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Biomedical subjects

E Robin

Publications and source records attributed to E Robin.

At least 37 records · Page 2Linked to original sources
PubMed1997

Search for impact remains at the Frasnian-Famennian boundary in the stratotype area, southern France.

In order to detect whether the end-Frasnian worldwide biotic crisis is related to an extraterrestrial impact, the global stratotype section of the Frasnian-Famennian boundary and auxiliary sections within the stratotype area have been examined for impact indicators: iridium. Ni-rich spinel bearing spherules and glassy microtektites. This area is particularly well suited to the search for discrete events because it exhibits biostratigraphically continuous sections of sedimentologically homogenous off-shore deposits. Different environmental settings on oxygenated deep-water seamounts, such as the stratotype section at Coumiac, and in oxygen-depleted depressions (La Serre section) are available. The latter is investigated in more detail because it is the least condensed across the boundary, which is determined by the first occurrence of the typical morphotype of Palmatolepis triangularis, the indicator of the first Famennian conodont biozone. Samples from the biostratigraphically defined boundary and adjacent levels failed to provide significantly high Ir values and no Ni-rich spinel or microtektite has been recovered. This is in contradiction with the results of earlier investigations carried out by H. Geldsetzer on the same section. In contrast, the values of Ir concentrations that we measured are always very low or not detectable. The small overabundances observed in some samples, which are about two orders of magnitude lower than what is currently observed at the Cretaceous-Tertiary boundary, are probably due to the accumulation of the normal flux of cosmic dust during periods of relatively low depositional rates or to a terrestrial origin. At present, we have no evidence that an extraterrestrial impact occurred at the F-F transition.

Biological Evolution↗
PubMed1997

Excessive proliferation matched by excessive apoptosis in myelodysplastic syndromes: the cause-effect relationship.

The paradox of pancytopenia despite cellular bone marrows (BM) was investigated in 120 patients with myelodysplastic syndromes (MDS). Detailed cell cycle kinetics were examined following in vivo infusions of iodo--and/or bromodeoxyuridine (IUdR/BrdU), while the incidence of apoptosis was measured by in situ end labeling (ISEL) of fragmented DNA. Results showed that MDS are highly proliferative disorders with an equally high incidence of apoptotic intramedullary cell death accounting for the paradox of cellularity/cytopenia. By double-labeling BM biopsy sections for ISEL/BrdU we found the peculiar situation of "signal antonymy" where S-phase cells were frequently apoptotic, a phenomenon so far only seen in MDS biopsies. The cause-effect relationship of this excessive proliferation/apoptosis is discussed at length.

Apoptosis↗
PubMed1997

Cell cycle kinetic studies in 68 patients with myelodysplastic syndromes following intravenous iodo- and/or bromodeoxyuridine.

Sixty-eight patients with myelodysplastic syndromes (MDS) received sequential infusions of iodo- and/or bromodeoxyuridine for cell kinetic analysis. Bone marrow biopsy sections were treated by appropriate antibodies and a labeling index (LI), duration of S-phase (Ts), and total cell cycle time (Tc) of myeloid cells were determined. The mean LI was 28.4%, Ts was 11.8 hours and Tc was 40.7 hours. The %LI decreased as the disease evolved from refractory anemia toward transformation to acute leukemia (p = 0.04). Double-labeling of biopsy sections for apoptosis and proliferation showed that 30-90% of S-phase cells in MDS patients were simultaneously apoptotic or "antonymous." We conclude that MDS are highly proliferative disorders in which the ineffective hematopoiesis is probably the result of excessive apoptosis rather than slow proliferation.

Apoptosis↗
PubMed1997

[Pancreatoblastoma in adults].

Pancreatoblastoma is a rare pancreatic tumor, which usually occurs during childhood. We describe here the ninth adult case in a 21-year-old woman, who died 7 months after diagnosis despite complete surgical resection and adjuvant chemotherapy. Pancreatoblastoma in adults has a poor prognosis, at variance with what may be observed in childhood.

Adult↗
PubMed1996

Novel insights into the biology of myelodysplastic syndromes: excessive apoptosis and the role of cytokines.

