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Biomedical subjects

C Martin

Publications and source records attributed to C Martin.

At least 541 records · Page 30Linked to original sources
PubMed1995

The NACP/synuclein gene: chromosomal assignment and screening for alterations in Alzheimer disease.

The major component of the vascular and plaque amyloid deposits in Alzheimer disease is the amyloid beta peptide (A beta). A second intrinsic component of amyloid, the NAC (non-A beta component of amyloid) peptide, has recently been identified, and its precursor protein was named NACP. A computer homology search allowed us to establish that the human NACP gene was homologous to the rat synuclein gene. We mapped the NACP/synuclein gene to chromosome 4 and cloned three alternatively spliced transcripts in lymphocytes derived from a normal subject. We analyzed by RT-PCR and direct sequencing the entire coding region of the NACP/synuclein gene in a group of patients with familial early onset Alzheimer disease. No mutation was found in 26 unrelated patients. Further studies are required to investigate the implication of the NACP/synuclein gene in Alzheimer disease.

Age of Onset↗
PubMed1995

Use of conjugative and thermosensitive cloning vectors for transposon delivery to Mycobacterium smegmatis.

Conjugative, thermosensitive shuttle plasmids capable of transfer from Escherichia coli to Mycobacterium smegmatis were constructed. They contain both an E. coli replicon and a thermosensitive derivative of the pAL5000 mycobacterial replicon. Using a temperature shift protocol, the conjugative plasmid, pJAZ11 was used to deliver the transposon Tn611 from E. coli into the chromosome of M. smegmatis. Analysis of transconjugants revealed the random insertion of the transposon.

Cloning, Molecular↗
PubMed1995

Presence of specific platelet-activating factor binding-sites in neuroblastoma N1E-115 cells.

In this study we reported evidence for the existence of specific binding sites for platelet-activating factor (PAF) in neuroblastoma N1E-115 cells. The specific [3H]PAF binding reached a steady state level within 60 min at 25 degrees C. Scatchard analysis of the specific [3H]PAF binding revealed the presence of two apparent populations of binding sites. The high-affinity binding site possessed a Kd1 of 2.5 +/- 0.6 pM and Bmax1 = 57.3 +/- 20.0 fmol/mg protein. The low-affinity binding site possessed a Kd2 = 3.2 +/- 1.0 nM and Bmax2 = 4.4 +/- 2.1 pmol/mg protein. Furthermore, the total [3H]PAF binding was partially displaced by unlabelled PAF, PAF antagonists BN 52021 and BN 50730 in a dose-dependent manner. This study confirms the presence of specific PAF receptors in neuronal cells.

Animals↗
PubMed1995

Selective digestive decontamination in multiple trauma patients: cost and efficacy.

A double-blind randomized placebo-controlled study was carried out to evaluate the efficacy and the cost of selective digestive decontamination (SDD) to prevent nosocomial pneumonia in multiple-trauma patients. Nosocomial infections, particularly pneumonia, were more frequent in the placebo group. The most common infectious agent was Staphylococcus: Staphylococcus aureus in the placebo group and Staphylococcus epidermidis in the SDD group. Methicillin-resistant Staphylococcus epidermidis was detected more often in the SDD group. No methicillin-resistant Staphylococcus aureus was observed in this study. Fewer patients in the SDD group required antibiotherapy. SDD resulted in a saving of about 41% in drug expenditure.

Adolescent↗
PubMed1995

Apolipoprotein E genotypes in Parkinson's disease with and without dementia.

The apolipoprotein E gene (Apo E) type 4 allele is a genetic risk factor influencing the development and age of onset of Alzheimer's disease. Because Parkinson's disease shares many characteristics of Alzheimer's disease, we studied the frequencies of Apo E genotypes in a cohort of 52 Parkinson's disease patients with dementia and 61 patients without dementia. Dementia was determined per National Institute of Neurological and Communicative Disorders and Stroke criteria and Mattis Dementia Rating Scale (DRS) < 126. Normal cognition was defined as DRS > 132. Apo E genotype and allele frequencies did not differ between demented and nondemented parkinsonian patients. Neither group's genotype and allele frequencies differed from that of a nondemented population of 78 controls. We conclude that the Apo E epsilon 4 allele influences neither the development of Parkinson's disease nor the dementia associated with Parkinson's disease.

Age of Onset↗
PubMed1995

Comparative efficacy of hamamelis distillate and hydrocortisone cream in atopic eczema.

