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Biomedical subjects

C Martin

Publications and source records attributed to C Martin.

At least 613 records · Page 34Linked to original sources

Penetration of ciprofloxacin into bronchial secretions from mechanically ventilated patients with nosocomial bronchopneumonia.

The aim of the study was to evaluate the penetration of ciprofloxacin into bronchial secretions from mechanically ventilated patients with nosocomial bronchopneumonia. For this purpose, in each patient studied, simultaneous serial blood and bronchial secretion samples were obtained over a 12-h period on days 2 and 4. Eight patients were included in the study. Ciprofloxacin was given at a dose of 200 mg over 30 min by using an automatic pump. Ciprofloxacin was measured by high-performance liquid chromatography. Peak levels of drug in serum were 2.95 +/- 1 mg/liter on day 2 and 2.43 +/- 0.7 mg/liter on day 4. Peak and trough levels in bronchial secretions were 0.95 +/- 0.51 and 0.21 +/- 0.12 mg/liter, respectively, on day 2 and 0.76 +/- 0.17 and 0.18 +/- 0.14 mg/liter, respectively, on day 4. The ratios of peak concentrations in bronchial secretions/serum were 0.32 +/- 0.11 and 0.33 +/- 0.06 on days 2 and 4, respectively. The ratios of the area under the concentration-time curve from 0 to 12 h (AUC0-12) for bronchial secretions/those for serum were 0.66 +/- 0.40 and 0.55 +/- 0.30 on days 2 and 4, respectively. A significant positive correlation was found on day 4 between the AUC0-12 for serum and the AUC0-12 for bronchial secretions. No significant correlations were found between peak values in serum and bronchial secretions.

Aged↗

CS31A capsule-like antigen as an exposure vector for heterologous antigenic determinants.

CS31A is a multimeric surface protein surrounding certain enterotoxigenic and septicemic bovine Escherichia coli strains. The possibility of using CS31A as a carrier of foreign antigenic determinants was investigated. Introduction of heterologous viral epitopes into the CS31A major subunit, ClpG, was successfully performed in the V3 region of the molecule which encodes for an immunodominant linear epitope. E. coli K-12 strains producing the hybrid CS31A molecules or the purified chimeric proteins were used for mice immunization. By using the C epitope derived from the S protein of the porcine transmissible gastroenteritis virus, significant antiviral antibody titers were elicited and seroneutralization of the virus was demonstrated, confirming that the molecular environment in V3 is favorable for antigen presentation. These results indicate that synthesis of CS31A hybrid proteins by the wild-type strain 31A could become a powerful tool for the development of oral vaccines directed against mucosal pathogens.

Amino Acid Sequence↗

Penicillin-binding protein 2b of Streptococcus pneumoniae in piperacillin-resistant laboratory mutants.

In Streptococcus pneumoniae, alterations in penicillin-binding protein 2b (PBP 2b) that reduce the affinity for penicillin binding are observed during development of beta-lactam resistance. The development of resistance was now studied in three independently obtained piperacillin-resistant laboratory mutants isolated after several selection steps on increasing concentrations of the antibiotic. The mutants differed from the clinical isolates in major aspects: first-level resistance could not be correlated with alterations in the known PBP genes, and the first PBP altered was PBP 2b. The point mutations occurring in the PBP 2b genes were characterized. Each mutant contained one single point mutation in the PBP 2b gene. In one mutant, this resulted in a mutation of Gly-617 to Ala within one of the homology boxes common to all PBPs, and in the other two cases, the same Gly-to-Asp substitution at the end of the penicillin-binding domain had occurred. The sites affected were homologous to those determined previously in the S. pneumoniae PBP 2x of mutants resistant to cefotaxime, indicating that, in both PBPs, similar sites are important for interaction with the respective beta-lactams.

Amino Acid Sequence↗

Compared with crystalloid, colloid therapy slows progression of extrapulmonary tissue injury in septic sheep.

