Evaluation of an alternative in vitro test battery for detecting reproductive toxicants.

The application of alternative methods in developmental and reproductive toxicology is challenging in view of the complexity of mechanisms involved. A battery of complementary test systems may provide a better prediction of developmental and reproductive toxicity than single assays. We tested twelve compounds with varying mechanisms of toxic action in an assay battery including 24 CALUX transcriptional activation assays, mouse cardiac embryonic stem cell test, ReProGlo assay, zebrafish embryotoxicity assay, and two CYP17 and two CYP19 activity assays. The battery correctly detected 11/12 compounds tested, with one false negative occurring, which could be explained by the absence of the specific mechanism of action of this compound in the battery. Toxicokinetic modeling revealed that toxic concentrations were in the range expected from in vivo reproductive toxicity data. This study illustrates added value of combining assays that contain complementary biological processes and mechanisms, increasing predictive value of the battery over individual assays.

Quantitative assessment of chronic thalamic stroke.

The procedure presented quantitatively assesses thalamic lesions in the chronic phase of an ischemic episode. The structural MR images of 19 patients with ischemia in the thalamus were assessed by radiologic inspection. An independent rater allocated the damage to the thalamic nuclei. The assessments showed 89% accordance with the radiologic inspection (P < .001). This procedure ranks the extent of the damage to thalamic nuclei and accounts for postacute rearrangement of the neural tissue.

Amending reduced fish-meal feeds with marine lecithin, but not soy lecithin, improves the growth of juvenile cobia and may attenuate heightened responses to stress challenge.

Sparing of marine resources in aquafeeds can be environmentally and economically advantageous; however, fish meal (FM) replacement can affect the production performance and physiological competence. Phospholipids are increasingly understood to be involved in maintaining growth and vigour in fish and may be deficient in reduced FM formulations. Accordingly, we evaluated the growth and stress tolerance of juvenile cobia fed typical (50% FM) or reduced FM feeds (12% FM) with or without phospholipid amendment [1% marine lecithin (12% FM + Marine PL) or soy lecithin (12% FM + Soy PL)] for 6 weeks in triplicate tanks (N = 3) in a recirculation aquaculture system. The 50% FM feed yielded significantly superior growth and growth efficiency in comparison with the 12% FM and 12% FM+ Soy PL feeds, but the 12% FM+ Marine PL feed yielded comparable results to 50% FM feed. A low-water stress challenge induced elevated plasma glucose, cortisol and lactate levels in all treatments. However, a significant interaction (diet × stress) effect suggested a lesser cortisol response among fish fed the 12% FM+ Marine PL and 50% FM diets. These findings demonstrate that growth performance and, perhaps, resilience of cobia raised on reduced FM feeds may be improved by the addition of marine-origin phospholipid to the diet.

The "PIP scandal" - Complications in Breast Implants of Inferior Quality: State of Knowledge, Official Recommendations and Case Report.

Following the clinical observation of high rate of ruptures of breast implants of the French manufacturer Poly Implant Prothèse (PIP), the French Health Products Safety Agency (Afssaps) removed these products from the market in March 2010. Physical and toxicological tests confirmed the use of silicone of improper quality both for the shell and the gel filling. Until now (12/2011), no acute toxicity or mutagenicity could be observed, but 20 cases of malignancies occured in carriers of PIP-prostheses. By means of a clinical example, we summarize the official recommendations of the Afssaps and its German equivalent, the Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) for diagnosis and treatment in women with PIP breast implants. Furthermore, we intend to raise awareness for the fact that the German GfE Medizintechnik and the Dutch manufacturer Rofil distributed the identical product with a different label. Supplementary, the medical and medico-legal aspects of the "PIP scandal" are discussed.

[Osteointegration of an alumina matrix composite ceramic with a porous surface: mechanical and histological results of an animal experiment]. / Osteointegration einer Alumina-Matrix-Composite-Keramik mit poröser Oberfläche: Eine mechanische und histologische Untersuchung im Tierversuch.

