[Granulomatous uveitis and CREST syndrome: a case study]. / Uvéite granulomateuse et Crest syndrome. A propos d'un cas.

PURPOSE: To report a case of recurrent granulomatous panuveitis associated with CREST syndrome. OBSERVATION: A 74-year-old patient with CREST syndrome presented with unilateral granulomatous panuveitis in a pseudophakic eye. She had undergone cataract surgery 6 months before. The patient reported a vision loss that had been evolving for 1 month. Visual acuity was noted at 20/400. The initial clinical examination highlighted retrodescemetic precipitates and granulomatous precipitates on the IOL. A vitreous tyndall was noted. Funduscopic examination revealed papillary edema and cystoid macular edema, confirmed by fluorescein angiography. RESULTS: Topical treatment consisting in corticosteroid eye drops associated with mydriatics controlled uveitis in a few weeks. Visual recovery was 20/30. No granulomatous uveitis etiology could be highlighted. The diagnosis of chronic endophthalmitis was also ruled out. CONCLUSION: The diagnosis retained was uveitis associated with CREST syndrome. To our knowledge, this association has only been reported twice in the literature.

Life span, cancer and non-cancer diseases in mouse exposed to a continuous very low dose of gamma-irradiation.

PURPOSE: To analyse the life-span and pathologies of mice living under a continuous very low-dose gamma-irradiation. MATERIAL AND METHODS: We exposed 300 C57B1/6J female mice, 3 weeks old, to 10 cGy year(-1) gamma-rays while 300 control mice lived in the same room. Irradiation was delivered continuously by thorium nitrate. We kept all the animals until natural death and performed autopsy. RESULTS: No difference was observed in life-span (mean lifespan +/-SE: 805.2 +/- 9.62 days for controls and 815 +/- 9.57 days for irradiated mice), weight curves or food intake. At autopsy, cancer was present in 40.9% of controls and 37.9% of irradiated mice. They were mainly represented by lymphomas (23.7 and 24.9%) and histiocytic sarcomas (12.6 and 8.7%, respectively, for controls and irradiated mice). Vascular diseases occurred in 24.1% of controls and 23% of irradiated mice. Infections were present at autopsy in 14.1 and 12.3%, respectively, of controls and irradiated animals. No statistical difference was observed at the end of the experiment for cancer or non-cancer diseases between the two groups. CONCLUSION: Continuous 10 cGy year(-1) gamma-irradiation had no adverse effect on malignant or non-malignant diseases in this strain of mouse.

Increased expression of cytosolic phospholipase A2, 5-lipoxygenase and 5-lipoxygenase-activating protein in rat peritoneal macrophages during ovalbumin-induced sensitization.

BACKGROUND: Macrophages are involved in immediate hypersensitivity reactions by their ability to release leukotrienes involved in the symptomatology of allergy. To date it is unknown whether this ability to secrete leukotrienes has been favoured by modifications, occurring during the sensitization phase, of the enzymes involved in leukotriene metabolism. OBJECTIVE: We used ovalbumin-sensitized rats to study the expression of cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP) in peritoneal macrophages during active sensitization. We compared basal and challenged (PMA, A23187 and allergen) arachidonic acid (AA) metabolism of macrophages from control (cPM) and sensitized (sPM) rats. Then we tested, in cultured cPM, whether IL-4, the predominant cytokine of sensitization process, could reproduce the enzymatic modifications occurring in macrophages during sensitization. METHODS: cPLA2, 5-LO and FLAP expression was assessed by Western blotting. The arachidonic acid (AA) metabolism study was performed after incorporation of tritiated AA in macrophages and analysis of secreted tritiated eicosanoids. RESULTS: Ovalbumin-sensitization of rats increased cPLA2, 5-LO and FLAP expression in peritoneal macrophages. These increased expressions were not paralleled by modifications of basal and PMA- or A23187-stimulated AA metabolism of sPM. However, when macrophages encountered the specific allergen for a second time, sPM secreted higher levels of leukotrienes than cPM. IL-4 induced FLAP expression in cPM but had no effect on cPLA2 and 5-LO expression. CONCLUSION: Active sensitization of rats induces an increase, in peritoneal macrophages, of the enzymes involved in leukotriene metabolism. The increased leukotriene secretion of sPM in response to ovalbumin challenge may be favoured by this increased expression of cPLA2, 5-LO and FLAP that, however, is not able to lead to modifications of macrophage AA metabolism in any circumstance. Our results also suggest that IL-4 is not the major element originating the enzymatic modification induced by sensitization in peritoneal macrophages.

Influence of continuous, very low-dose gamma-irradiation on the mouse immune system.