The paradox of myelodysplastic syndromes (MDS) which present with pancytopenias despite cellular bone marrows (BM) was investigated by conducting detailed studies of proliferation and apoptosis in 89 MDS patients. Our results demonstrated a rapid rate of both proliferation as well as apoptosis. Levels of three cytokines, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and interleukin-1 beta (IL-1 beta) were measured in the same patients. High levels of TNF-alpha were found to correlate with high levels of apoptosis in 83 MDS patients (P = 0.0045). We propose a dual role for TNF-alpha (or other cytokines) in the pathogenesis of MDS. On the one hand, TNF-alpha induces apoptosis in the maturing cells causing pancytopenia while on the other, it stimulates the proliferation of the primitive progenitors accounting for the hypercellular BM frequently seen in MDS. A new model for MDS is presented. The initial abnormality probably affects a primitive hemopoietic progenitor which acquires a growth advantage leading to monoclonal hemopoiesis, which in turn makes these cells susceptible towards acquiring additional mutations and appearance of cytogenetically marked (or unmarked) clones. Cytokines such as TNF-alpha whose source is presently unknown, then contribute towards the clinical syndrome of pancytopenia and hypercellularity.

Antigens, CD34↗
PubMed1996

A paradigm shift in myelodysplastic syndromes.

A poorly defined transforming event(s) affects the pluripotential bone marrow (BM) stem cell in myelodysplastic syndromes (MDS), conferring a growth advantage upon it which leads eventually to monoclonal hematopoiesis. The progeny of this transformed ancestor undergo recognizable albeit dysplastic maturation. We propose that this picture is further complicated by a variety of cytokines, tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta) and interleukin 1beta (IL-1beta) which exert a dual effect on the diseased cells. The immature CD34+ cells are stimulated to proliferate, while their later differentiated daughters are induced to undergo apoptosis accounting for the clinical syndrome of pancytopenia despite hypercellular BMs. Studies directed at measuring the rates of proliferation and apoptosis as well as the levels of TNF-alpha, TGF-beta and IL-1beta confirm this hypothesis and are presented in greater detail. A novel approach towards MDS therapy emerges as a result of this paradigm shift based upon the premise that anti-cytokine therapy would prevent excessive intramedullary apoptosis and result in improved cytopenias as well as cause a slowing down of the diseased precursor cell proliferation resulting in resumption of polyclonal hematopoiesis. Because a number of cytokines function through common lipid second messengers, interruption of this pathway should theoretically cause disruption in the signalling of a cascade of cytokines.

Apoptosis↗
PubMed1996

[Hepatic encephalopathy after injection of lanreotide, a somatostatin analog].

We report one case of hepatic encephalopathy following the administration of a somatostatin analogue (lanreotide) in a patient with a pancreatic endocrine tumor and liver metastases. Hepatic insufficiency was absent. The diagnosis of hepatic encephalopathy relied upon a positive re-challenge test, elevated veinous ammonemia, suggestive findings on electroencephalogram and lack of recurrence after lanreotide discontinuation. Encephalopathy was thought to be due to a significant decrease in hepatic blood flow caused by lanreotide; an associated thrombosis of the portal vein may have played a facilitating role.

Aged↗
PubMed1995

Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. Corticoresistance and effective treatment by cyclosporine A.

We report a case of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome treated with cyclosporine A. Features of primary biliary cirrhosis were pruritus, high titer of antimitochondrial antibodies, inflammatory infiltrates surrounding interlobular bile ducts, and periportal granuloma. Features suggestive of autoimmune hepatitis were high titer of antinuclear antibodies, very high total immunoglobulins, and piecemeal necrosis. Because corticosteroids and ursodeoxycholic acid were inefficient, cyclosporine A was started at a dose of 3 mg/kg/day. A dramatic improvement in clinical condition, liver tests, and histology was noted. Discontinuation of cyclosporine A was followed by a clinical and histological relapse. Cyclosporine A reintroduction was again associated with a significant improvement. This case report suggests that in corticoresistant cases cyclosporine A could be an effective therapy for primary biliary cirrhosis-autoimmune hepatitis overlap syndrome.

Adult↗
PubMed1995

[Prevalence and risk factors of hepatitis C virus infection in a hospitalized population in a gastroenterology unit. Role of endoscopic biopsies].

