Comparison of dysplasia profiles in stimulated ovaries and in those with a genetic risk for ovarian cancer.

AIM: Ovarian epithelial dysplasia (OED) was first described after prophylactic oophorectomy for genetic risk of ovarian cancer. In light of Fathalla's incessant ovulation theory, this study was set up to describe the presence of ovarian abnormalities (dysplasia) after ovulation induction and to compare dysplasia profiles in stimulated and genetic risk ovaries. METHODS: One-hundred and twenty-four patients who had undergone salpingo-oophorectomies or ovarian cystectomies between 1990 and 2005 were reviewed. They were divided into three groups: (1) previous in vitro fertilisation (n=35); (2) prophylactic oophorectomies for genetic risk (n=27) and (3) fertile non-cancerous controls (n=62). Eleven cytological and architectural epithelial features were defined and a dysplasia score was calculated to quantify ovarian epithelial abnormalities. RESULTS: Mean dysplasia score was significantly higher in the genetic risk and stimulated ovary groups than in controls (9.55 versus 3.62, p<0.0001; 7.51 versus 3.62, p<0.0002, respectively). Cytological and architectural abnormalities were more frequent in the genetic risk group, while the profile of abnormalities was different in the genetic risk and stimulated groups. CONCLUSIONS: These findings support a possible relationship between OED and the use of ovulation-stimulating drugs. The increased dysplasia score in stimulated and genetic risk ovaries might be consistent with progression towards neoplastic transformation, and may justify the use of the term dysplasia or intraepithelial ovarian neoplasia. The observation of dysplasia in the stimulated group may differentiate women at risk. Conversely, the fact that the dysplasia profile after stimulation differs from that in genetic risk ovaries suggests that ovarian stimulation may predispose to a different evolution.

Cerebellar-pulmonary embolism, cause of death in the newborn.

A 28-year-old woman delivered twin girls. The first twin was delivered without any difficulty. The head of the second twin failed to descend with pushing. A special kind of obstetrical forceps, Thierry's spatulas, were used to extract the second twin in the occipito-posterior vertex position. She was declared dead after recording Apgar scores of 0 and 0 and after 35 min of resuscitation. An autopsy was performed for medico-legal reasons. Macroscopic examination of the brain showed a small area of leptomeningeal haemorrhage in the left sylvian fossa and the base of the brain. Histopathological studies demonstrated cerebellar tissue emboli in meningeal and pulmonary arteries. Excessive pressure on the suboccipital region during delivery can cause traumatic separation of the occipital chondral junctions, which may lead to separation of the occipital squama from lateral parts of the occipital bones. The inferior part of the occipital squama is displaced forward and upward into the posterior fossa. This produces tearing of the duramater and occipital sinuses leading to leptomeningeal haemorrhage in the posterior cranial fossa, often associated with cerebellar lesions. Major stretching and tearing of the posterior aspect of tentorium cerebelli in contact with the sinuses and the cerebellar cortex may also occur, inducing slight movement of the occipital bones and subsequent emboli. This case study is that of a newborn death due to pulmonary cerebellar tissue embolism occurring during delivery with Thierry's forceps, which are considered less traumatic to the foetal cranium. A review of the literature identified 17 other published cases. In difficult deliveries this pathology should sought carefully. Brain, lung and placenta tissue sections must be studied.

Fetal aqueductal glioneuronal hamartoma: a clinicopathological and physiopathological study of three cases.

