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Biomedical subjects

P Hofman

Publications and source records attributed to P Hofman.

At least 109 records · Page 6Linked to original sources

Loss of heterozygosity of the RB gene is a poor prognostic factor in patients with osteosarcoma.

PURPOSE: The usual therapy of osteosarcoma is neoadjuvant chemotherapy, followed by surgery, then by postoperative chemotherapy. There is no prognostic factor to predict, at diagnosis, the histologic response and final outcome. Inactivation of the retinoblastoma-susceptibility gene RB is associated with the pathogenesis of several human cancers. In primary osteosarcomas, loss of heterozygosity (LOH) at the RB locus has been found in greater than 60% of cases. The aim of this study was to determine the potential early prognostic value of LOH of RB gene on the biopsy material at diagnosis. PATIENTS AND METHODS: Forty-seven patients with primary osteosarcoma, treated in four French institutions, were studied. LOH was studied by polymerase chain reaction (PCR) of an informative RB DNA polymorphism. RESULTS: Assessment of LOH at the RB gene could be completed on 34 heterozygous patients only. LOH was found in 24 cases (70%). The event-free survival (EFS) rate at 60 months is 100% for patients without LOH, 43% for all patients with RB LOH, and 65% for nonmetastatic patients with RB LOH. The difference in EFS is highly significant at P = .008 and P = .024, respectively. Histologic response after preoperative chemotherapy did not show significant correlation with LOH status. CONCLUSION: RB gene LOH appears to be an early predictive feature for osteosarcomas that indicates a potential unfavorable outcome. RB LOH study might shortly help to identify high-risk patients earlier. If this is verified, therapy could then be adapted earlier to the individual's real risk of relapse.

Adolescent↗

[Maternal mortality in Nice. Results of a reproductive age mortality survey using death registries in the Nice University Hospital, 1986-1993].

OBJECTIVE: To define the rate of maternal death on the basis of maternal deaths recorded from January 1986 to May 1993. To determine whether the patients had received "standard" quality health care. METHOD: A Reproductive Age Mortality Survey was performed retrospectively on causes of death in women from 14 to 45 years of age; death registries and clinical records at the Nice University Hospital were used. RESULTS: There were 23 cases of pregnancy-associated death. Maternal mortality was 32.9 per 100000 live births. According to the INSERM survey, the "real" national rate would be 18.3 per 100000. This is a classical underestimation. The overmortality in Nice is partially explained by the AIDS epidemic which was the major cause of female deaths between 14 and 45 years (96/322). Nevertheless, there was an unsatisfactorily large number of cases in which standard obstetrical practises were not applied. This was often due to a combination of factors including poor obstetrical surveillance, insufficient attention by physicians, poor organisation of obstetrical care in the emergency room and referrals. Cesarean section was implicated in 7 out of 12 maternal deaths during the third trimester of pregnancy (58%). The cause of certain maternal deaths remained unexplained; amniotic embolus was always suggested. Unfortunately, an autopsy was performed in only 36% of the cases and its quality was insufficient to determine certain diagnosis.

Adolescent↗

[Adenomatoid tumors of the uterus. Study of 5 cases with immunohistochemical and ultrastructural confirmation of the mesothelial origin].

Five cases of adenomatoid tumors of the uterus (ATU) are reported. These benign lesions are discovered in 1% of the hysterectomy specimens, performed on 20- to 85-years-old women. Their frequency is certainly underestimated, since ATU have the same macroscopic appearance as leiomyomas. Histologically, ATU are formed by gland-like and pseudovascular lumens, lined by regular, cuboidal or flattened cells, and surrounded by hyperplastic smooth muscle bundles. Immunohistochemical coexpression of cytokeratin and vimentin confirms with a mesothelial histogenesis. The ultrastructural study, showing luminal microvilli and desmosomes supports the hamartomatous development of ATU, corresponding to mesothelial inclusions from the peritoneum into the myometrium. Some giant or diffuse ATU, which are clinically disturbing, are differentiated from carcinomatous or vascular proliferations by frozen section examination. The treatment is made by surgical excision.

Adenomatoid Tumor↗

Thyroid spindle epithelial tumor with thymus-like differentiation (the "SETTLE" tumor). An immunohistochemical and electron microscopic study.

An intrathyroid primary epithelial spindle-cell tumor with mucous cysts is described in a 9-year-old child. Histologically, this well-circumscribed tumor exhibited a nodular pattern, a prominent spindle cell component with minimal pleomorphism, and well-differentiated mucinous glands within fibrous bands. The spindle cells demonstrated diffuse immunopositivity for cytokeratin and vimentin. Electron microscopy of tissue sections demonstrated that cells contained bundles of cytoplasmic tonofilaments and numerous desmosomes. The light and electron microscopic features and immunohistochemical profile of this tumor were similar to those of recently described thyroid tumors that have been called "SETTLE" tumors (i.e., spindle epithelial tumor with thymus-like differentiation). These uncommon tumors can be considered intrathyroid thymoblastomas and must be regarded as potentially malignant lesions.