INTRODUCTION: The aim of this study was to analyse mechanically and histologically the osteointegration of porous-surfaced ceramic implants made of an alumina matrix composite (AMC) by assessing maximum shear strength and histomorphometric bone ongrowth. METHODS: The surfaces of the cylindrically shaped AMC test implants were characterised by a porosity of 40% and a pore size of 150 to 300 microm. A total of 24 test cylinders was implanted bilaterally into the femurs of 6 female adult Goettinger minipigs. 12 weeks after surgery the animals were sacrificed. 12 test implants were used for a push-out test and 12 test implants were evaluated histologically. RESULTS: The mean maximum shear strength of the bone-implant interface was 7.6 +/- 2.0 MPa. Direct bone attachment was found in 7.4 +/- 3.4% of the histologically analysed surfaces. CONCLUSION: In summary, porous-surfaced AMC test implants demonstrated good mechanical stability in spite of a low percentage of bone ongrowth. This discrepancy could potentially be explained by bone ingrowth into the pores and subsequent interlocking mechanisms.

The immunological basis of glutamatergic disturbance in schizophrenia: towards an integrated view.

This overview presents a hypothesis to bridge the gap between psychoneuroimmunological findings and recent results from pharmacological, neurochemical and genetic studies in schizophrenia. In schizophrenia, a glutamatergic hypofunction is discussed to be crucially involved in dopaminergic dysfunction. This view is supported by findings of the neuregulin- and dysbindin genes, which have functional impact on the glutamatergic system. Glutamatergic hypofunction is mediated by NMDA (N-methyl-D-aspartate) receptor antagonism. The only endogenous NMDA receptor antagonist identified up to now is kynurenic acid (KYN-A). KYN-A also blocks the nicotinergic acetycholine receptor, i.e. increased KYN-A levels can explain psychotic symptoms and cognitive deterioration. KYN-A levels are described to be higher in the CSF and in critical CNS regions of schizophrenics. Another line of evidence suggests that of the immune system in schizophrenic patients is characterized by an imbalance between the type-1 and the type-2 immune responses with a partial inhibition of the type-1 response, while the type-2 response is relatively over-activated. This immune constellation is associated with the inhibition of the enzyme indoleamine 2,3-dioxygenase (IDO), because type-2 cytokines are potent inhibitors of IDO. Due to the inhibition of IDO, tryptophan is predominantly metabolized by tryptophan 2,3-dioxygenase (TDO), which is located in astrocytes, but not in microglia cells. As indicated by increased levels of S100B, astrocytes are activated in schizophrenia. On the other hand, the kynurenine metabolism in astrocytes is restricted to the dead-end arm of KYN-A production. Accordingly, an increased TDO activity and an accumulation of KYN-A in the CNS of schizophrenics have been described. Thus, the immune-mediated glutamatergic-dopaminergic dysregulation may lead to the clinical symptoms of schizophrenia. Therapeutic consequences, e.g. the use of antiinflammatory cyclooxygenase-2 inhibitors, which also are able to directly decrease KYN-A, are discussed.

[Immunology in schizophrenic disorders]. / Immunologische Aspekte bei schizophrenen Störungen.

This manuscript deals with whether immune-mediated mechanisms of inflammation contribute to the pathogenesis of schizophrenia. A model is presented which integrates psychoneuroimmunologic findings and actual results from pharmacological, neurochemical, and genetic studies in schizophrenia. A pivotal role in the neurobiology of schizophrenia is played by dopaminergic neurotransmission, which is modulated by influences of the glutamatergic system. The decreased function of the glutamate system described in schizophrenia seems primarily mediated by N-methyl-D-aspartate (NMDA) receptor antagonism. Kynurenine acid is the only known endogenous NMDA receptor antagonist. In higher concentrations it blocks the NMDA receptor, but in lower concentrations it blocks the nicotinergic acetylcholin receptor, which has a prominent role in cognitive functions. Therefore, higher levels of kynurenine acid may explain psychotic symptoms and cognitive dysfunction. Several findings point out that prenatal infection, associated with an early sensitisation of the immune system, may result in an imbalance of the immune response (type 1 vs type 2) in schizophrenia. This immune constellation leads to inhibition of the enzyme indoleamin dioxigenase (IDO). It and tryptophane 2,3-dioxygenase (TDO) both catalyse the degradation from tryptophan to kynurenine. Due to the inhibition of IDO, tryptophan is metabolised to kynurenine primarily by TDO. In the CNS, TDO is located only in astrocytes, which are in particular activated in schizophrenia and in which kynurenine acid is the final product and can not be further metabolised. Therefore kynurenine acid accumulates in the CNS of schizophrenics and - due to its NMDA-antagonistic properties - leads to cognitive dysfunction and psychotic symptoms. This model describes the pathway of immune-mediated glutamatergic-dopaminergic dysregulation, which may lead to the clinical symptoms of schizophrenia. Therapeutic consequences (e.g. cyclo-oxygenase-2 inhibitors) are discussed.