We tested the hypothesis that the type of fluid infused to chronically maintain intravascular volumes would modify both microvascular integrity and cellular structure in extrapulmonary organs in hyperdynamic sepsis. After cecal ligation and perforation, awake sheep were treated for 48 h with 10% pentastarch (n = 9), 10% pentafraction (Du Pont Critical Care; n = 8), or Ringer lactate (n = 8) titrated to maintain a constant left atrial pressure. After 48 h of fluid therapy, biopsy samples were taken from the left ventricle and gastrocnemius for electron microscopy. At this time, all groups demonstrated a similar hyperdynamic circulatory response, increased systemic O2 utilization and organ blood flows, measured by radioactive microsphere injection. However, greater capillary luminal areas with less endothelial swelling and less parenchymal injury were found in septic sheep treated with pentastarch vs. Ringer lactate infusion in both muscle types. Pentafraction showed few benefits in study end points over pentastarch. Thus, we conclude that chronic intravascular volume resuscitation of hyperdynamic sepsis with pentastarch ameliorated the progression of both microvascular and parenchymal injury. These findings indicate that microvascular surface area for tissue O2 exchange in sepsis may be better preserved with chronically infused colloid, resulting in less parenchymal injury.

Animals↗

Relationship between Cr and breathing pattern in mechanically ventilated patients.

In mechanically ventilated patients the natural gas-conditioning process of the upper airways is bypassed by the use of an endotracheal tube or a tracheostomy. We hypothesized that under these conditions the breathing pattern may greatly influence the convective respiratory heat loss (Cr). Cr values were computed from minute ventilation (VE) and inspiratory and expiratory gas temperatures, which were measured in six patients under mechanical ventilation for the management of cranial trauma. In each patient the effects of 11-20 different breathing patterns were investigated. Relationships between Cr and VE and between combined tidal volume and respiratory frequency were obtained by simple and multiple linear regression methods, respectively. Comparison of the standard errors of estimate indicated that multiple linear regression gives the best fit. Thus, Cr was highly dependent on the breathing pattern and was not related only to VE. For the same VE value, Cr was higher when VE was achieved with high tidal volume and low respiratory frequency. These data are consistent with previous studies in which thermal exchanges through the upper airways were taxed by hyperventilation of frigid air.

Adult↗

Microvascular perfusion is impaired in a rat model of normotensive sepsis.

We hypothesized that normotensive sepsis affects the ability of the microcirculation to appropriately regulate microregional red blood cell (RBC) flux. An extensor digitorum longus muscle preparation for intravital study was used to compare the distribution of RBC flux and the functional hyperemic response in SHAM rats and rats made septic by cecal ligation and perforation (CLP). Using intravital microscopy, we found that sepsis was associated with a 36% reduction in perfused capillary density (from 35.3 +/- 1.5 to 22.5 +/- 1.0 capillaries/mm of test line) and a 265% increase in stopped-flow capillaries (from 0.9 +/- 0.2 to 3.3 +/- 0.4 capillaries/mm); the spatial distribution of perfused capillaries was also 72% more heterogeneous. Mean intercapillary distance (ICD) increased 30% (from 25.7 +/- 0.8 to 33.5 +/- 1.6 microns), and the proportion of capillary pairs with intercapillary distances > 33.8 microns (the 75th percentile of ICDSHAM) was greater with sepsis. Mean capillary RBC velocity increased 17% in CLP rats (391 vs 333 microns/s). Laser Doppler flowmetry was used to assess the functional hyperemic response of the extensor digitorum longus muscle before and after a period of maximal twitch contraction designed to increase oxygen demand. RBC flux was 36% lower in the CLP rats at rest. After contraction, RBC flux increased in both SHAM and CLP rats; however, the relative increase was less in the CLP group. We concluded that sepsis affects the ability of the skeletal muscle microcirculation to appropriately distribute RBC flux and to respond to increases in oxygen need.

Animals↗

Correlation of buccal mucosal transudate collected with a buccal swab and urine levels of cocaine.

In this preliminary study, the level of Benzoyl Ecgonine (BE), a metabolite of cocaine, was compared in urine and buccal mucosal transudate collected by a salt impregnated swab in volunteers admitted for cocaine use. The presence of BE (specificity) was verified by the SYVA EMIT method and the urine and transudate levels measured using the Sigma ELISA methods. Results were confirmed using Gas Chromatography/Mass Spectrometry. In all, 44 patients volunteered, and BE in urine or saliva confirmed that each volunteer had in fact used cocaine. The salt-impregnated swab permitted detection of cocaine or its derivative in 27 of the 44 cases. The paper discusses the possibility of using buccal mucosal transudate as collected by salt-impregnated buccal swab as a minimally-invasive measure of cocaine use. This method would allow positive confirmation by a witness that the sample came from a given patient.

Adult↗

Increase of motion between lumbar vertebrae after excision of the capsule and cartilage of the facets. A cadaver study.

