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Biomedical subjects

F Fend

Publications and source records attributed to F Fend.

At least 19 recordsLinked to original sources

Primary non-Hodgkin's lymphoma of the intestine: high prevalence of Epstein-Barr virus in Mexican lymphomas as compared with European cases.

Recent studies in Western European populations have shown that peripheral T-cell non-Hodgkin's lymphomas (T-NHLs) are associated with Epstein-Barr virus (EBV) in a higher percentage than sporadic B-cell NHL (B-NHLs), and that the frequency of EBV-positivity might be influenced by the primary site of the tumor. Because of the geographic differences in EBV expression in Burkitt's lymphoma (BL) and Hodgkin's disease (HD), and the lack of studies of sporadic NHL from developing countries, we decided to survey the presence of EBV in a series of primary intestinal lymphomas from patients in Mexico and in Western Europe, and to analyze whether EBV status is influenced by tumor phenotype, and geographic or ethnic determinants. Paraffin-embedded tissue from 43 primary intestinal NHLs (19 cases from Mexico and 24 from Western Europe) were examined, including 17 high grade B-NHLs, 9 low grade B-NHLs, and 17 T-NHLs; 6 of which were enteropathy associated T-cell lymphomas. The distribution of histologic subtypes was similar in both groups. The presence of EBV was investigated with a combined approach using a nested polymerase chain reaction technique as well as immunohistochemistry for latent membrane protein-1 and in situ hybridization for EBV early RNA transcripts (EBER 1/2) RNAs. The median age of the Mexican patients was significantly lower than the median age of the European patients (32 v 62 years). This difference was most pronounced in patients with T-cell lymphoma (24 v 63 years). EBER-positive tumor cells were detected in 13 of the 43 (30%) cases of primary intestinal lymphoma, including 5 of 26 sporadic B-NHL (3 high grade and 2 low grade), and 8 of 17 T-NHL, all of which were classified as pleomorphic, medium and large cell. The rates of EBV-positivity were markedly different for European and Mexican cases. Whereas 7 of 7 (100%) T-NHL and 5 of 12 (42%) sporadic B-NHL of Mexican origin were EBER-positive, only 1 of 10 T-NHL and 0 of 14 sporadic B-NHL from Europe showed EBER expression in tumor cells. Latent membrane protein was positive in only 2 of 43 cases, 1 of which was an EBER-negative high grade B-NHL from Mexico that showed intact total mRNA in control hybridization. CD30 expression was found in 4 of 8 EBV-positive T-NHL and in none of the EBV-positive B-NHL. In contrast to European cases, intestinal NHLs from Mexico show a very high frequency of EBV-positivity, which is not limited to T-NHL, but includes a significant proportion of B-NHL. This study strongly suggests that similar to HD and probably BL, there are important epidemiologic differences in EBV association in intestinal T-cell NHL between European and Mexican populations. These differences might be the result of environmental factors, for example, earlier contact with childhood viruses on intestinal lymphomagenesis.

Adolescent

Non-Hodgkin lymphoma with exclusive involvement of the heart and the gastrointestinal tract.

An extranodal high-grade B-cell lymphoma, centroblastic type, with exclusive involvement of the heart, stomach and small bowel was detected at post-mortem examination following the death of an 80-year-old man. Autopsy revealed massive cardiomegaly with a total heart weight of 1800 g owing to an intramyocardial tumour involving the right ventricle, and multiple mucosal tumour plaques and nodules in the stomach and small bowel. The case highlights the difficulties of diagnosing cardiac lymphoma clinically even in the presence of a large tumour mass.

Aged

Intramural right atrial myocardial hemangioma treated by emergency surgery.

An unusual case of myocardial cavernous hemangioma causing dissection of the right atrial wall is described. A subsequent intramural hematoma presented as an extensive pseudotumor of the heart and was complicated by hematopericardium and tamponade. Tumor resection could be performed successfully. Diagnostic approach, surgical treatment and histopathological findings are presented.

Aortic Dissection

An aggressive subtype of B-CLL is characterized by strong CD44 expression and lack of CD11c.