Child↗

Atypical leishmaniasis in a patient infected with human immunodeficiency virus.

Visceral leishmaniasis is an anthropozoonosis endemic in the south of France. Its occurrence among patients infected with human immunodeficiency virus (HIV), in whom it presents with uncommon clinical, biological, and evolutionary signs, is being reported more and more often. We describe a case of leishmaniasis in an HIV-seropositive man that we believe is unique with respect to the cutaneous and then visceral location of the disease and the discovery at necropsy of an adrenal and myocardial leishmanial infiltrate.

AIDS-Related Opportunistic Infections↗

Atypical cutaneous histological features of visceral leishmaniasis in acquired immunodeficiency syndrome.

Cutaneous lesions in Mediterranean visceral leishmaniasis (VL) are very unusual, except for the presence of Leishmania organisms in cutaneous Kaposi's sarcoma in patients with acquired immunodeficiency syndrome (AIDS). We have identified two unusual cutaneous histological features of VL in three patients with AIDS not described previously; two had "silent leishmaniasis," and in the third, Leishmania organisms were present in sweat ducts, suggesting transepithelial elimination through eccrine sweat glands and/or eccrine epithelial tropism.

AIDS-Related Opportunistic Infections↗

Expression of the antigen recognized by mAb GB36 in normal skin and in skin tumours.

GB36, a mouse monoclonal antibody (mAb) raised against an epithelial antigen of the human trophoblast, reacts with the epithelial basement membrane of chorionic villi; it does not react with the invasive extravillous cytotrophoblast. Expression and characterization of the antigen of GB36 (designated GBA36) were investigated in normal keratinocytes by immunoprecipitation, immunofluorescence and immunoelectron microscopic studies. Immunoprecipitation experiments demonstrated that the proteins identified on keratinocytes by mAb GB36 and a rat mAb anti-integrin alpha 6 (GoH3) were the same. Using immunofluorescence and immunoelectron microscopic methods, GBA36 was localized on the cell membrane facing the epithelial basal lamina of basal keratinocytes. GBA36 distribution in benign and malignant skin tumours was evaluated by immunostaining methods (immunofluorescence and immunoperoxidase). Analysis of tumours revealed that whereas benign epithelial tumours and intradermal naevi displayed high levels of GBA36, the expression of this antigen decreased progressively in spinocellular and basal cell carcinomas, and in cutaneous melanomas in relation to invasiveness. During cell transformation, GBA36 undergoes quantitative alterations, and expression is down-regulated. Although the functional relevance of these changes remains unknown, the correlation of decreased GBA36 expression with tumour progression may indicate a role for altered integrin expression in tissue invasion by human skin carcinoma and melanoma.

Adult↗

[Colonic Histoplasma capsulatum pseudotumor in AIDS. Morphological and immunohistochemical diagnosis of an isolated lesion].

The authors report a case of a 35-year-old man with acquired immunodeficiency syndrome (AIDS) and a left colonic mass with Histoplasma capsulatum (H. capsulatum). The look-up performed looking for disseminated infection was negative. In the absence of positive cultures, the diagnosis was determined morphologically based on the presence of yeast observed by light and electron microscopy. The diagnosis was also verified by positive immunofluorescence using specific anti-Histoplasma antibodies. Gastrointestinal histoplasmosis is a frequent complication of AIDS, particularly in some endemic areas of America. Association with a disseminated mycotic infection is then common. Histoplasmosis is less frequently diagnosed in Europe and isolated involvement of the colon is exceptional. When the mycological study is not performed or is negative, only morphological and immunohistochemical methods are able to establish the diagnosis and eliminate other mycotic diseases occurring during AIDS.

AIDS-Related Opportunistic Infections↗

[Muscular involvement in the course of AIDS. Anatomo-clinical study of 17 cases].

We report 17 patients seropositive for the human immunodeficiency virus, with muscle tissue involvement in different stages of the disease. Some patients are treated with azidothymidine (AZT). Others have no opportunistic infections. In all cases, there are some muscular symptoms such as progressive symetric and proximal muscular weakness with myalgias, elevated serum muscle enzymes, abnormal electromyogramma and very often a peripheral neuropathy. The muscle biopsy reveals the following features: rarely a focal muscular opportunistic infection in advanced stage of the disease is observed; a polymyositis is quite often the first clinical manifestation of the disease; a myopathy with mitochondrial involvement is observed in some of the AZT treated patients; some cachectic, under nourrished, bedridden patients present a type II muscle fiber atrophy. We conclude that a muscle biopsy could help us in our therapeutic planning directing us to a corticotherapy in the polymyositis, mitochondriopathies and wasting syndrome. Interruption alone of AZT or associated with a treatment by carnitine could allow remission of the muscular pathology.