Seventeen fresh segments of cadaveric lumbar spines were tested in flexion, extension, and axial rotation. The resulting angular rotations were measured with the use of a goniometer and a three-dimensional system of video analysis. Measurements of flexibility were made, in order, in the intact spine; after decompression (bilateral total laminectomies, partial medial facetectomies, and foraminotomies); after excision of the capsule and cartilage of the facets; and after cancellous bone had been packed into the facet defects. Decompression resulted in a slight increase in the sagittal and axial ranges of motion. Subsequent excision of the capsule and cartilage of the facets, as in preparation for an arthrodesis of the facets, resulted in a significant increase in both the sagittal (5.7 +/- 2.9 degrees, mean and standard deviation) (p < 0.001) and the axial (1.4 +/- 0.9 degrees) (p < 0.01) ranges of motion compared with the motion in the intact specimen and with the motion in the specimen after only decompression had been done (p < 0.01 and p < 0.05, respectively). Packing of bone in the facets did not significantly reduce motion. It was calculated that the increase in the sagittal range of motion after excision of the capsule and cartilage of the facets would increase the tensile strain in a graft between the transverse processes of the fourth and fifth lumbar vertebrae (18 +/- 1 per cent tensile strain [mean and 95 per cent confidence interval] for the intact vertebrae and 25 +/- 1 per cent for the vertebrae in which the facets had been excised).

Biomechanical Phenomena↗

Clinical pharmacokinetics of cefotetan.

Cefotetan is a 7-alpha-methoxy beta-lactam. A long serum half-life and resistance to beta-lactamase hydrolysis have made cefotetan an attractive chemotherapeutic agent, and the results of clinical trials worldwide have demonstrated its efficacy in a wide variety of clinical situations. Cefotetan can be administered intravenously (bolus or infusion) or intramuscularly with lidocaine (lignocaine) 0.5%. Mean peak plasma concentrations are almost linearly related to dose. The volume of distribution is between 8 and 13L and is not different from other cephalosporins. No accumulation is seen after repeated doses and no metabolite has been detected in either plasma or urine. Total body clearance is 1.8 to 2.9 L/h. Renal clearance accounts for about 64 to 84% of a dose, and 75% of a dose is excreted in the urine within 24 hours. The plasma elimination half-life is between 3 and 4 hours after intravenous and intramuscular doses. Half-life is considerably prolonged in patients with renal impairment (up to 10 hours). Cefotetan concentrations are likely to be active against susceptible bacteria in most tissues and body fluids. Breast milk and cerebrospinal fluid concentrations are low. The recommended dosage is 1g every 12 hours, increasing to 2g in severe infections and 3g in life-threatening infections. In surgical prophylaxis, a single dose of 2g is given with the induction of anaesthesia; an additional dose of 2g may be administered 12 hours later. In children over 6 months, the recommended dosage is 30 mg/kg given 12-hourly. In patients with a creatinine clearance of 10 to 40 ml/min (0.6 to 2.4 L/h), the dose is halved or the dosage interval is doubled. When creatinine clearance is less than 10 ml/min (0.6 L/h), the dose is quartered or the dosage interval quadrupled.

Absorption↗

Isolation and characteristics of the protozoal and bacterial fractions from bovine ruminal contents.

Four cows were fed once a day either a Cocksfoot hay diet (H) or a diet consisting of 65% hay and 35% pelleted ground barley (HB). 15(NH4)2SO4 was continuously infused into the rumen as a microbial marker and ruminal digesta samples were collected during the 24-h postprandial period for the isolation of liquid-associated protozoa and bacteria (LAP, LAB) and particle-associated bacteria (PAB). There were marked differences between ruminal pH diurnal variations with diets H and HB. Irrespective of the diet and sampling time, the chemical composition (OM, N, DAPA, 15N) of the protozoa was clearly different from that of the bacteria (P < .001). The LAP contained more OM but less N and 15N than the bacterial fractions. The DAPA used to validate the isolation technique for the mixed ciliate population was not detected in protozoal fractions. The OM content of LAB was lower than that of PAB, whereas the N, DAPA, and 15N contents were higher. The observed effects of diet (P < .01) on LAP mean N contents were due to the different N contents of the LAP samples isolated 23 h after feeding and were correlated with the variation in the number of Endodiniomorphid protozoa (r = .72; P < .05). The N content of LAB was not affected (P > .05) by diet but that of the PAB was increased on diet HB (P < .05). The diet did not affect the 15N content of any of the three microbial populations. However, the 15N content of the bacteria decreased shortly after feeding (P < .001).