In a retrospective study based on 107 B-CLL patients, the expression of the adhesion molecules CD44, CD11a, CD11b, CD11c, CD18, CD25 and CD54 was analysed in bone marrow cryostat sections by immunohistochemistry. CD44 expression clearly identified two subgroups of B-CLL patients with different clinical course. In particular, CD44-positive patients presented with advanced disease, more often displayed a diffuse pattern of bone marrow infiltration, and had a worse prognosis. 33/61 patients positive for CD44 died within the observation period compared to 7/46 patients negative for CD44 (P = 0.0012). Multivariate analysis emphasized the independent prognostic value of CD44 expression for overall survival (P = 0.022). In contrast, patients positive for CD11c showed a longer survival, with 9/40 patients dying within the observation period compared to 31/67 negative for CD11c (P = 0.0013). Patients lacking CD11c were in advanced Rai and Binet stage. Multivariate analysis confirmed CD11c as a relevant independent prognostic marker (P = 0.033). Moreover, CD11c was able to separate patients with significantly different prognosis in the subgroup of CD44-positive cases. 4/18 patients positive for CD44 and CD11c died before median survival time was reached. Patients positive for CD44 but negative for CD11c had an adverse prognosis: 29/43 patients died, median survival time was 33.4 months. Our results indicate that CD44 positivity and CD11c negativity are associated with more advanced disease and worse prognosis in B-CLL and suggest CD44-positive/CD11c-negative cases represent a more aggressive form of the disease.

Adult

An unusual case of a splenic gamma/delta T-cell lymphoma with angiocentric tendency and haemophagocytic syndrome.

We report here an unusual post-thymic T-cell neoplasia of the spleen associated with a rapidly progressive haemophagocytic syndrome. The lymphoma was classified as a medium- to large sized pleomorphic T-cell lymphoma with angiocentric tendency (CD3+, CD43+, CD45RO+ CD45+). Clonality was confirmed by PCR and revealed rearrangement of the T-cell receptor gamma chain. Serological tests excluded a recent EBV infection and in situ hybridization with the EBER probe was negative. Haemophagocytic syndrome was the initial finding in an otherwise symptomless patient and this deteriorated with progression of the T-cell malignancy. Both, the T-cell lymphoma and the haemophagocytic syndrome remained unaffected by chemotherapy. Splenic gamma/delta T-cell lymphoma associated with haemophagocytosis is an uncommon entity which has until now not been widely recognized.

Aged

Automated cell differentiation of bronchoalveolar lavage samples with two-step image analysis.

OBJECTIVE: To establish an easy method for performing an automated differential cell count on bronchoalveolar lavage (BAL) cytocentrifuge samples using morphometric parameters acquired by a digital image analyzer. STUDY DESIGN: The study population comprised 20 satisfactory cytocentrifuge preparations routinely processed in our laboratory. Images of at least 40 fields of interest were digitized and stored. The images were analyzed to assess the planimetric parameters. These were used for cell identification. Basic morphometric parameters were acquired by an automated image analysis procedure. The results obtained by this method are compared to those of the manual counting procedure. RESULTS: Following sequential analysis, computerized identification corresponded, in > 97% of the cells, to the results of manual cell typing. After data analysis, < 1% of cells remained unidentifiable. CONCLUSION: Although the number of specimens evaluated is not yet large enough to allow a definitive statement, the use of image analysis systems seems a promising approach in automated differential cell counting in BAL preparations.

Bronchoalveolar Lavage Fluid

Minimal residual disease in hairy-cell leukemia after treatment with 2-chlorodeoxyadenosine.

