Longterm follow‐up of children with traumatic optic nerve avulsion

Purpose: We report the longterm follow‐up of children with optic nerve avulsion (ONA) caused by traumatic events. The remarkable differences in courses and outcomes may elucidate the spectrum of ONA‐associated symptoms and injuries. Methods: During the last 15 years, three children with ONA were referred to our department. These cases are presented with special attention to their longterm follow‐up. Results: Two patients suffered from complete ONA after head injury. The third patient presented with partial ONA caused by a bicycle accident. Longterm follow‐up varied between 7 and 15 years. In the first patient, a pale swollen retina without any visible retinal vasculature was observed early in the course of follow‐up. The retina later completely detached. In the second patient, extended fibroglial scarring occurred and an extremely large epiretinal membrane formed and was finally released spontaneously into the vitreous. The third patient developed only mild fibroglial scarring and retinal pigment epithelium hyperplasia. The optic nerve head in this patient came to resemble a morning glory disc. Conclusions: Optic nerve avulsion can adopt different courses and outcomes in different patients. Final visual outcome seems to depend on the degree of visual acuity immediately after injury. Substantial intraocular architecture changes can occur as a result of ONA.     

A repository of bio-specimens from Mayak workers exposed to protracted radiation

A repository of bio-specimens that includes organs from 700 deceased workers employed at the first nuclear weapons facility "Mayak" and donations of blood, buccal cells, and tissues removed at the time of surgery and/or biopsy from the members of the Mayak cohort undergoing medical treatment or diagnostic procedures has been established at the Southern Ural Biophysics Institute, in Ozyorsk, Russian Federation. The autopsied tissues include formaline-preserved organs, paraffin blocks, and histology slides. For all, occupational, dosimetry, and detailed medical information is available. For 359 individuals, information on malignant tumors, i.e., lung (171), stomach (51), liver (28), and intestine (19), as well as 32 cases of leukemia, are available. External gamma exposures are known for 95% of the 700 autopsies, of whom 560 were exposed to protracted doses exceeding 0.5 Gy, with known maximum annual doses ranging from 0.01-0.5 Gy for about 46%, and annual doses exceeding 0.5 Gy for 48%. Plutonium body burden is known for 73%, of which 40% had body burden greater than 1.5 kBq, and 15% of individuals had body burdens greater than 11.85 kBq. Newly collected specimens include frozen lymphocytes, EBV-immortalized B-cells, frozen erythrocytes, and DNA as well as frozen tumors. Donations were obtained to date from more than 1,600 individuals. For these donors external doses of exposure exceeded 0.5 Gy for 83%, and plutonium body burden exceeded 1.48 kBq for 30%. A Web site describing the Repository that also includes forms for tissue requests can be accessed at http://www.subi.ru/RHTR.     

Gadolinium activates and sensitizes the vanilloid receptor TRPV1 through the external protonation sites

Gadolinium is a recognized blocker of many types of cation channels, including several channels of the transient receptor potential (TRP) superfamily. In this study, we demonstrate that Gd(3+), in addition to its blocking effects, activates and potentiates the recombinant vanilloid receptor TRPV1 expressed in HEK293T cells. Whole-cell currents through TRPV1 were induced by Gd(3+) with a half-maximal activation achieved at 72 microM at +40 mV. Gd(3+), at concentrations up to 100 microM, lowered the threshold for heat activation and potentiated the currents induced by capsaicin (1 microM) and low extracellular pH (6). Higher concentrations of Gd(3+) (>300 microM) blocked the TRPV1 channel. Neutralizations of the two acidic residues, Glu600 and Glu648, which are the key residues conferring the proton-sensitivity to TRPV1, resulted in a loss of Gd(3+)-induced activation and/or a reduction in its potentiating effects. A trivalent nonlanthanide, Al(3+), that possesses much a smaller atomic mass than Gd(3+) blocked but did not activate or sensitize the TRPV1 channel. These findings indicate that Gd(3+) activates and potentiates the TRPV1 by neutralizing two specific proton-sensitive sites on the extracellular side of the pore-forming loop.     

