Search PubMed⌕ Search

Biomedical subjects

C Martin

Publications and source records attributed to C Martin.

At least 451 records · Page 25Linked to original sources
PubMed1997

Soluble CD30 levels in plasma and cerebrospinal fluid in multiple sclerosis, HIV infection and other nervous system diseases.

The CD30 molecule, a member of tumor necrosis factor superfamily, has been suggested to be preferentially expressed and released in soluble form by activated T cells that produce T helper 2 type (Th2) cytokines. To evaluate whether determination of soluble CD30 (sCD30) levels could have a diagnostic value in diseases associated with Th1 and Th2 cytokine involvement, we investigated sCD30 in plasma and cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS), HIV infection and other nervous system diseases. There was no statistically significant difference for plasma sCD30 levels in these clinical groups. However, patients with HIV infection had higher levels of sCD30 in CSF than MS patients. The mean sCD30 values were 3 to 6 folds higher in plasma than in CSF in all patient groups. No relationships were found between sCD30 levels and different clinical variables of MS and HIV infection, except that higher plasma sCD30 levels in HIV-infected patients were found in those with higher CD4+ T cell counts (> 200 x 10(6)) compared to the group with lower cell counts. The findings indicate that determinations of plasma and CSF sCD30 levels in MS and HIV infection have limited or no value as diagnostic or prognostic indicator.

Adult↗
PubMed1997

Absence of seven human herpesviruses, including HHV-6, by polymerase chain reaction in CSF and blood from patients with multiple sclerosis and optic neuritis.

Several members of the herpesvirus family have been implicated in the pathogenesis of multiple sclerosis (MS). Recently, HHV-6 viral antigen has been demonstrated in association to MS plaques, as well as DNA from human herpesvirus 6 (HHV-6) in cerebrospinal fluid from a few MS patients by polymerase chain reaction (PCR). In the present study, CSF from patients with MS, optic neuritis and other neurological diseases, as well as consecutive CSF and serum samples from MS patients included in a clinical trial with acyclovir, were analysed by nested PCR for the presence of DNA from herpes simplex virus 1 and 2, Epstein-Barr virus, varicella zoster virus, cytomegalovirus, human herpesvirus 6 and 7. No virus DNA was found in any CSF (n = 115) or serum (n = 116) sample. These findings argue against a continuous disseminated herpesvirus infection in MS, but do not rule out a lesion-associated, low-grade herpesvirus infection within the MS brain.

Adolescent↗
PubMed1997

Mutation of arginine 134 to lysine alters the pK(a)s of key groups involved in proton pumping by bacteriorhodopsin.

Arginine 134 is located near the extracellular surface of bacteriorhodopsin (bR) and may interact with one or more nearby glutamate residues. In the bR mutant R134K, light-induced Schiff-base deprotonation (formation of the M intermediate) exhibits several kinetic components and has a complex pH dependence. The kinetics and pH dependence of M formation were analyzed using the following general guidelines for interpreting M formation: (1) The fastest component of M formation reflects the redistribution of the Schiff-base proton to D85, the usual proton acceptor, in response to the change in the proton affinities of the Schiff base and D85 early in the photocycle; (2) Two additional components of M formation reflect transitions between spectroscopically similar substates of M. By applying these guidelines, supplemented by information about the pK(a)s of D85 and the proton release group from acid (purple-to-blue) and alkaline titrations of the absorption spectra of the unphotolyzed R134K pigment, we explain the pH dependence of M formation as being due to titration of the counterion, D85, and of the proton release group. We calculate, in R134K, that the pKa of D85 is 4.6 in the unphotolyzed state, while the pKa of the proton release group is 8.0 in the unphotolyzed state but drops to approximately 5.8 in the M intermediate. The same value for the pKa of the proton release group in the M intermediate is obtained when we use photocurrent measurements to monitor proton release. The altered values of these pK(a)s relative to the corresponding values in wild-type bR suggest that D85 and the proton release group are coupled more weakly in R134K than in the wild type.

Arginine↗
PubMed1997

Teicoplanin in cardiac surgery: intraoperative pharmacokinetics and concentrations in cardiac and mediastinal tissues.

