Bispectral index values and propofol concentrations at loss and return of consciousness in patients with frontal brain tumours and control patients.

BACKGROUND: The influence of frontal brain tumours on bispectral index (BIS) measurements and propofol requirements is unknown. The primary aim of our study was to determine whether BIS values recorded at loss and return of consciousness (LOC and ROC, respectively) differ between patients with unilateral frontal brain tumours and control patients. Secondary goals were to compare propofol requirements for LOC and to determine whether there were significant inter-hemispheric differences between BIS values in tumour and control patients. METHODS: We enrolled 20 patients with a frontal brain tumour and 20 control patients. Bilateral BIS measurements were done during induction of propofol anaesthesia, during recovery of consciousness, and during a second induction of anaesthesia. The isolated-forearm test was used to determine the moments of LOC1, ROC, and LOC2. Arterial blood samples were obtained every 4 min for determination of measured propofol concentrations. RESULTS: The median BIS values recorded at LOC1, ROC, and LOC2 did not differ between the groups. There were no significant inter-hemispheric differences in BIS in tumour and control patients. The median [inter-quartile range (IQR)] total propofol doses at LOC1 were 82 (75-92) and 78 (68-91) mg in tumour and control patients, respectively. The median (IQR) measured plasma propofol concentrations at LOC1 were 12 (9-14) and 13 (11-15) µg ml(-1) in the tumour and control groups, respectively. CONCLUSIONS: The presence of a frontal brain tumour did not affect ipsilateral BIS values, and so need not influence the placement of unilateral BIS electrodes if BIS monitoring is used to titrate propofol anaesthesia.

Type I interferons are involved in the development of ultraviolet B-induced inflammatory skin lesions in systemic lupus erythaematosus patients.

OBJECTIVE: To investigate the involvement of type I interferons and endothelial cell adhesion molecules in the development of ultraviolet B (UVB)-induced systemic lupus erythaematosus (SLE) skin lesions. METHODS: A total of 19 SLE patients and 13 controls were irradiated with two minimal erythaemal doses(MED) of UVB. Subsequently, skin biopsies were analysed (immuno) histologically over 10 days, for expression of IFNalpha-induced MxA, numbers of plasmacytoid dendritic cells (pDC), and expression of endothelial cell adhesion molecules, namely E-selectin, ICAM-1, and L-selectin ligand. Additionally, MxA expression was compared to its expression in nine established cutaneous lupus erythaematosus(CLE) lesions of SLE patients. RESULTS: Before irradiation IFNalpha-induced MxA was expressed at significantly higher levels in non-lesional skin of SLE patients compared to healthy controls. In patients developing infiltrates upon UVB irradiation, MxA expression increased further, reaching expression levels similar to or exceeding levels in CLE-skin lesions. In these patients, MxA expression was sustained up to day 10, in contrast to patients not developing infiltrates in whom expression decreased. No noteworthy numbers of plasmacytoid dendritic cells (pDC) were detected in nonirradiated skin or at any time after UVB exposure in SLE patients or controls. MxA expression correlated with influx of T-cells and monocytes/macrophages, and with expression of E-selectin and ICAM-1. CONCLUSION: Development of UVB-induced SLE skin lesions involves a skewing towards production of Th1-associated cytokines, such as IFNalpha. In turn, this may lead to up-regulation of E-selectin and ICAM-1 resulting in recruitment of T-cells and macrophages.

[Intersexuality in horses]. / Intersexualität beim Pferd.

Intersexuality is a rare congenital anomaly of horses. Diagnosis of intersexuality is difficult because there are usually no specific changes in the reproductive tract visible. During a period of five years, ten patients with reduced fertility or suspected intersexuality respectively were investigated using cytogenetic, molecular genetic, histopathological and endocrinological methods. In one case a 64,XX/63,X0 mosaicism was found. In six cases male pseudohermaphroditism was verified. These patients showed a male karyotype, testes and rudimentary parts of a female reproductive tract were present. One horse was suspected to be a male pseudohermaphrodite but the gonads were not examined. One horse was suspected to be affected by an XX-sex several syndrome and in one case a SRY-negative XY-sex reversal syndrome was most likely. In the case of an XX-sex reversal syndrome, there is a female chromosomal constitution, an uterus and cranial parts of the vagina are present but also testes tissue and possibly an enlarged penis like clitoris. Here an XX-sex reversal syndrome was suspected but not confirmed as it was not possible to examine the gonads and verify tissue from testes. Therefore a pseudohermaphroditismus femininus could not be excluded. In cases of XY-sex reversal syndrome the patients show a male chromosomal constitution, parts of a female reproductive tract but no testes tissue is present. For the horse described here, a deletion of the SRY gene was the most likely cause for the XY-sex reversal syndrome.

