Creutzfeldt-Jakob disease after pituitary-derived human growth hormone therapy: two cases with valine 129 homozygous genotype.
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Adult↗
Biomedical subjects
D Dormont
Publications and source records attributed to D Dormont.
[Quality of life analysis in patients treated for breast cancers].
OBJECTIVES: Evaluate the different quality of life parameters in treated breast cancer patients. TYPE OF STUDY: Retrospective analysis from 1977 to 1987. STUDY SITE: Bichat, Lariboisière and Tenon Hospitals. PATIENTS: 239 operated patients, with or without irradiation following or before chemotherapy, with or without hormonotherapy. Patients were divided into 4 groups according to age. STUDY PARAMETERS: Essentially, gynaecologic consequences of treatments (flush, menstrual cycles, fertility, vaginal dryness, breast reconstruction), effect of tamoxifen on genital organs and osteopenia. MAIN RESULTS: Tamoxifen acts as an oestrogen both on genital organs and bones. CONCLUSION: The impact of substitutive hormone therapy on quality of life should be evaluated in randomized studies.
Adult↗
[A study network of human spongiform encephalopathies: 1st results].
Several French teams including clinicians and researchers have created a group within the European network for the study of Creutzfeldt-Jakob disease and other human spongiform encephalopathies. The main objectives are to monitor the incidence of the disease and to search for possible risk factors with a case-control study. The diagnosis is based on neuropathological studies or the identification of an abnormal protein prion in cerebral fragments. The sequence of the gene encoding for the prion protein has was studied from blood or cerebral samples. The early results indicate that the incidence, mortality and clinical presentation remain relatively constant compared with earlier studies. Studying the expression of the 129 codon of the prion protein gene has led to the verification that homozygous methionine/methionine forms predominate in sporadic forms.
Case-Control Studies↗
MR of isolated leptomeningeal glioma.
We report the MR study of a case of high-grade glioma that mimics leptomeningeal carcinomatosis. Superficial gliomas should thus be included in the differential diagnosis of isolated meningeal enhancement.
Adult↗
[Human transmissible subacute spongiform encephalopathy].
Human transmissible spongiform encephalopathies (TSE) are rare chronic subacute degenerative diseases of the central nervous system (CNS) which include Creutzfeldt-Jakob disease (CJD), Kuru, Gerstmann-Sträussler-Scheinker syndrome (GSS), and Fatal Familial Insomnia (FFI). CJD can be either inherited or sporadic. All these diseases are always fatal. Neuropathological features are mainly constituted of neuronal vacuolisation, neuronal death, gliosis with hyperastrocytosis; plaques might be evidenced in kuru and GSS. Neither inflammatory syndrome nor demyelination is detectable. No virus like structure could be identified reproducibly. Human TSE are transmissible to non human primates and rodents. Iatrogenic CJD have been described after tissue grafting (cornea, dura mater), neurosurgery, electrophysiology investigation, and treatment with pituitary derived gonadotrophins and growth hormone. Molecular biochemistry of the CNS investigation revealed that a host encoded protein, the prion protein (PrP), accumulates proportionally to the infectious titer: this abnormality is the only detectable hallmark in TSE. Infectious fractions contain no detectable specific nucleic acid, and are mainly constituted of PrP under an isoform which resists to proteinase K digestion (PrP-res). The PrP gene (PRNP) is located on chromosome 20 in humans. Several mutations of this gene have been described in all inherited TSE (CJD, GSS, and IFF). No treatment is available today. Agents inducing TSE (TSA) are not known: several authors claim that TSA are only constituted of PrP-res; others support the hypothesis of a conventional agent with a specific genetic information.
Animals↗
Present status of computerized tomography and angiography in the diagnosis of cerebral thrombophlebitis cavernous sinus thrombosis excluded.