UNLABELLED: Fetal hydrocephalus due to aqueductal stenosis is classified into two main groups: congenital (X-linked, atresia, septa and forking) and acquired (post-infectious or post-hemorrhagic, gliosis and tumors). MATERIAL AND METHODS: We report three fetal cases presenting with severe hydrocephalus, two of which being apparently sporadic, and the third possibly inherited. On macroscopic examination, no associated malformations were identified, either craniofacial dysmorphy, or visceral abnormalities. Neuropathological study revealed massive hydrocephalus caused by narrowing of the Aqueduct of Sylvius. Histological examination evidenced a nodular, well-demarcated mass producing into the aqueductal lumen, and containing numerous immature proliferating glioneuronal cells. Immunohistochemical analyses did not suggest a developmental abnormality of the subcommissural organ but rather a hamartomatous malformative process. RESULTS: Hamartoma of the posterior fossa has been rarely reported. Post-natal cases have been described in the cerebello-pontine angle or in the quadrigeminal plate, and have always been diagnosed as pilocytic or low-grade astrocytomas. In our cases, the lesions could be related to so-called pencil glioma, sometimes associated with type 1 neurofibromatosis and, to our knowledge, have never been described prior to birth. The occurrence during fetal life and the progressive maturation of the nodules are more likely in favor of a hamartomatous process. CONCLUSION: Even though they could sporadically occur, an accurate genetic counseling should be required in order to ensure that there is no familial history of Recklinghausen disease, and to provide a more precise evaluation of recurrence risk.

Diffuse EGFR staining is associated with reduced overall survival in locally advanced oesophageal squamous cell cancer.

Squamous cell carcinoma of the oesophagus (SCCO) is still a pathology of bad prognosis. Specific therapies are now developed against epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2, c-kit receptor (CD117), vascular endothelial growth factor (VEGF) and p53 protein. This study was aimed at assessing their expression in a large series of SCCO, as well as their potential therapeutic interest in this pathology. Immunohistochemical expression of these factors was assessed retrospectively in 107 cases of SCCO with primary surgery, as well as their relationships to recurrence, metastasis and overall survival on a long-term follow-up. Human epidermal growth factor receptor 2 and CD117 were expressed in less than 3% of the cases. Epidermal growth factor receptor and p53 were overexpressed in 68.2 and 66.4% of the cases, and VEGF in 38.3%. Epidermal growth factor receptor overexpression was significantly related to vascular invasion (P=0.023). Its diffuse positivity was significantly related in multivariate analysis to higher local recurrence (P=0.006) and lower overall survival (P=0.003), in a subgroup of patients of poor outcome who had received postoperative adjuvant treatment. These results highlight the great potential prognostic and therapeutic interest of evaluating EGFR diffuse positivity in locally advanced SCCO.

Recombinant humanised anti-HER2/neu antibody (Herceptin) induces cellular death of glioblastomas.

Glioblastoma multiforme (GBM) remains the most devastating primary tumour in neuro-oncology. Targeting of the human epithelial receptor type 2 (HER2)-neu receptor by specific antibodies is a recent well-established therapy for breast tumours. Human epithelial receptor type 2/neu is a transmembrane tyrosine/kinase receptor that appears to be important for the regulation of cancer growth. Human epithelial receptor type 2/neu is not expressed in the adult central nervous system, but its expression increases with the degree of astrocytoma anaplasia. The specificity of HER2/neu for tumoral astrocytomas leads us to study in vitro treatment of GBM with anti-HER2/neu antibody. We used human GBM cell lines expressing HER2/neu (A172 express HER2/neu more than U251MG) or not (U87MG) and monoclonal humanised antibody against HER2/neu (Herceptin). Human epithelial receptor type 2/neu expression was measured by immunohistochemistry and flow cytometry. Direct antibody effect, complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity were evaluated by different cytometric assays. We have shown, for the first time, the ability of anti-HER2/neu antibodies to induce apoptosis and cellular-dependent cytotoxicity of HER2/neu-expressing GBM cell lines. The results decreased from A172 to U251 and were negative for U87MG, in accordance with the decreasing density of HER2/neu receptors.

Systemic effects on bone healing of a new hyaluronic acid-like bacterial exopolysaccharide.