[Familial occurrence of a congenital defect of the keratinisation of the skin in German Angus calves]. / Familiäres Auftreten einer angeborenen Verhornungsstörung der Haut bei zwei Kälbern der Rasse Deutsche Angus.

Congenital dysfunction of the keratinisation of the epithelium was diagnosed in two female German Angus calves born on the same farm. The relationship coefficient between the two affected Angus calves was 34.38%. The clinical findings were similar to ichthyosis congenita as the alterations of the skin were present at birth and the levels of zinc in the blood were not decreased. However, parakeratosis could not be completely excluded as skin alterations were partly parakeratotic. On account of the close relationship between the two affected calves a genetic cause is likely for the present cases.

The bovine aristaless-like homeobox 4 (ALX4) as a candidate gene for syndactyly.

The ALX4 (aristaless-like homeobox 4) gene encodes a paired-type homeodomain transcriptional activator and plays a major role in anterior-posterior pattern formation during limb development. Here, the cloning, genomic structure and expression of the bovine ortholog of the ALX4 gene are reported. The bovine ALX4 gene consists of four exons and is located on BTA15q28-->q29 in a region syntenic to HSA11p11.2. The transcribed ALX4 mRNA encodes a 397-amino-acid protein showing a paired-type homeodomain and a C-terminal stretch of amino acids known as the OAR- or aristaless domain. The predicted protein shares 92.5% identity to human and mouse ALX4 proteins and all three species share almost complete identity in the conserved domains. ALX4 expression was detected by reverse transcriptase polymerase chain reaction in bovine fetal limb bones. The ALX4 gene was evaluated as a candidate gene for bovine syndactyly which has been mapped on the telomeric region of cattle chromosome 15. Sequencing of the four exons with flanking sequences of the bovine ALX4 gene from a panel of 14 affected animals belonging to German Holstein, German Fleckvieh and crossbreds, and 27 unaffected individuals from German Holstein revealed five silent SNPs within the coding region out of eleven SNPs in total. Four SNPs were polymorphic in the affected animals, but in comparison to the genotyped unaffected individuals the genotype distribution showed no evidence for an association to the phenotype. Therefore our data indicate that the ALX4 gene can probably be excluded as candidate gene for bovine syndactyly in the examined animals.

Molecular characterization of the equine collagen, type IX, alpha 2 (COL9A2) gene on horse chromosome 2p16-->p15.

The mammalian collagen, type IX, alpha 2 gene (COL9A2) encodes the alpha-2 chain of type IX collagen and is located on horse chromosome 2p16-->p14 harbouring a quantitative trait locus for osteochondrosis. We isolated a bacterial artificial chromosome (BAC) clone containing the equine COL9A2 gene and determined the complete genomic sequence of this gene. Cloning and characterization of equine COL9A2 revealed that the equine gene consists of 32 exons spanning approximately 15 kb. The COL9A2 transcript encodes a single protein of 688 amino acids. Thirty two single nucleotide polymorphisms (SNPs) equally distributed in the gene were detected in a mutation scan of eight unrelated Hanoverian warmblood stallions, including one SNP that affects the amino acid sequence of COL9A2. Comparative analyses between horse, human, mouse and rat indicate that the chromosomal location of equine COL9A2 is in agreement with known chromosomal synteny relationships. The comparison of the gene structure and transcript revealed a high degree of conservation towards the other mammalian COL9A2 genes. We chose three informative SNPs for association and linkage disequilibrium tests in three to five paternal half-sib families of Hanoverian warmblood horses consisting of 44 to 75 genotyped animals. The test statistics did not reach the significance threshold of 5% and so we could not show an association of COL9A2 with equine osteochondrosis.

Adolescent melanoma: risk factors and long term survival.