In order to evaluate the contribution of computerized tomography (CT) to the diagnosis of cerebral thrombophlebitis, a series of 28 cases was reviewed and compared with data from the literature. In an examination carried out 4 to 5 days of its constitution the thrombus may be directly visualized as a spontaneous hyperdensity. This early but very transient sign, called "cord sign", can easily be overlooked, which explains why it was found in only 5 of our 28 cases and in 2% of the largest series of the literature. The thrombus thereafter becomes hypodense and can be intensified by peripheral contrast enhancement which produces the classical "delta sign". This sign is more frequent: 13/28 in our series and 16 to 30% in published cases. It is usually found in the superior sagittal sinus and must be distinguished from anatomical variations which are common at that level. These two direct signs acquire a greater value when associated with such indirect signs as diffuse or localized cerebral oedema (12 to 52%) and venous ischaemia (22 to 59%). Venous ischaemia is characterized by its strong bleeding potential (more than 50% of the cases) and by its usually favourable course; these two elements and its site differentiate it from arterial ischaemia. Finally, venous stasis is responsible, in 5 to 19% of the cases, for intense enhancement of the tentorium cerebelli; this sign is not specific but easy to evidence and of great value when associated with a direct sign. Dilatation of cortical veins, found in 4 of our 28 cases, also seems to be an interesting sign which, to our knowledge, has not yet been mentioned in the literature. Since in 3.6 to 26% of the cerebral thrombophlebitis the CT scan is normal, a negative CT examination does not rule out this disease, and in many cases the exploration must be rapidly completed by angiography or MRI. Because it is non-invasive and very sensitive to flows, MRI has become the key examination to assert the diagnosis. Angiography is now restricted to those cases where cases where MRI cannot be performed promptly or to certain, purely cortical thrombophlebitis which might pass unnoticed at MRI. When carried out and interpreted cautiously, angiography always shows the venous thrombosis, its exact size and its suppletive network. The results of this study show that MRI alone can diagnose cerebral thrombophlebitis in most patients, that CT well done and interpreted often provides useful but seldom sufficient indices, and that angiography should be reserved for difficult cases.
Cavernous Sinus↗
MRI in cerebral venous thrombosis.
Fifty-three patients with cerebral venous thrombosis (CVT) were explored by MRI. Three types of signal abnormalities were observed in thrombosed sinuses: 1) isosignal on T1-weighted sequence and low-intensity signal on T2-weighted sequence (early stage); 2) high-intensity signal on T1-and T2-weighted sequences (intermediate stage); 3) isosignal on T1-weighted sequence and high-intensity signal on T2-weighted sequence (late stage). Signal abnormalities in dural sinuses enabling CVT to be diagnosed were absent in 2 out of 53 cases. Twenty-six out of 53 patients had venous infarction. These lesions were haemorrhagic in 20 cases. MRI made it possible to follow the course of CVT in 15 cases, showing partial or complete recanalization of the occluded sinuses in 14 cases. Our study confirmed that MRI is an excellent non-invasive method to explore CVT. It diagnoses the venous thrombosis, studies parenchymal lesions and follows the course of CVT under treatment. However, MRI is less sensitive than arteriography, particularly in cases of CVT involving only the cortical veins.
Adolescent↗
A technique of measuring the precision of an MR-guided stereotaxic installation using anatomic specimens.
PURPOSE: To develop a method for direct measurement, using anatomic specimens, of the precision of MR-guided stereotaxic location and to describe its application to a 1.5-T MR unit with a Leksell stereotaxic frame. METHODS: Small pieces of gelfoam (1 X 1 X 1 mm), soaked in gadopentetate dimeglumine, were stereotaxically introduced into formalin-fixed human heads using a Leksell D (three experiments) or G (nine experiments) stereotaxic frame. The head and the frame were then introduced into a 1.5-T MR unit. The target coordinates (as set on the stereotaxic frame by one investigator) were then compared with the MR-determined stereotaxic coordinates (calculated independently by another investigator). The imprecisions Ex, Ey, and Ez in each direction were defined as the differences between the calculated and the chosen coordinates. RESULTS: Regarding the three targets studied with the D frame, mean imprecision Ex was 1.08 +/- 0.50 mm (mean +/- SEM), Ey 0.83 +/- 0.58 mm, and Ez 0.75 +/- 0.25 mm. For the nine targets studied with the G frame, Ex was 0.48 +/- 0.17 mm, Ey 0.69 +/- 0.14 mm, and Ez 0.82 +/- 0.13 mm. Statistical analysis of the results showed no significant difference between Ex or Ey and half the size of a pixel, indicating that, in the axial plane, stereotaxic MR precision is limited only by pixel size. A statistically significant difference was observed in the coronal plane between Ez and half the size of a pixel, but it must be stressed that Ez remained smaller than 1 mm. CONCLUSION: MR-guided stereotaxic location can be used with confidence for most diagnostic, functional, and therapeutic procedures.
Calibration↗
Breast cancer: effect of tamoxifen on the mineral density of bone.