OBJECTIVES AND METHODS: In order to study the prevalence and risk factors of HCV infection in a population hospitalized in a Gastroenterology Unit, 3,767 patients were tested for serum anti-HCV, and 2,607 filled out a questionnaire about risk factors. RESULTS: With the RIBA 2 test, the overall prevalence was 5.9%. Because of the age distribution, two populations were studied. In patients younger than 45, intravenous drug use was the only independent risk factor linked to serum anti-HCV positivity (Odds ratio: 151, CI 95%: 66.9-340). In patients older than 45, the independent risk factors were chronic liver disease (Odds ratio: 8.5, CI 95%: 4.4-16.8), per-endoscopic biopsies (Odds ratio: 2.7, CI 95%: 1.4-5.4), and blood transfusions (Odds ratio: 1.8, CI 95%: 0.9-3.5). Two variables were dominant for the entire population: IV drug use and chronic liver disease. In patients without these factors, only one risk factor was linked to serum anti-HCV positivity: perendoscopic biopsies (Odds ratio: 5.2, CI 95%: 1.6-16.5). CONCLUSION: These results suggest that HCV may be transmitted by perendoscopic biopsies.

Adult↗
PubMed1994

CD44 mediates hyaluronan binding by human myeloid KG1A and KG1 cells.

Hyaluronan-binding function of the CD44 molecule has not been so far detected in myeloid cells. To study pure populations of primitive myeloid cells, we investigated the hyaluronan-binding function of the CD44 molecule from three myeloid cell lines: KG1a, KG1, and HL60. Both KG1a and KG1 cells express the CD34 antigen characteristic of the hematopoietic stem cells and HL60 cells do not; accordingly, KG1a and KG1 cells are generally considered as the most primitive and HL60 cells as the most mature of these cell lines. Measurement of cell adhesion to hyaluronan-coated surfaces (using 51Cr-labeled cells) and of aggregate formation in hyaluronan-containing solutions, showed that 45% of KG1 cells and 22% to 24% of KG1a spontaneously bind to hyaluronan, whereas HL60 cells do not either spontaneously or after treatment with a phorbol ester. Hyaluronan binding by KG1a and KG1 cells is mediated by CD44, because it is specifically abolished by monoclonal antibodies (MoAbs) to this molecule. The binding might require phosphorylation by protein kinase C and perhaps also by protein kinase A, because it is prevented by staurosporine, which inhibits these enzymes. 12-O-tetradecanoylphorbol-13-acetate (TPA) which activates protein kinase C, rises to 80% the proportion of KG1 and KG1a cells that bind hyaluronan; this activation is dependent on protein synthesis, for it is abrogated by cyclophosphamide, a protein synthesis inhibitor. Binding of TPA-treated cells to hyaluronan is only partly inhibited by MoAb to CD44: this suggests that TPA may induce synthesis of a hyaluronan-binding protein distinct from CD44. Considering the abundance of hyaluronan in human bone marrow, these results suggest that CD44 may be involved in mediating precursor-stroma interaction.

Alkaloids↗
PubMed1994

The malpractice crisis and the rate of actual malpractice.

In summary, the major concern of healthcare providers regarding malpractice should be its impact on patient welfare and its reduction to an irreducible minimum, rather than concern for physicians' insurance, etc. Medicine, rather than acting defensively, should provide leadership in reducing the malpractice toll on patients. Primary remedial steps should involve the prevention of patient injury and/or death. Actual malpractice is an enormous public health problem with a yearly morbidity of approximately 350,000 patients, and a yearly mortality of approximately 50,000 patients. Effective measures would not only save lives and improve patient welfare but would eliminate enormous healthcare expenditures. The way to reduce malpractice costs, direct and indirect, is to reduce malpractice.

Data Collection↗
PubMed1992

Phenotypic and functional analysis of tumour-infiltrating lymphocytes from patients with melanoma and other metastatic cancers.

Thirty tumour specimens, among which were 17 melanomas, were cultured with recombinant interleukin-2 (IL-2) in order to produce tumour-infiltrating lymphocytes (TIL). In the melanomas, three categories of TIL were characterised. The first, containing mostly CD3+ and CD8+ cells, lysed only autologous tumour cells; the second, containing mostly CD3+ and CD4+ cells, lysed both autologous tumour cells and allogeneic cells lines; the third, with mixed phenotype although cytotoxic for K562 targets, did not kill melanoma cells. The optimal conditions for a good development of TIL were established: we found that the lymph node or cutaneous origin of the tumour was unimportant, a 2 h enzymatic treatment was optimum and that TIL grew well in AIM V serum free medium. Therefore the easiness and the reproducibility of the TIL cultures from melanoma tumour samples allows the rapid development of therapeutic trials in metastatic melanoma.

