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Biomedical subjects

F Berger

Publications and source records attributed to F Berger.

At least 145 records · Page 8Linked to original sources

High gastrin releasing peptide receptor mRNA level is related to tumour dedifferentiation and lymphatic vessel invasion in human colon cancer.

The neuropeptide bombesin stimulates tumour cell proliferation in vitro. Through pharmacological testing, 20-40% of human colorectal tumours have been shown to be equipped with bombesin/gastrin releasing peptide receptor (GRP-R). The aim of the present study was to test whether GRP-R expression is correlated with tumour characteristics and usual prognostic factors in colorectal adenocarcinomas. A sensitive reverse transcription (RT)-competitive polymerase chain reaction (PCR) method was validated by studying GRP-R mRNA in separated layers of normal colonic wall, and GRP-R mRNA levels (in parallel with binding studies) in colon cancer cell lines LoVo and Caco-2. GRP-R mRNA levels were then determined in 29 surgical tumour specimens and the results compared with tumour histology and, using histochemistry, with the accumulation of p53 protein and a Ki-67 cell proliferation index. The mRNA was not detected in normal colonic epithelium, whereas a distinct signal was observed after amplification in 27/29 (93%) tumour specimens. Estimates of mRNA levels in the 27 positive tumours ranged from 52 to 8000 amol/0.25 microgram total RNA, and were significantly higher in poorly/moderately differentiated tumours (P < 0.05) and in tumours with lymphatic vessel invasion (P < 0.01). There was no relationship with p53 accumulation or to the proliferation index. Our results show that GRP-R mRNA can be detected in most colorectal tumour specimens, and suggest a link between high mRNA levels and both tumour dedifferentiation and lymph vessel invasion, but not proliferation.

Aged↗

Endosperm development.

There is a renewal of interest in endosperm development. Recent studies are leading the way to a better understanding of fundamental processes such as cell cycle control and the mechanisms of imprinting. A more global view of interactions between the endosperm and the embryo is emerging and will initiate an integrated approach to the study of seed development.

Arabidopsis↗

Transcatheter closure as standard treatment for most interatrial defects: experience in 200 patients treated with the Amplatzer Septal Occluder.

To judge whether an Amplatzer Septal Occluder can be used as standard therapy instead of surgery for closure of atrial septal defects we report our experiences in 200 patients. Of these patients, 127 had an atrial septal defect with haemodynamically significant left-to-right shunt, 68 patients a persistent oval foramen after presumed paradoxical embolism, and 5 had a fenestration after Fontan-repair. Mean age was 29.8 years (0.8 to 77.7 years). Body weight ranged from 6.9 to 120.0 kg (mean 51.5 kg). After diagnostic cardiac catheterization, and balloon-sizing of the defect, we implanted Amplatzer Septal Occluders with stents of 4 to 28 mm diameter. Follow-up studies were obtained after 48 hours, and one, six, and twelve months. Transcatheter closure of the atrial septal defect proved successful in all without any relevant residual shunts. In particular, complete closure was achieved in all patients after presumed paradoxical embolism. The mean period of follow-up is 9.5 months, with a range from 0.4 to 23.5 months, giving a total of 1898 patient months. The occlusion rate after three month was 98.1%. A trivial haemodynamically insignificant residual shunt remained in 1.9% of the patients. Fluoroscopy times ranged from 0 to 43.5 minutes, with a median of 8.7 minutes. The excellent results in the short and medium term in children and adults have resulted in using this device routinely at the present time for closure of central atrial septal defects up to a diameter of 28 mm. Final judgement, however, is only possible after long-term follow-up.

Adult↗

Comparison of acute effects on right ventricular haemodynamics of surgical versus interventional closure of atrial septal defects.

OBJECTIVES: We compared the acute effects on right ventricular haemodynamics of surgical versus transcatheter closure of medium-sized atrial septal defects. METHODS: We studied 47 consecutive patients with a defect in the oval fossa and a ratio of pulmonary to systemic flows between 1.5: 1 and 2: 1. They were divided into two groups according to whether the defects were closed by surgery, performed in 23 patients, or by interventional catheterization, achieved in 24 patients. By means of transthoracic cross-sectional echocardiography, we measured right ventricular end-diastolic and endsystolic volumes and calculated ejection fractions. These calculations were performed before, and between 1 and 7 days after closure of the defect. RESULTS: Before closure of the defect, all patients had an enlarged right ventricle with normal function. After closure by either method, there was no difference in the rate of normalization of end-diastolic volume, but endsystolic volume remained enlarged. Thus, the calculated ejection fraction was lower than before closure. CONCLUSIONS: There was no difference in right ventricular volumes or function early after closure of atrial septal defects, irrespective of whether this was achieved surgically or via transcatheter closure.

