Clinical value of negative skin tests to iodinated contrast media.

BACKGROUND: Several studies have shown that skin tests are useful tools for the diagnosis of iodinated contrast medium (ICM) allergy, but the real number of false negative results is not known. OBJECTIVE: To evaluate the negative predictive value of ICM skin tests. MATERIAL AND METHODS: One hundred and fifty-nine patients tested in our department because of a previous ICM reaction over the last 9 years were called and asked standardized questions about ICM re-exposure. RESULTS: Twenty-nine patients had been re-exposed to ICM. There were 20 (69.0%) females and the median age was 55 (34-60) years. The median time interval between the reaction and skin testing was 11.9 (1.6-21.5) years. Twenty-four patients (82%) had an immediate reaction, four a non-immediate (13.8%) reaction and no data were available for one patient. Two patients had positive ICM skin tests previously and were re-exposed to a negatively skin-tested ICM and did not react. Only two patients presented a mild reaction during ICM re-injection: one immediate (generalized urticaria lasting for 3 days) and one non-immediate maculopapular reaction. The patient with urticaria was re-tested and re-challenged (negative). The other patient was unable to return for re-testing. CONCLUSION: Skin testing for ICM hypersensitivity has a negative predictive value of 96.6% (95% CI: 89.9-103.2) and none of the reactions in skin-test-negative patients were severe. Multi-centric large surveys are still needed for confirmation.

Autism, language delay and mental retardation in a patient with 7q11 duplication.

BACKGROUND: Chromosomal rearrangements, arising from unequal recombination between repeated sequences, are found in a subset of patients with autism. Duplications involving loci associated with behavioural disturbances constitute an especially good candidate mechanism. The Williams-Beuren critical region (WBCR), located at 7q11.23, is commonly deleted in Williams-Beuren microdeletion syndrome (WBS). However, only four patients with a duplication of the WBCR have been reported to date: one with severe language delay and the three others with variable developmental, psychomotor and language delay. OBJECTIVE AND METHODS: In this study, we screened 206 patients with autism spectrum disorders for the WBCR duplication by quantitative microsatellite analysis and multiple ligation-dependent probe amplification. RESULTS: We identified one male patient with a de novo interstitial duplication of the entire WBCR of paternal origin. The patient had autistic disorder, severe language delay and mental retardation, with very mild dysmorphic features. CONCLUSION: We report the first patient with autistic disorder and a WBCR duplication. This observation indicates that the 7q11.23 duplication could be involved in complex clinical phenotypes, ranging from developmental or language delay to mental retardation and autism, and extends the phenotype initially reported. These findings also support the existence of one or several genes in 7q11.23 sensitive to gene dosage and involved in the development of language and social interaction.

Protein kinase Cgamma autoimmunity in paraneoplastic cerebellar degeneration and non-small-cell lung cancer.

BACKGROUND: The clinical and immunological profiles of patients with paraneoplastic cerebellar degeneration (PCD) and non-small-cell lung cancer (NSCLC) are not well known. OBJECTIVE: To review the clinical and immunological features of patients with PCD, NSCLC and without well-characterised onconeural antibodies. METHODS: The clinical features of nine patients with the diagnosis of classical PCD and NSCLC, included in our archives, were retrospectively reviewed. The presence of antibodies to cerebellar components was determined by immunohistochemistry and immunoblot of rat cerebellum. A cDNA library of human cerebellum was screened with the positive sera to identify the antigen. RESULTS: Nine patients with PCD and NSCLC were identified. Six patients were men, and the median age at diagnosis of PCD was 63 (range 47-73) years. PCD was completely reversed in two patients, and partially in one, after treatment of the tumour. The serum of one of the patients with PCD showed a unique reactivity with Purkinje cells. The screening of a cerebellar-expression library resulted in the isolation of protein kinase Cgamma (PKCgamma). PKCgamma immunoreactivity was not observed in the serum of 170 patients with non-paraneoplastic neurological syndromes, 27 patients with PCD, no onconeural antibodies and small-cell lung cancer, and 52 patients with NSCLC without paraneoplastic neurological syndromes. The NSCLC from 11 patients without PCD did not express PKCgamma at either the RNA or protein level. However, many cells of the NSCLC of the patient with PKCgamma antibodies expressed PKCgamma. CONCLUSION: PCD occurs in patients with NSCLC without typical onconeural antibodies and is associated with immune reactions against key proteins of the Purkinje cells.

New approach for visualizing estrogen receptors in target cells using inherently fluorescent ligands and image intensification.

