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Biomedical subjects

V Fridman

Publications and source records attributed to V Fridman.

At least 19 recordsLinked to original sources

Sinonasal involvement as a rare extraintestinal manifestation of Crohn's disease.

Crohn's disease is a chronic idiopathic slowly developing transmural inflammation of the digestive system. It usually involves the small intestine and/or the area around the anus but can also affect the entire gastrointestinal tract anywhere from the mouth to the anus. Extra intestinal manifestations occur frequently and multiple organ systems may be affected: the skin, joints, spine, eyes, liver and bile ducts. In contrast, nasal manifestations are extremely rare and only a few cases have been reported up to date in the worldwide literature. The authors report two cases with nasal manifestations concomitant to intestinal Crohn's disease and go over the relevant literature on such an association.

Acute Disease↗

[A bilateral dysgerminoma: a rare presentation of the Swyer syndrome].

Swyer syndrome is a pure gonad dysgenesis associating 46 XY karyotype, primary amenorrhea, presence of female internal genital tract and bilateral streak gonads in a phenotypic female. The diagnosis is usually made at adolescence when the primary amenorrhea is investigated. We report the case of a 25-year-old XY woman who developed a bilateral dysgerminoma from undifferentiated gonads.

Adult↗

Evidence of a limited contribution of feto-maternal interactions to trophoblast differentiation along the invasive pathway.

Trophoblast differentiation is a key event in human placental development. During extravillous trophoblast (EVT) differentiation, stem cells from the anchoring villi detach from their basement membrane and proliferate to form aggregates called trophoblast cell columns (TCCs). They subsequently invade the decidua and differentiate into interstitial and endovascular trophoblasts. The influence of the decidua on EVT differentiation is controversial. We therefore compared the pattern of trophoblast differentiation marker expression in viable intrauterine and tubal pregnancies, as decidual cell markers (prolactin [PRL] and insulin-like growth factor binding Protein-1 [IGFBP1]) were only expressed in endometrial implantation sites. Extravillous trophoblast differentiation in anchoring villi from uterine and ectopic pregnancies exhibited a comparable phenotypical switch: alpha6 integrin subunit, E-cadherin, EGF receptor, Ki 67 and connexin 40 were localized in the proximal part of the TCC, while alpha5beta1 and alpha1 integrins, c-erb B2, hPL and HLA-G were expressed by invasive cytotrophoblasts. The cyclin-dependent kinase inhibitors p16 and p57 were mainly detected in invasive cytotrophoblasts some distance from the columns. However, the TCC was markedly longer in tubal pregnancy than in intrauterine pregnancy. These findings suggest that the decidua is not necessary to trigger EVT invasion, but that it is likely to limit the extent of the TCC and to accelerate the onset of EVT migration.

Biomarkers↗

[HER2 gene amplification assay: is CISH an alternative to FISH?].

The HER2 proto-oncogene encodes a transmembrane protein, which is considered to function as a growth factor receptor. Overexpression of this protein found by immunohistochemistry in about 20% of infiltrating breast carcinomas, has a predictive value of response to treatment by trastuzumab, an anti-HER2 humanized monoclonal antibody. Search for HER2 gene amplification is necessary to adapt the immunohistochemical technique quality and also in the cases of delicate analysis or weak overexpression. It is usually carried out by Fluorescence In Situ Hybridization (FISH). A more recent hybridization technique, named CISH because of its chromogenic revelation is an alternative method, which gives highly correlated results with FISH. We present details of this technique, which may be more familiar for the pathologists than FISH, because reading analysis is similar to that of immunohistochemical staining.

Breast Neoplasms↗

En bloc excision of nonpalpable breast lesions using the advanced breast biopsy instrumentation system: an alternative to needle guided surgery?

This study was prospectively conducted to evaluate the clinical potential of the advanced breast biopsy instrumentation (ABBI) system as an alternative to needle localization and open surgery in the management of nonpalpable breast lesions (NPBL). One hundred and eighty-six consecutive patients were referred for management of NPBL. Thirty-six underwent an ABBI procedure, offered as a first step before possible surgery for lesions which would in any case have required complete excision. The 18 patients with a malignant ABBI biopsy underwent re-excision of the biopsy site and axillary dissection was carried out in cases of infiltrating carcinoma. The other 150 patients underwent image-guided needle biopsy. Following these procedures, 60/150 (40%) patients underwent needle-guided surgery. Finally, 96/186 (51%) patients required complete excision. A total of 43 benign lesions and 53 carcinomas were confirmed. Thirty-six out of 96 (38%) excisions were obtained with the ABBI system; 17/43 (40%) benign lesions and 11/53 (21%) carcinomas were completely removed with the ABBI system. Out of 9 malignant specimens with a pathological size less than 10 mm, 5/9 (55%) had tumor-free margins and in 8/9 (89%) no residual disease was found at re-excision. The preliminary results of this study suggest that, in selected cases, en bloc excision using the ABBI procedure could be an alternative to conventional surgery.