Critical Size Defect (CSD) technique was used to evaluate the systemic activities on bone regeneration capacity of a newly discovered hyaluronic acid-like exopolysaccharide synthesized by a bacteria originating from a deep sea hydrothermal vent. Some systemic effects were previously detected on earlier experiments. A 5 mm diameter hole was made on each parietal bone of male rats. The right hole was filled with 0.5 mg of a new bacterial exopolysaccharide referenced HE 800, while the left hole remained free of any treatment. After 21 days, the holes and surrounding tissues were examined by direct examination, X-rays, and histological staining. Using HE 800, bone healing was almost complete after only 21 days in the treated hole and always complete in the control side by some systemic effect. Neovascularization was also observed along with an organized trabecular bone on both sides. No abnormal bone growth or conjunctival abnormalities were noticed. At the end of the experiment, 90.1% ( +/- 5.2) bone healing (n = 20) was observed on the treated side; conversely, the control side animals demonstrate an amazing healing 100% (+/- 0.5) by a systemic effect.

A new bone-healing material: a hyaluronic acid-like bacterial exopolysaccharide.

Critical size defect (CSD) technique was used to evaluate the bone regeneration capacity of a newly discovered hyaluronic acid-like exopolysaccharide synthesized by a bacteria originating from a deep sea hydrothermal vent. A 5 mm-diameter hole was made on each parietal bone of male rats. The right hole was filled with either a new bacterial exopolysaccharide referenced HE 800 or with collagen used as negative control, while the left hole remained free of any treatment. After 15 days, the holes and surrounding tissues were examined by direct examination, X-ray films, and histological staining. Using HE 800, bone healing was almost complete after only 15 days, with osteoblasts onto lying external bone surfaces and enhancing osteocyte inclusion. Neovascularization was also observed along with an organized trabecular bone. No abnormal bone growth or conjunctival abnormalities were noticed. At the end of the experiment, 95.9% (+/-6.2) bone healing (n = 20) was observed. Conversely, the collagen-treated animals did not demonstrate significant healing-17.8% (+/-18.1).

[Sudden death of a two-year-old boy with influenza A virus infection: study of an autopsy case]. / Décès brutal et infection à virus Influenza A chez un enfant de deux ans: étude d'un cas autopsique.

UNLABELLED: Influenza A virus infections are common in childhood and infancy and are often underdiagnosed while serious or lethal forms are rare. CASE-REPORT: We describe a case of sudden death in a two-year-old boy. Pathologic findings at autopsy were consistent with Myxovirus influenzae A virus infection and the virus was isolated by post mortem PCR. CONCLUSION: In the case of sudden death in infants, especially if pathologic findings are compatible with a viral infection, PCR may allow identification of the causative virus.

Giant axonal neuropathy locus refinement to a < 590 kb critical interval.

Giant axonal neuropathy (GAN) is a rare autosomal recessive neurodegenerative disorder, characterised clinically by the development of chronic distal polyneuropathy during childhood, mental retardation, kinky or curly hair, skeletal abnormalities and, ultrastructurally, by axons in the central and peripheral nervous systems distended by masses of tightly woven neurofilaments. We recently localised the GAN locus in 16q24.1 to a 5-cM interval between the D16S507 and D16S511 markers by homozygosity mapping in three consanguineous Tunisian families. We have now established a contig-based physical map of the region comprising YACs and BACs where we have placed four genes, ten ESTs, three STSs and two additional microsatellite markers, and where we have identified six new SSCP polymorphisms and six new microsatellite markers. Using these markers, we have refined the position of our previous flanking recombinants. We also identified a shared haplotype between two Tunisian families and a small region of homozygosity in a Turkish family with distant consanguinity, both suggesting the occurrence of historic recombinations and supporting the conclusions based on the phase-known recombinations. Taken together, these results allow us to establish a transcription map of the region, and to narrow down the GAN position to a < 590 kb critical interval, an important step toward the identification of the defective gene.

[Interest in placental apposition as an epidemiological marker for malaria]. / Intéret de l'apposition placentaire comme marqueur épidémiologique du paludisme.

Three studies about relation between pregnancy and malaria have been conducted in CAR. The comparative study between plasmodic indexes (PI) et placental appositions (PAP) had shown that PAP offers biggest sensibility in the diagnosis of malaria infection (37.1% for PAP versus 17.1% for PI). The comparison of the PAP with placental anatomopathological study (PAN) revealed the same sensibility of both technics but the PAP's realization is very easy, at the opposite PAN's realization is long and requires sophisticated equipment. Moreover, PAP allows the differentiation between recent and post-malaria infection. The simultaneous realization of the PAP and chloroquinaemia had allowed to develop a surveillance of chloroquine resistance level of Plasmodium falciparum to amino-4-quinolines.

