Biomedical subjects

M Arand

Publications and source records attributed to M Arand.

At least 37 records · Page 2Linked to original sources

PubMed2001

[Computer assisted surgery, 2001 development and prospects. Results of a congress at Reisensburg Castle, 23-24 November 2000]].

The progress in computer assisted surgery (CAS) is influenced by new technologies in imaging as well as by the input of the users. At present, CAS procedures are established in dorsal spine instrumentation, prosthetics and long bone surgery. Present status and future of CAS was a topic of an expert meeting at the Reisensburg castle. Imaging will speed up in the future using multi-detector techniques. C-arm navigation will gain more information using the 3D technology intraoperatively. CT based navigation procedures are standard in spine and will be established in pelvic surgery. CAS in robotics at the moment means the use of robot-assistance. A new concept is the modality-based navigated surgery, which can be used at various skeletal locations. Visualization of patient data will improve using 3D semi-transparencies with real time update. In the future it will be mandatory to find algorithms to fuse the different possibilities and techniques. A new concept of surgical training is necessary to teach CAS procedures. Therefore discussion must go on to improve these systems.

Forecasting↗

PubMed2001

Early inflammatory mediator response following isolated traumatic brain injury and other major trauma in humans.

The inflammatory response following isolated traumatic brain injury (TBI) is characterised by the release of pro- and anti-inflammatory mediators. In order to determine the important mediators regarding survival and outcome of patients with severe traumatic isolated head injuries, we performed this prospective preclinical and clinical study starting upon arrival at the site of the accident. After approval by the local ethics board committee, 94 multiple-injury patients were enrolled. Of these, 72 patients suffered from major injuries; the other 22 patients had a severe isolated brain injury and were allotted to subsets of survival or nonsurvival. Of the pro- and anti-inflammatory mediators (cytokines, arachidonic acid metabolites and soluble adhesion molecules), interleukin-6 (IL-6), IL-12 and malone dialdehyde (MDA) appeared to be of specific importance; maximum IL-6 plasma levels were eightfold higher in cases of nonsurvival than in those of survival. Patients that did not survive TBI were the only ones to express an IL-12 increase, whereas survivors and patients with other major trauma did not show any increase within the first 24 h. An early distinct decrease of MDA showed in patients who did not survive TBI, in contrast to survivor patients who exposed almost constant levels during the first 24 h.

Adult↗

PubMed2001

Internal fixation on the lower cervical spine--biomechanics and clinical practice of procedures and implants.

The decision to opt for a particular internal fixation procedure of a traumatized unstable lower cervical spine should be based on analysis and implementation of scientific and clinical data on the biomechanics of the intact, the unstable and the implant-fixed spine. The following recommendations for surgical stabilization of the lower cervical spine seem, therefore, to be justified. Firstly, the surgical procedure should be to bring about decompression, realignment, and stability. Secondly, the anterior approach should be the primary and preferred one. With regard to surgical and positioning technique, this access clearly involves fewer problems than the posterior approach; if required, unrestricted additional cord decompression can take place; implant fixation is technically simple, and the fusion is under direct compression, thus allowing optimal fusion healing. The awareness of instability and type of implant permits functional therapy, above all for the paraplegic patient. Thirdly, for traumatic conditions, posterior methods should be reserved for exceptional indications. The restriction to this approach is that the anterior column must be intact and a multi-segmental fixation must be used. Posterior fixation seems, therefore, to be more appropriate for degenerative, rheumatoid or tumorous instabilities than for traumatic instabilities. The cerclage wire technique depends on intact osseous posterior elements, while after laminectomy only implants fixed with screws can create safe stability. The disadvantages of the posterior access for the proprioception of the cervical muscles and the subjective symptoms of the patient are known and must be taken into account. Fourthly, combined techniques are indicated for highly unstable or particularly complex injuries. On the cervicothoracic junction, or in cases of Bechterew's disease, the decision is justifiably made in favor of this technique, which can be performed as a one-stage or two-stage operation. Finally, whenever possible, selection of the implant should take into account the foreseeable developments in diagnostic procedures, and therefore, in view of the modern imaging techniques likely to be used in any follow-up examinations required later, the implant chosen should be made of titanium.

Biomechanical Phenomena↗

PubMed2001

[Incidence of complications of the screw osteosynthesis of odontoid process fractures].