Adult↗

Assessment of tumor angiogenesis in invasive breast carcinomas: absence of correlation with prognosis and pathological factors.

Different retrospective studies have shown that microvessel counting (MVC) is an independent prognostic marker for clinical outcome in breast cancer. The aim of this study was to evaluate the prognostic value of MVC alone or in association with classical clinicopathological parameters, as well as the reproducibility of the technique. We analyzed a retrospective series of 216 cases of breast carcinoma. Tissue sections were stained for Factor-VIII-related antigen. Microvessel quantification was performed at x400 magnification in the three most vascular areas of the tumors (hot spots). Mean and highest values were studied. Furthermore, a semi-quantitative evaluation of MVC was performed by use of an image-analysis system. The effect of multiple factors on survival was tested under a Cox multivariate proportional hazards model. In ten cases, a study of the reproducibility was done by evaluating MVC in different sections of the same block and in different blocks of a same tumor. There was no association between MVC (determined at a microscopic level or by image analysis) and overall survival or relapse-free survival. No association was found with tumor size, tumor grade, and lymph-node status. The study of reproducibility showed a very high intra-tumoral variation of MVC. The intra-individual coefficient of variation (CV) varied between 20 and 80%. This study did not show any significant correlation between angiogenesis, as assessed by MVC, and relapse-free survival or overall survival in infiltrating breast carcinomas. The low reproducibility of the MVC for the same tumors suggests that this technique must still be optimized before routine application.

Aged↗

Electrochemical investigation of cellobiose oxidation by cellobiose dehydrogenase in the presence of cytochrome c as mediator.

An important aspect of the cytochrome c electrochemistry is the possibility of coupling the 'heterogeneous reactions' with other redox enzymes. Cellobiose dehydrogenase, a 89170 Da glycoprotein that contains both FAD and a b-type haem as prosthetic groups, donates electrons to a number of acceptors, including cytochrome c. While haem b is surrounded mainly by acidic amino acids, cytochrome c displays positive charged lysine groups around the haem site. Thus a fast reaction between both proteins is explicable. In the presence of cellobiose, a catalytic current was observed, owing to the interaction of cellobiose dehydrogenase with electrostatically adsorbed cytochrome c. Adsorption of cytochrome c provides a technological model surface for vectorial electron transfer.

Carbohydrate Dehydrogenases↗

Dynamic changes in electrogram morphology at functional lines of block in reentrant circuits during ventricular tachycardia in the infarcted canine heart: a new method to localize reentrant circuits from electrogram features using adaptive template matching.

INTRODUCTION: Fractionated, low-amplitude or long-duration electrograms have limited specificity for locating reentrant circuits causing ventricular tachycardia (VT). In this study a new method is described, adaptive template matching (ATM), based on the quantification of beat-to-beat changes in electrograms, for locating functional reentrant circuits that are relatively stable and cause monomorphic VT. METHODS AND RESULTS: Monomorphic VTs were induced in 4-day-old infarcted canine hearts by programmed stimulation and reentrant circuits mapped in the epicardial border zone with a 196 or 312 bipolar electrode array. For ATM analysis, a template electrogram from each electrode, during an early cycle, was matched with all subsequent (input) electrograms at the same site by weighting the inputs of amplitude, duration, average baseline, and phase lag. The mean square error (MSE) between template and input was the criterion used to adapt the weights, and was also a measure of changes in electrogram shape that occur from cycle to cycle. The variance of each of the weighting parameters at all electrode sites were plotted on a representation of the electrode array, and the location of the functional lines of block bounding the central common pathway of reentrant circuits with figure-of-eight characteristics, overlaid on the ATM map. Peaks of high variance were found to be coincident with functional lines of block during all tachycardia episodes. CONCLUSION: Specific beat-to-beat changes in electrograms occur at functional lines of block in reentrant circuits that can be quantified by ATM analysis, suggesting that these regions might be located without activation mapping. The method might be useful to guide ablation catheter position.

Animals↗

[Prognostic evaluation of human solid tumors by immunohistology].