PURPOSE: To investigate whether continuous, very low-dose gamma-irradiation (10 cGy/year) modifies immune parameters in mice. MATERIAL AND METHODS: C57BL/6 female mice, 4 weeks old, were irradiated for 24 months and compared with control mice living in the same room. B- and T-cell subsets were evaluated by flow cytometry before and after stimulation with lectins; subclasses of immunoglobulins were determined by ELISA 2, 4, 6, 8, 12, 18 and 24 months after the beginning of the irradiation. RESULTS: No difference was found in the percentage of CD4(+) and CD8(+) cells in the thymus and the spleen, or in the reactivity of T-cells to lectins. While the number of B-cells in the spleen remained unchanged, a significant decrease of IgG1, IgG2b and IgG2a was observed after respectively 12, 18 and 24 months of irradiation. CONCLUSION: The parameters of cellular immunity studied were not affected by this chronic low-dose of irradiation, but this dose rate is probably too low to induce the hormetic effect previously described. Further investigations are necessary to assess whether the decline of immunoglobulin secretion is indicative of a lower rate of infectious diseases or a defect in B-cell function.

Effect of a continuous gamma irradiation at a very low dose on the life span of mice.

BACKGROUND: There is epidemiological evidence that suggests there are beneficial effects of ionizing radiation at low doses. Some experimental studies confirmed this hormetic effect with doses of about 1 cGy/day, but no data concerning very low dose rates are available. OBJECTIVE: The aim of this study was to determine the life span of mice exposed to very low doses of ionizing radiation. METHODS: Six hundred female C57BL/6 mice, 1 month old, were exposed to chronic gamma irradiation at very low dose rates of 7 or 14 cGy/year. These doses are about 25 or 50 times higher than background, but much lower than the doses of about 1 cGy/day used in previous experiments. Three hundred mice living in the same room were used as controls. RESULTS: The life span, after the beginning of the experiment, determined by the survival time of 50% of each population, is increased in irradiated mice: 549 days in controls, 673 days in both irradiated groups. The differences are significant between the control and the irradiation mice. Differences between mice irradiated with 7 or 14 cGy are not significant. CONCLUSIONS: These results confirm the possibility of a nonharmful effect (hormesis) of ionizing radiation. They demonstrate that the paradigm, which states that low-dose effects can be predicted high-dose effects, cannot be systematically applied in radiation biology in general and gerontology in particular.

Clinical characteristics and light and transmission electron microscopic sperm defects of infertile men with persistent unexplained asthenozoospermia.

OBJECTIVE: To determine, with the use of transmission electron microscopy (TEM), the proportion of patients with permanent unexplained asthenozoospermia (<30% motility) who have an abnormality of sperm axonemal and periaxonemal structures. DESIGN: Retrospective study. SETTING: A university-affiliated public hospital. PATIENT(S): Sixty-one infertile men whose semen was submitted to TEM analysis because of persistent unexplained asthenozoospermia. MAIN OUTCOME MEASURE(S): The results of quantitative TEM analysis of the tails of the spermatozoa. INTERVENTION(S): None. RESULT(S): Based on a comparison with the axonemal anomalies observed in nine fertile control patients, the infertile population was divided into three groups: group I, with no detectable axonemal defects (26.2%); group II, with axonemal anomalies in either the midpiece or the principal piece (29.5%); and group III, with axonemal anomalies in both the midpiece and the principal piece (44.3%). However, defects in the mitochondrial sheath, fibrous sheath, and sperm head (acrosomic and postacrosomic cap) were observed in at least 50%, 30%, and 50%, respectively, of the patients in each group. The proportion of dense fiber anomalies of the midpiece increased significantly from group I to group III. No differences were observed between the three groups in sperm characteristics, anamnesis information, or clinical data. CONCLUSION(S): In patients with persistent unexplained asthenozoospermia, the frequent association of periaxonemal anomalies with axonemal deficiencies strongly suggests that axonemal deficiencies are not the unique cause of decreased motility.

Cytotoxic effect of interferon-alpha2a in combination with all-trans retinoic acid or cisplatin in human ovarian carcinoma cell lines.

Ovarian cancer has a poor prognosis due to the frequent appearance of a drug-resistant state. An alternative therapeutic approach may lie in combinations of conventional chemotherapeutic agents with new classes of drug, such as interferons (IFN) and differentiation-inducing agents. There is clinical evidence that both IFN-alpha2a-all-trans retinoic acid (ATRA) and IFN-alpha2a-cisplatin have significant activities on growth of malignant cells, cell differentiation or programmed cell death in solid tumors. In order to throw more light on the cellular basis of these findings and to optimize a schedule of such drug combinations, we examined the cytotoxic effects of various combinations on five human ovarian carcinoma cell lines. The experiments were based on a clonogenic assay on plastic. The different cell lines exhibited different sensitivities to the three drugs tested. Using the cell line most sensitive to these drugs, we then examined the effect of different sequences of two drug combinations. We observed a potentiation after pretreatment with ATRA followed by IFN-alpha2a and ATRA or after pretreatment with IFN-alpha2a followed by IFN-alpha2a and cisplatin. Using this schedule of administration, cytotoxic interactions between the two drugs were investigated by median effect analysis. Synergism or antagonism were observed depending on the intrinsic sensitivity of the cell line to the first drug and the concentrations used. The magnitude of these interactions was found to be influenced by the cellular sensitivity to the second drug. These results show that schedules of drug combinations are not easy to design and may help account for the various failures and the discrepant effects observed in clinical trials.