Some patients in apparent complete remission of hairy cell leukemia (HCL) after 2-chlorodeoxyadenosine (2-CdA) treatment may have minimal residual disease (MRD). This study examines detection of minimal residual disease by immunohistological staining using the monoclonal antibody (MoAb) B-ly 7 in 11 patients with complete remission of hairy cell leukemia (HCL) after 2-CdA therapy administered between 1990 and 1993. In all 11 cases, residual hairy cells could be detected by MoAb B-ly 7 (0.1 to 7.5%, median 0.65%). At a follow-up period of 7 - 29 months (median 19.3), 9 of these patients remained in complete remission, whereas 2 patients relapsed 22 and 27 months after 2-CdA therapy. To determine whether flow-cytometric analysis of hairy-cells in bone marrow aspirates and peripheral blood cells are comparable with results obtained by immunostaining with B-ly 7 in bone marrow biopsies, available data using CD-19/CD-11c double-staining were analyzed. In 5 of 10 cases no hairy-cells could be detected in bone marrow aspirates, and in 6 partly different cases no hairy-cells were detectable in peripheral blood using flow-cytometry, although immunostaining of bone marrow biopsies using B-ly 7 revealed hairy-cells (ranging form 0.1 to 7.5%) in these cases. These results indicate that therapy with 2-CdA does not eradicate hairy cell leukemia despite complete remission according to conventional criteria. Minimal residual disease might be responsible for subsequent relapse. We conclude that routine immunohistological examination of bone marrow biopsies with B-ly 7 should be performed for assessment of MRD. Flow cytometric investigations of mononuclear cells of bone marrow aspirate or peripheral blood seem valuable for regular long term monitoring of MRD, but does not substitute for immunostaining of bone marrow biopsies.

Adult

Fulminant hepatic failure in a child as a potential adverse effect of trimethoprim-sulphamethoxazole.

UNLABELLED: Trimethoprim-sulphamethoxazole (TMP-SMZ) is considered a safe drug for treatment of infectious bacterial diseases in children. Side-effects are rare and generally take the form of a hypersensitivity reaction to the sulphamethoxazole component of the drug. Hepatic injury usually presents as a transient elevation of liver enzymes, which is of little clinical relevance. Fulminant liver failure due to TMP-SMZ has been reported in only six adults and never in children. We here report a 5-year-old girl who developed fulminant liver failure 3 weeks after her third exposure to TMP-SMZ. After a biphasic clinical course she underwent successful liver transplantation. CONCLUSION: Trimethoprim-Sulphamethoxazole may cause fulminant liver failure in children. The disease can run a biphasic clinical course and liver transplantation must be considered as the therapeutic option for these patients.

Biopsy

Gastric malt lymphoma with crystalline immunoglobulin inclusions and secondary immunoblastic lymphoma in a cervical lymph node.

A case of gastric B cell lymphoma of the mucosa-associated lymphoid tissue (MALT) with crystalline immunoglobulin inclusions in monotypic plasma cells is reported, which initially presented as a secondary immunoblastic lymphoma in a cervical lymph node. The low-grade MALT lymphoma was diagnosed 14 months after detection of the nodal high-grade lymphoma, but rare crystal-containing plasma cells of identical immunoglobulin isotype found in the immunoblastic lymphoma retrospectively confirmed a common clonal origin. The diagnostic significance of crystalline immunoglobulin inclusions and the unusual initial presentation of MALT lymphoma as a secondary high-grade lymphoma at a distant nodal site are discussed.

Aged

Chronic active Epstein-Barr virus disease in a case of persistent polyclonal B-cell lymphocytosis.

Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare haematological disorder. It is characterized by activated and morphologically atypical B lymphocytes and polyclonal IgM production and has been associated with female sex, cigarette smoking, and HLA-DR7 expression. We report a case of PPBL with intermitting symptoms compatible with a chronic fatigue syndrome, recurrent erythema nodosum and multiforme. Serological findings suggested a chronic active Epstein-Barr virus (EBV) infection. Messenger RNA of EBV immediate early gene transactivation BZLF1 was detected in peripheral blood lymphocytes by reverse transcriptase PCR indicating a persistent replication of the virus. Over 2 years of observation we detected varying numbers of atypical lymphocytes. These cells hybridized with a probe specific for the EBV internal repeat region (BamHI W) which indicates a productive infection. Of interest, no reaction was observed with a probe specific for the latency-associated small RNAs (EBERs). The immunological phenotype of the polyclonal B cells was similar to B-cell lines immortalized by EBV in vitro, expressing a number of activation molecules (CD23, CD25, CD54) and the bcl-2 protein. In summary, our findings suggest that persistent EBV replication might be crucial in the development of lymphoproliferative disorders such as PPBL.