Adolescent↗

Transcatheter closure of atrial septal defects under echocardiographic guidance without X-ray: initial experiences.

BACKGROUND: Transcatheter closure of atrial septal defects is performed under fluoroscopy, but echocardiography has gained an important role in the procedure. With the new Amplatzer Septal Occluder a device has become available which is easy to implant with minimal fluoroscopy time. We developed an interventional procedure with this device under transesophageal echocardiography alone without fluoroscopy. METHODS AND RESULTS: Four patients (3 to 16 years of age, bodyweight 14 to 60 kg) with atrial septal defects centrally located in the oval fossa were elected for transcatheter closure. After sedation with midazolam and propofol a diagnostic and interventional catheterization was performed in all cases without fluoroscopy. Oxymetric shunt was Qp: Qs = 1.7 (1.5 to 2.1). Under transesophageal echocardiography, the defects were sized over the wire with a balloon catheter. Mean balloon stretched diameter was 10 mm (7 to 14 mm). Under transesophageal echocardiography an Amplatzer Septal Occluder was placed into the defect. In two patients this was achieved with a 5 MHz monoplane pediatric transducer, in two patients a 10mm 5 MHz multiplane probe was used. Complete closure was achieved in all patients and no complications were encountered. CONCLUSION: We conclude that in selected cases with an atrial septal defect located in the oval fossa and clear-cut echocardiographic findings, an Amplatzer Septal Occluder can be safely deployed under echocardiographic guidance alone.

Adolescent↗

Aggressive primary mediastinal non-Hodgkin's lymphomas: a study of 29 cases.

Aggressive primary mediastinal non-Hodgkin's lymphomas (NHL) represent a particular entity among intrathoracic neoplasms. Twenty-nine patients with primary mediastinal aggressive NHL diagnosed and treated in the author's institution were studied. According to the Revised European-American Lymphoma (REAL) classification, there were 15 diffuse large B-cell, eight T-lymphoblastic, four anaplastic, one large T-cell and one Burkitt's lymphomas. The study group consisted of 14 females and 15 males, with a mean age of 38 yrs. Symptoms arose from an aggressive anterior mediastinal mass, with a high prevalence of superior vena caval syndrome, pleural, and pericardial effusions. At the time of diagnosis, disease was confined to supradiaphragmatic areas in 24 patients, while subdiaphragmatic nodal or extranodal involvement was also present in five. All patients received a combination of aggressive chemotherapy regimens, mainly according to the French protocols for the treatment of NHL. A chest radiograph response of <50% after the first course of chemotherapy and failure to achieve a complete remission after the first line of chemotherapy were significantly associated with unfavourable prognosis. Overall 5-yr and 9-yr survival rates were 55 and 48%, respectively. Patients properly diagnosed and treated with a combined modality of chemotherapy can experience prolonged survival.

Adult↗

Differential ethylene sensitivity of epidermal cells is involved in the establishment of cell pattern in the Arabidopsis root.

Root hairs of Arabidopsis roots develop on trichoblasts located over the anticlinal (radial) walls of underlying cortical cells. Non-hair cells, on the other hand, develop on atrichoblasts overlying the periclinal (tangential) walls of cortical cells. Dark-grown wild-type seedlings, which produce little ethylene, are largely root hairless. Exogenous treatment of dark-grown plants with either ethylene or 1-aminocyclopropane-1-carboxylic acid (ACC) restores the development of root hairs in cells overlying the anticlinal cortical cell walls, indicating that cells in this position are more sensitive to ethylene than atrichoblasts. We used mutations in genes that overproduce ethylene (eto1, eto2, eto3 and eto4) to illustrate the positive regulatory role of ethylene. The preferential development of root hairs on epidermal cells overlying the cortical anticlinal cell walls in these mutants also illustrates that trichoblasts are more sensitive to ethylene than atrichoblasts. CTR1 is a negative regulator of the ethylene response and might, therefore, be a candidate regulator of differential sensitivity. CTR1 mRNA is expressed in all cell types in the root, suggesting that its transcriptional pattern alone cannot account for the differential sensitivity of epidermal cells to ethylene. Cellular mapping of wild-type and mutant roots supports previous findings indicating that ethylene acts after, and perhaps independently, of TTG during the establishment of cell fate in the root epidermis.