AIMS: To report the adolescent melanomas with focus on differences in clinical characteristics, prognostic factors, disease free (DFS) and overall survival (OS) in comparison with adults. METHODS: A single institution retrospective study in which 49 adolescent patients were compared to an adult group of 972 patients. The 10-year DFS, 10-year OS and prognostic factors were calculated for both groups. RESULTS: The median age for the adolescent patients was 17 (range 12-19) years and 49 (range 20-93) years for the adult patients. Median follow-up time was 92 (range 4-366) months. Adolescent patients presented more often with locally advanced melanoma (p<0.01). The median Breslow thickness was 1.6 vs 2.0mm for the adults (p=0.075). Increasing age, ulceration, Breslow thickness, tumour location, male gender and stage at diagnosis were calculated to be negative prognostic factors for the adult group. In the adolescent group, only the stage at diagnosis was a significant negative predictor. The 10-year DFS and OS for the adolescent patients and adult group were not significantly different regarding AJCC stages I-III. CONCLUSION: Although adolescent patients presented more often with locally advanced disease, there are no significant differences in the 10-year DFS and OS between adolescent and adult patients. In our series, we could not confirm the prognostic factors found in the adult group for the adolescent patients, except for the stage at diagnosis.

[Aphakia in a German Holstein calf]. / Aphakie bei einem Kalb der Rasse Deutsche Holsteins.

Aphakia and further malformations of both eyes were diagnosed in a female German Holstein calf. Besides aphakia of the left eye, the calf exhibited microphthalmia, glaucoma and a hypoplastic uveoscleral tissue. Additional findings in the right eye were buphthalmus and glaucoma. Instead of aphakia, pathohistological and investigations revealed a very small (microphakia) and luxated lens. Neither the clinical nor the pathological examination revealed further malformations of other organs. A BVD infection could be excluded as cause for the ocular malformations observed. A deficiency or excess of vitamine A was unlikely because this would have also applied to all other calves born at the same time on the farm. An inbreeding coefficient of 3.168% for the malformed calf and the exclusion of environmental causes for these malformations of the eyes let us suppose a hereditary problem.

Root effect of Panulirus interruptus hemocyanin.

Panulirus interruptus hemocyanin exhibits a progressive decrease in oxygen affinity and a parallel loss of cooperativity with decrease in pH, resulting in an apparent loss of the oxygen-binding capacity of the protein. For a characterization of this system, oxygen-binding curves have been determined over the complete range of oxygen saturation, applying a special technique which involves high-pressure spectrophotometry. Although the oxygen-binding behavior as a function of pH is complex and cannot be described within the frame of a simple two-state Monod-Wyman-Changeux model, the observed Root effect is clearly related to a progressive stabilization of a low oxygen affinity state of the protein and functional heterogeneity is not apparent.

Molecular cloning, expression analysis and assignment of the porcine tumor necrosis factor superfamily member 10 gene (TNFSF10) to SSC13q34-->q36 by fluorescence in situ hybridization and radiation hybrid mapping.

We have cloned the complete coding region of the porcine TNFSF10 gene. The porcine TNFSF10 cDNA has an ORF of 870 nucleotides and shares 85% identity with human TNFSF10, and 75% and 72% identity with rat and mouse Tnfsf10 coding sequences, respectively. The deduced porcine TNFSF10 protein consists of 289 amino acids with the calculated molecular mass of 33.5 kDa and a predicted pI of 8.15. The amino acid sequence similarities correspond to 86, 72 and 70% when compared with human, rat and mouse sequences, respectively. Northern blot analysis detected TNFSF10-specific transcripts (approximately 1.7 kb) in various organs of a 10-week-old pig, suggesting ubiquitous expression. Real-time RT-PCR studies of various organs from fetal (days 73 and 98) and postnatal stages (two weeks, eight months) demonstrated developmental and tissue-specific regulation of TNFSF10 mRNA abundance. The chromosomal location of the porcine TNFSF10 gene was determined by FISH of a specific BAC clone to metaphase chromosomes. This TNFSF10 BAC clone has been assigned to SSC13q34-->q36. Additionally, the localization of the TNFSF10 gene was verified by RH mapping on the porcine IMpRH panel.

Absence of Lyme borreliosis among patients with presumed Bell's palsy.

