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Biomedical subjects

C Martin

Publications and source records attributed to C Martin.

At least 37 records · Page 2Linked to original sources

Starch branching enzymes belonging to distinct enzyme families are differentially expressed during pea embryo development.

cDNA clones for two isoforms of starch branching enzyme (SBEI and SBEII) have been isolated from pea embryos and sequenced. The deduced amino acid sequences of pea SBEI and SBEII are closely related to starch branching enzymes of maize, rice, potato and cassava and a number of glycogen branching enzymes from yeast, mammals and several prokaryotic species. In comparison with SBEI, the deduced amino acid sequence of SBEII lacks a flexible domain at the N-terminus of the mature protein. This domain is also present in maize SBEII and rice SBEIII and resembles one previously reported for pea granule-bound starch synthase II (GBSSII). However, in each case it is missing from the other isoform of SBE from the same species. On the basis of this structural feature (which exists in some isoforms from both monocots and dicots) and other differences in sequence, SBEs from plants may be divided into two distinct enzyme families. There is strong evidence from our own and other work that the amylopectin products of the enzymes from these two families are qualitatively different. Pea SBEI and SBEII are differentially expressed during embryo development. SBEI is relatively highly expressed in young embryos whilst maximum expression of SBEII occurs in older embryos. The differential expression of isoforms which have distinct catalytic properties means that the contribution of each SBE isoform to starch biosynthesis changes during embryo development. Qualitative measurement of amylopectin from developing and maturing embryos confirms that the nature of amylopectin changes during pea embryo development and that this correlates with the differential expression of SBE isoforms.

1,4-alpha-Glucan Branching Enzyme

Biochemical and molecular characterization of a novel starch synthase from potato tubers.

An isoform of starch synthase from potato tubers which is present both in the stroma of the plastid and tightly bound to starch granules has been identified biochemically and a cDNA has been isolated. The protein encoded by the cDNA is 79.9 kDa and has a putative transit peptide and a distinct N-terminal domain which is predicted to be highly flexible. It is similar in both amino acid sequence and predicted structure to the granule-bound starch synthase II (GBSSII) of pea embryos. When expressed in Escherichia coli, the mature protein has starch synthase activity. The importance of the isoform has been assessed by biochemical measurements and antisense transformation experiments in which the amount of the isoform in the tuber is severely and specifically reduced. Both approaches indicate that the isoform contributes a maximum of 15% of the total starch synthase activity of the tuber. It is suggested that this isoform and the GBSSII of pea embryos represent a widely distributed class of isoforms of starch synthase. The contribution to total starch synthase activity of members of this class probably varies considerably from one type of storage organ to another.

Amino Acid Sequence

CDP571, a humanized antibody to human tumor necrosis factor-alpha: safety, pharmacokinetics, immune response, and influence of the antibody on cytokine concentrations in patients with septic shock. CPD571 Sepsis Study Group.

OBJECTIVES: To determine the safety of a "humanized" antibody to human anti-tumor necrosis factor-alpha (TNF-alpha) in patients with septic shock, and to examine the pharmacokinetics, immune response, and influence of the antibody on cytokine concentrations in this patient group. DESIGN: Prospective, randomized, placebo-controlled, phase II multicenter clinical trial, with escalating doses of a fully humanized anti-TNF-alpha antibody (CDP571). SETTING: Seven academic intensive care units in Europe. PATIENTS: Forty-two patients with rapidly evolving septic shock who received CDP571 in addition to standard supportive care. INTERVENTIONS: Patients received intravenously either placebo or one of four single doses of CDP571: 0.1, 0.3, 1.0, or 3.0 mg/kg. MEASUREMENTS AND MAIN RESULTS: The humanized anti-TNF-alpha antibody was well tolerated. The overall all-cause 28-day mortality rate was 62%. Mortality rate was similar in the placebo and treatment groups, except that all six patients who received 0.3 mg/kg of CDP571 died within 7 days. This outcome, which was not dose-related, is consistent with the poorer prognostic characteristics of this group at baseline. The peak CDP571 concentrations and area under the curve increased proportionately with the dose. The low level of the immune response detected had little effect on the ability of circulating CDP571 to bind TNF-alpha and on the pharmacokinetics of the antibody. An abrupt reduction in circulating TNF-alpha concentration was observed 30 mins after CDP571 administration at all active dosage levels. While interleukin-1 beta and interleukin-6 plasma concentrations decreased with time in all dosage groups, these cytokine concentrations decreased more rapidly during the initial 24 hrs in the treatment groups than in the placebo group. CONCLUSIONS: The humanized anti-TNF-alpha antibody, CDP571, is well tolerated and able to cause a dose-dependent reduction in circulating TNF-alpha concentrations in patients with septic shock. Further studies are needed to determine the efficacy of this antibody to improve the survival rates of critically ill patients with severe sepsis.