Bone morphogenetic protein 7 (bmp-7) stimulates proteoglycan synthesis in human osteoarthritic chondrocytes in vitro.

BMP-7 is a member of the TGF-beta superfamily which is supposed to be one of the most potent anabolic factors of chondrocytes. In this study we analysed the effect of BMP-7 on three dimensional cultured chondrocytes with and without serum. Cartilage samples from fourteen patients with osteoarthritis of the knee were harvested and chondrocytes were cultivated in alginate-beads with and without serum supplementation (10% FCS). BMP-7 was added in three different concentrations (200, 600 and 1000 ng/ml). After 4 and 21 days PG concentration was determined by a Blyscan-Assay. For gene expression analysis of aggrecan (AGG) quantitative Lightcycler-PCR was used to estimate the mRNA levels. Under serumfree culture conditions there was no stimulation after 4 days but there was a twofold increase of PG concentration after 21 days. Using BMP-7 together with serum supplemented medium we found comparable results, however not as pronounced. AGG expression was increased only after 4 days but not after 21 days. Beside a stimulatory effect under serumfree conditions we also found a stimulatory effect of BMP-7 in the presence of serum. This study pronounces that BMP-7 might be a suitable anabolic activator of osteoarthritic chondrocytes.

Behavioral and neurochemical phenotyping of Homer1 mutant mice: possible relevance to schizophrenia.

Homer proteins are involved in the functional assembly of postsynaptic density proteins at glutamatergic synapses and are implicated in learning, memory and drug addiction. Here, we report that Homer1-knockout (Homer1-KO) mice exhibit behavioral and neurochemical abnormalities that are consistent with the animal models of schizophrenia. Relative to wild-type mice, Homer1-KO mice exhibited deficits in radial arm maze performance, impaired prepulse inhibition, enhanced 'behavioral despair', increased anxiety in a novel objects test, enhanced reactivity to novel environments, decreased instrumental responding for sucrose and enhanced MK-801- and methamphetamine-stimulated motor behavior. No-net-flux in vivo microdialysis revealed a decrease in extracellular glutamate content in the nucleus accumbens and an increase in the prefrontal cortex. Moreover, in Homer1-KO mice, cocaine did not stimulate a rise in frontal cortex extracellular glutamate levels, suggesting hypofrontality. These behavioral and neurochemical data derived from Homer1 mutant mice are consistent with the recent association of schizophrenia with a single-nucleotide polymorphism in the Homer1 gene and suggest that the regulation of extracellular levels of glutamate within limbo-corticostriatal structures by Homer1 gene products may be involved in the pathogenesis of this neuropsychiatric disorder.

Ensuring global standards for medical graduates: a pilot study of international standard-setting.

Increasing physician and patient mobility has led to a move toward internationalization of standards for physician competence. The Institute for International Medical Education proposed a set of outcome-based standards for student performance, which were then measured using three assessment tools in eight leading schools in China: a 150-item multiple-choice examination, a 15-station OSCE and a 16-item faculty observation form. The purpose of this study was to empanel a group of experts to determine whether international student-level performance standards could be set. The IIME convened an international panel of experts in student education with specialty and geographic diversity. The group was split into two, with each sub-group establishing standards independently. After a discussion of the borderline student, the sub-groups established minimally acceptable cut-off scores for performance on the multiple-choice examination (Angoff and Hofstee methods), the OSCE station and global rating performance (modified Angoff method and holistic criterion reference), and faculty observation domains (holistic criterion reference). Panelists within each group set very similar standards for performance. In addition, the two independent parallel panels generated nearly identical performance standards. Cut-off scores changed little before and after being shown pilot data but standard deviations diminished. International experts agreed on a minimum set of competences for medical student performance. In addition, they were able to set consistent performance standards with multiple examination types. This provides an initial basis against which to compare physician performance internationally.

The role of the human thalamus in processing corollary discharge.