Four fluorescent estrogen ligands were investigated as agents for visualization of estrogen receptors in cells: 2-(2,4-dihydroxyphenyl)-6-hydroxy-3-benzofurancarboxylic acid delta-lactone (coumestrol) and 9(11)-dehydro-12-oxoestradiol [12-oxo-1,3,5-(10),9(11)-estratetraene-3, 17 beta-diol] (12-oxoestradiol), which are inherently fluorescent compounds; and tamoxifen [Z)-1-[4-(2-dimethylaminoethoxy)phenyl]-1,2-diphenyl-1-butene) and 4-hydroxytamoxifen [Z)-1-[4-(2-dimethylaminoethoxy) phenyl]-1-(4-hydroxyphenyl)-2-phenyl-1-butene), which become maximally fluorescent only after ultraviolet irradiation. By conventional fluorescence techniques, these agents can be detected down to 10(-8) M in water, but only to 10(-6) to 10(-7) M in protein solutions; however, by photon-counting spectrofluorimetry, coumestrol and 12-oxoestradiol can be detected in protein solutions down to 5 X 10(-10) M. Three of these compounds have good affinity for the estrogen receptor: coumestrol (20%); 12-oxoestradiol (12%); and 4-hydroxytamoxifen (37%), relative to estradiol (100%). Under conditions where autoradiographic controls indicate that most of the estrogen receptor of MCF-7 human breast cancer cells is in the nucleus, we could demonstrate nuclear fluorescence using 10(-9) M concentrations of coumestrol, 12-oxoestradiol, and 4-hydroxytamoxifen. This nuclear fluorescence was abolished by a 200-fold excess of diethystilbestrol and could only be observed through a fluorescence microscope equipped with a microchannel image intensifier and a video camera detector that together provide a sensitivity enhancement of approximately 10(4). These studies indicate that the estrogen receptor in breast cancer cells can be visualized by fluorescence techniques, provided that the visualizing ligands have adequate affinity and specificity for the receptor and appropriate fluorescence characteristics, and provided that the fluorescence instrument has adequate sensitivity to observe fluorescence emission from cells treated with nM concentrations of the fluorescent agents.

Oligoclonal T-cells in blood and target tissues of patients with anti-Hu syndrome.

T-cell clones of unknown significance (TCUS), assessed by monoclonal or oligoclonal T-cell patterns in PCR-DGGE, were detected in blood of 7/9 patients with anti-Hu syndrome. Clonal patterns were also detected in 2/2 neoplastic lymph nodes, and in 2/2 inflamed dorsal root ganglia from three patients. Only some T-cell clones found in target tissues were also detected in blood or non-target tissues, and likely corresponded to TCUS. In one patient, an identical T-cell clone was found in both neoplastic lymph node tissue and dorsal root ganglia, but not in blood. Dorsal root-infiltrating lymphocytes were cytotoxic CD8(+) TIA-1(+) T-cells. They were often found in close contact to sensory neurons, most of which expressed MHC-1. Taken together, these data support a direct effector role of cytotoxic CD8(+) T-cells, the same clones being likely operative in sensory neuron damage and immune-mediated tumor growth control.

[Applications of antisense oligonucleotides in oncology]. / Applications des oligonucléotides antisens en cancérologie.

The development of biotechnologies offers considerable potential for new therapeutical approaches, targetting nucleic acids as information bearing molecules responsible for various pathologies. Gene therapy has, up to now, mainly aimed at compensating deficiencies of gene expression, through complex molecular and cellular constructions. Recently, an increasing interest has focused on short nucleotidic sequences (thus relatively easy to synthetize), or oligonucleotides, which could be able to specifically block the expression of mutated or overexpressed genes. When the target of these oligonucleotides is the mRNA of such genes, the strategy is called "antisense". This strategy has already led to a number of successful results in experimental models in vitro. Much more rare are actual effects in animal models and clinical trials are just being sketched. A review on the current state of the art will enlighten the physiological potential of these new molecules but also underline the still numerous issues before controlling therapeutical applications.

[Fine-needle aspiration biopsy and analysis of estrogen receptors in breast cancer]. / Ponction-aspiration à l'aiguille fine et dosage des récepteurs d'oestrogènes dans le cancer du sein.

Estrogen receptor concentration was measured in fine needle aspirates from 98 human mammary carcinomas. We performed a biochemical radiolabeled assay by the Charcoal-Dextran procedure on cytosols obtained after homogenization in a saline hypertonic buffer (0,4 M KCl) and centrifugation at 105,000 g. DNA content of the pellets was measured by fluorimetry. A sample of about 10(6) cells, containing at least 10 micrograms of DNA, was needed to obtain a reliable result. In this report, 74 samples were over 10 micrograms of DNA each. The analysis of these samples showed that, in 39 cases (52,8%), the estrogen receptor level was over the limit of 500 fmol/mg of DNA. In 5 cases (6,7%), the range was between 500 to 600 fmol/mg DNA and, in 30 cases (40,5%), it was under 500 fmol/mg DNA and was considered as negative. For 15 patients, estrogen receptors were determined on the same tumor, as removed by fine needle aspiration and by a surgical procedure (6 cases) or drill-biopsy (9 cases). There was a good correlation between the receptor content in needle aspirates and in tissue specimens for 13 cases out of 15.

