[Cisplatin-induced hearing loss in children in relation to eye color]. / Cisplatininduzierte Hörstörungen bei Kindern in Abhängigkeit von der Pigmentierung der Iris.

BACKGROUND: Cisplatin is commonly used as a chemotherapeutic agent in the treatment of solid tumors. Ototoxicity is an important side-effect. Melanin in the inner ear either plays an otoprotective role or has a negative influence on hearing. The concentration of cochlear melanin correlates with its concentration in the iris. PATIENTS AND METHODS: We retrospectively examined 65 children (37 males, 28 females, average age 7.5 years) treated with cisplatin at the University Clinic of Muenster, Germany. We checked whether their eye color could be inferred from the prevalence and extent of cisplatin-induced hearing loss. RESULTS: We found a hearing loss of >20 dB in 29 light-eyed and in 21 dark-eyed patients. Seven light-eyed and eight dark-eyed patients did not suffer from hearing impairment. Using the chi(2)-test on these four parameters, we found no significant connection between iris pigmentation and the prevalence or extent of hearing loss, although light-eyed children (80.6%) suffered more from hearing loss than dark-eyed children (72.4%). After the end of therapy with cisplatin, the prevalence of hearing loss was 83.3% in children up to 6 years and 71.4% in children older than 6 years. The average cumulative dose of cisplatin was 372 mg/m(2) of body surface in children with hearing loss, compared to 390 mg/m(2) in children without hearing loss. CONCLUSION: We found no significant correlation between iris pigmentation (eye color) and hearing loss. Cisplatin-induced hearing loss occurs frequently and requires repeated monitoring.

[Fetal wound healing: current status and new perspectives]. / Fetale Wundheilung. Aktueller Stand und neue Perspektiven.

The characteristic of fetal wound healing is scarless wound repair in early gestation. During the last two decades, intensive research efforts have focused on unraveling the molecular regulations underlying the phenomenon of scarless wound healing. Better understanding of synthesis and degradation will enable us to develop important therapeutic options for the prevention and reduction of scarring. The aim of this article is to present an overview, discuss the most important research works of the last two decades on the field of fetal wound healing, and report current therapeutic developments for the modulation of adult wound repair. Recent experimental results using these new therapeutic approaches are very promising and present great possibilities and chances for future surgery.

Expression of Epstein-Barr virus membrane antigen gp350/220 in E. coli and in insect cells.

The Epstein-Barr virus open reading frame BLLF1 encodes the major envelope glycoproteins gp350 and gp220. Fragments of the gp350/220 gene were expressed in Escherichia coli in order to define regions of the polypeptide chain reacting with human sera. The C-terminal half of the protein was sufficient for recognition by all VCA-positive sera tested. A membrane anchor truncated version of gp350/220 was expressed in insect cells using the baculovirus system. Proteins of different sizes were specifically detected in the cells while a glycosylated 220-kDa protein was secreted. The insect cells were tested for their suitability as tools for performing monospecific immunofluorescence.

Bothrops atrox snake bite in a six-year-old child.

A rare case of snake bite poisoning presenting as disseminated intravascular coagulation is presented. It is important to consider this entity in the differential diagnosis of children presenting with acute bleeding disorders in the West Indian islands where Bothrops atrox is present, namely, in Trinidad, St. Lucia and Martinique.

Flow cytometric analysis of Epstein-Barr virus (EBV) latent membrane protein expression in EBV-infected Raji cells.

In cultures of the latently Epstein-Barr virus (EBV)-infected Burkitt's lymphoma cell line Raji, the detectable amount of the EBV-encoded latent membrane protein (LMP) is transiently increased after addition of fresh nutrient medium containing foetal calf serum. In the current study, the relative amount of LMP and DNA in Raji cells was determined by biparametric flow cytometry analysis at different times after the addition of fresh medium with 10% foetal calf serum to a dense Raji culture. A transient increase in the proportion of LMP-positive cells was observed during the lag phase of the culture. Subsequently, a subpopulation of cells, which had been arrested in the G0 or G1 phase, simultaneously started to progress through the cell cycle. Neither the amount of LMP in the cells, nor the enhanced expression of LMP, was restricted to a certain phase of the cell cycle. Further analysis revealed that the number of LMP-positive cells proceeding simultaneously from the G1 to the S phase of the cell cycle is about the same as the total number of cells changing phases. These results suggest that LMP expression might be one step in the pathway leading to growth activation of resting cells in cultures of the immortalized Raji cell line.

Characterization of a latent protein encoded by the large internal repeats and the BamHI Y fragment of the Epstein-Barr virus (EBV) genome.

Analysis of EBV nuclear antigen 1 (EBNA 1) encoding transcripts by cDNA characterization revealed a potentially polycistronic message generated by long-range splicing of several exons (Speck, S., and Strominger, J., Proc. Natl. Acad. Sci. USA 82, 8305-8309, 1985). Besides the open reading frame encoding EBNA 1, two other open reading frames are found in the EBNA 1-specific cDNA. The first reading frame consists of several exons from BamHI W and Y viral genome fragments (W1, W2, Y1, and Y2). In our experiments, the W1 exon was expressed in the tryptophan-regulated expression vector pATH11. Rabbit sera, raised against the bacterial fusion protein, recognized one or two proteins of molecular weights between 30,000 and 100,000 in several EBV genome harboring Burkitt lymphoma and EBV immortalized peripheral blood cell lines. Although, in a few cell lines from both groups no specific protein could be detected. Immunofluorescence analysis and characterization of subcellular distribution demonstrated that this W/Y fragment encoded latent protein is located, in part, in the cytoskeleton fraction, and in the chromatin. In addition, 2-D immunoblot analysis revealed post-translational modifications of this latent protein, probably due to phosphorylation. In DNA-binding studies on DNA cellulose columns, this W/Y encoded latent protein exhibited specific DNA binding activities.