Adult↗
PubMed1989

High-dose, multiple-alkylator chemotherapy with autologous bone marrow reinfusion in patients with advanced non-small cell lung cancer.

Fifteen patients with Stage IV lung cancer both untreated and previously treated were enrolled into a high-dose chemotherapy program with multiple alkylating agents and autologous bone marrow reinfusion. Eight patients received cyclophosphamide at 7.5 gm/m2 over 3 days with thiotepa escalated from levels of 1.8 mg/kg to 6.0 mg/kg over 3 days. Seven patients received the above dose of cyclophosphamide plus thiotepa at 675 mg/m2 and oral melphalan escalated from levels of 0.75 mg/kg to 2.5 mg/kg over 3 days. Both regimens are part of larger Phase I-II clinical studies. The median time to recovery of more than 500 granulocytes and more than 50,000 platelets per microliter was 16 and 27 days, respectively. Two patients died as a consequence of severe, overwhelming infections during their period of aplasia. Of the 13 evaluable patients, no patients achieved a complete response and seven patients (47%) obtained a partial response. The median duration of response was 12 weeks. Other nonhematologic toxicities included nausea/vomiting, diarrhea, mucositis, skin rash, hemorrhagic cystitis, and cardiomyopathy. Since there are substantial toxicities associated with high-dose chemotherapy and responses of such brief duration, further investigation with these drug combinations is not warranted.

Adult↗
PubMed1987

A phase I-II study of bialkylator chemotherapy, high-dose thiotepa, and cyclophosphamide with autologous bone marrow reinfusion in patients with advanced cancer.

Twenty patients with disseminated cancer both untreated and previously treated received bialkylator chemotherapy, thiotepa, and cyclophosphamide and reinfusion of cryopreserved autologous bone marrow (ABMR). The cyclophosphamide dose was constant at 7.5 g/m2 over three days, while thiotepa was started at 1.8 mg/kg for three days in escalating dose by a modified Fibonacci schema to 7 mg/kg. The median time to recovery of more than 500 granulocytes and more than 50,000 platelets/microL was 18 and 27 days, respectively. Four patients died as a consequence of severe, overwhelming infections or progressive disease during their period of aplasia. Of the 18 evaluable patients, a complete response (CR) was achieved in three patients and a partial response (PR) in ten patients for an overall response rate of 72%. The median duration of response was 14 weeks. Other nonhematologic toxicities included nausea/vomiting, diarrhea, stomatitis, skin rash, and cardiomyopathy. The maximum tolerated dose (MTD) of thiotepa was 700 mg/m2 or 6 mg/kg for three doses. Although there are substantial toxicities associated with this regimen, high-dose thiotepa and cyclophosphamide produce high response rates in patients with disseminated cancer.

Adult↗
PubMed1985

Treatment of metastatic colorectal carcinoma with cisplatin and 5-FU.

Twenty patients with measurable metastatic colorectal carcinoma were treated every 3 weeks with cisplatin (100 mg/m2 iv) on Day 1 and 5-FU (1000 mg/m2/day by iv infusion over 24 hours) on Days 1-5. Seven patients were previously treated with chemotherapy. The mean performance status for all of the patients was 1.5 (Eastern Cooperative Oncology Group). None of the patients had an objective response to the chemotherapy; 11 patients had stable disease and nine had no response. This study demonstrates that the combination of cisplatin and 5-FU, administered at this dose and schedule, has minimal activity in patients with metastatic colorectal cancer.

Adenocarcinoma↗
PubMed1983

Multimodality therapy of stage III adenocarcinoma of the breast.

The results of a pilot multimodality program (surgery + radiotherapy + chemotherapy) are reported in 34 women with advanced stage III and IV adenocarcinoma of the breast. The median relapse-free survival for all patients was 24 months, with 74% of the premenopausal patients and 37% of the postmenopausal alive at five years (P = 0.18). The relapse rate was significantly lower in premenopausal patients when compared to the postmenopausal subgroup. Estrogen receptor status was not predictive for relapse or survival.

Adenocarcinoma↗