In this retrospective clinical study the incidence of complications in 58 consecutive, with anterior screw fixation stabilized patients after fractures of the odontoid process is evaluated. In 51 patients the fracture has been defined as type II according to Anderson, in 6 patients an oblique type II fracture was present and one patient showed a cephalad type III fracture. Preoperatively, in only 19 % of the patients (n = 11) no dislocation of the dens occurred. 32 patients were treated with single screw osteosynthesis, in 26 patients two screws were implanted. Significant complications with clinical relevance were registered in 14 patients (24 %), in 10 cases (17 %) an operative reintervention was required. Intraoperatively, in one patient a rupture of the carotid artery while winding around the motor drill occurred and in another case a complete malplacement of the screw posteriorly to the odontoid process was observed. A clearly excentric positioning of the implant was evaluated in 5 patients with a consecutive high rate of implant migration (n = 3). Two patients died perioperatively not related to the cervical injury. Postoperatively, one patient with a wound infection due to an iatrogenic perforation of the esophagus required reoperation as well as 4 patients with instability because of implant migration. Patients beyond the age of 65 years (n = 3) were significantly overrepresented in that group. In one case, the secondary intervention was caused by a pseudarthrosis of the dens axis. Complications without any relevance to the clinical and functional long term result were fusions in malposition of the odontoid process in 14 patients (24 %) and 10 (17 %) marginal screw perforations laterally. Differences in the use of one or two screws have not been observed in this study, although the investigations showed a tendency between marginal lateral screw perforations and double screw osteosynthesis and an increasing number of complications in the geriatric cohort.

Adolescent↗

PubMed2001

Differential effects of fluvoxamine and other antidepressants on the biotransformation of melatonin.

Melatonin, the predominant product of the pineal gland, is involved in the maintenance of diurnal rhythms. Nocturnal blood concentrations of melatonin have been shown to be enhanced by fluvoxamine, but not by other serotonin reuptake inhibitors. Because fluvoxamine is an inhibitor of several cytochrome P450 (CYP) enzymes, the authors studied the biotransformation of melatonin and the effects of fluvoxamine on the metabolism of melatonin in vitro using human liver microsomes and recombinant human CYP isoenzymes. Melatonin was found to be almost exclusively metabolized by CYP1A2 to 6-hydroxymelatonin and N-acetylserotonin with a minimal contribution of CYP2C19. Both reactions were potently inhibited by fluvoxamine, with a Ki of 0.02 microM for the formation of 6-hydroxymelatonin and 0.05 microM for the formation of N-acetylserotonin. Other than fluvoxamine, fluoxetine, paroxetine, citalopram, imipramine, and desipramine were also tested at 2 and 20 microM. Among the other antidepressants, only paroxetine was able to affect the metabolism of melatonin at supratherapeutic concentrations of 20 microM, which did not reach by far the magnitude of the inhibitory potency of fluvoxamine. The authors concluded that fluvoxamine is a potent inhibitor of melatonin degradation. Because this inhibitory action is also found in vivo, fluvoxamine might be used as an enhancer of melatonin, which might offer new therapeutic possibilities of fluvoxamine.

Antidepressive Agents, Second-Generation↗

PubMed2001

Combined anteroposterior spinal fixation provides superior stabilisation to a single anterior or posterior procedure.

Fusion is the main goal in the surgical management of the injured and unstable spine. A wide variety of implants is available to enhance this. Our study was performed to evaluate the stabilising characteristics of several anterior, posterior and combined systems of fixation. Six thoracolumbar (T11 to L2) spines from 13-week-old calves were first tested intact. Then the vertebral body of T13 was removed and the defect replaced and supported by a wooden block to simulate bone grafting. Dorsal implants consisting of a Universal Spine System (USS) fracture system and an AO Fixateur interne (AOFI), and ventral implants comprising of a Kaneda Classic, a Kaneda SR, a prototype of the VentroFix single clamp/single rod construct (SC/SR) and the VentroFix single clamp/double rod construct (SC/DR) were first implanted individually to stabilise the removal of the vertebral body. Simulating the combined anteroposterior stabilisations, all ventral implants were combined with the AOFI. The range of motion (ROM) was measured under loads of up to 7.5 Nm. The load was applied in a custom-made spine tester in the three primary directions while measuring the intervertebral movements using a goniometric linkage system. The dorsal systems limited ROM in flexion below 0.9 degrees and in extension between 3.3 degrees and 3.6 degrees (median values). The improved Kaneda System SR yielded a mean ROM of 1.8 degrees in flexion and in extension. The median rotation found with the VentroFix (SC/DR) was 3.2 degrees for flexion and 2.8 degrees for extension. Reinforcement of the ventral constructs with a dorsal system reduced the ROM in flexion and extension in all cases to 0.4 degrees and lower. In rotation, the median ROM of the anterior systems ranged from 2.7 degrees to 5.1 degrees and for the posterior systems from 3.9 degrees to 5.7 degrees, while the combinations provided a ROM of 1.2 degrees to 1.9 degrees. In lateral bending, the posterior implants restricted movement to 1.1 degrees, whereas the anterior implants allowed up to 5.2 degrees. The combined systems provided the highest stability at less than 0.6 degrees. Our study revealed distinct differences between posterior and anterior approaches in all primary directions. Also, different stabilisation characteristics were found within the anterior and posterior groups. Combinations of these two approaches provided the highest stability in all directions.

