Inflammatory central nervous system disease in lupus-prone MRL/lpr mice: comparative histologic and immunohistochemical findings

The brains of pathogen-free autoimmune MRL/lpr, NZBWF1 and NZB mice were examined for central nervous system (CNS) inflammation in premoribund 8-week-old animals and at ages when active systemic lupus erythematosus (SLE) was present. CNS inflammation was observed only in MRL/lpr mice. Immunohistochemical studies of brains from young MRL/lpr mice found that infiltrates were composed primarily of CD4+ cells. Older MRL/lpr mice (22 and 26 weeks of age) had CD4+ cells predominantly, but CD8+ and B220+ cells were also present. Perivascular leakage of IgG was a prominent and unexpected finding in the MRL/lpr model. Congenic MRL/+ mice with late-onset autoimmunity had no inflammatory cells in brain tissue, and there was no perivascular staining with IgG or albumin. Our findings suggest that MRL/lpr mice are a useful model for studies of lupus-associated CNS inflammatory disease, and perivascular leakage may be a primary mechanism for entry of IgG into the brain.     

Bancroftian filariasis in French Polynesia. Epidemiologic status and perspectives after a 35-year preventive campaign

The authors assess of three decades of struggle against Bancroftian filariasis in French Polynesia. Wuchereria bancrofti var. pacifica, aperiodic filaria, and Aedes polynesiensis, mosquito with high parasitologic output, set up a cycle very well adapted to the Polynesian environment; after numerous tests, the chemoprophylaxis with diethylcarbamazine (3 mg/kg/half-year) of all the exposed population has been decided, in association with methods of vector-control (use of predatory crustaceans). However, the achievement of this strategy is impeded by economical contingencies and the endemic comes up again particularly in areas close to eradication. Entomological clues show a high transmission over the greater part of French Polynesia.     

A new diagnostic method of spondylodiscitis. Magnetic resonance imaging

Twenty four patients who were hospitalized for a suspicion of spondylodiscitis were prospectively evaluated with magnetic resonance imaging (MRI), radiology and radionuclide studies. Fifteen patients had an infectious spondylodiscitis, four had a vertebral degenerative disease, four had a rheumaticus spondylodiscitis, one had a chemical spondylodiscitis. The microbiological examinations and the clinical development bore the diagnosis out. Seven patients underwent Indium 111 scanning. The results of this scanning were correlated with MRI results. The MRI was performed with a 0.35 T whole body superconducting unit using spin echo technique. All patients were studied in the sagittal plane with two pulse sequences and more often with a surface-coil: TR 500 msec./TE 28 msec. and TR 2,000 msec./TE 60 msec. In all cases of true infectious spondylodiscitis the MRI results finding were characteristics. On the image obtained with the TR 500 msec./TE 28 msec., there was a confluent decreased signal intensity from the vertebral bodies and the intervertebral disk space. On the image obtained with TR 2,000 msec./TE 60 msec. there was an increased signal intensity from the vertebral bodies and the intervertebral disk space. The other spondylodiscitis have given a different MRI imaging, it was a confluent decreased signal intensity from the vertebral bodies and the intervertebral disk space on the twice pulse sequences. different images were obtained during the evolution of the infectious: first we observed a modification of the vertebral signal then the typical image that we described then a normal signal of the vertebral bodies with a pathological signal from the intervertebral disk space at last a degenerative intervertebral disk.(ABSTRACT TRUNCATED AT 250 WORDS)     

Potent activity of 5-fluoro-2'-deoxyuridine and related compounds against thymidine kinase-deficient (TK-) herpes simplex virus: targeted at thymidylate synthase