Animal Feed↗

Energy cost of standing and circadian changes in energy expenditure in the preruminant calf.

An experiment was conducted with four preruminant calves to measure the energy cost and the diurnal pattern of physical activity in tethered, fed calves and to determine whether differences in activity could interfere with the interpretation of circadian changes in heat production. Measurements were carried out in large respiration chambers (3,650 L of inner volume), and a computation method was presented that allowed the calculation of the energy cost of standing for each standing period. This cost averaged 449 cal.kg BW-1.h-1 (SE = 41.6, n = 4). It represented a 23 to 27% increase in heat production above that measured in the lying state. This estimate and its standard error were lower than values obtained by regression (2,131 cal.kg BW-1.h-1, SE = 862.2, n = 8). The energy cost of standing was highest after meal times and lowest at night. These variations could reflect the nonuniform activity patterns of calves while standing. The time spent standing per hour showed the same variations during the day as the energy cost of standing. Noteworthy, the elevated energy expenditure measured in the 1st h after the morning meal was due to activity cost rather than to meal thermogenesis. Standardization of diurnal heat production profiles to a given activity pattern thus seemed to be necessary.

Animals↗

A 'quality of life questionnaire' adapted to duodenal ulcer therapeutic trials.

In order to compare subpopulations of duodenal ulcer (DU) patients a quality of life (QoL) questionnaire (self-administered) was developed with the objective of investigating: (i) general parameters of health and well-being, and (ii) dimensions specifically adapted to patients with DU. For the former, Ware's MOS SF-36 was selected as a central core, with 36 items investigating 9 dimensions, and for the latter the anxiety scale (5 items) of the Psychological General Well-being Index (PGWBI) questionnaire and a further 5 dimensions (13 items) resulting from a preliminary survey of ulcer patients were selected. Validation of the proposed questionnaire was obtained for: linguistic aspects, content (i.e. ability to cover problems of patients suffering from DU), internal consistency, reliability, and sensitivity (i.e. analysis of discrimination between three groups of patients (acute DU episode, remission and control). The final version of the Quality of Life in Duodenal Ulcer Patients (QLDUP) questionnaire, which includes 54 items investigating 15 dimensions, appears to be a sensitive and reproducible tool, the simplicity of which makes it suitable for monitoring long-term treatments in DU.

Duodenal Ulcer↗

A quality of life study in five hundred and eighty-one duodenal ulcer patients. Maintenance versus intermittent treatment with nizatidine.

Quality of life (QoL) is commonly assessed for evaluating the process and outcome of treatment but has not been studied in duodenal ulcer (DU) disease. The recently developed and validated Quality of Life in Duodenal Ulcer Patients (QLDUP) questionnaire allowed the study of various dimensions according to treatment regimens. This study was conducted to compare QoL over a one-year follow-up period in DU patients randomized to two treatment regimens: maintenance versus intermittent (no maintenance) treatment with nizatidine. A total of 581 patients with endoscopic evidence of DU healing were randomly allocated to receive either nizatidine 150 mg/day for one year (Group A) or intermittent treatment (Group B). In both groups, symptomatic relapses were treated with nizatidine 300 mg/day for 6 weeks. The QLDUP questionnaire, which provides a QoL profile from 54 items divided up into 15 dimensions, was completed by all patients at entry and again at the time of a visit every 2 months for one year. The one-year symptomatic relapse rates were 8.0% and 33.5% in Group A and Group B, respectively (p < 0.001). The intent-to-treat analysis showed that patients in Group A had better QoL scores than those in Group B as regards 8 QoL dimensions, including ulcer-specific and non-specific dimensions. Differences between treatments were significant after 4 months, and this was sustained until the one-year assessment. The overall gain in QoL was significantly greater in Group A than in Group B with respect to 11 QoL dimensions. In conclusion, maintenance treatment with nizatidine for DU improved QoL to a larger extent than when intermittent therapy was used.

Adult↗

In vitro comparative study on nephrotoxicity of cyclosporine A, its metabolites M1, M17, M21, and its analogues cyclosporines C and D in suspensions of rabbit renal cortical cells.