Animals↗

PubMed2001

Quantitative assessment of the expression of melanoma-associated antigens by non-competitive reverse transcription polymerase chain reaction.

The assessment of tumor-associated antigens (TAA) recognized by T lymphocytes is a prerequisite for diagnosis and immunotherapy of melanoma. Different reverse transcription-polymerase chain reaction (RT-PCR) protocols allowing the quantification of the TAA mRNA expression in the solid tumor or the detection of circulating melanoma cells have been described. We have recently shown a positive correlation between the amount of specific product formed by RT-PCR and the staining intensity in immunohistochemical analysis of the corresponding sample. Here we describe a quantification procedure based on the direct digitization of the PCR products after separation on ethidium bromide-stained agarose gels, followed by computer-assisted densitometry. To standardize our method, we examined the linear range of the densitometric quantification procedure as reflected by the correlation of signal intensity to the amount of the corresponding DNA. As an internal measure for the so-termed cDNA in the different samples after RNA isolation and reverse transcription, a beta-actin PCR was introduced. Subsequently, we chose four sets of primers for the melanoma-associated antigens MAGE1, tyrosinase, Melan A/MART-1 and gp100/Pmel17 and performed PCR analysis over a range of cycle numbers. In each case, the amplification rate remained constant up to at least 26 cycles under the respective conditions. Plotting the logarithm of the amount of product against the cycle number yields a slope that equals the logarithm of the amplification rate. The amount of starting material can be determined from the intercept with the ordinate. In summary, the method introduced in the present work allows the quantification of TAA in melanoma which might be important for the monitoring of disease. Technically the method is sound and sensitive, avoids post-PCR manipulations and can be performed with the standard equipment of a molecular biology laboratory. It can be applied also to other solid tumors and leukemias.

Antigens, Neoplasm↗

PubMed2000

Induction of primary NY-ESO-1 immunity: CD8+ T lymphocyte and antibody responses in peptide-vaccinated patients with NY-ESO-1+ cancers.

Cancer-testis antigen NY-ESO-1 is one of the most immunogenic tumor antigens defined to date. Spontaneous humoral and CD8+ T-cell responses to NY-ESO-1 are detected in 40-50% of patients with advanced NY-ESO-1-expressing tumors. A clinical trial was initiated to study the immunological effects of intradermal vaccination with 3 HLA-A2-binding NY-ESO-1 peptides in 12 patients with metastatic NY-ESO-1-expressing cancers. Seven patients were NY-ESO-1 serum antibody negative, and five patients were NY-ESO-1 serum antibody positive at the outset of the study. Primary peptide-specific CD8+ T-cell reactions and delayed-type hypersensitivity responses were generated in four of seven NY-ESO-1 antibody-negative patients. Induction of a specific CD8+ T-cell response to NY-ESO-1 in immunized antibody-negative patients was associated with disease stabilization and objective regression of single metastases. NY-ESO-1 antibody-positive patients did not develop significant changes in baseline NY-ESO-1-specific T-cell reactivity. However, stabilization of disease and regression of individual metastases were observed in three of five immunized patients. These results demonstrate that primary NY-ESO-1-specific CD8+ T-cell responses can be induced by intradermal immunization with NY-ESO-1 peptides, and that immunization with NY-ESO-1 may have the potential to alter the natural course of NY-ESO-1-expressing tumors.

Amino Acid Sequence↗

PubMed2000

Monitoring CD8 T cell responses to NY-ESO-1: correlation of humoral and cellular immune responses.