5-Fluorouracil, 5-fluorouridine (FUrd), 5-fluoro-2'-deoxyuridine (FdUrd), 5-fluorocytidine (FCyd), 5-fluoro-2'-deoxycytidine (FdCyd), 5-trifluoro-2'-deoxythymidine (F3dThd), and the 5'-monophosphates and 3',5'-cyclic monophosphates thereof were found to inhibit thymidine kinase-deficient (TK-) mutant strains of herpes simplex virus (HSV) at a much lower concentration than the wild-type (TK+) HSV strains. Other 5-substituted 2'-deoxyuridines that have previously been recognized as potent thymidylate synthase inhibitors behaved in a similar fashion. The activity of FdUrd, FdCyd, F3dThd, and their 3',5'-cyclic monophosphates against TK-HSV was readily reversed by 2'-deoxythymidine (dThd) but not by 2'-deoxyuridine (dUrd). These compounds also inhibited the incorporation of [6-3H]dUrd into DNA at a concentration which was up to 5 orders of magnitude lower than the concentration at which the incorporation of [methyl-3H] dThd was inhibited. Thus, while not being a target for the well established anti-HSV compounds in TK+HSV-infected cells, thymidylate synthase appears to be an important target in TK-HSV-infected cells. In addition to dTMP synthase, TK-HSV-infected cells appear to reveal other therapeutically exploitable targets such as OMP decarboxylase (towards pyrazofurin), CTP synthase (towards carbodine and its cyclopentenyl analogue), dihydrofolate reductase (towards methotrexate), and S-adenosylhomocysteine hydrolase (towards neplanocins).     

L’électroencéphalogramme n’est pas un examen légitime pour la confirmation du diagnostic de mort cérébrale

PURPOSE: In France, legislation mandates that the clinical diagnosis of brain death be confirmed by one paraclinical test before organ donation is allowed. That test may be either the electroencephalogram (EEG) or cerebral angiography. We report a case in which the clinical diagnosis of brain death was first confirmed by two EEGs performed according to the French guidelines, but ruled out by cerebral angiography. Considering that the EEG is no longer recommended to establish the diagnosis of brain death, we discuss the relevance of maintaining the EEG for brain death diagnosis in France. CLINICAL FINDINGS: A 58 yr-old man was admitted to the intensive care unit because of coma secondary to a massive subarachnoid hemorrhage with herniation below the falx shown by computed tomography. Clinical criteria of brain death were rapidly present. Two EEGs first confirmed the diagnosis but a four-vessel cerebral angiography was finally performed because the patient moved spontaneously. This cerebral angiography showed flow in the right internal carotid artery. A computed tomography performed the next day definitely confirmed the absence of brain death and organ donation did not occur. CONCLUSIONS: This case demonstrates the limitations of the EEG for this indication and suggests that angiography should be preferred. French legislation is probably maladjusted and would benefit by incorporating guidelines of other countries like Canada. International harmonization of criteria for brain death diagnosis would also be welcome.     

Reduced tumor growth in vivo and increased c-Abl activity in PC3 prostate cancer cells overexpressing the Shb adapter protein

Background  

Induction of apoptosis is one strategy for treatment of prostate cancer. The Shb adapter protein has been found to regulate apoptosis in various cell types and consequently human prostate cancer 3 (PC3) cells were transfected to obtain cells overexpressing Shb in order to increase our understanding of the mechanisms regulating PC3 cell apoptosis.     

Development of the Qualeffo–31, an osteoporosis-specific quality-of-life questionnaire

Introduction Vertebral deformities are a common consequence of osteoporosis and are known to decrease quality of life. The Qualeffo–41 is a quality-of-life questionnaire especially developed for measuring quality of life in patients with vertebral deformities. It consists of 41 questions arranged in five domains: pain, physical function, social function, general health perception, and mental function. The objectives of this study were: (1) to develop a shorter version of the Qualeffo–41 by removing redundant questions; and (2) to investigate the scale characteristics, reliability, and validity of this shorter version. Methods The study was performed using data from the Qualeffo validation study and the Multiple Outcomes of Raloxifene Evaluation (MORE) study. The analyses were performed in patients with vertebral deformities (n=579). Factor analysis on polychoric correlations and an item response theory (IRT) model, i.e., the generalized partial credit model (GPCM), were used to create a shorter version of Qualeffo–41. Using GPCM, scoring weights were computed for all items. Results Three items were removed from the data set because of too many missing values. Factor analysis identified three instead of five domains: (1) pain, (2) physical function, and (3) mental function. Five items had factor loadings <0.4 and were not included in the GPCM. After excluding several items, the domains pain (four items), physical function (18 items), and mental function (nine items) showed a good, reasonable, and excellent fit, respectively. This indicates that the mental function domain and the pain domain are more unidimensional than the physical function domain. All three domains showed a very high correlation (r ≥0.95) with the corresponding domains of the Qualeffo–41. Conclusions Qualeffo–31 was developed, consisting of three domains with a reasonable to excellent fit to the GPCM. Although the fit to the GPCM supports the construct validity of the Qualeffo–31, validation in a new study should be performed before using it in practice.