PubMed Health⌕ Search

Biomedical subjects

D Samson

Publications and source records attributed to D Samson.

At least 55 records · Page 3Linked to original sources
PubMed1998

Quality assessment of whole genome mapping data in the refined familial spastic paraplegia interval on chromosome 14q.

Autosomal dominant familial spastic paraplegia (AD-FSP) is a genetically heterogeneous neurodegenerative disorder characterized by progressive spasticity of the lower limbs. Three loci on chromosome 14q (SPG3), 2p (SPG4), and 15q (SPG6) were shown to be responsible for AD-FSP. Analysis of recombination events in three SPG3-linked families allowed us to narrow the critical interval from 9 to 5 cM. An approximately 5-Mb YAC contig comprising 32 clones and 90 STSs was built from D14S301 to D14S991, encompassing this region of 14q21. Fifty-six ESTs assigned previously to this region with radiation hybrid (RH) panels Genebridge 4 and G3 were precisely localized on the YAC contig. The 90 STSs positioned on the contig were tested on the TNG RH panel to compare our YAC-based map with an RH map at a high level of resolution. Comparison between our map and the whole genome mapping data on this interval of chromosome 14q is discussed.

Chromosome Mapping↗
PubMed1998

Distribution of hematocrit values after aneurysmal subarachnoid hemorrhage.

Low hematocrit values are common after subarachnoid hemorrhage and may be associated with elevated cerebral blood flow and transcranial Doppler ultrasound (TCD) velocities, which may confound the interpretation of velocity as an indicator of vasospasm. The exact distribution of hematocrit among a neurosurgical population would be useful in assessing the magnitude of this difficulty but has not been previously reported. A database containing hematocrit values recorded at TCD examinations over a period of 7 years was reviewed. Two thousand four hundred thirteen hematocrit values were recorded for 575 patients. The distribution of hematocrit values was recorded among patients and among TCD studies. Eighteen percent of the patient population achieved a hematocrit of 26% or less at some point in their hospital stay, whereas 57% of patients achieved a hematocrit of 30% or less. Six percent of the TCD studies were associated with a hematocrit of 26% or less, while 33% of the studies were associated with a hematocrit of 30% or less.

Blood Flow Velocity↗
PubMed1997

A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family.

A candidate gene for Branchio-Oto-Renal (BOR) syndrome was identified at chromosome 8q13.3 by positional cloning and shown to underlie the disease. This gene is a human homologue of the Drosophila eyes absent gene (eya), and was therefore called EYA1. A highly conserved 271-amino acid C-terminal region was also found in the products of two other human genes (EYA2 and EYA3), demonstrating the existence of a novel gene family. The expression pattern of the murine EYA1 orthologue, Eya1, suggests a role in the development of all components of the inner ear, from the emergence of the otic placode. In the developing kidney, the expression pattern is indicative of a role for Eya1 in the metanephric cells surrounding the 'just-divided' ureteric branches.

Adult↗
PubMed1997

CD34 counts to predict the adequate collection of peripheral blood progenitor cells.

An essential prerequisite for successful procurement of sufficient autologous peripheral blood progenitor cells (PBPC) for engraftment is the optimal timing of collection. A number of surrogate markers of peripheral blood progenitor cells were analysed to identify a single test which could predict the optimum time to harvest, providing at least 2 x 10(6) CD34+ cells/kg patient body weight. The study comprised 95 patients undergoing varied mobilisation regimens with chemotherapy and G-CSF for both solid tumours and haematological malignancies. One hundred and fifty-seven PBPC harvests were collected. Full blood counts (FBC) and CD34+ cell enumeration was performed on blood samples taken during the mobilisation period and immediately prior to leucapheresis (pre-harvest). All PBPC collections were assayed for colony-forming cells and CD34+ cells in addition to a FBC. The white cell count on the day of harvest showed only weak correlation with the total number of CD34+ cells in the collection (r = 0.30). In contrast, the absolute number of circulating CD34+ cells strongly correlated with the CD34+ cell and CFU-GM yield of the corresponding apheresis product. Provided the mobilisation sample contained > or =20 x 10(6) CD34+ cells/ml, 94% of single collections, performed the following day, contained > or =2 x 10(6) CD34+ cells/kg.

