Vestibular disorders following head injury in children

One hundred and ninety-nine child patients with blunt head injury were examined. Spontaneous and/or positional nystagmus (greater than or equal to 7 degrees/s) was observed immediately after trauma in 46% of cases, 6-12 months (average 10.2 months) later in 20%, and 2-8 years (average 4.7 years) later in 18%. Central ENG disturbances were found immediately after trauma in 43% of cases, 6-12 months later in 24%, and 2-8 years later in 12%. Only 1.5% of the child patients suffered from vertigo more than 6 months after trauma. The results of the study led to the conclusion that head injuries cause about as many similar objective vestibular lesions in children as in adults but fewer subjective symptoms.     

Development of the standard reference plane for the Heidelberg retina tomograph

Background: Topometry of the optic disc is the quantitative assessment of the structure of the optic nerve head by means of three- dimensional parameters. The parameter values depend on definitions of intraocular reference planes. Purpose: To describe the development of intraocular reference planes in laser scanning tomography for the Heidelberg Retina Tomograph (HRT) using image intrinsic data with a fixed offset reference plane (320 μm) and to present a contour-line-based ”flexible” standard reference plane (”SRP”) for calculation of intrapapillary stereometric parameters taking the interindividual variability of optic disc topography into account.Methods: Ten-degree triple images were obtained by laser scanning tomography from 99 glaucoma eyes and 180 normal eyes. The images were evaluated to assess the variability of height measurements of an optic disc border contour-line segment (6° width) corresponding to the site of the papillo-macular bundle as indicated by the average optic disc surface inclination angle. Results: The average optic disc surface inclination angle was –7°±3° below the horizontal meridian (0°). The 6° wide contour-line segment for the SRP was chosen according to the average surface inclination angle (–10° to –4°). The reproducibility of the SRP-segment height measurements was 16.0±10.8 μm for normal eyes and 23.4±18.0 μm for glaucoma eyes. To ensure that the automatic reference level determination for intrapapillary parameters remained below the disc border height, we defined the SRP level at a 50 μm offset (>2 SD of average segment height reproducibility in glaucoma) added to the individual height position of the 6° contour line segment. Conclusion: The flexible standard reference plane allows for automatic determination of intrapapillary variables once a disc border contour line is interactively defined. In contrast to a fixed offset reference plane (e.g. 320 μm below the mean retina height), the interindividual variability of optic disc topography (oblique insertion, glaucomatous surface flattening) is respected at the cost of the need for an accurate optic disc border outline. Received: 9 March 1999 Revised: 26 August 1999 Accepted: 29 September 1999     

Expression of intermediate filaments in ovarian and uterine tumors

We studied the expression of cytoskeletal intermediate filaments in different types of ovarian and uterine sarcomas and carcinomas. In both uterine and ovarian leiomyosarcomas, in endometrial stromal sarcomas, and also in ovarian sarcomas, most tumor cells appeared to be positive for desmin, the muscle type of intermediate filament protein. In most of the tumors, vimentin was present only in some neoplastic cells and in the vascular endothelia. Interestingly, both uterine and ovarian malignant mixed mesodermal tumors appeared to express several types of intermediate filaments, most of the stromal cells being positive for vimentin or desmin, and the epithelial component expressing keratin. The results show that most of the sarcomatous tumors of the ovary and uterus express mainly muscle type of intermediate filament protein. The results also demonstrate the ability of cells of mesodermal origin to express epithelial cytoskeleton markers--cytokeratins.     

The Souter-Strathclyde elbow arthroplasty. A clinical and radiological study of 525 consecutive cases

We present the results of 525 primary Souter elbow arthroplasties undertaken in 406 patients between 1982 and 1997. There were 372 women and 34 men with a mean age of 57 years; 119 patients had a bilateral procedure. The elbows were affected by chronic inflammatory disease, usually rheumatoid arthritis, which had been present for a mean of 24.7 years (2 to 70). In about 30% the joints were grossly destroyed with significant loss of bone. In 179 elbows the ulnar components were metal-backed and retentive; in the remaining 346, with better bone stock, non-retentive, all-polyethylene prostheses were used. Because of complications, 108 further operations were required in 82 patients. During the early years the incidence of complications was higher. Dislocation was the indication for 30 further procedures in 26 patients. Thirty patients underwent 33 revision procedures for aseptic loosening, 12 had 29 operations because of deep infection, two for superficial infection, and 14 further operations were done for other reasons. The cumulative rate of success, without aseptic loosening, five and ten years after surgery, was 96% and 85%, respectively.     

Identification of PKCalpha isoform-specific effects in cardiac myocytes using antisense phosphorothioate oligonucleotides