APACHE

Comparison of concentrations of two doses of clavulanic acid (200 and 400 milligrams) administered with amoxicillin (2,000 milligrams) in tissues of patients undergoing colorectal surgery.

The concentrations of clavulanic acid and amoxicillin were determined in sera and different abdominal tissues of 17 patients who underwent elective colorectal surgery. Patients were randomly allocated to two groups. At the time of induction of anesthesia, patients in group 1 were given 200 mg of clavulanic acid with 2,000 mg of amoxicillin and patients in group 2 received 400 mg of clavulanic acid with 2,000 mg of amoxicillin. In both groups, the initial dose was administered again after 2 h. Blood samples were collected to determine peak and trough antibiotic levels. Serial blood samples were also collected at predetermined periods (opening and closure of the abdominal cavity and surgical anastomosis). Abdominal wall fat, epiploic fat, and colonic wall tissue samples were collected simultaneously. Antibiotic concentrations were determined by high-performance liquid chromatography. Increasing the dose of clavulanic acid to 400 mg resulted in significantly higher peak and trough levels in serum (P < 0.03). Following the injection of 400 mg, mean concentrations of clavulanic acid in the fatty tissues were significantly increased at the time of opening (P < 0.02). The concentrations of clavulanic acid and amoxicillin in fatty tissues were 17 to 52% and 12 to 23% of the levels in sera, respectively. In the colonic wall, the concentrations of clavulanic acid and amoxicillin were 52 to 63% and 49 and 27% of the levels in sera, respectively. In sera, clavulanic acid given at a dose of 200 or 400 mg reached or exceeded the concentrations found to be effective in vitro to reduce the MICs of amoxicillin from the resistant to the susceptible category for 90% of the potential pathogens. In most of the tissues investigated, increased the dose of clavulanic acid to 400 mg resulted in a significantly higher number of samples with concentrations found to be effective in vitro (72 versus 11%; P < 0.05). In conclusion, increasing the dose of clavulanic acid to 400 mg resulted in higher levels in sera and improved penetration into the abdominal tissues in patients undergoing colorectal surgery.

Adipose Tissue

Genetic diversity of Pseudomonas aeruginosa strains isolated from patients with cystic fibrosis revealed by restriction fragment length polymorphism of the rRNA gene region.

The restriction fragment length polymorphism patterns of rDNAs from Pseudomonas aeruginosa strains isolated from the respiratory tracts of patients suffering from cystic fibrosis were obtained to evaluate the genetic polymorphism of this population of strains. Eighty-seven P. aeruginosa strains isolated from 87 patients from diverse areas of France and the ATCC 10145 strain were examined. Four restriction enzymes were used: BamHI, ClaI, EcoRI, and PstI. Forty-nine strains (56%) were in the three most frequent ribotypes (ribotypes R1 to R3). In addition, hierarchical clustering analysis of the data showed that 71 of the 88 strains (81%) clustered at a distance of less than one-third of the greatest distance observed in the total population. This indicates that clinical isolates implicated in the pathology of cystic fibrosis present a low degree of heterogeneity of rRNA operons, in contrast to the heterogeneity of strains of P. aeruginosa isolated from patients with various other pathologies. This relative homogeneity of rRNA genes was observed independently of the clinical status of the patient and the colony morphology.

Adolescent

Chromosomal DNA fingerprinting analysis using the insertion sequence IS6110 and the repetitive element DR as strain-specific markers for epidemiological study of tuberculosis in French Polynesia.