Antigens, CD

Role of Epstein-Barr virus and soluble CD21 in persistent polyclonal B-cell lymphocytosis.

The expression of EBV proteins and immunological properties were studied in the first stable cell line (SM) established from a patient presenting with persistent polyclonal B-cell lymphocytosis (PPBL). SM cells which represent a small population of EBV-positive atypical cells found in the peripheral blood of the patient express the KI-1 antigen (CD30) as well as the proto-oncogene bcl-2 product and cell surface markers of mature activated B lymphocytes. The cells harbour an EBV subtype A genome and contain EBNA2 protein. This argues against a transformation-incompetent virus as the main cause of the chronic active EBV infection observed in our patient. Latent membrane protein (LMP1) was weakly expressed and found predominantly in a perinuclear localization, a location which could lead to decreased immunogenicity in vivo. Similar to the EBV-transformed marmoset cell line B95-8, SM cells were in part productively infected as transcription of the immediate early gene BZLF1 could be shown and in some cells high levels of EBV-genome were detected by in situ hybridization with a BamH1 W-probe. Comparable to the atypical cells in the peripheral blood of the patient. EBV small RNAs were not detected with EBER-specific probes. Of interest, we noticed a markedly increased production of soluble CD21 (sCD21) antigen by SM cells as compared to LCL-type Burkitt's lymphoma cell lines. This could explain the elevated sCD21 levels observed in the serum of our PPBL patient and confirms our previous findings in patients with acute EBV infection. It also suggests a possible role of sCD21 in EBV-mediated regulation of the immune response and provides a possible explanation for the dysregulation of the humoral immune system observed in PPBl patients.

B-Lymphocytes

Identification of a favorable subgroup of patients with generalized immunocytomas by follicular dendritic cells.

In the present study, 89 patients with generalized immunocytoma were analyzed retrospectively for the prognostic influence of clinical features and of immunophenotype using bone marrow biopsies. Univariate analysis selected the following variables as significant for survival: age over 60 years (p = 0.021), Rai and Binet stage (p = 0.008 and 0.004, respectively), presence or absence of follicular dendritic cells (FDC, p = 0.036), presence or absence of anemia (p = 0.037). Multivariate regression analysis showed independent prognostic significance of age (p = 0.001), Rai stage (p = 0.003), and the presence of follicular dendritic cells (p = 0.010). Comparing CD5 positive and CD5 negative immunocytomas, no survival advantage for one of the two groups was seen. Presence of follicular dendritic cells clearly identified a favorable prognostic subgroup: of the 89 patients presented, only three of 18 (16.6%) with detectable FDC in bone marrow died within the observation period, as compared to 34 of 71 (52.1%) patients without FDC. Multivariate analysis emphasized the independent prognostic value of the presence of FDC. The high predictive capacity of follicular dendritic cells could add useful information to the commonly used Rai and Binet staging systems for immunocytoma.

Adult

Seminomas positive for Epstein-Barr virus by the polymerase chain reaction: viral RNA transcripts (Epstein-Barr-encoded small RNAs) are present in intratumoral lymphocytes but absent from the neoplastic cells.

A possible role of Epstein-Barr virus (EBV) in the pathogenesis of testicular germ cell neoplasms has been suggested repeatedly, but direct evidence for an association of testicular cancer with EBV is lacking. We examined 26 cases of classical seminoma, two spermatocytic seminomas, and 12 cases of nonseminomatous or combined germ cell tumors for the presence and cellular location of EBV with a combined approach using the polymerase chain reaction and nonradioactive in situ hybridization for EBV-encoded small RNAs (EBER1/2). After exclusion of cases without amplifiable DNA, 4/21 (19%) seminomas, but none of the other tumors, were positive for EBV by polymerase chain reaction. In situ hybridization for EBER1/2 showed rare positive lymphocytes, probably latently infected B-cells, in two of these four EBV-positive cases. No EBER-positive tumor cells were found in any of the analyzed tumors. The occurrence of EBV-positive lymphoid cells was not correlated to the frequency of intratumoral lymphocytes, including B-cells, which were present in seminomas in significant numbers. Our study demonstrates the absence of EBV from the neoplastic cells of testicular germ cell tumors and makes a direct role of EBV in the development of these malignancies improbable. Whether the presence of EBER-positive lymphocytes in some seminomas simply reflects the normal occurrence of latently infected cells in lymphoid tissue of seropositive individuals or is influenced by local factors remains to be determined.

