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Biomedical subjects

F Berger

Publications and source records attributed to F Berger.

At least 217 records · Page 12Linked to original sources

[Diabetic mastopathy with epithelioid fibroblasts :differential diagnosis from an infiltrating lobular carcinoma of the breast. Report of two cases].

Two cases of diabetic mastopathy are reported. The patients presented with a rapidly increasing mammary mass. The pathologic findings of diabetic mastopathy usually consist of a lymphocytic lobulitis, a dense stromal fibrosis and prominent epithelioid fibroblasts. In our two cases, the latter findings were initially misinterpreted as malignant cells of an invasive lobular carcinoma. These lesions were first described in longstanding insulin dependent diabetics but recent reports showed that they could also occur in patients with other auto-immune disorders (systemic lupus erythematous, hypothyroidism). Diabetic mastopathy may reoccur locally and the treatment remains to be determined.

Adult↗

Retinoids induced t-PA synthesis by C6 glioma cells--role in tumoral haemorrhagic necrosis.

Treatment of rat C6 glioma with high doses of 13 cis-retinoic acid (cRA) was responsible for death related to haemorrhagic necrosis localized to the tumor. Our aim was to explore this adverse effect of retinoid treatment. We show that cRA-treated C6 glioma at 25 mg/kg/day for 18 days exhibits in vivo an increase T-PA activity, which is responsible for a localized tumor fibrinolytic activity. Production of t-PA is supported by specific enhancement of gene expression, as was shown by the increase in t-PA mRNA (x 2.3). This production is a direct effect of cRA when treating the tumor, since tumor cells themselves do not produce enough t-PA and treatment of control rats does not increase the t-PA level. T-PA production by rat C6 glioma is in vivo related to the specific synthesis of t-PA by the C6 cell-line. The stimulation of C6 cell-line by cRA in vitro is dose-dependent and reached a maximum for 3 and 30 microM at the 72nd h. So cRA-treated C6 glioma cells produce t-PA which appears to be the major species associated with the fibrinolytic activity-induced intra-tumoral haemorrhage after exposure to retinoid treatment.

Animals↗

[Pancreatectomy for intraductal papillary mucinous tumor of the pancreas].

Twelve cases of pancreatectomy for intraductal papillary-mucinous tumor of the pancreas operated between August 1985 and February 1996 are reported. Mean age of the patients was 57.6 years (range: 25 to 77 years). Two of them were female and 10 were male. Ten patients underwent a pylorus preserving pancreaticoduodenectomy, one patient a segmental isthmic pancreatectomy and one other a left pancreatectomy. Histologic examination of the operative specimen showed benign ademomatosis with severe dysplasia in 3 cases, intramucosal or microinvasive carcinoma in 7 cases and invasive carcinoma in 2 cases. Two patients died during the period of follow-up, one at 20 months from metastases, the other one at 33 months accidentally. The 10 remaining patients were alive and disease-free with a follow-up of 3 to 93 months (mean time of follow-up: 38 months). Pancreatectomy is indicated without delay as soon as the diagnosis of this uncommon tumor is obtained.

Adenocarcinoma, Mucinous↗

[Intravascular malignant lymphoma (ex-malignant angioendotheliosis). 3 cases].

Malignant angioendotheliomatosis is an intravascular proliferation of tumour cells in the small arteries, veins and capillaries. Its lymphomatous origin has been proved recently by immunohistochemistry. It is a rare, generally rapidly fatal condition. Less than 150 cases have been reported in the literature. We report three cases. Long course fever with delayed neurologic disturbances were observed in the first case and long course fever, hyponatraemia, corticotropic and gonadotropic insufficiency in the second. The third case began with febrile meningo-encephalitis. Diagnosis was made at autopsy in the two first cases and on evidence from kidney needle-biopsy in the third. Clinical manifestations are polymorphic and frequently simulate vasculitis. Neurologic signs are the most common. Histologically, kidneys, skin, endocrine glands, lungs, muscles and most of the organs may be involved. Surprisingly lymph nodes, bone marrow and spleen are often free from disease. Current treatment is based on polychemotherapy. Earlier diagnosis of the disease should improve the prognosis as observed in our third patient.