The concentrations of teicoplanin in the sera and mediastinal and heart tissues of 23 patients undergoing cardiac surgery were measured after two regimens of teicoplanin administration. Intraoperative pharmacokinetic parameters were also obtained. Patients were randomized into two groups. Those in group 1 were given teicoplanin at 6 mg x kg(-1) intravenously at the time of induction of anesthesia. Patients in group 2 were given teicoplanin at 12 mg x kg(-1) during the same period. The maximum concentration in serum (71 +/- 20 and 131 +/- 44 mg x l(-1)), the minimum concentration in serum (3.6 +/- 1.3 and 6.8 +/- 2.1 mg x l(-1)), the area under the concentration-time curve (AUC) from 0 to 12 h (108 +/- 20 and 217 +/- 38 microg x h x ml(-1)), and the AUC from 0 h to infinity (154 +/- 36 and 292 +/- 77 microg x h x ml(-1)) were twice as high after 12-mg x kg(-1) injections as after 6-mg x kg(-1) injections. No differences in mean residence time (9.7 +/- 4.9 and 8.4 +/- 2.7 h) or terminal half-life (8.5 +/- 3.8 and 7.5 +/- 2.3 h) were observed. Teicoplanin penetrated mediastinal and heart tissues but not sternal bone, where the antibiotic was detectable in only 1 of 13 patients in group 1 and 2 of 10 patients in group 2. In group 1, 7 of 13 patients had teicoplanin concentrations in tissue that were lower than the MIC for 90% of the strains of potential pathogens tested (MIC90) that cause infection after cardiac surgery. All of the patients in group 2 but one had teicoplanin concentrations in tissue (other than in sternal bone) far in excess of the MIC90 for the potential pathogens. In conclusion, the 12-mg x kg(-1) regimen of teicoplanin is followed by a significant increase in teicoplanin concentrations in heart and mediastinal tissues and should be preferred to the 6-mg x kg(-1) regimen if teicoplanin is selected for antimicrobial prophylaxis in open heart surgery.

Adult↗
PubMed1997

Interlaboratory agreement among results of human papillomavirus type 16 enzyme-linked immunosorbent assays.

Serological assays for measuring antibodies to human papillomavirus type 16 (HPV-16) virus-like particles (VLPs) have become important epidemiologic tools in recent years. However, the interlaboratory replicability of these assays has not been assessed. In this investigation, three laboratories tested a panel of specimens obtained from two different groups: 265 subjects in a vulvar cancer case-control study and 107 healthy volunteer blood donors. Each laboratory used an enzyme-linked immunosorbent assay (ELISA), but no attempt was made to standardize assay procedures among the three laboratories. The data showed good day-to-day intralaboratory replicability in laboratory 1 (correlation coefficient, > or = 0.88) and good intra-assay variability in laboratory 3 (correlation coefficient, > or = 0.93). Interlaboratory correlations, likewise, ranged between 0.61 and 0.80 in both case-control study subjects and healthy blood donors, indicating that ELISA optical density (OD) values between laboratories were linearly related regardless of the population. Kappa coefficients (kappa), based on each laboratory's categorical interpretation of its results (as positive or negative), showed good agreement (kappa, > 0.6) in case-control study subjects and moderate agreement (kappa, > or = 0.4) in blood donors, a population that had few strongly positive sera. When OD values near seropositive cutoffs were treated as indeterminates, there was little discordance between laboratories in either population. The data suggest that each laboratory measured the same humoral immune response and that their HPV-16 VLP ELISAs performed similarly (Pearson correlations). Interlaboratory differences, however, probably due to reagents and procedures, were considerably greater than intralaboratory day-to-day variability. Interlaboratory agreement in determining seropositivity (kappa) could be improved by sharing positive and negative serum controls and by treating marginal results as indeterminate. As part of continuing cooperation to improve interlaboratory agreement, we are preparing bulk serum control specimens to be shared and made available to interested researchers.

Enzyme-Linked Immunosorbent Assay↗
PubMed1997

No effect of the alpha1-antichymotrypsin A allele in Alzheimer's disease.