Adolescent↗
PubMed1997

Dendritic cells generated from the blood of patients with multiple myeloma are phenotypically and functionally identical to those similarly produced from healthy donors.

Using a combination of GM-CSF, SCF, flk-2/flt-3 ligand, and IL-4, dendritic cells (DC) have been generated in vitro from the adherent fraction of mononuclear cells isolated from the blood of patients with MM. Analysis of cell yield showed no significant difference in DC yield (numbers or percentage of leucocytes) or total number of leucocytes generated in myeloma cultures compared to similar cultures prepared using mononuclear cells from the blood of healthy donors. The mean number of DC produced after 10d of culture were 8.19 x 10(5) and 9.87 x 10(5) cells (41% and 51% of all leucocytes) for the myeloma and normal cultures respectively. Flow cytometry investigation of phenotypic markers including CD1a, HLA-DR, CD80 (BB1/B7.1) and CD86 (B70/B7.2), and functional status (stimulatory potential in allogeneic mixed leucocyte reactions (MLR)) confirmed the generation of cells phenotypically identified as cultured DC. In addition, these cells were more effective than PBMC at stimulating allogeneic PBMC proliferation. These data demonstrate no difference between DC generated from patients with MM and healthy donors. This study was considered a prerequisite for future investigations directed towards developing effective immunotherapies for myeloma.

Adult↗
PubMed1997

Clustering of mutations responsible for branchio-oto-renal (BOR) syndrome in the eyes absent homologous region (eyaHR) of EYA1.

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder, characterised by the association of branchial, otic and renal anomalies with variable degrees of severity. We have recently identified EYA1 , a human homologue of the Drosophila eyes absent gene, as the gene underlying this syndrome. The products of both genes share a highly conserved 271 amino acid C-terminal region (eyaHR). The eyaHR was also found in the products of two other human genes (EYA2 and EYA3), demonstrating the existence of a novel gene family. We report here on the complete genomic structure of EYA1. This gene consists of 16 coding exons and extends over 156 kb. It encodes various alternatively spliced transcripts differing only in their 5' regions. Sequence analysis of the entire EYA1 coding region was performed for 20 unrelated patients affected by BOR syndrome, and six novel mutations were identified. Among these mutations, two are missense mutations, highlighting amino acid residues essential for the function of the EYA1 protein, and one mutation comprises a de novo Alu insertion into an exon. This insertion presumably occurs by retrotransposition, and the mobile Alu element has a poly(A) tail that is unstable throughout generations. To date, 14 mutations have been detected in BOR patients, all of which are different. However, all the mutations are located within or in the immediate vicinity of the eyaHR; the significance of this clustering is discussed.

Amino Acid Sequence↗
PubMed1997

Does electrothrombosis occur immediately after embolization of an aneurysm with Guglielmi detachable coils?

Current options for treating cerebral aneurysms include surgical clipping and placement of Guglielmi detachable coils (GDCs). The latter system is reported to induce acute aneurysmal occlusion by a mechanism of electrothrombosis. We report our observations in the case of a ruptured aneurysm treated with GDCs and then surgically exposed 2 hours later. The lack of thrombus within the aneurysm and around the coils led us to question the mechanism of action of GDCs.

Aneurysm, Ruptured↗
PubMed1996

Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: a retrospective case-matched study from the European Group for Blood and Marrow Transplantation.