In a prospective study, 69 patients with a presumed idiopathic (Bell's) peripheral facial palsy were clinically and serologically evaluated for the presence of Lyme borreliosis. In addition, their clinical spectrum was compared with clinical manifestations collected retrospectively in nine patients with symptomatic peripheral facial palsy due to Lyme borreliosis. The seroprevalence of Borrelia burgdorferi antibodies, determined by flagellum enzyme-linked immunosorbent assay, among 69 patients with idiopathic peripheral facial palsy (6%) and 153 healthy controls (4.5%) was not significantly different (odds ratio, 1.28; 95% confidence interval, 0.27 to 5.25). None of the patients with idiopathic peripheral facial palsy had or experienced the development of Lyme borreliosis. All patients with Lyme peripheral facial palsy had additional manifestations not present in patients with idiopathic peripheral facial palsy. These findings show that patients with a Lyme peripheral facial palsy can be differentiated from patients with idiopathic peripheral facial palsy by clinical examination. Therefore, screening of antibodies to B burgdorferi among patients with idiopathic peripheral facial palsy without additional manifestations is not recommended.

Molecular characterization of the porcine TYK2 gene on SSC 2q1.3-->q2.1.

TYK2 is a member of the janus protein kinase family and plays an important role in the signal transduction of various cytokines including interferon alpha/beta. Cloning and characterization of the porcine TYK2 gene revealed a conserved organization with respect to other mammalian TYK2 orthologs. The porcine gene consists of 25 exons spanning approximately 26 kb and encoding a 5.3-kb mRNA. It is located in a GC-rich and gene-rich chromosome region and contains several CpG islands. The predicted 132-kDa TYK2 protein consists of 1,184 amino acids and shows 85% identity to the human TYK2 protein. The porcine TYK2 gene was localized by FISH and RH-mapping on SSC 2q1.3-->q2.1, which is in good agreement with established human-mouse-pig comparative maps.

Carcinogenicity testing of complete human diets in rats.

So far, in most animal experimental studies isolated food components have been tested. However, as components may interact with each other at different mechanistic levels, testing complex food mixtures more representative for human consumption patterns may better predict the ultimate carcinogenic risk. Studies were performed in Wistar rats using human and rat control diets to assess the effect of relevant food factors such as heat processing and the presence of non-nutrients in vegetables and fruit. The complete human diets, containing meat, bread and eggs, with or without vegetables and fruit, were composed according to mean consumption figures, balanced for macro- and micronutrients. Experiments were performed with spontaneous as well as with chemical-induced tumor models. Heat processing had no effect on tumor induction, while vegetables and fruit only exerted a protective effect on chemically induced tumors in rats fed low-fat animal diets. Data suggest interaction between major food factors in the human diet on colon carcinogenesis.

Control of follicle-stimulating hormone secretion by steroid-free bovine follicular fluid in the ovariectomized rat.

The effects of steroid-free bovine follicular fluid (bFF) and sodium phenobarbitone on spontaneous LH releasing hormone (LHRH)-induced secretion of FSH and LH were studied in ovariectomized rats. Luteinizing hormone releasing hormone was administered by infusion to rats anaesthetized with phenobarbitone. Bovine follicular fluid reduced FSH release and synthesis. Luteinizing hormone release remained unaffected after bFF treatment. Phenobarbitone reduced both FSH and LH release. The observed suppressive effects of bFF and phenobarbitone on FSH secretion were additive, suggesting that the basal release of FSH has an LHRH-dependent and an LHRH-independent component. Furthermore, bFF did not affect pituitary responsiveness of LH secretion to LHRH and reduced the responsiveness of FSH secretion only when administered some time before the LHRH challenge. The present observations support the view that in the ovariectomized rat the pituitary gland is the only site of action of inhibin-like activity as present in bFF.

A mola hydatidosa coexistent with a foetus in a bovine freemartin pregnancy.

Molar transformations of the bovine placenta are extremly rare phenomenona and the aetiology of this genuine placental disease is still unknown. In the present study, an uncommon case of a German Holstein Friesian foetus co-twinned with a hydatidiform mole is described. Cytogenetic and fluorescence in situ hybridization analysis of cell cultures as well as prove of the presence of the SRY gene sequence revealed a heterosexual twin pregnancy. A chimeric condition of the mole was also established. In addition, an XO cell population was detected in the co-twin as well as in the mole. Upon examination of microsatellites of the parents, the mole and the co-twin an androgenetic origin of the mole is suggested, supporting the hypothesis that molar transformation of the bovine placenta may be caused by an androgenetic origin. Furthermore, the present observation demonstrates that the freemartin condition in cattle can be induced even in cases where severe placental transformations had subsequently occurred and no foetus proper could be detected at delivery.

Long-term effects of ceftriaxone treatment on intraocular Lyme borreliosis.