Adult↗

1H MRS of human brain abscesses in vivo and in vitro.

Five patients, each with a brain abscess, were examined by means of 1H MR spectroscopic imaging in vivo. The aspirated pus was analyzed in vitro by means of 1D and 2D COSY 1H MRS. In addition to resonance lines from compounds (lactate, alanine and lipids) often found in the spectra from intracranial tumors, resonance lines were detected from a number of markers of infectious involvement (acetate, succinate, and various amino acids). These results suggest that 1H MRS in vivo might contribute in establishing noninvasively a differential diagnosis between brain abscess and tumor.

Acetates↗

Inhibition of pacemaker current by the bradycardic agent ZD 7288 is lost use-dependently in sheep cardiac Purkinje fibres.

The inhibition of the pacemaker current (if) in sheep cardiac Purkinje fibers by ZD 7288 [4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyrimidinium++ + chloride] is lost use-dependently. This disinhibition of if was investigated by using the two-microelectrode voltage-clamp technique. The pulse protocol consisted of a rest period (holding potential of about -50 mV, 1-10 micromol/l ZD 7288) followed by a train of test pulses (potential negative to -100 mV, stimulation frequency 0.05 Hz). At the beginning of the first test pulse there was an immediate reduction of if but inhibition was lost during continued stimulation. Activation of if is sigmoidal and the early delay in current activation was prolonged from 33 ms (no ZD 7288) to 424 ms (10 micromol/l ZD 7288). Therefore hardly any disinhibition occurred during short test pulses (0.5s). During longer test pulses (5 s, -120 mV, 10 micromol/l) disinhibition developed with a time constant of about 2 s. The inhibition of if by ZD 7288 was lost voltage-dependently. With 10 micro mol/l ZD 7288 the half-maximal disinhibition occurred at -92 mV and the slope factor of the disinhibition/voltage curve (Boltzmann relation) was 4.8 mV. The voltage-dependent disinhibition could be abolished largely by extracellular application of protease (0.5 mg/ml, 7 min). After prior disinhibition, reinhibition at the holding potential (about -50 mV) followed a bi-exponential time course indicating that inhibition may be produced by a fast (tau=0.7 min) and a slow component (tau=20-30 min). Increasing ZD 7288 concentration from 1 to 10 mu mol/l accelerated reinhibition, mainly by an increase of the amplitude (A) of the fast component. The ratio Afast/Aslow was 0.399 at 1 micromol/l and 2.65 at 10 micromol/l ZD 7288. The reinhibition of if was unchanged by shifting the holding potential from -50 mV to -20 mV. Trials to wash out the effects of 10 micromol/l ZD 7288 gave two results. The inhibition of if was slightly reversed after a wash-out of 1.5 h with drug-free solution. A second effect of the drug, the fast reinhibition, could be completely removed by wash-out. In summary if is inhibited by ZD 7288 at membrane potentials at which the virtual if gate is closed. Disinhibition occurs during long-lasting hyperpolarization but will hardly be operative in unclamped fibres under physiological conditions.

Animals↗

Plasma endothelin-1 in patients with left-to-right shunt.

Endothelin-1 (ET-1) has been implicated in the pathogenesis of pulmonary vascular disease in patients with congenital heart disease. We studied the effect of pulmonary blood flow on plasma ET-1 concentrations. Systemic venous, pulmonary arterial, and pulmonary venous blood samples were obtained from 40 patients with atrial septal defect II (n = 21), ventricular septal defect (n = 10), persistent ductus arteriosus (n = 6), and complete (n = 2) and partial (n = 1) atrioventricular canal at cardiac catheterization and analyzed by radioimmunoassay. Median age (range) was 5.2 years (8 months to 66 years), and the resistance ratio (Rp/Rs) was 0.08 (0.03 to 0.67). Pulmonary vein to pulmonary artery ET-1 ratio in patients with "high flow" (n = 26, Qp/Qs > or = 1.5; ET-1 ratio = 0.8) did not differ from those with "low flow" (n = 14, Qp/Qs < 1.5; ET-1 ratio = 1.0). We conclude that an increase in pulmonary blood flow alone does not result in an increase in plasma ET-1.