The potential nephrotoxicity of cyclosporine A (CsA), its three main metabolites: M1, M17 and M21, and its two analogues: cyclosporines C and D (CsC, CsD) was evaluated in vitro in suspensions of freshly isolated rabbit renal proximal tubular cells. This assessment involved the measure of enzyme release in the incubation media and the determination of Na+/K(+)-ATPase activity and glutathione content directly in the tubular cells. In vitro nephrotoxicity results of the six compounds tested could be respectively schematized as: CsA > CsD > CsC > M21 > M17, M1 It would be interesting to promote the study of promising CsC because of its low nephrotoxicity and its high immunosuppressive potency as previously reported.

Animals↗

Effects of cyclosporin on kidney glutathione metabolism and cytochrome P-450 in the rabbit: possible implication of eicosanoid metabolism.

This study was designed to assess Cyclosporin A (CsA) nephrotoxicity in the rabbit-possibly a more sensitive species than the rat-and to explore the mechanism of this toxicity with special attention to glutathione metabolism disturbances and cytochrome P-450 level in the kidney. CsA given for three days at a daily dose of 50 mg/kg (s.c.) induced nephrotoxicity as assessed by histological abnormalities and by a significant increase in blood urea nitrogen and urinary enzyme activities: N-acetyl-beta-D-glucosaminidase and L-gamma-glutamyl-transferase. This observed renal injury was of the same order as that obtained in the rat. In addition, there was a significant increase in oxidized glutathione content (40%) while reduced glutathione level remained unchanged. Concurrently, there was a significant decrease in renal cortex glutathione reductase (49%) and to a lesser extent in glutathione peroxidase activities (16%) whereas that of glutathione-S-transferase was not modified. A significant increase in renal cortex cytochrome P-450 (3-fold versus controls) was also observed. The mechanism of CsA nephrotoxicity is to be related to a cytochrome P-450 induction. This event could induce the observed impairments in renal glutathione metabolism and Na+K(+)-ATPase activity, via a possible increase in eicosanoid metabolism.

Animals↗

"Stockless" cost reduction in the operating room.

St. Paul-Ramsey Medical Center in St. Paul, MN became one of the first hospitals in the United States to initiate a "stockless" par level inventory system. Successes with stockless led the hospital to look at implementing it in the OR to achieve a reduction of expense to revenue. Materiel Management and Surgical Services discussed a number of issues relevant to implementing a stockless program, including product flow, accuracy and cost of case carts and preference cards, item pricing, committed usage of items brought into the system and establishment of a steering committee. Specific OR issues and practices required evaluation and adjustment, such as the routine use of emergency direct ordering. Information systems support was brought in and a products committee established to do education and oversee the program. Savings for 1993-94 were $185,146.

Cost Savings↗

[Penetration of vancomycin in cardiac and mediastinal tissues in humans].

Vancomycin penetration into heart tissues (valves, myocardium, auricles and pericardium) and mediastinal tissues (fat and sternal bone) after two regimens of administration was evaluated in a prospective, randomized study. Twenty adult patients undergoing mitral or aortic valve replacement were included in the study and divided into two groups of ten patients each: Group 1 patients were administered a 15 mg/kg intravenous dose of vancomycin over 90 min upon anesthesia. Group 2 patients received the same dose followed by a second 7.5 mg/kg intravenous dose of vancomycin over 30 min at time of initiation of the cardiopulmonary bypass. In both groups further vancomycin administrations (10 mg/kg) were performed on hour 8, 16 and 24. Plasma and tissue vancomycin concentrations were assayed by fluorescence polarization immunoassay. At different times of the surgical procedures (thorax opening and closure, period of cardiopulmonary bypass) 67 to 100% of the patients in group 1 had vancomycin concentrations in the studied tissues above the MIC 90 for Staphylococcus aureus (1 microgram/g) and Staphylococcus epidermidis (2 micrograms/g). In group 2, for the same periods and the same tissues, 72 to 100% of patients had adequate vancomycin concentrations. In group 1 patients, mean ratios of vancomycin tissue concentrations/MIC 90 were 6 +/- 2 to 20 +/- 4 for Staphylococcus aureus (MIC 90: 1 microgram/g) and 3 +/- 1 to 10 +/- 4 for Staphylococcus epidermidis (MIC 90: 2 micrograms/g). In group 2 patients, mean ratios were 8 +/- 3 to 20 +/- 4 for Staphylococcus aureus and 4 +/- 1 to 10 +/- 3 for Staphylococcus epidermidis. The use of a second dose of vancomycin in group 2 significantly increased plasma concentrations (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