The aim of this project is to evaluate the interest of new tumor markers in the most frequent solid tumors (breast, colon, prostatic cancers, ...). For each of these tumors, potential prognostic markers have been selected according to the literature and an immunohistologic technique has been developed to analyse them. We will first discuss the role of pathology in oncology, then briefly describe the analyzed markers and finally give information about a Web site (URL: http:/(/)www.ebm. lib.ulg.ac.be/index.htm) created to help clinicians exploit the laboratory results.

Biomarkers, Tumor↗

[Anatomo-pathologic examination of breast cancer: a prerequisite for optimal therapeutic choice].

Breast cancer represents the most frequent cause of cancer deaths in women in Belgium. At the time of diagnosis, the clinician must get the most accurate information on the anatomic features and staging in order to choose the most appropriate therapy. The pathologist play a central role in providing these data. The paper presents a summary of a standardized and reproducible procedure, which is currently used by the pathologists, according to the international recommendations. It consists of several successive steps, from macroscopic examination and dissection of the surgical specimen to histological analysis. The pathologist's protocol contains all the required data and emphasizes the parameters with the most significant prognostic value, such as the histological type and grade and the lymph node status.

Biopsy↗

Painful hyperplasia and hypertrophy of pacinian corpuscles in the hand: report of two cases with immunohistochemical and ultrastructural studies, and a review of the literature.

Hypertrophy and hyperplasia of pacinian corpuscles in the hand are very rare, with only 29 cases previously published. We describe two new cases in middle-aged patients whose chief complaint was progressive digital pain. Immunohistochemical and electronmicroscopic investigations indicated that the lump replicates the structure of enlarged pacinian corpuscles and should not be considered as a real tumor, nor connected to neurofibromatosis. No recurrence was observed after surgical excision. Although local trauma was encountered in 55% of the reported cases, the pathogenesis of such a lesion is still speculative.

Adult↗

Tricho-hepato-enteric syndrome: further delineation of a distinct syndrome with neonatal hemochromatosis phenotype, intractable diarrhea, and hair anomalies.

We report on two sibs with syndromal congenital iron storage disease. Prenatal symptoms were IUGR, hydramnios, and placental hyperplasia. Clinical anomalies included hypertelorism and sparse, thin, curly hair (trichomalacia). Clinical course was marked by intractable diarrhoea, with normal histological and enzymological studies, cholestatic jaundice, hepatomegaly appearing after 30 days, and progressive liver failure, leading to death after a few months. The only metabolic anomaly was progressive hypermethioninemia. Pathologic examination of both children showed a similar pattern of multivisceral iron deposit compatible with a diagnosis of neonatal hemochromatosis: extensive liver fibrosis or cirrhosis with nodular regeneration, cholestasis, ductular proliferation, and hepatic, pituitary, thyroidal, adrenal, and pancreatic iron deposition. The unusual course for neonatal hemochromatosis in both sibs combined with concordant extrahepatic anomalies suggest that they could have a specific iron storage syndrome with possible autosomal recessive inheritance, probably similar to the sibship reported by Stanckler et al. [Arch Dis Child, 57:212-216, 1982].

Amino Acid Metabolism, Inborn Errors↗

Assessment of Ki-67 antigen immunostaining in squamous intraepithelial lesions of the uterine cervix. Correlation with the histologic grade and human papillomavirus type.

A formalin-fixation and paraffin-processing resistant epitope of Ki-67 cell proliferation-associated antigen was immunohistochemically detected by the MIB-1 monoclonal antibody (Immunotech, Marseille, France) in 25 routinely processed cervical biopsies showing normal squamous epithelium or squamous metaplasia and in 65 cervical intraepithelial lesions (SILs) (44 low grade and 21 high grade SILs) with human papillomavirus (HPV) infection. Expression of Ki-67 antigen was exclusively confined to the parabasal and basal layers of normal and metaplastic epithelium. There was no significant difference of Ki-67 antigen immunostaining between normal cervical biopsies and cases of squamous metaplasia. In SIL specimens, the staining was markedly increased in the parabasal and basal layers and Ki-67-positive cells were also distributed in the intermediate (low grade SIL) or all layers of epithelium (high grade SIL). Statistically significant differences for the density of Ki-67 antigen-labeled cells, which were assessed with an image analysis system, were found in comparisons between normal or metaplastic epithelium and SILs (P < .001) and between low grade SILs and high grade SILs (P < .001). In our series of SILs, HPV 16/18 and 31/33/35/novel types, which were found in both low grade and high grade SILs, were significantly associated with higher densities of Ki-67 antigen-positive cells than HPV 6/11 types that were found exclusively in low grade SILs. There was no significant difference found between the densities of Ki-67 antigen-labeled cells in HPV 16/18-positive and HPV 31/33/35/novel types-positive tissues in our series of SILs taken as a whole or when segregating SILs into low grade and high grade.