The apolipoprotein E (ApoE)-epsilon4 allele is associated in a dose dependent manner to an increased risk for Alzheimer's disease. However, the ApoE-epsilon4 allele effect does not account for all patients with Alzheimer's disease, and the existence of other genetic risk factors has been postulated. Kamboh et al reported an association between Alzheimer's disease and the A allele of alpha1-antichymotrypsin (Aact) gene, which was not confirmed in a larger series more recently analysed. The ApoE and Aact genotypes were analysed in 314 patients with Alzheimer's disease and 173 healthy controls, confirming the dose dependent effect of the ApoE-epsilon4 allele. Nevertheless, even using odds ratios adjusted for age and sex, there was no significant effect of the Aact genotype on Alzheimer's disease or on the ApoE-epsilon4 allele associated risk for Alzheimer's disease.

Alleles↗
PubMed1997

Use of oxygen-15 to measure oxygen-carrying capacity of blood substitutes in vivo.

A method for determining oxygen-carrying capacity of blood substitutes has been developed using the short-lived cyclotron-produced positron-emitting isotope 15O. This method measures the oxygen-carrying capacity of the blood substitutes in vivo in the presence of red blood cells and allows determination of changes in the oxygen-carrying capacity over time after exchange transfusion. This method is applied to the blood substitutes of liposome-encapsulated hemoglobin (LEH) and cell-free hemoglobin (Hb). We have used 15O (half-life of 2 min) to quantitate the lung uptake and tissue delivery of [15O2]LEH. Lung uptake studies were performed in intubated, catheterized rats after a 40% exchange transfusion of bovine LEH (LEBH; 0.68 g Hb/kg body wt), human hemolysate LEH (LEHH; 1.0 g Hb/kg body wt), or free bovine hemoglobin (SFHS; 0.56 g Hb/kg body wt). A bolus inhalation of 15O2 (3-5 mCi) was given at 15 min, 3 h, and 24 h post-transfusion. Arterial blood samples were collected, spun, and separated into LEH, red blood cell, and plasma fractions. 15O activity and hemoglobin content were determined for each fraction. Oxygen-carrying capacity was calculated as a percentage of the original red blood cell fraction removed. For LEBH, the carrying capacity was 15% at 15 min, 13% at 3 h, and 1% at 24 h. For LEHH, the carrying capacity was 30% at 15 min, 26% at 3 h, and 19% at 24 h. The marked decrease in carrying capacity at 24 h for LEBH compared with LEHH was attributable to the increased formation of methemoglobin in the circulating LEBH rather than increased removal from circulation, because total hemoglobin concentrations measured for both LEH samples decreased at a similar rate during the 24 h. The presence of methemoglobin reductase and other naturally occurring antioxidants in the LEHH may be responsible for maintaining the higher levels of oxyhemoglobin. Oxygen-carrying capacity for SFHS also decreased over time but at a much sharper rate compared with both LEH formulations. The carrying capacity for SFHS of 8% measured at 15 min decreased to 0.3% at 3 h and undetectable levels at 24 h. This sharper decrease in carrying capacity for SFHS is attributable to the rapid removal of the hemoglobin from circulation.

Animals↗
PubMed1997

Role of lipoprotein-bound NEFAs in enhancing the specific activity of plasma CETP in the nephrotic syndrome.