Amino Acids, Cyclic↗

Therapeutic efficacy of the thymidine kinase/ganciclovir system on large experimental gliomas: a nuclear magnetic resonance imaging study.

Contradictory experimental results and human trials have questioned the clinical relevance of the HSVtk/ganciclovir system. To bypass the problem of transfection efficiency, we used a glioma cell line stably expressing the HSVtk gene, which was also fully characterized from gene to protein. We also designed a more clinically relevant experimental protocol, consisting of late GCV delivery on large tumor formations. In short-term studies, histological examination revealed a significant decrease in tumor volume in GCV-treated animals from day 1 or from day 10 after cell inoculation. We observed that late GCV delivery is as efficient as early delivery, probably because GCV can reach tumor cells more easily when neoangiogenesis occurs. In long-term experiments, the survival of treated rats bearing 15-day tumors was improved by 60% compared with C6 control animals. Surprisingly, a 30% survival rate was observed in C6TK control animals. Nuclear magnetic resonance imaging demonstrated, in all surviving animals, a complete regression of tumors without mass effect. These results clearly demonstrate that the HSVtk/GCV system remains a potent therapeutic strategy, even when tested in large tumors, in contrast with the microscopic tumor formations previously reported.

Animals↗

[13C]-Galactose breath test: correlation with liver fibrosis in chronic hepatitis C.

BACKGROUND: The galactose elimination capacity test is a quantitative liver function test that has been shown to be a potential surrogate marker for death in advanced chronic liver diseases. However, this test lacks sensitivity in early liver disease. The goal of this study was to evaluate a [13C]-galactose breath test (GBT) in a population of patients with chronic hepatitis C. DESIGN: The GBT was performed in 10 control subjects and 50 patients with chronic hepatitis C; the results were compared with the METAVIR pathological scoring of liver biopsy specimens and with standard biochemical liver function tests. RESULTS: In 10 patients, oral vs. intravenous administration of galactose yielded similar results for the GBT (3.01% +/- 0.12% dose h-1 for oral galactose vs. 2.98 +/- 0.21 for intravenous). The GBT was then performed orally in the remaining 40 patients and 10 control subjects. A significant difference was observed between control subjects and patients (4.51% +/- 0.18% vs. 2.97% +/- 0.14% dose h-1, P < 0.0001). A significant difference for GBT results was observed between each fibrosis stage, but not with regard to the activity score. CONCLUSIONS: The GBT results are dependent on the severity of liver fibrosis in chronic hepatitis C. Further studies are needed to evaluate the usefulness of the GBT for the follow-up of chronic hepatitis C.

Administration, Oral↗

Mycoplasma: a new potential vector for gene therapy?

The introduction of foreign genetic material in living cells is the basis of the current protocols of gene therapy. The concept that the de novo synthesis of a foreign therapeutic protein requires the entrance of the corresponding gene into target cells via virus or synthetic vectors is directly inherited from experiments on bacterial transduction or transformation. However, the difficulties inherent in the penetration and the expression of foreign DNA into eucaryotic cells are probably responsible for the low efficiency of this therapeutic approach. In this paper, we explore the possibility of avoiding these limiting critical steps by expressing the foreign gene on the surface rather than inside the target cells by the use of mycoplasma, the smallest reported living cell. The absence of transfer of genetic information between this vector and eucaryotic target cells, the sensibility of mycoplasmas to antibiotics and their cytadherance are among the interesting features of this potential vector. The interest of this new vector in the case, e.g. of the gene-directed enzyme prodrug therapy of solid tumors, is discussed.

Genetic Therapy↗

Transvenous closure of patent ductus arteriosus with Ivalon plugs. Multicenter experience with a new technique.