A retrospective case-matched analysis was performed comparing 189 myeloma patients treated with allogeneic bone marrow transplantation (allo-BMT) with an equal number of patients who received autologous stem cell transplantation (ASCT). Matching was performed with respect to gender and number of treatment lines before transplantation. The groups were comparable with the exception of median age (43 years for allo-BMT v 49 years for ASCT, P = .0001) and median posttransplant follow-up (46 months for allo-BMT v 30 months for ASCT, P = .0003). The overall survival was significantly better for ASCT than for allo-BMT, with a median survival of 34 months and 18 months, respectively (P = .001). However, this survival advantage was only observed in men, but not in women. The statistically significant survival advantage for ASCT was seen in most subgroups, ie, chemotherapy-responsive patients, patients who had received two or more treatment lines before transplantation, patients in partial remission, patients with an IgG-subtype, patients older than 46 years of age, patients with stage II disease, and patients with a low or high serum-beta-2-microglobulin at diagnosis. The main reason for the poorer survival in allo-BMT patients was higher transplant-related mortality (41% v 13% for ASCT, P = .0001), which was not compensated for by a lower rate of relapse and progression. However, in patients alive at 1 year posttransplant, there was a trend for better long-term survival (P = .09) and significantly better progression-free survival (P = .02) for allo-BMT as compared with ASCT. We conclude that the median survival is superior for ASCT. However, allo-BMT has a lower relapse rate, which results in a similar long-term outcome for both approaches, but a longer follow-up is needed to assess the final outcome.

Acute Disease↗
PubMed1996

Biochemical bone markers in patients with multiple myeloma.

Enhanced bone resorption is a characteristic finding in multiple myeloma (MM). The aim of this study was to assess the newer biochemical bone markers in patients with myeloma. We studied 17 MM patients--10 males (3 untreated, 5 in remission, 2 responding), 7 females (3 in remission, 4 responding) and 15 normal controls. Serum bone specific alkaline phosphatase (BSALP), osteocalcin (OC) and procollagen type 1 C-terminal peptide (PICP) were determined as markers of bone formation, while serum tartrate resistant acid phosphatase (TRAP), urinary deoxypyridinoline (Dpyr) and calcium (Ca) were determined as markers of bone resorption and the ratio of the levels of bone formation/resorption were determined. All markers were measured by enzyme immunoassays (Metra Biosystems), except for TRAP by an in-house enzymatic assay and Ca by the cresolphthalein method. The Dpyr and Ca were expressed as a ratio to urinary creatinine (Cr) excretion. There were significantly higher (i) (Dpyr/Cr)/PICP ratio in male MM patients than in controls (P < 0.05); (ii) (a) urinary Dpyr excretion (P < 0.001), (b) (Dpyr/Cr)/BSALP ratio (P < 0.0001) and (c) (Dpyr/Cr)/PICP (P < 0.0001) in the untreated male MM subgroup than controls; (iii) (Dpyr/Cr)/BSALP ratio (P < 0.05) in the untreated than in the responding male MM subgroup, (iv) (Dpyr/Cr)/PICP ratio (P < 0.05) in untreated male patients than in those in the remission subgroup. In conclusion, (a) Dpyr is a sensitive marker in assessment of bone resorption in MM patients; (b) (Dpyr/Cr)/BSALP or (Dpyr/Cr)/PICP ratio is even more sensitive in distinguishing the untreated from the other MM subgroups and controls. Therefore, the use of a combination of these markers may have a potential role in the management of patients with MM.

Acid Phosphatase↗
PubMed1996

A comprehensive genetic map of the human genome based on 5,264 microsatellites.

The great increase in successful linkage studies in a number of higher eukaryotes during recent years has essentially resulted from major improvements in reference genetic linkage maps, which at present consist of short tandem repeat polymorphisms of simple sequences or microsatellites. We report here the last version of the Généthon human linkage map. This map consists of 5,264 short tandem (AC/TG)n repeat polymorphisms with a mean heterozygosity of 70%. The map spans a sex-averaged genetic distance of 3,699 cM and comprises 2,335 positions, of which 2,032 could be ordered with an odds ratio of at least 1,000:1 against alternative orders. The average interval size is 1.6 cM; 59% of the map is covered by intervals of 2 cM at most and 1% remains in intervals above 10 cM.

Algorithms↗
PubMed1996

Intracavernous carotid artery aneurysms: the possible importance of angiographic dural waisting. A case report.