Plasma cholesteryl ester transfer protein (CETP) activity, evaluated by the transfer of radiolabeled cholesteryl esters from a tracer dose of tritiated HDL to the plasma apolipoprotein B-containing lipoproteins, was significantly higher in patients with untreated idiopathic nephrotic syndrome (n = 15) than in normolipidemic control subjects (n = 22) (81.5 +/- 8.4 versus 43.1 +/- 3.1 micrograms CE.mL-1.h-1, respectively; P < .001). The increased CETP activity in nephrotic plasma was explained by a significant rise in both the CETP mass concentration (3.2 +/- 0.2 versus 2.1 +/- 0.1 mg/L; P < .001), and the specific CETP activity, calculated as the ratio of CETP activity to CETP mass (25.3 +/- 1.7 versus 20.4 +/- 1.6 micrograms CE.mg-1.h-1; P < .05). Elevated CETP activity in nephrotic patients was shown to be associated with a significant decrease in the mean size of LDL (24.4 +/- 0.5 versus 26.3 +/- 0.5 nm; P < .0001) as well as in the relative abundance of HDL2a (29.6 +/- 1.6% versus 34.8 +/- 1.1%; P < .05). The nephrotic syndrome was characterized by a significant increase in the relative proportion of lipoprotein-bound nonesterified fatty acids (NEFAs) (35.4 +/- 7.7% versus 7.6 +/- 3.0% of total; P < .01), leading to a significant increase in the electronegative charge of LDL (-4.3 +/- 0.1 versus -3.9 +/- 0.1 mV; P < .05) and HDL (-11.5 +/- 0.1 versus -11.1 +/- 0.2 mV; P < .05). Compared with native, non-supplemented plasma, removal of lipoprotein-bound NEFAs by addition of fatty acid-poor albumin to total plasma from nephrotic patients or control subjects significantly decreased CETP activity and specific CETP activity. Specific CETP activity no longer differed between nephrotic and control groups after albumin supplementation (19.7 +/- 1.5 versus 17.7 +/- 1.5 micrograms CE.mg-1.h-1; NS). It is concluded that, in addition to elevated CETP mass concentration, lipoprotein-bound NEFAs, by increasing the negative electrostatic charge of nephrotic lipoproteins, can facilitate the CETP-mediated neutral-lipid transfer reaction in total plasma from nephrotic patients.

Adult↗
PubMed1997

Does transfusion practice affect mortality in critically ill patients? Transfusion Requirements in Critical Care (TRICC) Investigators and the Canadian Critical Care Trials Group.

In 4,470 critically ill patients, we examined the impact of transfusion practice on mortality rates. As compared with survivors, patients who died in intensive care units (ICU) had lower hemoglobin values (95 +/- 26 versus 104 +/- 23 g/L, p < 0.0001) and were transfused red cells more frequently (42.6% versus 28.0%, p < 0.0001). In patients with cardiac disease, there was a trend toward an increased mortality when hemoglobin values were < 95 g/L (55% versus 42%, p = 0.09) as compared with anemic patients with other diagnoses. Patients with anemia, a high APACHE II score (> 20), and a cardiac diagnosis had a significantly lower mortality rate when given 1 to 3 or 4 to 6 units of allogeneic red cells (55% [no transfusions] versus 35% [1 to 3 units] or 32% [4 to 6 units], respectively, p = 0.01). Adjusted odds ratio (OR) predicting survival were 0.61 (95% CI; 0.37 to 1.00, p = 0.026) after 1 to 3 units and 0.49 (95% CI; 0.23 to 1.03, p = 0.03) after 4 to 6 units compared with nontransfused anemic patients. In the subgroup with cardiac disease, increasing hemoglobin values in anemic patients was associated with improved survival (OR = 0.80 for each 10 g/L increase, p = 0.012). We conclude that anemia increases the risk of death in critically ill patients with cardiac disease. Blood transfusions appear to decrease this risk.

APACHE↗
PubMed1997

Nebulization and anti-Pseudomonas aeruginosa activity of colistin.

Colistin aerosols are frequently administered to patients with cystic fibrosis. However, questions arise concerning the effect of both jet and ultrasonic nebulizers on the properties of the drug. The aim of this study was to characterize the anti-Pseudomonas aeruginosa (PA) activity of colistin after jet (Pari LL) and ultrasonic (DP100) nebulization. A bench study was performed by capturing the aerosols, determining the drug mass, and assessing its anti-PA activity. Because the inhaled mass of colistin had to be entirely recovered for the bacteriological study, it was assessed by isotopic methods, mixing the drug with a 99mTc-labelled tracer and demonstrating that 99mTc activity accurately predicted the mass of colistin. Colistin was extracted from the filters and its antibiotic activity was determined using the method employed for the study of the bacteriostatic and bactericidal power of serum on the ATCC 27853 PA strain. The postnebulization minimum inhibitory concentrations (MIC) were 1.9 micrograms.mL-1 with DP100 and 0.5 microgram.mL-1 with Pari LL. These values were less than two dilutions different from the 1 microgram.mL-1 MIC of non-nebulized colistin. We conclude that neither jet nebulization nor ultrasonic nebulization alter the antibiotic properties of colistin and that both systems can be used to nebulize colistin.