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Adult↗
Recombinant human growth hormone and insulin-like growth factor I induce PrP gene expression in PC12 cells.
Growth factors like NGF are known to increase the expression of PrP gene, a housekeeping gene which is responsible for susceptibility to transmissible spongiform encephalopathies. We evaluated in vitro the effect of recombinant human growth hormone (hGH) and one of its in vivo effectors, the insulin-like growth factor I (IGF-I), on PrP gene expression in PC12 cells. We observed a 30% increase of PrP mRNA level after 7 day treatment by hGH at 10 micrograms/ml and potentiation of NGF effect (reaching four times baseline expression as opposed to three times baseline with NGF alone). IGF-I induced a dose-dependent increase of PrP mRNA up to twice baseline at a dose of 100 ng/ml and had an additive effect with NGF at 10 ng/ml. These preliminary results indicate that growth promoting factors may play a role in the PrP gene regulation within neuron-like cells.
Animals↗
Complement and virus-specific antibody-dependent infection of normal B lymphocytes by human immunodeficiency virus type 1.
We tested the susceptibility of human purified, normal B lymphocytes to human immunodeficiency virus type 1 (HIV-1) infection, in the presence or absence of complement-sufficient serum and of virus-specific antibodies. Virus replication was detected when cells were infected in the presence of both complement and anti-HIV antibodies (C'-ADE conditions), by day 2 postinfection. Similar results were obtained when B lymphocytes were purified either from peripheral blood (three healthy donors) or from tonsils (four individuals with chronic tonsillitis). HIV infection was shown by polymerase chain reaction (PCR) detection of proviral sequences (gag and pol genes), by p24 antigen synthesis, and by cocultivation assay with MT2 cells. The higher p24 production was obtained when B cells were preactivated for 2 days by phorbol 12-myristate 13-acetate (PMA) before infection and then cultured in the presence of low-molecular weight B-cell growth factor (LMW-BCGF). Expression of virus envelope glycoprotein (gp) 120 could also be detected on a subpopulation of B cells (CD19+, CD22+) by flow cytometry. Blocking experiments with monoclonal antibodies (MoAbs) against CD4, CD21 (complement receptor 2 [CR2]), CD35 (CR1), CD19, and CD5 surface molecules indicated that infection of B cells involves CD4, CD21, and CD35 antigens. Indeed, blocking of CD4 receptor inhibited 10% of p24 production, and blocking of both CD21 and CD35 led to extinction of p24 signal. CR-dependent pathway is thus a major route for C'-ADE of HIV infection in normal B cells. Our results emphasize the importance of studying interactions between HIV and the complement system for better understanding infection mechanisms and the major dysfunctions of B cells in HIV-infected individuals.
B-Lymphocytes↗
In vitro infection of human macrophages with human T-cell leukemia virus type 1.
The tropism of the human T-cell leukemia virus type 1 (HTLV-1) for the cells of monocyte-macrophage lineage was evaluated by the coculture of blood monocyte-derived macrophages, with irradiated cells of HTLV-1 producing cell lines MT2 or C91/PL. The susceptibility to HTLV-1 was assessed by the detection of viral DNA using the polymerase chain reaction method. HTLV-1 gene expression in the cells was detected using in situ hybridization and by immunofluorescent staining of viral antigen. The presence of type C virus-like particles detected by electron microscopy and the ability to infect normal cord blood lymphocytes demonstrated that the infected macrophages produced infectious virus. These results indicate that human macrophages are susceptible in vitro to productive HTLV-1 infection, and thus might be involved in the pathogenesis of HTLV-1-related diseases.
Cells, Cultured↗
Correlation between HIV provirus burden and in utero transmission.
OBJECTIVE: No predictive parameters of in utero or perinatal vertical transmission of HIV to newborns are known at present. Vertical transmission may be related to several biological parameters of maternal HIV infection: (1) immunological parameters (neutralizing antibodies); (2) the concentration of viral particles and/or infected cells; and (3) the selection of HIV subspecies of particular cellular tropism. The present study was designed to examine the relationship between cellular viral burden and transmission, and between maternal viral burden and CD4+ cell count and clinical status at delivery. METHOD: We investigated mother-to-infant HIV-1 transmission at delivery in a cohort of 51 pairs of mothers and newborns. Twelve infants were HIV-infected, as determined by successive polymerase chain reaction and culture determinations within the first 6 months of life, and nine of these were diagnosed as HIV-infected during the first week of life. We determined peripheral blood mononuclear cell proviral DNA burden using a quantitative polymerase chain reaction assay. Polymerase chain reaction was performed in the HIV-1 gag gene, using [32P]-end-labelled primers. External standard DNA samples were from the 85-14 F2 cell line, which contains a unique defective proviral DNA genome. RESULTS: There was a linear relationship between the logarithms of c.p.m. and the number of HIV-1 DNA copies. CONCLUSION: We have previously reported that the number of HIV provirus copies in maternal blood cells is related to transmission of the virus. Quantification of the HIV provirus by polymerase chain reaction may be used as a predictive parameter of vertical transmission if accompanied by an exhaustive clinical and biological follow-up during pregnancy.