NY-ESO-1, a member of the cancer-testis family of antigens, is expressed in a subset of a broad range of different human tumor types. Patients with advanced NY-ESO-1-expressing tumors frequently develop humoral immunity to NY-ESO-1, and three HLA A2-restricted peptides were defined previously as targets for cytotoxic CD8(+) T cells in a melanoma patient with NY-ESO-1 antibody. The objectives of the present study were (i) to develop enzyme-linked immunospot (ELISPOT) and tetramer assays to measure CD8(+) T cell responses to NY-ESO-1, (ii) to determine the frequency of CD8(+) T cell responses to NY-ESO-1 in a series of HLA-A2 patients with NY-ESO-1 expressing tumors, (iii) to determine the relation between CD8(+) T cell and humoral immune responses to NY-ESO-1, and (iv) to compare results of NY-ESO-1 ELISPOT assays performed independently in two laboratories with T cells from the same patients. NY-ESO-1 ELISPOT and tetramer assays with excellent sensitivity, specificity, and reproducibility have been developed and found to correlate with cytotoxicity assays. CD8(+) T cell responses to HLA-A2-restricted NY-ESO-1 peptides were detected in 10 of 11 patients with NY-ESO-1 antibody, but not in patients lacking antibody or in patients with NY-ESO-1-negative tumors. The results of ELISPOT assays were concordant in the two laboratories, providing the basis for standardized monitoring of T cell responses in patients receiving NY-ESO-1 vaccines.

Antibody Formation↗

PubMed2000

Identification of the putative brain tumor antigen BF7/GE2 as the (de)toxifying enzyme microsomal epoxide hydrolase.

Malignant gliomas are the main cause of death from primary brain tumors. Despite surgery, radiation, and chemotherapy, patients have a median survival of less than a few years; therefore, it is clearly imperative to investigate new ways of treatment. The development of new therapeutic strategies for brain tumors is dependent on a better understanding of the differences between normal and tumoral brain cells. Our group had described previously a Mr 48,000 antigen defined by reactivity with two monoclonal antibodies (GE2 and BF7) obtained by immunization of mice with human glioblastoma cells. Here, we describe the identification of the GE2/BF7 antigen as microsomal epoxide hydrolase (mEH), a drug-metabolizing enzyme that is involved both in toxification and detoxification of carcinogens. We initially used immunoaffinity purification using GE2 and BF7 and analyzed the purified proteins by microsequencing. Edman degradation identified 15 amino acids of the NH2-terminal sequence that were 100% identical to mEH. To further confirm the identity of the BF7/GE2 antigen as mEH, we showed that the protein immunopurified with GE2 and BF7 was recognized by an anti-mEH antibody and that in vitro and in vivo synthesized human mEH is recognized by BF7 and GE2 antibodies. Furthermore, anti-mEH antibody recognizes an antigen expressed both in gliomas and reactive astrocytes, as do BF7 and GE2. Finally, we demonstrate that in contrast to what has been reported in rat embryo fibroblasts, p53 does not regulate mEH mRNA expression in glioma cells.

Animals↗

PubMed2000

Identification of NY-ESO-1 epitopes presented by human histocompatibility antigen (HLA)-DRB4*0101-0103 and recognized by CD4(+) T lymphocytes of patients with NY-ESO-1-expressing melanoma.

NY-ESO-1 is a member of the cancer-testis family of tumor antigens that elicits strong humoral and cellular immune responses in patients with NY-ESO-1-expressing cancers. Since CD4(+) T lymphocytes play a critical role in generating antigen-specific cytotoxic T lymphocyte and antibody responses, we searched for NY-ESO-1 epitopes presented by histocompatibility leukocyte antigen (HLA) class II molecules. Autologous monocyte-derived dendritic cells of cancer patients were incubated with recombinant NY-ESO-1 protein and used in enzyme-linked immunospot (ELISPOT) assays to detect NY-ESO-1-specific CD4(+) T lymphocyte responses. To identify possible epitopes presented by distinct HLA class II alleles, overlapping 18-mer peptides derived from NY-ESO-1 were synthetized and tested for recognition by CD4(+) T lymphocytes in autologous settings. We identified three NY-ESO-1-derived peptides presented by DRB4*0101-0103 and recognized by CD4(+) T lymphocytes of two melanoma patients sharing these HLA class II alleles. Specificity of recognition was confirmed by proliferation assays. The characterization of HLA class II-restricted epitopes will be useful for the assessment of spontaneous and vaccine-induced immune responses of cancer patients against defined tumor antigens. Further, the therapeutic efficacy of active immunization using antigenic HLA class I-restricted peptides may be improved by adding HLA class II-presented epitopes.