Cervix Uteri↗

Epidemiology of hepatitis D virus (delta) infection in Yugoslavia.

In 614 HBsAg-positive Yugoslavian patients, radioimmunoassay testing for anti-delta showed the presence of this antibody in serum in 11.2%. Of the patients, 213 belonged to a risk group (i.v. drug users, hemophiliacs, hemodialysed patients and patients with posttransfusion hepatitis); a significant number of these patients (63; 29.6%) were found to have anti-delta. A second group was composed of 401 HBsAg-positive patients from the general population (patients with acute hepatitis B, with fulminant hepatitis B and patients with chronic HBV infection); delta infection was found only in six (1.5%). Immunohistochemical methods failed to demonstrate the delta antigen in the livers of 73 patients with chronic HBV infection. Testing the liver of 36 patients with fulminant hepatitis B for delta antigen demonstrated this reactivity in only one (2.8%) liver sample. Delta antigen was also found in the liver of a female patient who underwent biopsy in 1972. The results of this study suggest the HDV is not endemic in Yugoslavia; however, it is frequently found in patients at risk of blood exposure, primarily i.v. drug users.

Adult↗

Brain-associated autoimmune features in heroin addicts: correlation to HIV infection and dementia.

We report here on brain associated autoimmune features in opiate-dependent subjects. This study includes 107 (37 HIV + and 70 HIV -) hospitalized heroin-addicted subjects on a methadone maintenance program, and 45 healthy individuals. Human brain S100 protein, neuron specific enolase (NSE), myelin basic protein (MBF), and old tuberculin (OT) were used as antigens in the study. Serum autoantibodies to brain antigens S100, NSE and MBP were detected by ELISA, whereas delayed hypersensitivity skin reactions were evaluated after intradermal injection of S100, NSE, MBP and OT (control brain-irrelevant antigen). In drug-dependent subjects, 68.2% produced anti-S100, 56.1% anti-NSE and 20.5% anti-MBP autoantibodies, while the incidence of autoantibodies in control healthy individuals was 4.4%, 2.2% and 0%, respectively. Occurrence and amount of anti-S100 and anti-NSE autoantibodies were much higher in HIV + than in HIV - heroin-abusing adults. In drug abusers, the incidence of positive delayed hypersensitivity skin reactions were as follows: 67.2% to S100, 51.4% to NSE, 14.9% to MBP, and 94.3% to OT. In control subjects, the occurrence of hypersensitivity reactions to brain antigens was insignificant. Cutaneous reactions were more frequent in HIV - addicts. The incidence of both autoantibodies and delayed skin responses was positively related to the duration of drug abuse, worsening of HIV infection, and dementia. The high incidence of autoantibodies and delayed hypersensitivity skin reactions to S100 and NSE human brain antigens in heroin-abusers indicates that heroin dependence, as well as HIV infection, are associated with a hyperergy towards brain-related autoimmune phenomena. It has been suggested that the brain-associated autoimmune phenomena in HIV + heroin-addicts represent a hyperimmune phase which precedes immunodeficiency that occurs in the further development of HIV infection.

Adult↗

Influence of the length of the small bowel graft on the severity of graft versus host disease.

The influence of the length and origin of a small bowel graft on graft versus host disease (GVHD) was studied in 33 (Lewis x brown Norway) F1 hybrids transplanted with different types of Lewis small bowel grafts. Recipients of an entire small bowel graft (N = 9), a jejunal graft (N = 6), or an ileal graft (N = 6) displayed a similar acute lethal GVHD, with 100% mortality rate and equivalent survival time (15 +/- 0.7, 16.8 +/- 0.9, and 16 +/- 0.6 days, respectively) (P greater than 0.01). On the other hand, 80% of the recipients of a segmental jejunal graft (N = 10) recovered from a transitory form of GVHD and regained weight similarly to the isografted rats (N = 4). It was concluded that the entire small bowel, jejunum, and ileum can provoke an equivalent GVHD after transplantation, whereas a segment of jejunum decreases the intensity of GVHD, probably by reducing the amount of transplanted lymphoid tissue.

Analysis of Variance↗