Corollary discharge signals play an important role in monitoring self-generated movements to guarantee spatial constancy. Recent work in macaques suggests that the thalamus conveys corollary discharge information of upcoming saccades passing from the superior colliculus to the frontal eye field. The present study aimed to investigate the involvement of the thalamus in humans by assessing the effect of thalamic lesions on the processing of corollary discharge information. Thirteen patients with selective thalamic lesions and 13 healthy age-matched control subjects performed a saccadic double-step task in which retino-spatial dissonance was induced, i.e. the retinal vector of the second target and the movement vector of the second saccade were different. Thus, the subjects could not rely on retinal information alone, but had to use corollary discharge information to correctly perform the second saccade. The amplitudes of first and second saccades were significantly smaller in patients than in controls. Five thalamic lesion patients showed unilateral deficits in using corollary discharge information, as revealed by asymmetries compared with the other patients and controls. Three patients with lateral thalamic lesions including the ventrolateral nucleus (VL) were impaired contralaterally to the side of damage and one patient with a lesion in the mediodorsal thalamus (MD) was impaired ipsilaterally to the lesion. The largest asymmetry was found in a patient with a bilateral thalamic lesion. The results provide evidence for a thalamic involvement in the processing of corollary discharge information in humans, with a potential role of both the VL and MD nuclei.

Medical education in China's leading medical schools.

This article gives a general overview of the evolution and present state of the undergraduate medical education system, programs, evaluation methods and conferred degrees in contemporary China. The publication is based on the information collected from on-site visits to the eight (8) leading medical universities, medical education conferences, visits to Ministries of Health and Education and their staff, and the contribution of Chinese medical education experts. As the Ministry of Education of the People's Republic of China (PRC) approves all tracks and strives for uniformity of educational programs as a cornerstone of quality, this overview reflects the general content of all five- and seven-year medical education programs that have provided the great majority of physicians since the founding of the People's Republic of China.

Activities of extract and constituents of Banisteriopsis caapi relevant to parkinsonism.

Dopamine deficiency is characteristic of Parkinson's disease (PD) and treatments aim at elevating levels by administration of its precursor L-dihydroxyphenylalanine (L-DOPA), or inhibiting monoamine oxidases (MAOs), thus preventing its breakdown. Reports of improvements in PD patients treated with Banisteriopsis caapi extracts stimulated investigation of B. caapi stem extract and its two ingredients, harmine and harmaline for these activities. Tests for MAO inhibition using liver homogenate showed that extract and harmaline showed a concentration-dependent inhibition of MAO A (IC(50) 1.24 microg/ml and IC(50) 4.54 nM, respectively) but had little effect on MAO B activity. The extract at 2.5 mg/ml caused a highly significant increase in release of [3H]dopamine from rat striatal slices, as did 200 microM harmine and 6 microM harmaline. In both these experiments, the amount of harmine present could not account for the total activity of the extract. The ability of harmine and harmaline to stimulate dopamine release is a novel finding. These results give some basis to the reputed usefulness of B. caapi stem extract in the treatment of PD.

Soluble interleukin-2 receptors increase during the active periods in cluster headache.

OBJECTIVE: To investigate whether cytokines are altered during the active period of cluster headache. BACKGROUND: Patients with cluster headache show activation of the hypothalamus in PET studies and via endocrinologic parameters. Data also suggest an inflammatory process occurs in cluster headache. A connection between the presumed inflammatory cause, an immunological activation, and the hypothalamus could be generated by certain cytokines. DESIGN AND METHODS: ELISA was used to determine the serum levels of soluble interleukin-2 receptors, interleukin-1, interleukin-6, and 2 soluble interleukin-6 receptors (sIL-6R and soluble gp130) in 18 patients with cluster headache (6 women and 12 men) during the cluster period and in 17 healthy controls who were headache-free (3 women and 14 men). RESULTS: Patients with cluster headache had significantly increased soluble interleukin-2 receptors (413.6+/-223 U/mL vs. 290.0+/-112 U/mL; P <.05) compared with controls. Serum levels of interleukin-1 (0.29+/-0.30 pg/mL vs. 0.13+/-0.13 pg/mL, n.s.), interleukin-6 (0.87+/-0.6 pg/mL vs. 0.91+/-0.7 pg/ml; n.s.), soluble interleukin-6 receptors (33,131+/-8,349 pg/mL vs. 35,063+/-7,606 pg/mL; n.s.), or soluble gp130 (289+/-59 pg/mL vs. 283+/-20 pg/mL; n.s.) did not differ between the 2 groups, although patients with cluster tended to have higher interleukin-1 values. CONCLUSIONS: Because elevated soluble interleukin-2 receptors indicate T cell activation, our findings suggest immune activation during cluster headache. Because interleukin-2 can activate the hypothalamus and stimulate the release of Corticotropin-releasing Factor (CRF), interleukin-2 could link a putative immunological cause of cluster headache with the observed hypothalamic activation. Systemic changes of interleukin-1 or the interleukin-6 system do not seem to play a role in cluster headache, as no alterations of serum levels were observed. Even so, unchanged serum levels do not exclude limited local production.