Metallothionein expression in human lung and its varying levels after lung transplantation. Toulouse Lung Transplantation Group.

The aim of this study was to determine the lung levels of metallothionein (MT), a free radical scavenger, because oxygen-derivated free radicals (ODFRs) have been involved both in reperfusion injury of transplanted lungs and in cardiac or renal allograft destruction. First, MT localization was evaluated in 14 normal human lung biopsy specimens. Then, in lung transplant recipients, MT content in BAL fluid (BALF) and its transcription rate in alveolar macrophages (AMs) were determined. The BALFs of 69 patients were separated into six groups: lung transplant recipients in clinically stable condition (CSR), those with acute rejection (AR), asymptomatic cytomegalovirus infection (ACMV), cytomegalovirus pneumonitis (CMVP), bronchiolitis obliterans syndrome (BOS), and patients without transplants who served as control subjects (NTCs). In normal lungs, 83% of AMs were positively stained. MT staining was also observed in pleural endothelial cells and basal cells from bronchial epithelium. In lung transplant recipients, MT levels in BALF were significantly higher in patients with CSR, AR, ACMV, and CMVP compared with NTCs, while during BOS, MT had a significantly lower level compared with other lung transplant groups. However, no difference among groups was found concerning MT-II messenger RNA expression in AMs, showing that, as in normal lung, AMs are not the only cells that produce MT. These data report for the first time to our knowledge MT cell distribution in human lung with specific emphasis on its enhanced levels after lung transplantation, even in the absence of complication. Possible correlation among MT levels, ODFRs, cytokine levels, and corticosteroid treatment during complications of lung transplantation are discussed.

Ultrastructural identification of Sertoli cells in the semen of subfertile men. About four cases.

In this work Sertoli cells were identified in the semen of subfertile men using transmission electron microscopy. This observation is rare and has only been reported before once. These results would favour of seminiferous epithelium alterations and could be correlated with the presence of immature seminal line elements or non sperm cells in prospective studies.

[Alveolar lavage cytological data in lung transplants free of bronchial superinfection. Toulouse Lung Transplantation Group]. / Données cytologiques du lavage alvéolaire chez le transplanté pulmonaire indemne de surinfection bronchique. Groupe de Transplantation Pulmonaire de Toulouse.

Total and differential cells counts from 173 bronchoalveolar lavages (BAL) carried out in 19 lung transplanted recipients have been analysed. The patients were separated into seven groups: (a) those without detectable complications (86 BAL); (b) those with acute rejection (AR) (26 BAL); (c) those with bronchiolitis obliterans (BO) (21 BAL); (d) those with intra-alveolar cytomegalovirus (CMV) but asymptomatic (11 BAL); (e) those with an associated intra-alveolar CMV and AR (7 BAL); (f) those with CMV pneumonia (11 BAL); (g) those with infectious pneumonia excluding CMV (11 BAL). The alveolar cytological data were compared to those from control subjects who were smokers (7 BAL) or non-smokers (8 BAL). Excluding the BO group, the total cell count from the BAL of transplanted patients was significantly higher than in the non-smoking controls and was approaching that of the smoking controls. The lymphocytes count was significantly higher in transplanted patients without complication and in the AR group than in the controls, but there was no significant difference between the two groups. There was a significantly greater eosinophilia at the time of AR than either before or after. Eosinophilia was also higher in grade 3 AR than in grade 1 or 2 AR. These data stress the absence of any correlation between the lymphocyte count in the BAL and the existence of AR. Alternatively, the alveolar eosinophilia observed at the time of AR does not allow the possibility of an infection to be elimitated with certainty.

[Excretory azoospermia: contribution of exploratory and curative surgery. Apropos of a follow-up of 33 patients]. / Les azoospermies excrétoires: apport de la chirurgie exploratrice et curative. A propos du suivi de 33 patients.