The polymorphism of Mycobacterium tuberculosis strains was evaluated in French Polynesia, an area with a low incidence of tuberculosis and a population which has been geographically stable during recent decades. Nonrepetitive strains isolated from 64 patients during 1991 and 1992 were subjected to DNA restriction fragment length polymorphism (RFLP) analysis, using the insertion sequence IS6110 and the repetitive element DR as probes. Thirty-eight different IS6110 RFLP types were identified. They could be clustered in 11 groups. All the members of each group are identical or differ by one to three bands. All the other strains are gathered in the miscellaneous group. In some cases, transmission of strains with identical RFLP types between patients of the same family or between patients living in the same area was identified. Strains exhibiting similar IS6110 RFLP types also exhibited identical DR RFLP patterns, confirming that strains with similar types were genetically linked. Strains belonging to two different IS6110 clusters exhibited the same DR RFLP type. These data may also indicate a common origin for these strains and evolution to new IS6110 types. The results obtained in this study suggest that not only reactivation of latent tuberculous infections but also active transmissions are still occurring in French Polynesia.

Adolescent

Pulmonary fibrosis correlates with outcome in adult respiratory distress syndrome. A study in mechanically ventilated patients.

STUDY OBJECTIVE: The present study was carried out to evaluate the prognostic value of pulmonary fibrosis diagnosed on the basis of pulmonary samples obtained by fiberscopic transbronchial lung biopsy (TBLB) in patients treated for severe established adult respiratory distress syndrome (ARDS). DESIGN: Prospective cohort study. SETTING: Intensive Care Unit of a University Hospital. PATIENTS: Consecutive patients with a diagnosis of established ARDS. INTERVENTIONS: Samples of pulmonary tissue (3 to 6 in each patient) were obtained by fiberoptic TBLB. Severity of pulmonary fibrosis was assessed based on pathologic changes. Hematoxylin and eosin and Masson's trichrome stains were performed on each tissue sample. MAIN RESULTS: Twenty-two lung specimens were obtained from 25 consecutive patients with ARDS of various origin (postsurgical complications, 7 patients; multiple trauma, 8 patients; medical problems, 7 patients). Transbronchial lung biopsy was complicated by small or moderate hemorrhage in three patients. No case of pneumothorax was identified. Pathologic findings showed that 14 patients (64%) had pulmonary fibrosis, either mild (9 patients) or moderate to severe fibrosis (5 patients). In the patients with pulmonary fibrosis, mortality rate was 57% (8 out of 14 patients), which was significantly different (p < 0.02) from the 0% mortality rate observed in patients without pulmonary fibrosis. Severity of pulmonary fibrosis (mild vs moderate and severe) did not influence outcome. With the exception of pathologic findings, characteristics of patients with and without pulmonary fibrosis (PaO2, PaCO2, the ratio of PaO2 to fraction of inspired oxygen, and positive end-expiratory pressure) were not different. CONCLUSION: In the study patients, pulmonary fibrosis diagnosed on the basis of TBLB was closely related to fatality in established ARDS.

Adult

Comparing two heat and moisture exchangers with one vaporizing humidifier in patients with minute ventilation greater than 10 L/min.

STUDY OBJECTIVE: To evaluate in patients submitted to minute ventilation > 10 L/min the ability to preserve patients' heat and humidity of two heat and moisture exchangers (HMEs) and one vaporizing humidifier (VH). DESIGN: Prospective, randomized, comparative, non-blinded study. SETTING: Intensive care unit of a university hospital. PATIENTS: Nine tracheally intubated, mechanically ventilated patients, sedated and submitted to mechanical ventilation with minute ventilation > 10 L/min. INTERVENTIONS: Using the psychrometric method, relative humidity (RH) and absolute humidity (AH) of inspired gas were obtained as well as temperature of inspired gas and tracheal temperatures (maximal and minimal). Following a randomized order, each patient was ventilated for two 24-h periods with a vaporizing humidifier (Bennett Cascade 2, Bennett; France) and one of two HMEs: Pall Ultipor filter BB50 (Pall Biomedical; France) or DAR Hygroster filter (Peters; France). Both were first tested for a 45-min period and then the HME that achieved the best performance in terms of temperature and water preservation was tested for 24 h. MEASUREMENTS AND RESULTS: During the 45-min test period, the Pall Ultipor HME achieved a lower performance than the other two systems for any of the studied parameters (p < 0.05 to p < 0.0001). The DAR Hygroster HME achieved lower temperature of inspired gas (29.9 vs 32.0 degrees C, p < 0.005) and lower absolute humidity (29.3 vs 33.2 mg H2O/L, p < 0.005) than the Bennett Cascade 2. After 24 h of use, lower values of temperature of inspired gas (28.5 vs 32.0 degrees C, p < 0.002) and of AH (28.0 vs 33.6 mg H2O/L, p < 0.001) were obtained with the DAR Hygroster HME than with the Bennett Cascade 2. No differences were found between the two systems for the other tested parameters. At that time, no patients had RH lower than 97% and absolute humidity lower than 23 mg H2O/L with the use of the DAR Hygroster HME. CONCLUSIONS: In patients with minute ventilation > 10 L/min, the DAR Hygroster HME showed a thermic and humidification capability similar to the reference system, the Bennett Cascade 2 VH. In these patients, the Pall Ultipor HME had a significantly lower capability.