In a double-blind, randomized, paired trial lasting 14 days in 72 patients with moderately severe atopic eczema, hamamelis distillate cream (5.35 g hamamelis distillate with 0.64 mg ketone/100 g) was compared with the corresponding drug-free vehicle and 0.5% hydrocortisone cream, and reductions of the basic criteria of severe atopic eczema (delta values of the sum scores), i.e. itching, erythema and scaling, were evaluated. Thirty-six patients in each group were treated, which allowed the detection of a 10% difference between verum and control (confirmatory study). Effects were compared using Wilcoxon's test. The mean sum scores of the basic criteria of the test areas were 5.3-5.5. All treatment regimens significantly reduced itching, erythema and scaling after 1 week. Hydrocortisone proved superior to hamamelis distillate. The basic criteria scores decreased by 2.7 and 1.6, respectively. The delta values of the minor criteria and the global rating of efficacy were also used to indicate the difference between these preparations. Hamamelis distillate cream, however, did not differ from the vehicle. Mean delta values of basic criteria were 1.8 and 2.0, respectively. All preparations were well tolerated. Unwanted cutaneous reactions occurred in six patients, although due to their inflammatory nature and their confinement to vehicle-treated patients, they may not represent true adverse effects but rather a lack of efficacy. The results prove the superiority of low-dose hydrocortisone cream over hamamelis distillate cream, and the therapeutic outcome following this preparation was no better than following the base preparation. The mild, yet unmistakable anti-inflammatory effect of hamamelis cream in experimental models of inflammatory skin disease was thus not reflected by an efficacy in patients with atopic eczema greater than that obtained from the base preparation.

Administration, Topical↗
PubMed1995

Optimal timing of granulocyte colony-stimulating factor (G-CSF) administration after bone marrow transplantation. A prospective randomized study.

The positive role of G-CSF in hastening the myeloid recovery of patients undergoing allogeneic bone marrow transplantation (ALLO-BMT) or autologous bone marrow transplantation (ABMT) has recently been established. Considerable knowledge about adequate doses and route of administration has been accumulated in the past few years. Nonetheless, the optimal time to start growth-factor administration remains undetermined. We have performed a stratified study according to the source of hematopoietic progenitors (ALLO-BMT or ABMT), underlying disease and its stage, and acute graft-versus-host disease (GVHD) prophylaxis regimen and randomized patients in two arms: group A, which started G-CSF on day 0 (36 patients), and group B, which started on day +7 post-BMT (39 patients). The same dose (5 micrograms/kg/day) and route of administration were employed in both groups. We found no significant differences in the time to reach an absolute neutrophil count (ANC) of 0.1, 0.5, and 1 x 10(9)/l and 50 x 10(9) platelets/l (medians: 10 and 11, 14.5 and 14, 17 and 16, 23 and 24 days, respectively, in groups A and B). We did not find differences in the days of fever or days on antibiotic treatment with less than 1 x 10(9)/l ANC, rate of bacteriemia, or days of hospitalization in both groups. In contrast, a considerable saving of G-CSF in B group was found (mean days of infusion in group A, 18, versus 11 in group B) (p < 0.0001). This is equivalent to a saving of 1120 $US per patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Sepsis reduces isoflurane MAC in a normotensive animal model of sepsis.

Patients with sepsis often require anaesthesia for surgical procedures. Anaesthesia can be unpredictable and the most haemodynamically stable agents are used. No data are available for the minimum alveolar concentration (MAC) requirements in such patients or in animal models of sepsis. We have characterized the effect of sepsis on the MAC of isoflurane in a normotensive rodent model of sepsis. The minimum inhibitory concentration (MIC) of isoflurane to an identical stimulus was determined for rodents subjected to caecal ligation and perforation (CLP n = 8), or sham laparotomy (n = 7). The calculated MAC of isoflurane was reduced in the septic animals compared with the sham animals (MAC of isoflurane, CLP = 0.8%, sham = 1.4% P < 0.003). No statistical differences were found in the haemodynamic variables measured in either group. Isoflurane leads to haemodynamic stability during anaesthesia in this animal model of sepsis. However, the MAC requirement for isoflurane is reduced by sepsis.

Anesthetics, Inhalation↗
PubMed1995

In vitro metabolism of cyclosporin A with rabbit renal or hepatic microsomes: analysis by HPLC-FPIA and HPLC-MS.

Cyclosporin A (CsA) is in vivo mainly metabolized by hepatic cytochrome P450 IIIA to more than 21 metabolites, the major ones known as: M1, M17 and M21. The aim of this work is to explore the in vitro metabolism of CsA after incubation, in the presence of NADPH, with renal or hepatic microsomes obtained from rabbits pretreated with rifampycin (enzyme inducer) or erythromycin (enzyme inhibitor). The presumed metabolites were separated by semi-preparative high-performance liquid chromatography (HPLC) and identified in each collected fraction by fluorescence polarization immunoassay (FPIA) (HPLC-FPIA) using a non-specific polyclonal antibody. They were also analyzed by HPLC-mass spectrometry (MS) using fast atom bombardment (HPLC-MS-FAB). Five collected fractions gave positive results with FPIA. The major metabolites found were M1, M17 and M21 after identification by HPLC-MS-FAB and comparison with three corresponding standard metabolites. The CsA biotransformation rates were calculated by the amount of unmetabolized CsA and were linear with time. These mean rates (Vm) for 12-min incubation by renal microsomes of rabbits treated with rifampicin or erythromycin or untreated (control) were 0.11, 0.02 and 0.04 nmol/min x mg microsomal protein, respectively. These rates were 15-, 37-, and 30-fold lower than those obtained with hepatic microsomes of rabbits treated identically. As CsA metabolites are less cytotoxic than the parent drug, this weak renal biotransformation of CsA after in vitro incubation should be one of the mechanisms of its in vivo nephrotoxicity.