Enhancement of Epstein-Barr virus membrane protein (LMP) expression by serum, TPA, or n-butyrate in latently infected Raji cells.

The BamHI Nhet region of the EBV DNA is known to code for two proteins. One is a membrane protein (LMP) with an apparent molecular weight of 60,000 on SDS-PAGE which is expressed in latently EBV infected cells. The second protein, so far unidentified, is presumably a late protein with a calculated molecular weight of 28,000 Da. Antisera against both proteins were generated by immunizing rabbits with either a fusion protein containing 155 amino acids of the C-terminus of LMP and a 37,000 mol wt piece of the bacterial anthranilate synthase or with a C-terminal synthetic peptide of 7 amino acids. These sera reacted with a protein varying in size between 60,000 and 65,000 mol wt on SDS-PAGE, found in all cell lines harboring EBV. In addition, these sera identified a second protein with an apparent molecular weight of 49,000 on SDS-PAGE in B95-8, P3HR-1, and M-ABA cells, which is presumably identical with the 28,000-Da protein mentioned above. Furthermore, with these sera a positive cytoplasmic immunofluorescence in 1 to 10% of the cells was obtained, depending on the cell line examined. Analyzing the nonproducer Raji cell line, the number of immunofluorescence-positive cells and the amount of the 60,000 protein, as judged by immunoblotting, was rapidly increased by addition of fresh medium with 10% fetal calf serum as well as by the tumor promoter TPA or to an even higher extend by n-butyrate. The kinetics of induction reached a maximum 24 hr after addition of medium plus 10% fresh serum or TPA or n-butyrate and decreased after 24 to 48 hr. Since the induction of the EBV early antigen (EA) associated proteins by TPA or n-butyrate exhibits a diverse kinetic with a maximum at 72 hr, the regulation of the 60,000 protein synthesis appears to be different from known EA-associated proteins.

Increased use of medical services and antibiotics by children who claim a prior penicillin sensitivity.

On surveying 3,467 children (ages 0 to 19 years) who were members of a health maintenance organization in Spokane, Washington, we found that 95 of 1,497 respondents (6.3%) claimed a past intolerance to penicillin-like agents. We investigated the costs of providing medical care for these 95 children and a random sample of 187 children who did not claim prior penicillin sensitivity. During a two-year period of observation, the children who claimed prior penicillin reactions had a significant increase in the average number of medical visits, the average number of antibiotic prescriptions, the average wholesale cost of antibiotic prescriptions and the average antibiotic cost per patient per month of observation. These children have an increased exposure to antibiotics that may increase their risk for adverse drug reactions.

Expression of an early Epstein-Barr virus antigen (EA-D) in E. coli. Brief report.

The 1.34 kb BcII-BgIII-fragment of the BamHI-M region of Epstein-Barr virus genome, comprising the complete BMRF1 open reading frame, was cloned into the tryptophan regulated E. coli expression vector pATH1. The resulting fusion protein, having a molecular weight of 80 kd, is recognized not only by anti-early antigen (EA)-positive human sera but also by the monoclonal antibody R3 directed against the diffuse component of EA (EA-D). A possible use for this fusion protein as an indicator protein in diagnosis of IgA antibodies against EA-D is presented.

[Endocrine fertility-restricting factors in clomiphene therapy]. / Endokrine fertilitätsein-schränkende Faktoren bei der Clomiphen-Therapie.

A marked discrepancy between a high ovulation rate (70-80%) and a low pregnancy rate (30-35%) is generally observed during clomiphene therapy in female infertility. Disturbances in follicular maturation, inadequate secretory transformation of the endometrium and influence on the quality of cervical mucus are discussed as cause for this phenomenon. The purpose of this study was to investigate whether changes in endocrine patterns might lead to these changes thus limiting the success of clomiphene therapy. In 7 patients gonadotropins, prolactin, ovarian and adrenal androgens, sexual hormone binding globuline (SHBG) and plasma levels of clomiphene were measured at short intervals during a stimulated cycle. The increase of testosterone and androstendione promoted by clomiphene during the follicular phase is in accordance with previous observations. The decline in SHBG due to an antioestrogenic effect on its hepatic production leads to an additional increase in free, biologically active androgens. These androgens interfere with follicular maturation, causing atresia and premature luteinisation. As a direct effect of clomiphene on the adrenal gland, we observed an elevation of DHEAS. The significance of this finding remains unclear. During the follicular phase prolactin remained suppressed inspite of supraphysiological oestrogen levels. In the late luteal phase the diminished antioestrogenic influence on lactotrophic cells causes a 80% rise in prolactin that in some cases may impair luteal function. The average plasma half-life of clomiphene was found to be 12 days. This is in accordance with the half-life of the closely related compound tamoxifen. Clomiphene, also present in the luteal phase of the cycle, may cause inadequate secretory transformation of the endometrium by blocking endometrial oestrogen receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

[A contribution to pigmented villonodular synovitis of the shoulder joint (author's transl)]. / Beitrag zur Synovitis villonodularis pigmentosa des Schultergelenkes.

Pigmented villonodular synovitis of the shoulder joint, particularly with osseous invasion, is a rare disease. Typical clinical, roentgenological and histological criteria are pointed out on the basis of the case report of one of the authors' own patients. Aetiology and pathogenesis of the changes are discussed. This disease must be included in differential diagnostic deliberations in the shoulder joint region as well, where it may be superficially confused with malignant tumours of the joint.