Administration, Inhalation↗
PubMed1997

Tyrosine nitration as a mechanism of selective inactivation of prostacyclin synthase by peroxynitrite.

Vascular tone critically depends on the endothelial release of nitric oxide and prostacyclin. Superoxide anions counteract these relaxations by trapping nitric oxide under formation of peroxynitrite. As we have recently reported, peroxynitrite is able to inhibit prostacyclin formation in aortic microsomes (Zou et al., 1996). Here we show that peroxynitrite also blocks purified prostacyclin synthase with an IC50 value of about 50 nM and with a similar sensitivity also inhibits the enzyme activity in the EaHy 926 endothelial cell line. Thromboxane synthase, having the same heme-thiolate (P450) structure and a closely-related mechanism was unaffected by peroxynitrite. Anti-nitrotyrosine antibodies reacted positive by a Western blot after treatment of the purified enzyme with 1 microM peroxynitrite. Tetranitromethane also inhibited the enzyme activity which, like the inhibition by peroxynitrite, could be partially prevented in the presence of the substrate analog U46619. The simultaneous generation of superoxide and nitric oxide proved to be as efficient as a bolus of peroxynitrite which supports a possible inactivation of prostacyclin synthase under in vivo conditions. This substantiates an often suggested crucial role of superoxide in the pathophysiology of the cardiovascular system.

Animals↗
PubMed1997

Corrective osteotomy for malunited, volarly displaced fractures of the distal end of the radius.

Twenty-five patients who had had an opening-wedge osteotomy for the treatment of a malunited, volarly displaced fracture of the distal end of the radius were studied retrospectively. The indications for the operation were pain and functional limitations rather than the degree of anatomical deformity. Fifteen patients were men and ten were women; their average age was forty-six years (range, twenty-one to eighty-four years). Preoperative radiographs revealed an average ulnar inclination of 14 degrees, an average ulnar variance of five millimeters, and an average volar inclination of 24 degrees. Extension of the wrist averaged 25 degrees; flexion of the wrist, 53 degrees; supination of the forearm, 41 degrees; and pronation of the forearm, 64 degrees. The average grip strength was a force of seventeen kilograms compared with a force of forty kilograms in the contralateral hand. At an average of sixty-one months (range, eighteen to 114 months) after the osteotomy, supination of the forearm had improved to an average of 69 degrees and pronation had improved to an average of 75 degrees (p < 0.05 for both). Extension of the wrist had improved to an average of 55 degrees, and grip strength had improved to a force of thirty kilograms (p < 0.05 for both). Volar inclination averaged 5 degrees; ulnar variance, zero millimeters; and ulnar inclination, 22 degrees. A reoperation was performed in eleven patients. Seven patients had removal of the hardware only, two had a procedure involving the distal radioulnar joint, one had a procedure because the site of the osteotomy had not healed, and one had a median-nerve release. The functional result was rated as very good in ten patients, good in eight, fair in three, and poor in four.

Adult↗
PubMed1997

A long-circulating co-polymer in "passive targeting" to solid tumors.

A co-polymer of O-methyl polyethylene(glycol)-O'-succinate (MPEGs, m.w. 5100) and poly-l-lysine (PL, median m.w. 32700, degree of polymerization 256) has been synthesized by covalent grafting. The resultant MPEGs-PL (30% modification degree of epsilon-amino groups) had a hydrodynamic diameter corresponding to a 690 kD protein. Free amino groups (180/mol of the co-polymer) were used for conjugation of diethylene pentaacetic or succinic acid residues to MPEGs-PL. The potential of the resultant compound as a carrier of therapeutic and diagnostic drugs was studied using a rodent carcinoma models. The co-polymer had a blood pool half-life of 36h in adenocarcinoma-bearing rats. Radioactively labeled preparations were resistant to trans-chelation with apotransferrin and stable in blood for 24 h. The co-polymer accumulated in solid tumors at the level of 1.5-2% injected dose/g of tumor in 24 h. At that time, 34-40% of the accumulated polymer was associated with tumor cell fraction. The co-polymer non-covalently associated with cis-diamminedichloroplatinum(II), showed a cytostatic effect against mouse F9 carcinoma, and induced a reversal in tumor growth after intravenous administration.