Adolescent↗

Cellular effects of olomoucine, an inhibitor of cyclin-dependent kinases.

Olomoucine (2-(2-hydroxyethylamino)-6-benzylamino-9-methylpurine) has been recently described as a competitive inhibitor (ATP-binding site) of the cell cycle regulating p34cdc2/cyclin B, p33cdk2/cyclin A and p33cdk2/cyclin E kinases, the brain p33cdk5/p35 kinase and the ERK1/MAP-kinase. The unusual specificity of this compound towards cell cycle regulating enzymes suggests that it could inhibit certain steps of the cell cycle. The cellular effects of olomoucine were investigated in a large variety of plant and animal models. This compound inhibits the G1/S transition of unicellular algae (dinoflagellate and diatom). It blocks Fucus zygote cleavage and development of Laminaria gametophytes. Stimulated Petunia mesophyl protoplasts are arrested in G1 by olomoucine. By arresting cleavage it blocks the Laminaria gametophytes. Stimulated Petunia mesophyl protoplasts are arrested in G1 by olomoucine. By arresting cleavage it blocks the development of Calanus copepod larvae. It reversibly inhibits the early cleavages of Caenorhabditis elegans embryos and those of ascidian embryos. Olomoucine inhibits the serotonin-induced prophase/metaphase transition of clam oocytes; furthermore, it triggers the the release of these oocytes from their meiotic metaphase I arrest, and induces nuclei reformation. Olomoucine slows down the prophase/metaphase transition in cleaving sea urchin embryos, but does not affect the duration of the metaphase/anaphase and anaphase/telophase transitions. It also inhibits the prophase/metaphase transition of starfish oocytes triggered by various agonists. Xenopus oocyte maturation, the in vivo and in vitro phosphorylation of elongation factor EF-1 are inhibited by olomoucine. Mouse oocyte maturation is delayed by this compound, whereas parthenogenetic release from metaphase II arrest is facilitated. Growth of a variety of human cell lines (rhabdomyosarcoma cell lines Rh1, Rh18, Rh28 and Rh30; MCF-7, KB-3-1 and their adriamycin-resistant counterparts; National Cancer Institute 60 human tumor cell lines comprising nine tumor types) is inhibited by olomoucine. Cell cycle parameter analysis of the non-small cell lung cancer cell line MR65 shows that olomoucine affects G1 and S phase transits. Olomoucine inhibits DNA synthesis in interleukin-2-stimulated T lymphocytes (CTLL-2 cells) and triggers a G1 arrest similar to interleukin-2 deprivation. Both cdc2 and cdk2 kinases (immunoprecipitated from nocodazole- and hydroxyurea-treated CTLL-2 cells, respectively) are inhibited by olomoucine. Both yeast and Drosophila embryos were insensitive to olomoucine. Taken together the results of this Noah's Ark approach show that olomoucine arrests cells both at the G1/S and the G2/M boundaries, consistent with the hypothesis of a prevalent effect on the cdk2 and cdc2 kinases, respectively.

Animals↗

Value of endobiliary brush cytology and biopsies for the diagnosis of malignant bile duct stenosis: results of a prospective study.

BACKGROUND: Before considering a nonsurgical method of management of a bile duct stenosis, a tissue diagnosis is highly desirable. In a prospective study we have evaluated the feasibility and reliability of endobiliary brush cytology and biopsies performed at the time of endoscopic retrograde cholangiography. METHODS: Two hundred thirty-three consecutive patients underwent an attempt at endobiliary brush cytology and biopsies of bile duct stenosis when no mass was detected on ultrasound and CT scan. RESULTS: The material for cytology was sufficient for analysis in 210 cases (90%) and biopsies were obtained in 128 cases (55%). One hundred fifteen patients had both cytology and biopsies (49%). For the diagnosis of malignant stenosis, the sensitivity was 35% for cytology, 43% for biopsies, and 63% for the combination of cytology and biopsies. For both cytology and biopsies, the specificity was 97%. In the cases of cancer primarily involving the bile ducts, the sensitivity was 86% when combining both cytology and biopsies. CONCLUSIONS: Endobiliary sampling is technically difficult and has a limited sensitivity for the diagnosis of malignant biliary stenosis. Biopsies should be combined with cytology to increase the sensitivity.