Adolescent

Circadian changes in energy expenditure in the preruminant calf: whole animal and tissue level.

A study was conducted using four preruminant calves to determine the contribution of portal-drained viscera, liver, and hindquarters to circadian changes in total energy expenditure, after removing variations due to behavioral patterns. Indirect calorimetry and in vivo arterio-venous techniques were used. Standing time was longer (P < .01) after the meals and shorter (P < .01) at night. These variations were associated with higher (P < .01) energy cost of standing immediately after the meals and lower (P < .01) ones at night. When these behavioral effects were removed, total energy expenditure of lying calves was shown to be stable between the morning and evening meal, to increase by 11.5% and remained elevated during the 6 h after the evening meal, and to reach the lowest values at night. Portal-drained viscera and liver contributed 32.8 to 53.7% and 29.1 to 32.2%, respectively, to the circadian variations calculated for calves that were always standing. Changes in splanchnic tissue energy expenditure resulted from combined modifications in blood flow and O2 extraction rate. The contribution of hindquarters could not be clearly established. Overall, portal-drained viscera, liver, and hindquarters contributed 17.2, 12.8, and 18.0%, respectively, to total energy expenditure of standing calves. Their respective in vivo metabolic activities averaged 1.08, 2.10, and .25 mumol of O2 consumed.min-1.g-1 of fresh tissue.

Animals

[Penetration of ceftriaxone (1 or 2 gr intravenous) into mediastinal and cardiac tissues in man].

Ceftriaxone penetration into heart tissues (valves, myocardium, auricles and pericardium) and mediastinal tissues (fat and sternal bone) was evaluated after two regimens of ceftriaxone administration. Ten patients were given 1,000 g intravenously of ceftriaxone 30 min. before anesthesia. Ten other patients received the same dose and then a second 1,000 mg dose at the time of initiation of cardiopulmonary bypass. Similar and very satisfactory ceftriaxone tissue penetrations were observed in both groups. However, for some patients in the two groups and mainly in the sternal bone at the time of thorax closure, ceftriaxone levels in tissues were less than the MICs for some potential pathogens (Methicillin susceptible Staphylococcus aureus and Staphylococcus epidermidis). During the different steps of the surgical procedures all patients in both groups had tissue levels greater than the MICs for Gram negative aerobic bacilli, except for Pseudomonas spp.

Adult

[Widened retrolabyrinthine approach. Value in the surgery of acoustic neuroma with attempt of hearing preservation].

The retrolabyrinthine approach was described several years ago, however its use was restricted to functional surgery of the cerebellopontine angle. Its detractors reproach its narrowness. But a large approach to the cerbellopontine angle can be performed after an extended exposure of the posterior and middle fossa dura, and section of the endolymphatic sac. This approach was used in 5 cases of acoustic neurinomas stage I and II, with normal hearing. Hearing preservation was obtained in 2 cases. We had deafness in 2 cases who had extensive tumor in the bottom of the internal auditory canal.

Hearing Disorders

Biomechanical effects of different surgical procedures on the extensor mechanism of the patellofemoral joint.