Animals↗
PubMed1995

Effect of gemfibrozil on the concentration and composition of very low density and low density lipoprotein subfractions in hypertriglyceridemic patients.

The effect of gemfibrozil treatment on very low (VLDL) and low (LDL) density lipoprotein subfractions has been investigated in 9 moderate hypertriglyceridemic (HTG) patients (triglyceride (TG) levels 237-426 mg/dl). Three VLDL subfractions, VLDL1 (Sf 175-400), VLDL2 (Sf 100-175) and VLDL3 (Sf 20-100) and 4 LDL subspecies, LDL1 (1.023-1.028 g/ml), LDL2 (1.029-1.037 g/ml), LDL3 (1.038-1.049 g/ml) and LDL4 (1.050-1.062 g/ml) were prepared by density gradient ultracentrifugation. High density lipoprotein (HDL) chemical composition and lipolytic activities after heparin injection were also determined. Gemfibrozil induced a net decrease in VLDL1 and VLDL2 concentrations (P < 0.01). Cholesteryl ester (CE) weight percent was significantly reduced in both VLDL1 and VLDL2 subfractions. VLDL3 concentration and composition were not changed by the treatment. Lipoprotein lipase (LPL) activity was reduced in HTG patients (P < 0.05). After treatment, LPL activity increased (P < 0.05) but remained lower than in control, normotriglyceridemic (NTG) subjects. Furthermore, gemfibrozil increased HDL cholesterol (P < 0.05) and normalised the elevated HDL2 and HDL3 TG content. The increase of LDL cholesterol, often observed after gemfibrozil treatment, was due to a rise in the LDL2 subfraction (1.029 < d < 1.037 g/ml), the main fraction present in control subjects. However, despite the significant decrease of total plasma TG (329 mg/dl vs. 174 mg/dl), LDL3 subfraction (1.038 < d < 1.049 g/ml) was not reduced.

Adult↗
PubMed1995

The evolution of heart, lung and liver transplantation services in Australia.

The introduction and operation of heart, lung and liver transplantation services in Australia have been assisted by a Nationally Funded Centres policy adopted by health ministers. Assessment for eligibility for support under the program has been undertaken by the Australian Health Technology Advisory Committee. Outcomes/survival rates at transplantation centres have compared favourably with results from other countries. As in other countries, shortage of donor organs has limited the number of procedures undertaken. Some concern remains regarding the viability of newer transplantation programs which are now being established in smaller centres of population.

Australia↗
PubMed1995

Alarms and diversions: the biochemistry of development.

In considering biochemical aspects of development over a range of different organisms--plants, animals, fungi and bacteria--some ubiquitous themes emerge. Many of the regulatory mechanisms being discovered in higher organisms have already been found in yeast, and there are examples of similar mechanisms in bacteria, notably, analogies and even homologies in multistep cascades involving phosphorylation and negatively acting steps; interplay between development and the cell cycle; and emerging evidence that metabolic pathways can be important developmental agents. On the other hand, those topics that remain resolutely organism-specific may serve as a warning to those who tend to overgeneralize, or as the nucleus for the next generation of general insights.

Animals↗
PubMed1995

Beta-endorphin in multiple trauma victims.

BACKGROUND: In animals and in humans, stress is known to be accompanied by increased beta-endorphin secretion. METHODS: Blood samples from 47 patients in a state of stress induced by multiple trauma were assessed for beta-endorphin concentration by radioimmunoassays. RESULTS: We show that there is a clearcut correlation (Spearman's R = 0.72, P = 2.1 x 10(-6) between the level of consciousness evaluated with the Glasgow score and levels of circulating beta-endorphin. In addition, beta-endorphin levels are higher than normal in patients with Glasgow coma with scores higher than seven, and lower than normal in those with Glasgow coma scores of seven or less. Finally, in the complete absence of stress (shown by the lack of brain activity in six irreversible coma patients), there is a severe drop in the level of circulating beta-endorphin. CONCLUSION: beta-endorphin serum levels correlate with the state of consciousness of multiple trauma patients.

Adult↗