[Improvement of osseointegration of bio-inert ceramics by modification of the surface--results of an animal experiment]. / Verbesserung der knöchernen Integration bioinerter Keramiken durch Modifikation der Oberfläche--Ergebnisse eines Tierversuchs.

The aim of this experimental study was to screen different surface structures of alumina and zirconia ceramic implants for their osteointegration properties. Alumina and zirconia ceramic test implants having different surface structures (smooth, macro-structured, corundum-blasted, porous) were implanted in the femora of mini-pigs, and left in situ for 12 weeks. After removal, the implants were evaluated macroradiographically and histologically. The smooth and macro-structured ceramic surfaces showed virtually no bony ingrowth, neither in the cortical nor the cancellous bone areas. In contrast, a rough surface finish or a porous surface structure allowed extensive bony ingrowth. The osteointegration rates varied between 20.5% and 41.7% (cancellous bone), and between 26.0% and 52.8% (cortical bone). With regard to the development of ceramic implants for clinical use, for example in the field of total hip replacement, these data provide a basis for further, more comprehensive studies.

Efficacy of oral ofloxacin for single-dose perioperative prophylaxis in general surgery--a controlled randomized clinical study.

BACKGROUND: Perioperative antibiotic prophylaxis surely reduces surgical infection rate. Pharmacokinetic data of oral ofloxacin in combination with its antibacterial spectrum suggest effective protection against perioperative infection. In addition, costs, adverse effects, and induction of microbial resistance are low. Therefore we performed a controlled randomized study comparing oral and intravenous single dose prophylaxis. METHODS: A total of 61 patients undergoing colonic or pancreatic resection randomly received either a single dose standard intravenous prophylaxis or ofloxacin 400 mg and metronidazole 500 mg orally 2 h before surgery. Postoperative infections were recorded for 3 weeks. RESULTS: Groups were very well comparable regarding age, overweight, concomitant disease, type and duration of surgery, blood loss, and volume support. Infectious complications occurred in 14.8% after parenteral and 3.3% after enteral antibiotic prophylaxis. There was no difference in post-operative hospital stay. CONCLUSION: The data demonstrate that single-dose oral ofloxacin is at least as effective as a standard intravenous prophylaxis in patients with colonic or pancreatic resection. It offers significant advantages regarding costs and ease of administration.

A novel long-QT 5 gene mutation in the C-terminus (V109I) is associated with a mild phenotype.

Mutations in the human minK gene KCNE1 have been linked to autosomal dominant and autosomal recessive long-QT (LQT) syndrome, a cardiac condition predisposing to ventricular arrhythmias. minK and KvLQT1, the LQT1 gene product, form a native cardiac K+ channel that regulates the slowly delayed rectifier potassium current I(Ks). We used single-strand conformation polymorphism and sequencing techniques to identify novel KCNE1 mutations in patients with a congenital LQT syndrome of unknown genetic origin. In 150 unrelated index patients a missense mutation (V109I) was identified that significantly reduced the wild-type I(Ks) current amplitude (by 36%) when coexpressed with KvLQT1 in Xenopus oocytes. Other biophysical properties of the I(Ks) channel were not altered. Since we observed incomplete penetrance (only one of two mutation carriers could be diagnosed by clinical criteria), and the family's history was unremarkable for sudden cardiac death, the 109I allele most likely causes a mild phenotype. This finding may have implications for the occurrence of "acquired" conditions for ventricular arrhythmias and thereby the potential cardiac risk for asymptomatic mutation carriers still remains to be determined.

Positional cloning of heart and soul reveals multiple roles for PKC lambda in zebrafish organogenesis.