Adult↗

Extracellular matrix and pattern in plant embryos: on the lookout for developmental information.

Cells of early plant embryos are totipotent yet follow different predetermined developmental pathways, producing embryos with well-defined autonomously developing tissues. Evidence is accumulating from a few model systems that information maintaining the determined state of a particular cell type is contained in a position-dependent manner in the extracellular matrix. This information can be released to signal back to the cell, thus controlling patterns of gene expression and influencing cell fate.

Cell Differentiation↗

The MINE regimen as intensive salvage chemotherapy for relapsed and refractory Hodgkin's disease.

BACKGROUND: Relapsed or refractory Hodgkin's disease (HD) patients were treated with an intensive salvage regimen (MINE) prior to high-dose therapy (HDT) with hematopoietic stem cell support. PATIENTS AND METHODS: One hundred HD patients who either failed to respond to a front-line chemotherapy regimen (induction failure, n = 41) or relapsed (untreated relapse, n = 54; resistant relapse, n = 5) were treated with the MINE regimen. Each course of MINE comprised mitoguazone 500 mg/m2 on days 1 and 5, ifosfamide 1500 mg/m2/d from day 1 to day 5, vinorelbine (Navelbine) 15 mg/m2 on days 1 and 5, and etoposide 150 mg/m2/d from day 1 to day 3. At least two courses were given at 4-week intervals. Then, 72 patients received HDT followed by hematopoietic stem cell support. RESULTS: After MINE salvage, 34 patients achieved a complete response (CR) and 39 a partial response, yielding an overall response rate of 75%. Patients with untreated relapse had a 92.5% response rate and those with resistant relapse or induction failure a 53% response rate. A total of 58 patients reached a CR at the end of all treatments; 12 of them relapsed. Sixty-six patients were alive with a median follow-up of 26 months, including 46 patients in CR. The 2-year survival rate for the entire group was 59%. By univariate analysis, patients with an interval between their last treatment and salvage longer than 12 months, untreated relapse, or good performance status at salvage are shown to have longer survivals. The main toxic effects were neutropenia, thrombocytopenia, and infectious episodes. Three patients died of MINE-related complications and three after HDT. CONCLUSION: Given early in the course of progressive HD, the MINE regimen reduced tumor burden in a high proportion of patients with relapsed or refractory disease. Responding patients further intensified with HDT have a better outcome than those who have not responded to salvage treatment.

Adolescent↗

Bcl6/Laz3 rearrangements in post-transplant lymphoproliferative disorders.

Post-transplant lymphoproliferative disorders (PTLD) are well-known complications of iatrogenic immune deficiency and are thought to result from the proliferation of B cells infected by the Epstein-Barr virus (EBV). Some large cell lymphomas occurring in the general population carry a rearrangement of the Bcl6/Laz3 zinc-finger-encoding gene. 15 EBV-associated PTLD were tested for the presence of Bcl6/Laz3 rearrangements by Southern blot analysis using two specific probes (F370, F372). One out of 15 cases displayed a rearranged band independent of the germline one. In contrast, 10 lymphoblastoid cell lines and one lymphoblastoid cell line passaged in an SCID mouse carried only germline alleles of Bcl6/Laz3 after Southern blot hybridization. This indicates that genetic abnormalities may also play an important role in the development of some PTLD.

Animals↗

Post-transplant lymphoproliferative disorders with genetic abnormalities commonly found in malignant tumours.