Search for correlation of CD8 T cell response to Epstein-Barr virus with clinical status in rheumatoid arthritis: a 15 month followup pilot study

OBJECTIVE: To assess in a longitudinal 15 month followup study the CD8 T cell response to immunodominant Epstein-Barr virus (EBV) antigens of 17 patients with rheumatoid arthritis (RA); and to seek an association between these responses and both clinical activity/severity of RA and a qualitative PCR for EBV in peripheral blood. METHODS: At each patient's visit every 3 months: (1) RA activity was assessed for Disease Activity Score (DAS-28); (2) a qualitative PCR for EBV was performed; (3) CD8 T cell response to EBV epitopes was screened in peripheral blood, using an autopresentation assay of 13 EBV peptides previously identified as immunodominant targets in RA synovia. Activation of anti-EBV CD8 T cells was evaluated by measuring the release of tumor necrosis factor-a. RESULTS: The semiquantitative CD8 T cell response to EBV roughly paralleled RA clinical activity in only 4/17 patients. No clear association could be found between positive PCR for EBV (performed at least once in 10/17 patients) and RA activity/severity or fatigue. Reactivity was not qualitatively broader in samples where PCR for EBV proved positive, and most often focused on one or 2 EBV antigens. However, these antigens differed between patients, as did the magnitude of CD8 T cell response to immunodominant antigens at different timepoints for the same patient. CONCLUSION: The CD8 T cell response to EBV paralleled clinical activity in only 4/17 patients. Our pilot study does not support the hypothesis that this CD8 response contributes to RA activity/flares, although the quantitative variations in the pattern of this reactivity over time confirmed that control of EBV manifestations was difficult in most patients with RA.     

Ouabain increases myofibrillar Ca2+ sensitivity but does not influence the Ca2+ release in human skinned fibres

The present study investigated the impact of the Na(+) pump inhibitor ouabain (g-strophanthin) on Ca(2+) sensitivity and Ca(2+) release in human right auricular trabeculae (coronary bypass) and in skinned muscle fibres from left ventricular myocardium (cardiac transplantation, dilated cardiomyopathy). A time-dependent increase in force of contraction was observed in right auricular trabeculae in response to ouabain (100 nM) before the intracellular Ca(2+) transient (fura-2) increased (n=6). In triton X-skinned fibres (no sarcoplasmic reticulum) of human failing myocardium, ouabain (1-100 nM) concentration-dependently increased tension at a free extracellular Ca(2+) concentration of 1 microM and the Hill coefficient of the Ca(2+)-dependent tension development. Ouabain (1-100 nM) did not directly induce a Ca(2+) release out of the sarcoplasmic reticulum, nor did it alter the caffeine (10 mM) induced sarcoplasmic reticulum Ca(2+) release in saponin-skinned fibre preparations in which the sarcoplasmic reticulum had been Ca(2+)-loaded. In conclusion, ouabain increases myofibrillar Ca(2+) sensitivity possibly due to an increase in the cooperativity of the thick and thin myofilaments. This mechanism may additionally contribute to the positive inotropic effect of ouabain.     

Rabbit neutrophil chemotactic protein (NCP) activates both CXCR1 and CXCR2 and is the functional homologue for human CXCL6

Neutrophil chemotactic protein (NCP) is a rabbit CXC chemokine with activating and chemotactic properties on neutrophilic granulocytes. Although its selective activity on neutrophils is demonstrated, its interactions with specific chemokine receptors are not defined. For further functional characterization, NCP was chemically synthesized and was found to be equipotent as natural NCP in neutrophil chemotaxis. To identify its human homologue, we separately expressed two potential rabbit NCP receptors (CXCR1 and CXCR2) in Jurkat cells. Pure synthetic NCP was equally efficient to promote chemotaxis through either rabbit CXCR1 or CXCR2. Moreover, chemotaxis assays on rabbit CXCR1 and CXCR2 transfectants showed that NCP uses the same receptors as interleukin-8 (IL-8), a major rabbit CXC chemokine, but not rabbit GROalpha, which only recognized CXCR2. In addition, specific inhibitors for CXCR1 or CXCR2 reduced rabbit neutrophil chemotaxis induced by NCP and rabbit IL-8. Furthermore, NCP and the structurally related human CXCR1/CXCR2 agonist CXCL6/GCP-2 (granulocyte chemotactic protein-2) cross-desensitized each other in intracellular calcium release assays on human neutrophils, further indicating that both chemokines share the same receptors. The inflammatory role of NCP was also evidenced by its potent granulocytosis inducing capacity in rabbits upon systemic administration. This study provides in vitro and in vivo evidences that NCP is the functional rabbit homologue for human CXCL6/GCP-2 rather than the most related CXCR2 agonist CXCL5/ENA-78 (epithelial cell-derived neutrophil activating peptide-78). It is concluded that the rabbit is a better model to study human neutrophil activation compared to mice, which lack CXCL8/IL-8.     