Animals↗
PubMed1997

Integrating clinical and support process design for effective health services.

With increased capitation and managed care competition, health care systems must demonstrate effective health services with predictable costs, timing, transitions, and health outcomes. By involving patients, payers, and multiple providers, a health care system can design integrated clinical and support processes across the continuum for defined populations. The goals are lower costs, increased payer and patient satisfaction, and improved health status. This article shares examples and experiences from four health care systems that teamed with Premier, Inc., to design an integrated services sequence for defined populations.

Adult↗
PubMed1997

Apolipoprotein E and Alzheimer disease: genotype-specific risks by age and sex.

The distribution of apolipoprotein E (APOE) genotypes as a function of age and sex has been examined in a French population of 417 Alzheimer disease (AD) patients and 1,030 control subjects. When compared to the APOE epsilon3 allele, an increased risk associated with the APOE epsilon4 allele (odds ratio [OR] [epsilon4] = 2.7 with 95% confidence interval [CI] = 2.0-3.6; P < .001) and a protective effect of the APOE epsilon2 allele (OR[epsilon2] = 0.5 with 95% CI = 0.3-0.98; P = .012) were retrieved. An effect of the epsilon4 allele dosage on susceptibility was confirmed (OR[epsilon4/epsilon4] vs. the epsilon3/epsilon3 genotype = 11.2 [95% CI = 4.0-31.6]; OR[epsilon3/epsilon4] vs. the epsilon3/epsilon3 genotype = 2.2 [95% CI = 1.5-3.5]). The frequency of the epsilon4 allele was lower in male cases than in female cases, but, since a similar difference was found in controls, this does not lead to a difference in OR between sex. ORs for the epsilon4 allele versus the epsilon3 allele, OR(epsilon4), were not equal in all age classes: OR(epsilon4) in the extreme groups with onset at < 60 years or > 79 years were significantly lower than those from the age groups 60-79 years. In epsilon3/epsilon4 individuals, sex-specific lifetime risk estimates by age 85 years (i.e., sex-specific penetrances by age 85 years) were 0.14 (95% CI 0.04-0.30) for men and 0.17 (95% CI 0.09-0.28) for women.

Age of Onset↗
PubMed1997

Use of nested polymerase chain reaction to identify feline herpesvirus in ocular tissue from clinically normal cats and cats with corneal sequestra or conjunctivitis.

OBJECTIVE: To use a nested polymerase chain reaction (PCR) to detect feline herpesvirus (FHV-1) DNA in conjunctiva or cornea from clinically normal cats and cats with conjunctivitis or corneal sequestra. SAMPLES: Conjunctival snip biopsy specimens from 50 cats with conjunctivitis and 50 clinically normal cats; 28 keratectomy specimens from 26 cats with sequestra, and 13 specimens from clinically normal cats. PROCEDURE: Tissue specimens were digested, and FHV-1 DNA was amplified, using a double round of PCR. Products were visualized by use of agarose gel electrophoresis. RESULTS: Polymerase chain reaction was positive in 27 of 50 (54%) conjunctival specimens from cats with conjunctivitis and 6 of 50 (12%) specimens from clinically normal cats. Difference in the results between cats with conjunctivitis and clinically normal cats was statistically significant. Polymerase chain reaction was positive in 5 of 28 (18%) corneal specimens from cats with sequestra and 6 of 13 (46%) clinically normal cats. Distribution of positive results between clinically normal cats and those with sequestra was not significant. CONCLUSION: Cats with conjunctivitis were more likely to have a positive PCR result than were clinically normal cats, making it likely that FHV-1 was associated with the disease state. Herpesvirus DNA could not be detected in most corneas from cats with sequestra. CLINICAL RELEVANCE: Polymerase chain reaction is a useful clinical test for identifying FHV-1 DNA in cats with conjunctivitis, yielding greater sensitivity over that of current available tests. Herpesvirus may be less of a cause of corneal sequestration in the commonly affected breeds, Himalayan and Persian, than other factors, such as lagophthalmos or corneal metabolic defects.

Acute Disease↗