Post-transplant lymphoproliferative disorders (PTLD) are potentially fatal complications of organ transplants. Impairment of the immune system by immunosuppressive drugs is the assumed cause of PTLD. The Epstein-Barr virus (EBV) is detected in most of the PTLD studied and is considered as the main aetiological agent. The clinical course of PTLD patients remains unpredictable, some lymphoproliferations regress after discontinuation of the immunosuppressive treatment, others behave as true malignant tumours. The mechanism by which a viro-induced lymphoproliferation evolves to an autonomous tumour remains unclear, and little is known about the genetic changes that occur during this process. We report two cases of fatal EBV-associated PTLD in heart transplant recipients. Both tumours were monoclonal and carried numerous chromosomal abnormalities, including a classic t(8;14)(q24;q32) with rearrangement of the MYC proto-oncogene. One tumour demonstrated an amplification of the proto-oncogene N-MYC. The EBNA2 gene was not expressed in tumoral cells, suggesting that the chromosomal abnormalities contributed the function of EBNA2 in these cells. The morphology of the tumours indicated that the cases presented here were not Burkitt's lymphomas. These findings provide some clues with regard to the genetic changes which lead to a B-cell malignancy in some transplant patients.

Adult↗

Primary pulmonary non-Hodgkin's lymphomas.

We report a retrospective study of the pathological features in 69 primary pulmonary non-Hodgkin's lymphomas which have previously been clinically reviewed. The tumours consisted of 61 (88%) low-grade and eight (12%) high-grade malignant lymphomas. Fifty-four of the low-grade malignant lymphomas were MALT lymphomas. Lymphoepithelial lesions were observed in bronchial, bronchiolar and alveolar lining. All tumours were composed of nodules, forming a lymphangitic pattern at the periphery and a confluent central mass. Invasion of pleura and vessels was often seen but this without any consequence on survival. Granulomas were found in 20% of cases. Six of the eight high-grade tumours were centroblastic and another two were B-cell lymphomas of undetermined type. In four cases, associated areas of low-grade malignant lymphoma with lympho-epithelial lesions indicated a preexisting MALT lymphoma. Clinical data suggest that limited surgery or non-aggressive chemotherapy can provide long-term survival in patients with such slowly developing neoplasms. However, non-invasive diagnostic methods need to be developed.

Adult↗

Anomalous origin of the left coronary artery from the pulmonary artery in adults.

Between March 1986 and December 1994, four adult patients underwent surgery for anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) at the German Heart Institute Berlin. The patients, aged 27, 35, 54, and 60, were all females. ALCAPA was diagnosed 3 to 8 months before surgery. The patients presented with cardiac murmur (two patients), abnormal ECG pattern (two patients), arrhythmia (one patient), and acute myocardial infarction (one patient). During surgery a two coronary system was established either by Takeuchi operation (one patient), interruption of the anomalous vessel and aortocoronary saphenous vein bypass (two patients), or internal mammary artery bypass (one patient). There were no postoperative deaths, however, one patient had to be reoperated because of a recurrent shunt. Clinical improvement was observed in all four patients with disappearance of fatigue, angina, dyspnea, and ischemic ECG changes. Despite having this long-standing congenital heart defect, adult and elderly patients with ALCAPA may benefit from surgical intervention to establish a two coronary system.

Adult↗

Performance of aortic and pulmonary homografts in the right ventricular outflow tract in children.

Cryopreserved homografts have been used at the German Heart Institute Berlin since October 1986. Until 31st May 1994, cryopreserved aortic (AA) or pulmonary (PA) homografts were implanted in the pulmonary position and followed up in 104 patients. The mean age at operation was 5.5 years. The patients were treated with 3-5 mg/kg aspirin daily after the operation for three months. They all had routine echocardiographic evaluation of their homografts, 47 patients were studied by heart catheterization. Excellent functional results of the homograft valves were found in 92 patients (88.5%). Early degeneration of the homograft conduit leading to reoperation was observed in 12 patients. Freedom from wall calcification was 18% in aortic and 78% in pulmonary homografts while freedom from valve dysfunction in aortic and pulmonary homografts at 60 months was 60% and 67%, respectively. Freedom from reoperation was 81% overall, 78% and 84% in patients with aortic and pulmonary homografts respectively (p < 0.05). In conclusion, pulmonary homograft has proved to be more durable than the aortic homograft in the pulmonary position, hence it is the preferential valve for RVOT reconstruction in children.

Age Factors↗