Thirty-three patients with azoospermia of apparently excretory origin underwent surgery for epididymis-deferens anastomosis and/or epididymal sperm puncture. Pathology examinations of the epididymal fluid and biopsies of the testicles or epididymis were performed at surgery. Based on the clinical presentation, sperm results and per-operative findings, patients were divided into six groups by etiology: idiopathic azoospermia (n = 5), post-infectious azoospermia (n = 15), agenesia of the excretory (n = 6) or secretory (n = 3) ducts, vasectomy (n = 2), and obstruction of the ejaculatory ducts (n = 2). Peroperative identification of spermatozoa at epididymal puncture or biopsy was statistically more frequent in patients with agenesis of the excretory ducts than in patients with post-infectious or idiopathic azoospermia. Biopsies of the testicle led to the diagnosis of secretory azoospermia in 3 cases and revealed a functional parenchyma in all the other groups of patients. Epididymis-deferens anastomosis was performed in 45% of the cases and was successful in 13%. Rate of fertility with the intracytoplasmic sperm injection was 33%; there was no difficulty in using fresh or frozen sperm. Clinical pregnancy was continued to term with frozen sperm. This study confirms that testicular function is preserved in excretory azoospermia. With or without epididymis-deferens anastomosis, epididymal spermatozoa can generally be preserved for later use. Couples should however be counselled on the delays to contraception which may vary from months to years.

[Breast metastasis from an ovarian adenocarcinoma]. / Métastase mammaire d'un adénocarcinome ovarien. A propos d'un cas.

We report the case of a 74 year-old woman who presented nodules of the breast 3 years after the diagnosis of a papillary adenocarcinoma of the ovary. The diagnosis of breast metastasis from the ovary was made by histologic examination.

Issues in methods and measurement of thermodilution cardiac output.

Criterion-related validity of the thermodilution cardiac output technique for cardiac output measurement has to have a high correlation (r = .91 to .98) with the direct Fick method, the gold standard of cardiac output measurement. Issues that can affect validity of the measurements include the position of the pulmonary artery catheter, the rate of injection of the indicator solution, the volume and temperature of the injectate, the timing of the injection of indicator solution during the respiratory cycle, the position of the subject, and the presence of concomitant infusions. Variation in measurement can be limited by considering the delivery system for the indicator solution, by recording time-temperature cardiac output curves, and by considering normal biologic variations.

[Simultaneous detection by non-isotopic in situ hybridization of human papilloma viruses and Epstein-Barr virus during the lytic cycle in oral hairy leukoplakia lesions]. / Détection simultanée de papillomavirus humains et du virus d'Epstein-Barr en cycle lytique dans des lésions de leucoplasie orale chevelue par hybridation in situ non isotopique.

Oral hairy leukoplakia is almost only described in patients infected by the human immunodeficiency virus. Epstein-Barr virus, sometimes associated with human papillomavirus, is always involved in the occurrence of these lesions. We have investigated two cases of oral hairy leukoplakia with the goal of detecting EBV and HPV by using both in situ hybridization and immunohistochemistry. EBV genome was detected with biotinylated BamHI W cDNA probe in the two cases. Furthermore, EBV was found to be in lytic phase as demonstrated by the strong signal observed with FITC-labelled anti-sense BHLF1 oligonucleotide probes. This finding was further supported by the absence of labelling with EBV-latent-cycle markers such as EBER1/2 oligoprobes and anti-latent membrane protein 1 antibody. In addition, these two cases were positive for HPV genomes: 31-33-51 (n = 1) and 31-33-51 plus 6-11 (n = 1) as detected by in situ hybridization using different sets of biotinylated probes. The signal obtained with in situ hybridization (both HPV and EBV) was localized to the upper layers of epithelial cells. The mechanism of oral hairy leukoplakia remains still unknown, but this work emphasizes the value of in situ hybridization with nonisotopic probes in the detection of viral nucleic acids on routinely processed tissue sections. The fact that these lesions seem to precede the AIDS phase emphasizes the clinical implications of this diagnosis in HIV infected patients.

[Value of the piribedil test in diagnosing migraine. Apropos of 150 cases]. / Intérêt du test au piribédil dans le diagnostic de la migraine. A propos de cent cinquante cas.

Patients with migraine show a hypersensitivity to dopamine or its agonists. One of these, piribedil, was administered as 0,1 mg/kg intravenously over 30 minutes to 150 subjects with either migraine or other types of headache. This test provoked nausea and vomiting in 94 p. cent of patients with migraine, and a rapid fall in blood pressure requiring immediate interruption of the infusion in 69 p. cent. In contrast, in those subjects with chronic non-migrainous headache the administration of piribedil had no effect in 61 p. cent and provoked a fall in blood pressure in only 16 p. cent. The piribedil test appears to possess good specificity vis-à-vis migraine, enabling a differential diagnosis from atypical periodic headache, a condition difficult to consider as migrain or psychogenic headache on clinical grounds alone.