Base Sequence↗
MRI in 31 patients with Behçet's disease and neurological involvement: prospective study with clinical correlation.
Thirty one patients with Behçet's disease and neurological manifestations were prospectively studied with MRI. Cerebral venous thrombosis was diagnosed in 10 patients. MRI performed during the acute illness in eight patients showed an abnormally high signal on the T2 weighted sequences in the occluded sinus. MRI showed minor flow abnormalities suggestive of partial recanalisation of the sinus in two cases at a later clinical stage. MRI can be an alternative, non-invasive, investigation to intravenous cerebral angiography. In 13 patients with central nervous system involvement, MRI performed during the acute illness showed multiple hyperintense lesions on T2 weighted sequences. They were usually less than 5 mm, scattered and confluent, mainly in the white matter, distributed in the hemispheric white matter in nine cases, brainstem in eight, basal ganglia and thalamus in five, and cortex in two. MRI abnormalities were usually associated with appropriate clinical deficits, but were larger and more disseminated than expected.
Adolescent↗
[Bone sterilization by radiation and the HIV virus].
An experimental study was performed to investigate the efficacy of irradiating HIV-contaminated allografts. Irradiation was achieved using an accelerator delivering 6.3 MeV electrons, and the viral strain was HIV-1/LAV-1. At an activity equivalent to 600.000 counts of reverse transcriptase activity per minute and per millilitre, irradiation permitted total inactivation of HIV. In the light of present data concerning plasma viremia in HIV-infected patients, this experiment suggested that irradiation minimizes as far as possible the risk of transmitting HIV infection through bone transplantation from a seronegative, contaminant donor. However, in view of the relative imprecision of viral sensitivity curves, irradiation does not authorize bone transplantation from a seropositive patient, even though the bone has been irradiated.
Animals↗
[Role of neutralizing antibodies in protection of the fetal from an HIV positive mother].
The goal of this study is to compare serum Titers of Neutralizing antibodies in HIV 1 infected mothers to the virological status of their newborns. 38 infant-mothers couples were tested. Serum Neutralizing antibodies Titers of the mothers were tested the day of birth. Virological status of new borns was determined by peripheric blood mononuclear cells culture and PCR. 18 Newborns were HIV 1 infected. In 9 cases mothers had no neutralizing antibodies: 7 newborns were HIV 1 infected. In 4 cases mothers had high level of neutralizing antibodies (< 640): none of the newborns was infected. In 25 cases mothers had intermediate value of neutralizing antibodies (between 80 and 320): 11 newborns were HIV 1 infected. Women with neutralizing antibodies to HIV 1, were less likely to transmit HIV 1 to their infants than pregnant women without neutralizing antibodies. Serum neutralizing antibodies titers of pregnant women might be of predictive value in vertical transmission of HIV 1. Further investigations are needed.
Acquired Immunodeficiency Syndrome↗
AIDS vaccine developments.
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AIDS Vaccines↗
Specific and non-specific immunity and protection of macaques against SIV infection.
The simian immunodeficiency virus is a retrovirus closely related to the human immunodeficiency viruses; it induces an AIDS-like disease in macaques, and provides therefore an obvious animal model for anti-lentiviral drug and vaccine strategy assessments. In our experiment, we immunized rhesus macaques with a purified and formalin-inactivated whole SIVmac251 antigen preparation. Most of these monkeys were still protected for more than 4 months following a heterologous SIVsm intravenous challenge. Both virus stocks, for vaccine preparation and challenge, were provided by culture supernatants of infected T cells of human origin. Four of the protected macaques were then reimmunized with the same antigen preparation and rechallenged intravenously with a homologous rhesus cell grown SIVmac251. Unexpectedly, all animals developed clinical and biological evidence of infection by day 15 after the second challenge.
Animals↗