Members of the mammalian protein kinase C (PKC) superfamily play key regulatory roles in multiple cellular processes. In the heart, PKC signaling is involved in hypertrophic agonist-induced gene expression and hypertrophic growth. To investigate the specific function of PKC signaling in regulating cardiomyocyte growth, we used antisense oligonucleotides to inhibit PKC alpha, the major isozyme present in the neonatal heart. Transfection of cultured neonatal cardiomyocytes with antisense PKCalpha oligonucleotides resulted in a marked reduction in both PKCalpha mRNA and protein levels. PKCalpha antisense treatment also reduced phenylephrine (PE)-induced PKC activity and perinuclear translocation of PKCalpha. Antisense inhibition of PKCalpha led to reduction of PE-induced increase in skeletal alpha-actin mRNA levels and atrial natriuretic peptide (ANP) secretion but had no significant effects on PE-induced beta-myosin heavy chain, ANP, or B-type natriuretic peptide (BNP) gene expression. On the other hand, antisense PKCalpha treatment attenuated endothelin-1-induced increase in ANP and BNP peptide secretion, whereas endothelin-1-induced gene expression of ANP and BNP remained unchanged. The hypertrophic agonist-induced growth of cardiomyocytes, characterized by increased [(3)H]leucine incorporation, was not affected with antisense PKCalpha treatment. Furthermore, we found that PE-induced increase in extracellular signal-regulated kinase (ERK) activity was partially inhibited by antisense PKCalpha treatment, implicating ERK as a downstream mediator for PKCalpha signaling. These results indicate that PKCalpha isozyme is involved in hypertrophic signaling in cardiomyocytes and provide novel strategies for future studies to identify other cellular targets controlled selectively by PKCalpha or other PKC isozymes.     

Influence of enriched environment on spatial learning following cerebral insult

The fact that our brain is continuously shaped by the environment and experience presents many challenges. It was noted several decades ago that exposure of a laboratory rat to a complex environment alters its brain and improves problem solving in complex tasks. Rats that are housed in an enriched environment can better compensate for brain lesion-induced deficits and resist neurodegeneration. In this article, the role of an enriched environment on brain plasticity following experimentally-induced lesions is discussed.     

The combination of HSV-tk and endostatin gene therapy eradicates orthotopic human renal cell carcinomas in nude mice

BACKGROUND AND METHODS: Gene therapy may offer a new tool for the treatment of renal cell carcinoma (RCC). We have tested a combination of cytotoxic and antiangiogenic gene therapy for wild-type orthotopic human RCC xenografts in nude mice using intratumoral adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) and endostatin (ES) gene therapy. In vivo magnetic resonance imaging, morphometry, immunocytochemistry, and survival were used to evaluate the treatment effect. Adenovirus-mediated marker gene transfers (GFP) were used as controls. Results: In vivo transduction efficiency, measured using GFP gene transfer, was 27+/-7%. The combination gene therapy with HSV-tk and ES adenoviruses resulted in a significant antitumor effect (P<.01) compared to single HSV-tk (n.s.) or ES (n.s.). In the survival study, all tumors with single gene therapy using HSV-tk, ES, and marker gene adenoviruses showed progression in magnetic resonance imaging. In contrast, the majority of the tumors in the combination treatment group remained dormant or were eradicated (57%). Survival of these mice equaled healthy nude mice, and was significantly prolonged (P<.0001) compared to HSV-tk (P<.028) and ES (n.s.) groups. Conclusions: It is concluded that the inhibition of angiogenesis using ES gene transfer together with the cytotoxic HSV-tk gene therapy results in a significantly improved treatment effect in RCC compared to the single gene treatments.     

Haemophilus influenzae type b (Hib) antibody concentrations and vaccination responses in patients with chronic lymphocytic leukaemia: predicting factors for response

We have recently demonstrated a moderate vaccination response rate of 43% against Haemophilus influenzae type b (Hib) conjugate vaccine among adult and elderly patients with chronic lymphocytic leukaemia (CLL). We now investigated demographic and immunological factors predicting the favourable response and protective antibody concentrations for Hib conjugate vaccine in CLL. Lower age was associated with protective pre- and post-vaccination antibody concentrations. High IgG1 and IgA concentrations were also associated with the protective efficacy. High IgM, in turn, was the best predictor of a significant vaccination response. Again, lower age seemed to be involved in this outcome. Judging from these findings, it would seem beneficial to vaccinate all CLL patients with conjugate vaccines at the presentation of the disease. Investigations of a new pneumococcal conjugate vaccine in CLL are warranted.     

Relationships of in vitro sensitivities tested with nine drugs and two types of irradiation in chronic lymphocytic leukemia

Extensive research into mechanisms of cytotoxic drug and irradiation resistance have produced few clinically encouraging results. In this report, we apply correlation analyses to drug and irradiation response results from a cohort of 36 classical B chronic lymphocyte leukemia (CLL) patients. Nine drugs and two types of irradiation were selected according to their usefulness in CLL therapy or on the basis of their otherwise interesting mechanisms of action. Part of the results concerning individual drugs have been previously published, but new correlation analyses are presented in this paper. Altogether 2376 duplicate cultures were performed in order to determine ID(80) values, i.e. doses causing an 80% inhibition in 4-day cultures when leucine incorporation was used as an indicator of cells vitality. Non-parametric Spearman's rank order correlation confirmed a tight relationship between 2-chlorodeoxyadenosine and fludarabine, as expected. Surprisingly, correlation between two P-glycoprotein-dependent drugs, vincristine and doxorubicin, was not demonstrable. A number of entirely unexpected correlations were identified between drugs with very different mechanisms of action: (i) chlorambucil and gamma-irradiation; (ii) 2-chlorodeoxyadenosine and vincristine; (iii) 2-chlorodeoxyadenosine and gamma-irradiation; (iv) fludarabine and cis-platin; (v) doxorubicine and gamma-irradiation; (vi) prednisolone and cyclosporin A; (vii) vincristine and verapamil. Our findings emphasize: (i) the usefulness of fresh tumor cells instead of cell lines in cytotoxicity studies; (ii) the great variation in cytotoxicity in individual patients, i.e. tumor cell heterogeneity, as well as patient heterogeneity; and (iii) an entirely unexpected finding that there were tight relationships in drug and irradiation responses between substances supposed to act with very different mechanisms.