[Plasmodial indices and malarial placentopathy in 299 parturients in Central Africa]. / Indices plasmodiques et placentopathies palustres chez 229 parturientes centrafricaines.

229 parturients were screened for malaria by blood smear test and examination of placenta (placental apposition and anatomopathological examination). Primiparous show higher sensibility to infection, with a weight deficit for newborn as a consequence of it. Placenta examination enables to diagnose twice as much malarial infestation than blood smear. Placental apposition appears to be an interesting indicator from the point of view of diagnosis and epidemiology.

Lympho-cutaneous Kaposi's sarcoma in an African pediatric AIDS case.

A case of disseminated Kaposi's sarcoma with lymphoid and mucocutaneous involvement in an African infant with acquired immune deficiency syndrome is reported. The child died within 2 months after recognition.

PIP: Co-infection with acquired immunodeficiency syndrome (AIDS) and Kaposi's sarcoma is not uncommon in Europe, but is rare in Africa and not previously reported in infants. This article documents the case of an 11-month-old African boy with lymphocutaneous Kaposi's sarcoma. The infant was brought to a hospital in the Central African Republic with chronic diarrhea and disseminated lymphadenopathy. Also present were fever, cough, weight loss, a gingivostomatitis with herpes-like vesicles, hepatomegaly, splenomegaly, and cervico-axillo-inguinal lymphadenopathy. The adenopathies 1st occurred when the infant was 7 months of age and were followed 1 month later by the emergence of 12 dark brown or black velvet raised cutaneous nodules. The diagnosis of Kaposi's sarcoma was confirmed by lymph node and skin nodule biopsies. Also indicative of Kaposi's sarcoma was the presence of abortive vascular foci at a distance from the skin's surface and the cell proliferation. Both the infant and his asymptomatic mother were seropositive for antibodies to human immunodeficiency virus (HIV)-1. The skin lesions in this case presented the special infiltrative characteristic of AIDS-related Kaposi's sarcoma. The infant died 2 months after presentation at the hospital. By the last weeks of his life, the cutaneous nodules had covered the entire body. Death was from pleuropneumopathy. Given the high prevalence of HIV-1 infection in the Central African Republic, more such cases can be expected.

[Preliminary study of stages of human meiosis in spermatocytes and ovocytes (author's transl)]. / Etude preliminaire de stades de la méiose humaine dans les spermatocytes et les ovocytes.

Human meiotic chromosomes, from spermatocytes and ovocytes, are described after observations of whole mount preparations under E.M. Small testicular and ovarian fragments are put in distillated water, then macerated; the cell suspension is spread on the surface of sheet copper grids covered with formvar plus collodion films. After dehydratation interesting stages are selected under L.M. before observations under E.M. Zygotene and pachytene are the most common stages. During pachytene the chromomeres are well individualized; the synaptonemal complex may be observed; chromatin fibers connect the chromosomes to nuclear pores, interchromosomal fibers joint the bivalents. Zygotene and pachytene bivalents are very similar in the male and the feminine germ cells.

[Autogenous ovary grafts in rabbits. Experimental study (author's transl)]. / Autogreffe ovarienne chez la lapine. Etude expérimentale.

The authors report the techniques used and the results obtained in a experimental study of autogenous ovary grafts in rabbits. The various methods of control--histological, hormonal and isotopic--used to measure the vitality of the grafts, showed their good quality. Active ovarian tissue was found to be present within the graft: 17 beta-oestradiol and progesterone secretion was demonstrated by means of radio-immunological plasma dosages and LH fixation in the ovarian tissue graft was shown by means of 131 iodine. This recovery was however accompanied by a loss of ovarian functional potential and chances of impregnation and gestation were reduced due to a strong peritoneal reaction.