in patients with ischemic finger ulcers were less pronounced than in those without, yet statistically significant increases of all evaluated parameters were observed in these patients too. No effects were seen in the contralateral untreated upper limb or in systemic blood pressure. Subjective symptoms (reduction of rest pain, numbness, vasospastic attacks) were improved in 25/27 (92.6%) patients, ischemic rest pain disappeared in 20/27 (74.1%), and complete healing of finger tip ulcerations within 1 month was achieved in 10/12 (83.3%) affected patients. No side effects were observed. This described method combines good clinical efficacy with lack of undesirable side effects and can be repeated easily. Therefore, this technique is recommended for broader clinical use.

Aged↗
PubMed1999

The mitochondrial TIM22 preprotein translocase is highly conserved throughout the eukaryotic kingdom.

The Mohr-Tranebjaerg syndrome (MTS), a neurodegenerative syndrome characterized by progressive sensorineural hearing loss, dystonia, mental retardation and blindness, is a mitochondrial disease caused by mutations in the deafness/dystonia peptide 1 (DDP1) gene. DDP1 shows similarity to the yeast proteins Tim9, Tim10 and Tim12, components of the mitochondrial import machinery for carrier proteins. Here, we show that DDP1 belongs to a large family of evolutionarily conserved proteins. We report the identification, chromosomal localization and expressional analysis of six human family members which represent further candidate genes for neurodegenerative diseases.

Amino Acid Sequence↗
PubMed1999

Genetic and structural characterization of the human mitochondrial inner membrane translocase.

Translocation of nuclear-encoded mitochondrial preproteins is mediated by translocases in the outer and inner membranes. In the yeast Saccharomyces cerevisiae, translocation of preproteins into the matrix requires the membrane proteins Tim23, Tim17 and Tim44, which drive translocation in cooperation with mtHsp70 and its co-chaperone Mge1p. We have cloned and functionally analyzed the human homologues of Tim17, Tim23 and Tim44. In contrast to yeast, two TIM17 genes were found to be expressed in humans. TIM44, TIM23 and TIM17a genes were mapped to chromosomes 19p13.2-p13.3, 10q11. 21-q11.23 and 1q32. The TIM17b gene mapped to Xp11.23, near the fusion point where an autosomal region was proposed to have been added to the "ancient" part of the X chromosome about 80-130 MY ago. The primary sequences of the two proteins, hTim17a and hTim17b, are essentially identical, significant differences being restricted to their C termini. They are ubiquitously expressed in fetal and adult tissues, and both show expression levels comparable to that of hTim23. Biochemical characterization of the human Tim components revealed that hTim44 is localized in the matrix and, in contrast to yeast, only loosely associated with the inner membrane. hTim23 is organized into two distinct complexes in the inner membrane, one containing hTim17a and one containing hTim17b. Both TIM complexes display a native molecular mass of 110 kDa. We suggest that the structural organization of TIM23.17 preprotein translocases is conserved from low to high eukaryotes.

Adult↗
PubMed1999

Determination of idarubicin and idarubicinol in rat plasma using reversed-phase high-performance liquid chromatography and fluorescence detection.

A reversed-phase high-performance liquid chromatographic method is described for the simultaneous determination of idarubicin and idarubicinol in rat plasma. Blood samples were analyzed from 16 rats which had received an intravascular dose of 2.25 mg kg(-1) idarubicin. After deproteinization with acetonitrile, the separation was performed with a LiChrospher 100 RP-18 column (5 microm), using fluorescence detection (excitation: 485 nm/emission: 542 nm). The mean recovery was 95.6% for idarubicin and 90.7% for idarubicinol, respectively. The detection limit was 0.25 ng ml(-1) using an injection volume of 50 microl. Daily relative standard deviation (RSD) was 3.2% (10 ng idarubicin/ml, n=10) and 4.4% (10 ng idarubicinol/ml, n=10).

Animals↗
PubMed1999

Loss-of-function mutations of SURF-1 are specifically associated with Leigh syndrome with cytochrome c oxidase deficiency.