Acquired Immunodeficiency Syndrome↗

[VLA and alpha6, beta4 integrins. Expression in normal and neoplastic human tissues].

Among the cellular adhesion molecules, the integrin family, more particularly the VLA (Very late antigen) integrins, is currently the subject of numerous investigations in pathology. These integrins are involved in cell-cell contact or cell-matrix adhesions. During neoplastic diseases, cellular expression of integrins changes and a study of the modifications could allow a new etiopathogenic approach carcinogenesis and metastatic phenomena. New prognostic factors may be defined in tumor pathology. We describe the general structure of integrins and the mechanisms of their binding with matricial ligands and with cytoskeleton. The expression of VLA integrins and the alpha6beta4 heterodimer on normal and neoplastic human tissues is then described. Finally, we describe the involvement of these proteins in tumor progression and tissue invasion.

Antigens, CD↗

High expression of the antigen recognized by the monoclonal antibody GB24 on human breast carcinomas: a preventive mechanism of malignant tumor cells against complement attack?

GB24 is a mouse monoclonal antibody raised against a common trophoblast-lymphocyte cross-reactive antigen. GB24 detects the membrane cofactor protein (MCP, CD46), a member of the complement regulatory protein family, which serves as a cofactor for factor 1 mediated cleavage of C3b. This study investigated the reactivity of GB24 on 38 breast carcinomas and 34 normal/benign breast tissues by immunochemistry as well as the reactivity of F2B7-2, an antibody specific to the decay accelerating factor (DAF, CD55) of the complement. GB24 staining was present on both normal tissue and benign lesions, but very strong diffuse reactivity was observed on carcinomas. This reactivity increased with the tumor grade. By contrast, malignant tumor cells lacked DAF expression. F2B7-2 antibody reacted weakly with benign epithelial cells. Results were studied by computer assisted image analysis to accurately define the mean optical densities. The densitometric analysis of MCP positive carcinomas showed a high intensity of the staining. Expression of MCP and DAF on MCF-7 cell lines was analyzed by flow cytometry. MCF-7 cell lines were strongly stained by mAb GB24 only. These data suggest that selectively enhanced expression of the antigen recognized by GB24 is associated with malignant breast disorders. This high expression, which may reflect a protective mechanism by which tumor cells survive complement activation, may prove useful as a marker of malignant transformation.

Adenocarcinoma↗

Histological and ultrastructural study of one case of oral bacillary angiomatosis in HIV disease and review of the literature.

Bacillary angiomatosis (BA) is a new clinicopathological entity defined as a pseudo-neoplastic capillary proliferation secondary to an opportunistic infection by one of two Rochalimaea sp.: R. quintana or R. henselae. Although BA is a recently recognised entity, numerous cases have been reported. Most of the patients affected are reported to have low absolute CD4 lymphocyte counts associated with AIDS. Yet, very few oral cases associated or not with cutaneous lesions have been reported or simply identified. Histopathological and ultrastructural features of one case of oral BA with gingival and palatal lesions are presented. Clinical aspects of oral BA do not hold pathognomonic features and the lesions may resemble either a reactive lesion of the gingiva, pyogenic granuloma or Kaposi's sarcoma. The lesion is characteristically composed of circumscribed lobular capillary proliferations and the presence of granular amphophilic material on haematoxylin and eosin sections surrounded by neutrophils and neutrophilic debris is a clue to diagnosis. Demonstration of bacilli in the interstitium by the Warthin-Starry silver method or, better, by electron microscopy is diagnostic. BA may contribute to the death of the patient but erythromycin has proved to be very effective treatment.

AIDS-Related Opportunistic Infections↗

Intestinal and extraintestinal Isospora belli infection in an AIDS patient. A second case report.

A 30-year-old black female, from Burkina Faso, had AIDS in 1990. She died in March 1993 following a cachexia secondary to a chronic intestinal isosporiasis. The autopsy revealed a massive parasitic infection by I. belli of the small intestine mesenteric and mediastinal lymph nodes and liver and spleen. The parasite stage observed in extra intestinal sites corresponded to unizoite tissue cysts. This is the first report of I. belli infection in liver and spleen.

AIDS-Related Opportunistic Infections↗

Oral leishmaniasis and Kaposi's sarcoma in an AIDS patient.

In the Mediterranean basin area, visceral leishmaniasis is an endemic disease caused by Leishmania donovani infantum. This study describes the clinical and pathological features of one patient with AIDS who had oral (tonsillar) leishmaniasis, caused by a viscerotropic zymodeme, concurrent with a Kaposi's sarcoma and with a CMV infection.

AIDS-Related Opportunistic Infections↗