Twelve patients with intraocular Lyme borreliosis suffering from vitreitis were treated with ceftriaxone intravenously. Eight patients had definitive Lyme borreliosis, and tentative diagnosis was made in four patients. After treatment with ceftriaxone, all 12 patients were followed up for more than one year. Vitreitis diminished in all patients and visual acuity improved in six patients. The best results were achieved in patients with definitive Lyme borreliosis.

The hearing loss associated with exposure to toluene is not caused by a metabolite.

Exposure to toluene causes a marked hearing loss in rats, and this effect has been observed in some human solvent abusers. The issue of whether toluene or one of its metabolites is responsible for this effect has not been examined. To attempt to resolve this issue, we manipulated the metabolism, and thus the circulating levels, of toluene as follows. Two groups of rats were exposed to phenobarbital (PB) in their drinking water (0.1%) for seven days to induce detoxifying liver enzymes; two other groups had access to PB-free water. Then half of the rats exposed to PB or water were exposed to filtered air or a concentration of toluene expected to cause hearing loss. Levels of toluene in blood were markedly reduced by the PB and the excretion of hippuric acid was increased. All rats were tested for auditory sensitivity by brainstem auditory-evoked response (BAER) audiometry using a 16-kHz tone pip. The rats exposed to toluene alone showed a marked reduction in the integrated BAER waveform, indicative of the expected hearing deficit. None of the other treated rats showed any deviation from controls (i.e., water and air). These results provide strong evidence that toluene itself is responsible for the auditory dysfunction. Toluene also caused the rats to increase their fluid consumption and urine output; these effects were not altered by PB. Identification of toluene as the proximal ototoxicant should facilitate the search for the mechanism of this effect.

Kinetic and thermodynamic parameters for oxygen binding to the allosteric states of Panulirus interruptus hemocyanin.

The temperature dependence of the oxygen binding equilibria and kinetics of Panulirus interruptus hemocyanin has been analyzed within the context of the two-state allosteric model. Oxygenation of the T-state is characterized by a more negative value of DeltaH than that of the R-state; therefore, cooperative effects in oxygen binding to P. interruptus hemocyanin are thermodynamically governed by favorable entropy changes. The allosteric transition in the unliganded derivative shows an enthalpy-entropy compensation effect. The activation enthalpies for oxygenation and deoxygenation of the T-state are larger than those for the R-state, while the activation entropies are favorable for the T-state and unfavorable for the R-state. Thus, the activation free energies for oxygen binding to the T- and R-states are similar, while for the deoxygenation reaction DeltaG++ is smaller for the T-state. The analysis reported confirms the applicability of the Monod-Wyman-Changeux two-state allosteric model to P. interruptus hemocyanin and yields a complete thermodynamic characterization of oxygen binding under both equilibrium and dynamic regimes.

Discrimination of tertiary and quaternary Bohr effect in the O2 binding of Helix pomatia beta-hemocyanin.

Simultaneous determination of proton uptake and oxygen binding has been carried out on Helix pomatia beta-hemocyanin under equilibrium conditions in the absence of buffer and at different initial pH values. Oxygen-binding isotherms of unbuffered H. pomatia beta-hemocyanin, in the presence of phenol red as pH indicator, have been determined employing a thin-layer apparatus. Application of this very accurate technique allows monitoring of proton uptake (or release) coupled to O2-binding also at extremes of saturation which are often difficult to explore and analyze. The data have been analyzed within the framework of the cooperon model (M. Brunori, M. Coletta and E. Di Cera, Biophys. Chem. 23 (1986) 215) and compared with those obtained in the presence of buffer. Comparison of pH changes with ligand binding of the T state over all the saturation range has allowed us to discriminate and obtain quantitative estimates of the Bohr protons associated with both oxygenation of the T state and quaternary allosteric transition; no protons are taken up or released during oxygenation of the R state. These results differ quantitatively from those obtained in the presence of buffer, which alters significantly the T state contribution to the overall Bohr effect.

Intermediate uveitis and Lyme borreliosis.

A case of chronic intermediate uveitis and associated classic snowbanking (pars planitis) with severe cystoid macular oedema probably due to Lyme borreliosis is reported. Despite a disease duration of 10 years the patient's ocular symptoms and visual acuity responded promptly to intravenous ceftriaxone treatment. This case demonstrates that periodic reevaluation of patients with intermediate uveitis is necessary to obtain a specific diagnosis which may include Lyme borreliosis.