Imaging and biodistribution of 125I tyramine oligonucleotide in nude mice bearing human breast tumor. Preliminary report.

Although the range of applications for antisense oligonucleotides is vast, current research concentrates mainly on virology and oncology. We have conducted in vivo and in vitro investigations of radiolabelling and biodistribution of a 22-mer phosphodiester oligonucleotide injected in athymic mice bearing xenograft of human mammary tumor (coculture: MCF7 and fibroblasts strain AF-11). Tumor/healthy tissue ratio of the 22-mer phosphodiester oligonucleotide fixation is high during the 24 hours after injection instead of fast elimination.

[Paraneoplastic intestinal pseudo-obstruction revealing small cell lung carcinoma: "the anti-Hu syndrome"]. / Pseudo-obstruction intestinale paranéoplasique révélatrice d'un carcinome pulmonaire à petites cellules: le syndrome anti-Hu.

A 67-year-old woman was admitted for intestinal pseudoobstruction associated with peripheral sensitive neuropathy. Jejunal biopsies performed during laparotomy, showed axonal degeneration and lympho-plasmocytic infiltration in myenteric plexus. High titer of seric anti-Hu antibodies suggested a paraneoplastic syndrome. Thoracic CT scan showed mediastinal lymph nodes. Their histological examination confirmed the diagnosis of metastatic small-cell lung carcinoma. Her condition gradually deteriorated despite supportive parenteral nutrition, chemotherapy, steroids and intravenous immunoglobulins. She died 12 months after the onset of symptoms.

[Arterial thrombosis in the course of nephrotic syndrome. Report of three cases]. / Les thromboses artérielles au cours du syndrome néphrotique. A propos de trois observations.

Vascular thrombosis remains severe complication in patients with nephrotic syndrome. Both venous and arterial thrombosis are observed. We report three new cases of arterial thrombosis in patients with nephrotic syndrome. The role of acquired hemostasis disorders, inducing hypercoagulability, is predominant. Extramembranous glomerulonephritis remains the most frequent cause of nephrotic syndrome, complicated by vascular thrombosis. Treatment is based on anticoagulation and corticosteroid therapy. Search for proteinuria should be part of the etiology work-up in all patients with vascular thrombosis of undetermined origin.

[Arterial complications of Behcet's disease. Report of 13 cases]. / Les complications artérielles de la maladie de Behçet. A propos de 13 cas.

Vascular involvement, usually venous thrombosis, is common in Behçet's disease. Arterial manifestations, usually aneurysms or more rarely occlusion, are less common. We analyzed 13 cases of Behçet's disease with arterial complications. This fourth series in the literature was collected over 11 years. There were 12 men and 1 woman, mean age 41 +/- 7 years. Mean delay to arterial complications was 5.8 years (maximum 20 years) after the first sign of the disease. In the 13 patients in our series, there were a total of 18 arterial lesions, including one aneurysm and one stenosis of the internal carotid artery. There were 2 cases (10%) with lesions of the aorta (aneurysms). Approximately half of the arterial lesions (7/18) involved the femoral artery. There were 11 localizations on the femoropopliteal axis (11 aneurysms). One aneurysm of the humeral artery was the only localization in the upper limb. Vascular involvement was limited to arterial lesions in 9/13 patients with multiple lesions at different localizations in 2 patients. In two others, a second arterial localization occurred secondarily. All patients except one were operated. Mid-term complications are: 1 death and 4 thrombi including 3 with good results after reoperation. In these patients with Behçet's disease, risk of severe complications is important, requiring long-term surveillance.

[Subacute neuropathy, multiple cancers, and Gougerot-Sjögren syndrome: contribution of anti-Hu antibody]. / Neuropathie subaiguë, cancers multiples et syndrome de Gougerot-Sjögren: intérêt des anticorps anti-Hu.

We report the case of a patient presenting a subacute, predominantly sensory neuropathy. The work up revealed a Sjögren's syndrome and a breast carcinoma. The presence of anti-Hu antibodies, identified by Western Blot using purified recombinant HuD protein, and the absence of the Hu antigen in the breast carcinoma ruled out the responsibility of the Sjögren's syndrome or breast carcinoma. In this context, the most likely diagnosis was a subacute neuropathy associated with small cell lung cancer, which was indeed discovered 3 years later.

Association of herpes simplex virus encephalitis and paraneoplastic encephalitis - a clinico-pathological study.