BACKGROUND: Cavernous carotid aneurysms are generally benign entities. Certain indications exist for their treatment, however, including transient ischemic events, subarachnoid hemorrhage or risk of subarachnoid hemorrhage, epistaxis or its risk, ophthalmoplegia, pain, and progressive visual loss. We feel certain angiographic features may indicate a greater likelihood that cavernous carotid aneurysms extend into the subarachnoid space, thus making their rupture a life-threatening event. METHODS: A case report of an intracavernous carotid aneurysm, which at surgery extended into the subarachnoid space, is described. RESULTS: In this particular case, deformation of the aneurysm (waisting) as seen at angiography was in retrospect an indication that the cavernous carotid aneurysm extended into the subarachnoid space, either through the dural ring or through the eroded dural roof of the cavernous sinus. This finding was verified at surgery when the lesion was explored and trapped. CONCLUSION: Angiographic waisting of a cavernous carotid aneurysm may indicate that the aneurysm extends into the subarachnoid space. Such extension means that rupture would be a life-threatening event. While deformation of the aneurysm may be secondary to compression against the optic nerve or anterior clinoid process with an intact layer of dura overlying the aneurysm, the neurosurgeon confronted with such findings should analyze such lesions carefully and consider surgical exploration.

Aged↗
PubMed1996

A randomized study of VAD therapy with either concurrent or maintenance interferon in patients with newly diagnosed multiple myeloma.

This randomized study was designed to determine whether response to VAD chemotherapy could be prolonged by using rh alpha-2b-interferon (IFN) at a dose of 3 mU three times per week, either concurrently with VAD (VIC) or as maintenance after completion of VAD (VIF). Maintenance IFN was given for 9 months in order for the duration of IFN therapy to be similar in both groups. 72 patients were randomized between December 1988 and August 1993. The majority of patients had poor prognostic features. The objective response rate was similar in each arm, 78% in VIF and 77% in VIC. Of the 56 responders, 33 have relapsed, three died in remission, and 18 proceeded to high-dose therapy, withdrew for other reasons or were lost to follow-up and were censored from analysis at the relevant time point. Only two patients remain in remission (both in partial remission). Median PFS was 15 months for both VIF and VIC, compared with 16.5 months for a historic control group treated with VAD alone (n.s.). The estimated median survival in VIF was 43 months and in VIC 22 months, compared with 45 months in the historic controls (n.s.). These findings indicate that neither maintenance nor concurrent IFN prolongs response to VAD.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

High-dose therapy in multiple myeloma.

Autologous transplantation in myeloma can prolong survival as compared with standard chemotherapy but cannot be considered curative, as the majority of patients relapse within 5 years. Contaminating myeloma cells can be detected in stem cell harvests in the majority of patients, and the possibility that these cells lead to relapse has prompted widespread current interest in the use of positive stem cell selection as a means of purging. Allogeneic bone marrow transplantation is associated with a high transplant-related mortality but a lower relapse risk. A graft-versus-myeloma effect has recently been proven by the demonstration of response to donor lymphocyte infusion in patients relapsing after allogeneic bone marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Feasibility and toxicity of interferon maintenance therapy after allogeneic BMT for multiple myeloma: a pilot study of the EBMT.

A pilot study was undertaken in order to determine the feasibility and toxicity of rh-alpha-2b-interferon as maintenance therapy after allogeneic BMT for multiple myeloma. The study incorporated planned dose escalation of interferon in successive patient cohorts from an initial dose of 1 MU three times weekly to a target dose of 3 MU three times weekly. No clinical complications were observed in five patients receiving a dose of 1 Mu three times weekly. At a dose of 2 MU three times weekly, one of seven patients developed acute GVHD, which was fatal. At a dose of 3 MU three times weekly, four of five patients developed acute or chronic GVHD, and the study was therefore terminated at this point. We conclude that the use of interferon in myeloma patients early after allogeneic BMT is associated with a significant risk of GVHD, which is dose-related, and that the maximum tolerated dose in the early post-transplant period is 1-2 MU three times weekly.

Adult↗