Antibodies, Monoclonal

Subcutaneous abscess due to gallstones lost during laparoscopic cholecystectomy.

No complications caused by gallstones lost during laparoscopic cholecystectomy have yet been described in the literature. In one animal study in rats, it has been shown that pigment calculi, but not cholesterol stones, lead to severe local inflammation of the abdominal cavity. We present a case of a chronic subcutaneous and subfascial abscess in the lower abdomen, which included multiple pigment calculi, six months after laparoscopic cholecystectomy. During the procedure, multiple small pigment calculi had been lost into the free abdominal cavity.

Abdomen

Detection of monoclonal B-cell populations in decalcified, plastic-embedded bone marrow biopsies with the polymerase chain reaction.

Polymerase chain reaction (PCR) has been employed successfully for the detection of clonal immunoglobulin gene rearrangements in paraffin-embedded clinical samples. The authors examined whether this technique can also be applied to fixed, decalcified, and plastic-embedded bone marrow biopsies. DNA extracted from 66 glycolmethacrylate-embedded trephine biopsy samples was amplified for the detection of rearranged VDJ regions of the immunoglobulin heavy chain genes using both a single-step and a semi-nested PCR technique. After exclusion of samples with inadequate DNA, clonality was confirmed in 16 (67%) of 24 cases with B cell malignancy, whereas all 11 non-B cell neoplasms, and 6 of 9 cases with normal bone marrow showed evidence of a polyclonal B cell population. Patterns indicating oligo- or monoclonality were observed in three plastic-embedded samples of normal bone marrow, although control PCR of frozen bone marrow samples obtained in parallel showed no evidence of clonality. Repeated PCR of these cases revealed inconsistent bands, probably due to the amplification of rare templates from polyclonal B cells. Decalcified, plastic-embedded bone marrow biopsies are suitable for PCR-based determination of B-cell clonality. To exclude the possibility of false-positive results, monitoring of template DNA quality and independent control amplifications are mandatory.

B-Lymphocytes

HDL and plasma phospholipids in coronary artery disease.

Lipid fractions of native plasma and of high-density lipoprotein (HDL) were analyzed, and the clotting times of native platelet-rich and -poor plasma were recorded in patients with coronary artery disease and age-matched control subjects not taking any medication known to alter plasma lipid levels, coagulation, or platelet aggregation. Patients with coronary artery disease had lower HDL cholesterol and particularly HDL phospholipids but elevated HDL triglycerides, plasma triglycerides and diglycerides, and fibrinogen. Plasma lysolecithin was diminished. Accelerated coagulation was observed in native plasma and may be related to these changes in plasma lipids. The HDL content in cholesterol may be less relevant than that in phospholipids, which, because of their amphiphilic properties, may be essential for the removal and transport of hydrophobic cholesterol. The lower lysolecithin levels also suggest diminished esterification of cholesterol and reduced degradation of phospholipids, which may add to the poor lysability of platelet-rich and thus phospholipid-rich thrombi. Coagulation inhibition may be related to HDL phospholipids: in control subjects they correlated directly with clotting times of platelet-rich and -poor plasma and inversely with fibrinogen. In contrast, the enhanced thrombus formation in coronary artery disease may be related to altered HDL and plasma phospholipids, in particular to increased phosphatidylethanolamine. These adverse changes, particularly diminished HDL phospholipids, may result in increased deposition and reduced degradation and transport of lipids from arteriosclerotic lesions and thrombi and may therefore be significant in the development of coronary artery disease.

Blood Coagulation Tests