A 57 year-old woman developed acute limbic encephalitis and brainstem dysfunction. Anti-HU antibodies were repeatedly detected in serum and CSF. Postmortem examination showed necrotic and hemorrhagic lesions in the temporal lobes characteristic of herpes simplex virus encephalitis, which was confirmed by immunocytochemistry, and Purkinje cell loss with proliferation of Bergman glia and myelin loss in the external aspect of the dentate nuclei characteristic of paraneoplastic encephalitis. PCR-assay performed on temporal tissue extracts was positive for HSV-1. There was no identifiable neoplasm. This unusual association raises the possibility of a link between the two diseases.

[Asphyxiating intra-alveolar hemorrhage: a rare form of fat embolism syndrome]. / Hémorragie intra-alvéolaire asphyxiante: forme rare du syndrome d'embolie graisseuse.

We report a case of a 23-year-old patient admitted for a right femur fracture resulting from a traffic accident. An intra-alveolar haemorrhage occurred 48 hours later, with asphyxia anaemia, haematic bronchial aspirations, and bilateral alveolar opacities at chest X-ray. This symptomatology was associated with fever, sub-conjunctival petechiae, major hypocholesterolemia, deterioration of renal function, and cholestasis. All these features suggested a fat embolism. Other possible aetiologies were discarded because of normal cardiovascular and immunologic systems and absence of infection. The outcome under symptomatic treatment was satisfactory within 15 days. The occurrence of intra-alveolar haemorrhage in post-traumatic fat embolism is a rare event caused by pulmonary capillary obstruction by fat emboli.

[Glomangioma of the popliteal fossa. Apropos of a case]. / Glomangiome du creux poplité. A propos d'un cas.

Glomus tumours are relatively uncommon lesions most frequently found in the extremitis, usually in the digits. They are most often solitary lesions but multiple tumours have been reported. If the triad of pain, tenderness and cold intolerance should raise the clinical suspicion of a digital glomus. The histological exam is necessary in the extra digital glomus. We reported a case of fossa poplitea glomangioma with tibialis nerve compression. The treatment of choice was a surgical exision. But the tumour have been redivided a year later without malign transformation.

[False hydatic aneurysm of the thoraco-abdominal aorta]. / Faux anévrysme hydatique de l'aorte thoraco-abdominale.

Arterial complications of hydatic disease are rarely encountered. We report a false hydatic aneurysm of the thoracoabdominal aorta revealed by ischemic embolism of the lower limbs. Surgical treatment included aorto-aortic prosthesis and albendazol for 6 months. Results at 18 months are excellent with negative hydatic serology. In endemic areas, hydatic disease is a possible cause of false aneurysms. Long-term surveillance is required after curative surgery and medical treatment.

Autism, language delay and mental retardation in a patient with 7q11 duplication.

Chromosomal rearrangements are found in a subset of patients with autism. Duplications involving loci associated with behavioural disturbances constitute an especially good candidate mechanism. The Williams-Beuren critical region (WBCR), located at 7q11.23, is commonly deleted in Williams-Beuren microdeletion syndrome (WBS). However, only four patients with a duplication of the WBCR have been reported to date. Here, 206 patients with autism spectrum disorders were screened for the WBCR duplication by quantitative microsatellite analysis and multiple ligation-dependent probe amplification. One male patient with a de novo interstitial duplication of the entire WBCR of paternal origin was identified. The patient had autistic disorder, severe language delay and mental retardation, with mild dysmorphism. The present report concerns the first patient with autistic disorder and a WBCR duplication. This observation indicates that the 7q11.23 duplication could be involved in complex clinical phenotypes, ranging from developmental or language delay to mental retardation and autism.

T cell response to Hu-D peptides in patients with anti-Hu syndrome.

The anti-Hu syndrome is the most common paraneoplastic neurologic syndrome but the exact mechanism of immune mediated neuronal injury remains unknown. Anti-Hu antibodies do not appear to play a pivotal role in the pathogenesis of the disease. To assess cell-mediated immunity, we selected 51 peptides from the Hu-D sequence and tested their ability to bind to six common HLA class I molecules. Stable complexes with purified HLA molecules were obtained with 19/51 (37%) selected peptides. Subsequently, the ability of the 19 HLA-binding peptides to stimulate T cells from 10 patients and 10 control subjects was evaluated by detecting IFN-gamma secretion. An anti-peptide T-cell response was observed in 7/10 Hu-positive patients but also in 3/10 control subjects. Overall, a significant T-cell activation occurred in response to 74% (14 out of 19) of the selected peptides in the Hu-positive patients vs. 16% (3 out of 19) in the control group (p < 0.001). In addition, T cells of patients tested within 3 months of the onset of anti-Hu syndrome responded to 82% (14 out of 17) of assessed Hu-D peptides vs. 37% (7 out of 19) in patients tested 1 year or more after developing the syndrome (p < 0.01). Thus, the present study suggests a role of cellular immunity during the course of anti-Hu syndrome.