Mutations of SURF-1, a gene located on chromosome 9q34, have recently been identified in patients affected by Leigh syndrome (LS), associated with deficiency of cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain. To investigate to what extent SURF-1 is responsible for human disorders because of COX deficiency, we undertook sequence analysis of the SURF-1 gene in 46 unrelated patients. We analyzed 24 COX-defective patients classified as having typical Leigh syndrome (LS(COX)), 6 patients classified as Leigh-like (LL(COX)) cases, and 16 patients classified as non-LS(COX) cases. Frameshift, stop, and splice mutations of SURF-1 were detected in 18 of 24 (75%) of the LS(COX) cases. No mutations were found in the LL(COX) and non-LS(COX) group of patients. Rescue of the COX phenotype was observed in transfected cells from patients harboring SURF-1 mutations, but not in transfected cell lines from 2 patients in whom no mutations were detected by sequence analysis. Loss of function of SURF-1 protein is specifically associated with LS(COX), although a proportion of LS(COX) cases must be the result of abnormalities in genes other than SURF-1. SURF-1 is the first nuclear gene to be consistently mutated in a major category of respiratory chain defects. DNA analysis can now be used to accurately diagnose LS(COX), a common subtype of Leigh syndrome.

Child, Preschool↗
PubMed1999

[Community emergency medical service. Epidemiology and quality of treatment in a rural district].

OBJECTIVES: Rapid aid provided by lay witnesses and emergency services can improve the outcome in medical emergencies arising in the community. We attempted to study the quality of first aid rendered by lay persons, paramedical personnel, and community medical practitioners attending out-of-hospital emergencies. We also evaluated the frequency of first aid provided before the arrival of specialised emergency physicians. METHODS: Over a period of six months all emergencies in a rural district of Germany leading to the pre-hospital medical service being dispatched were studied. Specialised community emergency physicians arriving at the site of the event recorded demographic, clinical, and process data using a standardised instrument. They also assessed the performance of lay persons, paramedical personnel, and community physicians providing immediate care. Implicit and explicit criteria were used. RESULTS: In 97% of cases analysed (n = 1150) members of the above mentioned groups were present before the arrival of the dedicated medical service. Lay persons were judged to provide inadequate care especially with regard to airway management and immobilisation of suspected fractures. For paramedical personnel, the administration of medication, venous lines and immobilisation turned out to be problematic areas. Medical practitioners fell below the defined standards especially in airway management, immobilisation and venous lines. CONCLUSION: Our project has shown how important the evaluated groups are for community emergency care. Despite methodological problems in this area of study, the shortcomings demonstrated may be targeted by future training at different levels.

Emergency Medical Services↗
PubMed1999

In vivo femoral intramedullary pressure during uncemented hip arthroplasty.

There is evidence in several animal and human studies that high intramedullary pressure in the femur is of causal significance for bone marrow release into the circulation, causing pulmonary fatty marrow embolization. A previous clinical study provided evidence that in uncemented hip arthroplasty, high intramedullary pressure and subsequent fat embolism with cardiorespiratory deterioration can occur. In this prospective clinical trial, the effect of five surgical techniques on the femoral intramedullary pressure was recorded intraoperatively in 36 patients during uncemented press fit hip arthroplasty. In Group A, the conventional surgical technique (slide hammer and femoral rasps) showed intramedullary hypertension during opening of the femoral canal, femur preparation, and prosthesis insertion. In Group B, a mechanical high frequency vibration rasp was used, instead of the slide hammer, and provided reduction of the intramedullary pressure peaks during opening of the femoral canal but could not prevent intramedullary hypertension during rasping and prosthesis insertion. In Group C, a modified surgical technique to prevent high intramedullary pressure reduced pressure peaks during opening of the femoral canal and resulted in a significant reduction of intramedullary pressure during femur preparation and prosthesis insertion compared with the conventional surgical technique used with Group A. In Group D the results of the modified surgical technique could be improved additionally by using the high frequency vibration rasp, instead of the slide hammer. In Group E conventional surgical technique in combination with a distal venting hole has not proven to be efficient in uncemented hip arthroplasty. Based on the results of this in vivo study, the proposed modified surgical technique in cementless hip arthroplasty can be recommended to avoid high intramedullary pressure peaks, which should minimize the risk of significant bone marrow release into the circulation and the risk for cardiorespiratory deterioration caused by fat embolism.

Aged↗