RATIONALE AND OBJECTIVE: The authors assess the clinical efficacy of transvenous closure of patent ductus arteriosus (PDA) with a new plug consisting of Ivalon foam and a platinum/iridium frame with four aortic and two pulmonary nitinol struts. The most widely used devices for transcatheter treatment of PDA (Porstmann plug, Rashkind umbrella, Botallo occluder, coils) have specific limitations inherent to their design (e.g., transarterial approach, residual shunts, limited retrieval). METHODS: Between 1994 and 1997, PDA closure was attempted in 33 children and 67 adolescents and adults in 7 clinical centers; PDA diameter was 2 to 11 mm. Plug diameter was 6 to 20 mm, and 8 to 16 F venous sheaths were used for insertion. RESULTS: Placement was successful in 98% (with a single plug in 88%, and a second or third plug in 10%) and unsuccessful in 2%. Plugs were retrieved after malpositioning in 12 of 12 patients and after pulmonary embolization in 2 of 3 patients. One patient underwent surgery for removal of an embolized plug. Complete PDA closure was proved by aortography and color Doppler echocardiography in 85% (40 of 43 patients with a PDA 2-3.9 mm, 30 of 36 patients with a PDA 4-5.9 mm, and 15 of 21 patients with a PDA 6-11 mm). During a median follow-up interval of 16 months, there were no complications (infection, hemolysis, fracture, embolization). CONCLUSION: The new plug device can be used successfully in patients with a PDA diameter up to 11 mm. Further investigations are underway to determine the definite clinical value of this technique.

Adolescent↗

Familial occurrence of nodular regenerative hyperplasia of the liver: a report on three families.

BACKGROUND/AIMS: Nodular regenerative hyperplasia of the liver is a histological lesion usually associated with systemic diseases, haematological malignancies, or drugs. Its prognosis depends on portal hypertension, which usually is well tolerated and requires medical management only. PATIENTS: Three unrelated families, in which two sibling adult male patients presented with nodular regenerative hyperplasia of the liver, were studied. METHODS: Complete clinical charts and liver biopsy specimens were available for all patients. In addition, explanted livers were available for examination for the two transplanted patients. RESULTS: There was no evidence of any of the various clinical situations known to be associated with nodular regenerative hyperplasia of the liver. Portal hypertension was severe, requiring surgical treatment in two cases. Renal lesions were present in three patients. In two patients, progressive evolution to liver atrophy and hepatic failure, associated with renal failure, led to combined liver and renal transplantation. CONCLUSIONS: This report describes the existence of familial cases of nodular regenerative hyperplasia of the liver, occurring without underlying or associated systemic disease, characterised by a poor clinical course and often associated with progressive renal failure.

Adult↗

Incidence of secondary pulmonary hypertension in adults with atrial septal or sinus venosus defects.

OBJECTIVE: To examine the incidence of raised pulmonary artery pressure and resistance in adults with isolated atrial septal defect within the oval fossa (so called secundum defect) or sinus venosus defect. DESIGN: A historical, retrospective, unrandomised study. SETTING: A tertiary referral centre. METHODS: Cardiac catheterisation was performed in all patients, with measurement of pulmonary artery pressure and resistance. Pulmonary to systemic flow ratio was calculated using the Fick principle. Pulmonary hypertension was defined as mean pulmonary artery pressure > 30 mm Hg, and increased resistance as an Rp/Rs ratio > 0.3. PATIENTS: All patients with a secundum atrial septal or sinus venosus defect who presented between July 1988 and December 1997 were enrolled in the study. RESULTS: Pulmonary artery pressure and resistance in the patients with sinus venosus defect (n = 31) was higher than in patients with atrial septal defect (n = 138). Pulmonary hypertension was present in 26% of patients with sinus venosus and in 9% of patients with atrial septal defect. The incidence of raised pulmonary vascular resistance was 16% in patients with sinus venosus and 4% in patients with atrial septal defect. The increase in resistance occurred at a younger age in sinus venosus defect than in atrial septal defect. CONCLUSIONS: Patients with sinus venosus defect have higher pulmonary pressures and resistances and develop these complications at younger age than patients with atrial septal defects. Thus they should be managed differently than patients with "simple" atrial septal defects.

Adult↗

CDK1 and cyclin A expression is linked to cell proliferation and associated with prognosis in non-Hodgkin's lymphomas.