Influence of maternal,obstetric and fetal risk factors on the prevalence of birth asphyxia at term in a Swedish urban population

BACKGROUND: The influence of maternal, obstetric and fetal risk factors on the prevalence of birth asphyxia at term in a Swedish urban population. OBJECTIVE: To investigate risk factors for Apgar score-defined birth asphyxia, birth asphyxia with hypoxic-ischemic encephalopathy and birth asphyxia-related death/disability. MATERIAL AND METHODS: Retrospective case-control study in term neonates with birth asphyxia defined as Apgar score < 7 at 5 min. Cases originating from nonasphyctic causes (e.g. infection, maternal sedation) were excluded. Hypoxic-ischemic encephalopathy was diagnosed according to criteria by Sarnat. Maternal, obstetric and fetal risk factors were registered in 225 cases of birth asphyxia diagnosed in 42 203 live births occurring in the urban Swedish population studied. A matched control group was used for statistical evaluation. RESULTS: Asphyxia was associated with single civil status, OR = 7.1 (95%CI 2.0, 27.6); intrauterine meconium release, OR = 4.1 (95%CI 1.8, 9.8); operative delivery, OR = 8.7 (95%CI 3.4, 24.6); breech delivery, OR = 20.3 (95%CI 3.0, 416.5); oxytocin augmentation, OR = 2.9 (95%CI 1.4, 6.3); cord complication, OR = 15.8 (95%CI 2.1, 341.5); external compression to assist delivery OR = 6.2 (95%CI 1.3, 45.7); and cardiotocography score, OR = 0.5 (95%CI 0.4, 0.6). Normal fetal heart rate variability, OR = 0.4 (95%CI 0.2, 0.6), repeated late decelerations irrespective of amplitude or repeated variable decelerations, OR = 29.4 (95%CI 5.7, 540.8) or occasional late or variable decelerations, OR = 2.2 (95%CI 1.3, 3.8), and no accelerations, OR = 5.2 (95%CI 2.0, 16.4), were associated with asphyxia. Operative or instrumental delivery was more common in all three asphyxia groups compared with controls. Leanness was a risk factor for asphyxia and for hypoxic-ischemic encephalopathy. Maternal age, smoking and illnesses, time of delivery (day/night, seasonal) and previous caesarean section were not associated with birth asphyxia. CONCLUSIONS: An association between neonatal asphyxia and cardiotocography parameters, intrauterine meconium release, operative delivery, breech delivery, single civil status, oxytocin augmentation, cord complication, external compression to assist delivery and neonatal leanness was found. Abnormal fetal heart rate variability, repeated late decelerations irrespective of amplitude or repeated variable decelerations, occasional late or variable decelerations and no accelerations were associated with asphyxia.     

Prolactin influences proliferation and apoptosis of a human IgE secreting myeloma cell line,U266

In certain types of solid tumours and lymphomas prolactin (PRL) potentiates tumour cell proliferation and exerts anti-apoptotic effect. Tumour cells themselves can produce PRL and express PRL-receptors. Hyperprolactinemia is associated with different tumours, also. Multiple myeloma (MM) is a haematological malignancy caused by the clonal expansion of terminally differentiated plasma cells in the bone marrow. Recently, we demonstrated PRL immunostaining in bone marrow cells of MM patients and an elevated level of serum PRL of MM patients with advanced disease. In the present study, we tested the effect of PRL on a U266 human myeloma cell line and demonstrated constitutive and melphalan-stimulated intracytoplasmic PRL in U266 cells. Exogeneous PRL inhibited the proliferation and immunoglobulin (Ig) production of U266 myeloma cells. Concerning etoposide-induced apoptosis, PRL had a double-faceted effect depending on the applied dose: high, pharmacological doses (corresponding to hyperprolactinemia), inhibited apoptosis, whereas near physiological doses exerted a pro-apoptotic effect. These data indicate a definite effect of PRL on a human myeloma cell line. We demonstrated a direct inhibition of PRL on tumour cell growth, while its reciprocal effect on apoptosis refers to an important regulatory role of PRL.     

Delayed hearing loss after neurovascular decompression

We report two unusual cases of delayed hearing loss after neurovascular decompression of structures within the cerebellopontine angle. In the first case, the patient noted a unilateral hearing loss 3 weeks after undergoing vascular decompression of the trigeminal nerve for tic douloureux. This gradually improved over an 18-month period. In the second case, the patient awoke on the 4th day after vascular decompression of the facial nerve for hemifacial spasm with a bilateral hearing loss that has remained unchanged after the onset. These are examples of delayed acoustic dysfunction occurring with a shift in surgically freed vessels and may have been induced by newly directed neurovascular compression or distortion.