Alleles↗

PubMed2000

Structure of Aspergillus niger epoxide hydrolase at 1.8 A resolution: implications for the structure and function of the mammalian microsomal class of epoxide hydrolases.

BACKGROUND: Epoxide hydrolases have important roles in the defense of cells against potentially harmful epoxides. Conversion of epoxides into less toxic and more easily excreted diols is a universally successful strategy. A number of microorganisms employ the same chemistry to process epoxides for use as carbon sources. RESULTS: The X-ray structure of the epoxide hydrolase from Aspergillus niger was determined at 3.5 A resolution using the multiwavelength anomalous dispersion (MAD) method, and then refined at 1.8 A resolution. There is a dimer consisting of two 44 kDa subunits in the asymmetric unit. Each subunit consists of an alpha/beta hydrolase fold, and a primarily helical lid over the active site. The dimer interface includes lid-lid interactions as well as contributions from an N-terminal meander. The active site contains a classical catalytic triad, and two tyrosines and a glutamic acid residue that are likely to assist in catalysis. CONCLUSIONS: The Aspergillus enzyme provides the first structure of an epoxide hydrolase with strong relationships to the most important enzyme of human epoxide metabolism, the microsomal epoxide hydrolase. Differences in active-site residues, especially in components that assist in epoxide ring opening and hydrolysis of the enzyme-substrate intermediate, might explain why the fungal enzyme attains the greater speeds necessary for an effective metabolic enzyme. The N-terminal domain that is characteristic of microsomal epoxide hydrolases corresponds to a meander that is critical for dimer formation in the Aspergillus enzyme.

Animals↗

PubMed2000

[Computer-assisted surgery].

The term "computer-assisted surgery" (CAS) contains a variety of different applications. Priorities in trauma surgery have navigation systems. In fact, two basically different developments can be distinguished: on one hand, the possibility of navigation, based on preoperative CT data sets; and on the other hand navigation in intraoperative C-arm images. With the present available navigation technology, it can be assumed that intraoperative CT-based tracking in the field of spinal surgery can be performed accurately, regardless of whether active or passive markers are used. Another navigation option is C-arm-based osteosynthesis of the proximal femur. An application of navigation assistance in the field of pelvic surgery is osteotomy and placement of iliosacral screws. Future developments will have to concentrate on the technical characteristics of each navigation system. Advantageous concepts of visualization may generate required information to the surgeon in a way that unconstrained interaction at the operation table is combined with simultaneous integration of virtual and computer-aided visual information. New tracking systems will allow the reconstruction of data sets after reposition of segmented bone fragments, so that also in complex pelvic fractures the implantation of screws after reposition will be possible. Computer-aided surgery is able to improve the precision of operations in trauma surgery. In future, further developments of navigation systems can be expected. This fact is supported by the establishment of faster and cheaper hardware, as well as more intelligent and user-friendly software.

Bone Screws↗

PubMed2000

[Limits of CT-based computer navigation in spinal surgery].

Computer-assisted and navigation-based therapeutic tools have found their first application in the field of spinal surgery. Meanwhile, the basic principles have been extended to other procedures, such as screw osteosynthesis of the pelvis and navigation of long bones. Commonly, all procedures except C-arm navigation are based on three-dimensional data sets. Data acquisition and processing as well as planning require specific steps, which should guarantee adequate accuracy and successful navigation. All steps up to intraoperative navigation and potential pitfalls in every part of the interaction are demonstrated, with reasons of undesired results presented.

Bone Screws↗

PubMed2000

[Temporary instrumentation in dixlocations, subluxations and fractures of the lower cervical spine].

The anterior interbody fusion with instrumentation seems to be the standard procedure in unstable traumatic lesions of the lower cervical spine. The goal of this study was to objective the outcome of patients, treated by only temporary stabilisation of the injured motion segment (without bone-graft fusion). Between 1990 and 1998 155 patients with traumatic lesions of the cervical spine were treated operatively, in 22 cases transfixation of the injured level without bone-graft application was performed, an implant-removal was carried out in 12 patients so long. Only patients were included into the study, who were less then 45 years old at trauma and who had no trauma related osseous or disc encrouchment of the spinal canal. Not included were patients with degenerative formations of the cervical spine at time of trauma. Until follow up all patients with implantat removal returned back to work in their former profession, 11 of 12 patients classified their result as excellent or good. No secondary instabilities or postraumatic disc prolapse were observed. Restmobility in flexion/extension of the injured level was demonstrated in 8 patients. The preservation of traumatized motion segments may reduce the incidence of degenerative alterations and hypermobilities in adjacent levels. The transfixation technique in anterior procedures leads to a reduced time of spinal exposure, complications as a result of spinal graft manipulation, pseudarthrosis or donor graft site problems are no more relevant.