Cellular proliferation is regulated by several kinasic complexes associating cyclins and their catalytic subunits cyclin-dependent kinases (CDKs). In order to gain insight into the mechanisms underlying proliferation in non-Hodgkin's lymphoma (NHL), we examined the expression of certain cell cycle regulatory proteins normally expressed in lymphoid cells, cyclins A, B, D3 and E and cdk1, 2, 4, and 6. In 70 patients presenting a previously untreated lymphoma, cyclins and CDKs were studied by Western blotting and quantified by densitometry. Flow cytometry study of DNA content was carried out for all patients in order to study cell proliferation and level of ploidy. The results were analysed according to the histological types, the immunological phenotypes of the lymphomas and the outcome of the patients. Cdkl and cyclin A were correlated with the percentage of cells in S and S+G2/M phases, and significantly different according to the grade of malignancy, with the lowest expression in low-, and the highest in high-grade NHL according to the Working Formulation. In B-NHLs, cdk1, cyclin A, as well as cdk2, cyclin D3 and E expression was higher in the aneuploid than in the euploid group. Our results point to some particularities of cell cycle regulation in two lymphoma sub-types: 1) a low expression of cyclin D3 and cdk6 in mantle cell lymphomas and 2) a discrepancy between the high proliferative activity and the level of protein expression in Burkitt's lymphomas. CDK1 and cyclin A showed a significant prognostic value for achievement of complete remission (Cdk 1) and for both disease free (cyclin A) and overall survival (cyclin A and cdk1): low protein level was associated with the best prognosis in B-NHLs. Our results show that differential cell cycle regulating protein expression may be associated with different biological and clinical behaviour of NHLs and confirm the usefulness of the study of cell cycle regulation as a tool for understanding lymphoid malignancies.

Adolescent↗

Indolent nonfollicular lymphomas: characteristics, treatment, and outcome.

Indolent lymphomas are defined by their low aggressiveness at diagnosis compared with large-cell or T-cell lymphomas: small lymph nodes or blood involvement usually existing for months or years, no B symptoms, and good performance status. However, except in mucosa-associated lymphoid tissue (MALT) lymphoma, the disease is usually disseminated and this indolent presentation does not preclude a good outcome. Indolent lymphomas consist of follicular lymphoma, small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), marginal-zone lymphoma (MZL), and mantle-cell lymphoma (MCL) as defined in the World Health Organization (WHO) classification. A review of morphologic characteristics, clinical presentation, prognostic factors, and outcome is presented here for each of these entities. Despite the absence of good prospective or retrospective studies in the literature, some orientations for the treatment of these patients are given, as well as some ideas for future studies.

Humans↗

[Solid pseudopapillary tumors of the pancreas. Pathology report of 13 cases].

OBJECTIVES: Solid pseudopapillary tumors of the pancreas are exceptional. The aims of our study were to reevaluate the mode of presentation of these tumors and to analyze the role of pathological examination in diagnostic assessment and prognostic evaluation. PATIENTS: We report the clinical, radiological and pathological findings in a retrospective series of 13 patients in whom a diagnosis of solid pseudopapillary tumor of the pancreas was made between 1983 and 1997. There were 12 females (median age: 22.5 years) and one male, aged 73. RESULTS: The tumor was discovered incidentally (3 cases) or because of nonspecific digestive symptoms (10 cases). Biological data were uninformative. The tumor was pancreatic in 12 cases and duodenal in 1. In all cases, imaging techniques showed an heterogeneous lesion with no or poor vascularization. A cystic component was identified in 4 cases. Surgical resection was performed in all cases. Pathological examination showed an encapsulated tumor in 8 cases, a non-encapsulated but well-limited lesion in 3 cases and an infiltrative tumor in 2 cases. At the time of diagnosis, multiple liver metastases were present in 1 case. Mean duration of follow-up was 24 months (range: 3-168). At last follow-up, all patients, including the patient with synchronous metastatic disease, were alive, without local recurrence. CONCLUSION: Our study confirms that most cases of solid pseudopapillary tumors of the pancreas present with a suggestive clinical picture, including their occurrence in young women and their good prognosis after surgical resection. However, our results also underline the occurrence of cases presenting with unusual features, including old age, male sex, extra-pancreatic localization and malignant evolution. Histopathological examination is essential for the establishment of the diagnosis but morphological data are of little prognostic value.

Adolescent↗