Loadbearing stresses in the patellofemoral joint were studied at different degrees of flexion before and after various surgical techniques recommended to treat knee disorders. Surgical procedures intended to reduce the intensity of stress were analyzed experimentally. The study was done using different experimental methods on whole knee specimens from fresh human cadavers that were not treated with formaldehyde. The results indicate that the most predictable procedure for increasing surface area and decreasing patellar stress is a combined procedure of anterior displacement of the anterior tibial tubercle by 1 cm while displacing it 0.5 to 1 cm medially.

Biomechanical Phenomena

Sensory receptors in the anterior uvea of the cat's eye. An in vitro study.

PURPOSE: To identify electrophysiologically the functional types of sensory fibers innervating the iris and the ciliary body of the cat's eye. METHODS: The uveal tract tract of cat's eye was excised and placed in a superfusion chamber. Recordings were made from single afferent units of ciliary nerve branches responding to mechanical stimulation of the iridal surface, the ciliary body, and the choroid with a nylon filament or a glass rod. Chemical sensitivity was explored by applying acetic acid, hypertonic NaCl, and bradykinin. Warm (60 degrees C) and cold (4 degrees C) saline and a servocontrolled thermode were used for thermal stimulation. RESULTS: Thirty per cent of the studied population of sensory units (n = 95) were spontaneously active when the recording was started. Approximately 30% of the fibers conducted in the lowest range of the A-delta group; the remaining 70% were C fibers. Sustained mechanical stimulation of the receptive area elicited a tonic response in approximately 60% of the units, and a phasic response in the remaining 40%. Exposure of the receptive field of mechanosensitive fibers to 600 mM NaCl evoked a long-lasting discharge in 50% of the units; application of 1 to 10 mM acetic acid elicited a short discharge in 30% of the fibers, often followed by inactivation. Bradykinin (1 to 100 microMs) produced a long-lasting response in almost 50% of the units. Warming the receptive field recruited 20% of the explored units, whereas 17% were activated by low temperature. CONCLUSIONS: Two main functional types of sensory fibers innervating the iris and the ciliary body were distinguished: (1) mechanoreceptors, corresponding to afferent units sensitive only to mechanical stimuli were generally silent at rest, had relatively higher force thresholds, and discharged phasically in response to long-lasting mechanical stimulation; (2) polymodal nociceptors, which were activated by mechanical as well as by chemical and/or thermal stimuli, usually displayed spontaneous activity, had lower force thresholds, and fired tonically upon sustained mechanical stimulation.

Acetates

["Optimized" retrolabyrinthine approach. Contribution of endoscopy of the cerebellopontine angle].

Retrolabyrinthic access was described long ago but was often found to narrow and progressively abandoned in favour of the retrosigmoid route. Certain modification in the initial technique, notably in wider dissection of the dura-mater of the sigmoid sinus and sometimes section of the endolymphatic canal provides a larger access to the ponto-cerebellous angle. A rigid 0 degree or 30 degrees endoscope can be introduced. In order to evaluate this method, we examined surgical specimens and subjects operated via retrolabyrinthic access for a neurinoma of the acoustic nerve in an attempt to preserve auditive function or for suspected vessel-nerve conflict. Our findings demonstrated that the retrolabyrinthic route allows direct access to the ponto-cerebellous angle doser to the vascular and nervous structures than the retro-sigmoid route and also provides remarkable endoscopic vision of the angle and its elements. This route is particularly interesting for surgery of acoustic neurinomas when attempting to preserve the auditive functions, for diagnosis and treatment of vessel-nerve conflicts, and to a lesser extent for vestibular neurotomy or for evaluating certain diseases difficult to diagnosis in the posterior cranial fossa.

Cerebellar Neoplasms

[Comparative study of recovery in neurosurgery after continuous perfusion of etomidate or propofol].

Two groups of patients were studied. Patients in group 1 were given 0.3 mg.kg-1 IV etomidate, 5 micrograms.kg-1 fentanyl and 0.6 mg.kg-1 atracurium for induction. Maintenance was obtained using continuous infusion of etomidate and fentanyl. Patients in group 2 were given propofol for induction and maintenance. Recovery was assessed with three parameters: time to recovery of spontaneous ventilation (SV), time to obey oral order (OO), and time to obey written order (WO). Time to OO and WO were significantly shorter in group 2.

Adult