Adult↗

PubMed2000

[Minimal invasive implant removal after retrograde intramedullary nailing of the distal femur].

Recently, the retrograde femoral nailing has become a procedure with increasing acceptance. Indications for the retrograde femur nail are distal femoral fractures including dia- and transcondylar fractures, supracondylar osteotomies and distal periprosthetic femur fractures after total knee joint replacement. Controversial discussion is carried on about the implant removal, which is potentially afflicted with further damage to the knee joint. To minimize the operative damage due to the implant removal, an arthroscopic assisted procedure has been selected. The arthroscopic assisted implant removal was possible in all of our patients. Intraoperatively, 2/3 of the patients showed normal age-related findings of the chondral and meniscal structures. The arthroscopic assisted implant removal is a gentle procedure, which allows minimal invasive extraction of retrograde femur nails and prevents secondary damage to the knee joint due to the otherwise difficult localisation of the implant. The advantages of this procedure concerning gentleness and diagnostic capabilities are as convincing, that we indicate implant removal of retrograde femur nails in all younger patients (< 60 years), except in periprosthetic fractures.

Arthroscopy↗

PubMed2000

Comparative stability of the "Internal Fixator" and the "Universal Spine System" and the effect of crosslinking transfixating systems. A biomechanical in vitro study.

In this study, the three-dimensional stabilizing capabilities of the AO-Internal Fixator (IF) and the new Universal Spine System (USS) were investigated. Both devices were tested without and with the cross-link system (IF, IFC, USS, USSC). To determine biomechanical characteristics, a human thoracolumbar spine instability model with resection of the vertebral body Th12 was created. The vertebral body was replaced by a spacer and transpedicular posterior stabilization was performed from Th11 to L1. All devices reduced the range of motion (ROM) significantly compared to the values of the intact specimen. In flexion the IFC showed the highest reduction of ROM (85% of intact), followed by the USSC, USS and IF (79% of intact). In extension the ROM was restored again most by the IFC (52% of intact), followed by the USSC, IF and USS (44% of intact). In lateral bending stability was provided by the USSC (right 78% and left 81% of intact), followed in right lateral bending by the IF, IFC and USS and in left lateral bending by the USS, IF and IFC. In axial rotation the ROM was reduced primary by the IFC (right 51% and left 46% of intact), followed in right axial rotation by the USS, USSC and IF, in left axial rotation by the USSC, USS and IF. Additional stability by crosslinking has been provided in the IF and the USS in flexion and extension, in the USS in lateral bending and in the IF in axial rotation nonsignificantly. The neutral zone (NZ) was reduced by posterior instrumentation in flexion/extension and right/left lateral bending significantly. In axial rotation only the USSC decreased the NZ below intact levels. The study showed no statistical significant differences in the stabilizing capabilities of the USS compared to the IF. For both implants the cross-link system increased stability in the chosen instability model insignificantly only.

Aged↗

PubMed1999

Acute hepatotoxicity of the polycyclic musk 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphtaline (AHTN).

Synthetic musks are present in fine fragrances, cosmetics, soaps and laundry detergents. One of the most important synthetic musks is 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydro-naphthaline+ ++ (AHTN; annual production: about 1500 metric tons). An increasing number of studies show that AHTN accumulates in surface water and fish and can be detected in human adipose tissue, as well in human milk. In the present report it is shown that a single high dose of AHTN leads to acute hepatic damage in rats, characterized by single cell necrosis, inflammation, swelling of liver parenchymal cells, and the presence of cytoplasmic condensations in the hepatocytes, while at the ultrastructural level disorganization of the rough endoplasmic reticulum and mitochondria as well as focal cytolysis is evident. Furthermore, evidence is presented that AHTN is not genotoxic, does not induce peroxisome proliferation, and does not lead to the induction of drug-metabolizing enzymes as phenobarbital and 3-methylcholanthrene do.

Animals↗