BACKGROUND: The Par-3/Par-6/aPKC complex is a key regulator of cell polarity in a number of systems. In Drosophila, this complex acts at the zonula adherens (adherens junctions) to establish epithelial polarity and helps to orient the mitotic spindle during asymmetric neuroblast divisions. In MDCKII cells, this complex localizes to the zonula occludens (tight junctions) and appears to regulate epithelial polarity. However, the in vivo role of this complex during vertebrate embryogenesis is not known, due to the lack of relevant mutations. RESULTS: We have positionally cloned the zebrafish heart and soul (has) mutation, which affects the morphogenesis of several embryonic tissues, and show that it encodes atypical protein kinase C lambda (aPKC lambda). We find that loss of aPKC lambda affects the formation and maintenance of the zonula adherens in the polarized epithelia of the retina, neural tube, and digestive tract, leading to novel phenotypes, such as the formation of multiple lumens in the developing intestine. In addition, has mutants display defects in gut looping and endodermal organ morphogenesis that appear to be independent of the defects in epithelial polarity. Finally, we show that loss of aPKC lambda leads to defects in spindle orientation during progenitor cell divisions in the neural retina. CONCLUSIONS: Our results show that aPKC lambda is required for the formation and maintenance of the zonula adherens during early epithelial development in vertebrates and demonstrate a previously undescribed yet critical role for this protein in organ morphogenesis. Furthermore, our studies identify the first genetic locus regulating the orientation of cell division in vertebrates.

Asymmetries of visual attention after circumscribed subcortical vascular lesions.

OBJECTIVE: To investigate the role of the basal ganglia and the thalamus for basic processes of visuospatial attention METHODS: Fifteen patients with acute circumscribed vascular lesions (10 with haemorrhage and five with infarction) were included in the study. The lesions were confined exclusively to subcortical structures, such as the basal ganglia, internal capsule, and thalamus, which was confirmed by initial CT on the day of referral and MRI taken 14-28 days after clinical onset. These patients were examined with two computerised attentional tasks (one detection and one search task) measuring spatial visual attention. RESULTS: There was a clear attentional asymmetry in patients with right hemispheric lesions (RHLs) in the visual search task. Seven out of eight patients with RHLs tended to be slower and/or missed significantly more target stimuli in the left sided part of a stimulus array consisting of 25 small squares than in right sided parts, although none of these patients showed signs of visual hemineglect in the visual detection task presenting visual information simultaneously to the right and left visual hemispace. All but one of these patients showed lesions in the posterior limb of the internal capsule and the putamen. On the other hand, patients with left hemispheric lesions were not impaired in the search task with only one patient showing more contralesional omissions of target stimuli than could be expected from the behaviour of normal controls. CONCLUSIONS: The results are in line with previous results showing a dominant role of right hemispheric neuronal structures for spatial attention. Furthermore, the data suggest that even with right hemispheric subcortical lesions without cortical involvement deficits in spatial orienting of attention to the left hemispace can be seen. These asymmetries of visual attention in the absence of neglect symptoms are supposed to be caused (1) by a disruption of the motor corticostriato-pallidothalamo-cortical neuronal circuit or (2) by a (partial) disconnection of relevant parts within the posterior attention network-namely, parietal and thalamic structures.

Pharmacokinetic basis for oral perioperative prophylaxis with ofloxacin in general surgery.

BACKGROUND: Perioperative prophylaxis is recommended to be administered intravenously which, compared to oral prophylaxis, is more expensive. However, pharmacokinetic data on oral perioperative prophylaxis in patients with preoperative surgical and anesthesiological preparation are not available. PATIENTS AND METHODS: 40 patients with open hernial repair or cholecystectomy (low-risk group), colonic or pancreatic resection (high-risk group) received a standard single-dose perioperative prophylaxis with 4.5 g mezlocillin and 0.5 g metronidazole intravenously in addition to 400 mg ofloxacin orally 2 h prior to surgery. Antibiotic concentrations were measured perioperatively and pharmacokinetic data calculated. RESULTS: Serum and tissue concentrations of ofloxacin were above the MIC90 of the potential bacterial spectrum for surgical infection throughout the entire operation. Pharmacokinetic data were not influenced by preoperative surgical or anesthesiological preparation. CONCLUSION: Tissue and serum concentrations and the antibacterial spectrum of orally administered ofloxacin suggest effective protection against perioperative infection. Pharmacokinetic data confirm that oral ofloxacin may be used effectively as single-dose perioperative antibiotic prophylaxis. Since there are no clinical data comparing oral and intravenous singLe-dose prophylaxis, a prospective randomized clinical trial should be performed.