The intrapulmonary oxygen store.
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Biomedical subjects
Publications and source records attributed to E Martin.
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The prognostic significance of magnetic resonance imaging (MRI) in the neonatal period was studied prospectively in 43 term infants with perinatal asphyxia. MRI was performed between 1 and 14 days after birth with a high field system (2.35 Tesla). Neurodevelopmental outcome was assessed by a standardized neurological examination and the Griffiths developmental test at a mean age of 18.9 months. The predictive value of the various MRI patterns was as follows: Severe diffuse brain injury (pattern AII+III; n = 7) and lesions of thalamus and basal ganglia (pattern C; n = 5) were strongly associated with poor outcome and greatly reduced head growth. Mild diffuse brain injury (pattern AI; n = 7), parasagittal lesions (B; n = 7), periventricular hyperintensity (D; n = 2), focal brain necrosis and hemorrhage (E; n = 3) and periventricular hypointense stripes (on T2-weighted images; F; n = 3) led in one third of the infants to minor neurological disturbances and mild developmental delay. Infants with normal MRI findings (G; n = 9) developed normally with the exception of one infant who was mildly delayed at 18 months. The results indicate that MRI examination during the first two weeks of life is of prognostic significance in term infants suffering from perinatal asphyxia. Severe hypoxic-ischemic brain lesions were associated highly significantly with poor neuro-developmental outcome, whereas infants with inconspicuous MRI developed normally.
Distribution volumes and metabolism determine the pharmacokinetics of midazolam. Cytochrome P450 3A4 has been considered a significant enzyme in its metabolism. Using heterologously expressed cytochrome P450 enzymes, we have confirmed the additional involvement of cytochromes P450 3A3 and 3A5 in the hydroxylation of the midazolam. Whereas cytochrome P450 3A3 metabolized midazolam to the same extent as cytochrome P450 3A4, cytochrome P450 3A5 increased its metabolism by a factor of 2.7. The relationship of alpha- to 4-hydroxylation of midazolam was approximately 1.3 for cytochromes P450 3A3 and 3A4, and approximately 8.8 for 3A5. The primary location of cytochromes P450 3A3 and 3A4 is the liver in contrast with cytochrome P450 3A5, which occurs predominantly in the kidney. Therefore, further in vivo study is required to prove conclusively that enzymes in the kidney are involved in the metabolism of midazolam. Nitrendipine itself is metabolized by cytochrome P450 3A enzymes and this was shown to inhibit human liver microsomal hydroxylation of midazolam and preferentially alpha-hydroxylation by about 77%. 4-Hydroxylation was inhibited to 32% of control by nitrendipine. In contrast with inhibition of 4-hydroxylation, alpha-hydroxylation would appear to be competitively inhibited. These findings may be relevant to drug interactions in combined therapy.
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The use of intravascular catheters is associated with infectious complications. Using plastic materials with antibacterial activity may reduce catheter-related bacterial colonization. A novel intravascular catheter impregnated with the antiseptics silver-sulphadiazine and chlorhexidine was tested in an in-vivo model using implantation of catheters into the internal jugular veins of rats. The rate and magnitude of bacterial colonization in groups with implantation of silver-sulphadiazine and chlorhexidine bonded (SSC) and control (C) catheters were assessed 3 and 7 days after intravenous implantation, and local challenge at the exit site by 10(7) cfu Staphylococcus epidermidis ATCC 35984. Significant reductions in the culture positivity of catheters were observed in the test compared with control groups. After 3 and 7 days, the magnitude of bacterial colonization of implanted catheter segments was significantly lower compared with control catheters (P < 0.01). These findings indicate that antiseptic-bonded catheters substantially reduce the incidence and magnitude of catheter-related bacterial colonization, and may subsequently reduce catheter-related infection.
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The influence of low doses of amphotericin B on the capacity of human monocytes to kill Candida albicans was investigated. Killing rates were quantified by a novel flow cytometric assay and were found to be 37% +/- 3% (standard error of the mean) after 3 h. Preincubation of monocytes for 6 to 20 h with low concentrations of amphotericin B (0.2 microgram/ml) resulted in a markedly augmented fungicidal capacity. Enhancement of killing was 80% +/- 11% (standard error of the mean) over that by the controls. This effect did not appear to be due to amphotericin B-dependent monocyte activation; the respiratory burst and expression of human leukocyte antigen-DR were unaltered, and no stimulation of interleukin-1 beta release occurred. Cell-associated amphotericin B was extracted with acetonitrile and was quantified by scanning spectrophotometry. Amphotericin B appeared to accumulate in the cells, and intracellular concentrations attained after overnight incubation in 1 microgram of the drug per ml were estimated to be in the range of 50 fg per cell. The fact that intracellular accumulation was responsible for the enhanced fungicidal capacity of monocytes was supported by the findings that killing of Staphylococcus aureus remained normal and enhancement of killing of an amphotericin B-resistant C. albicans strain was minimal. Dramatic enhancement of monocyte fungicidal capacity probably extends to other amphotericin B-susceptible fungi and could represent a hitherto unrecognized determinant underlying the curative properties and prophylactic efficacy of this drug.
This study addressed the effects of fluconazole and 5-fluorocytosine on the candidacidal activity of amphotericin B in the presence of human serum. A Candida albicans isolate that was susceptible to all three agents according to standard testing procedures was employed. Fungicidal activity was estimated by using a flow cytometric procedure that exploited the fact that yeast cells killed by amphotericin B diminish in size and take up propidium iodide. The following findings were made. (i) Fluconazole and 5-fluorocytosine each failed to inhibit pseudohyphal formation and cell aggregation even when applied at 10 and 50 micrograms/ml, respectively, for up to 10 h. Hence, these agents were not fungistatic when tested in the presence of serum. (ii) Simultaneous application of 5-fluorocytosine had neither enhancing nor inhibitory effects on the fungicidal activity of amphotericin B. However, yeasts that were preincubated for 20 h with 5-fluorocytosine became less susceptible to killing by amphotericin B. (iii) Fluconazole exerted a frank antagonistic effect on the fungicidal activity of amphotericin B. Thus, under our in vitro conditions, both fluconazole and 5-fluorocytosine can overtly antagonize the candidacidal action of amphotericin B.
Since nonencapsulated Haemophilus influenzae persists in the lower respiratory tracts of patients with chronic bronchitis despite the presence of specific antibodies, complement, and polymorphonuclear leukocytes (PMNs), opsonophagocytosis of H. influenzae was analyzed. Nonencapsulated H. influenzae isolated from the sputa of chronic bronchitis patients was labeled with fluorescein isothiocyanate and incubated with human PMNs in the presence of complement and antibodies for 30 min at 37 degrees C. Candida albicans was added to each sample as an internal standard, and the reduction of the number of bacteria was determined by flow cytometry. Fluorescence quenching with ethidium bromide was used to discriminate between intracellular and extracellular bacteria. Opsonophagocytosis of viable H. influenzae d1 was 17% +/- 29% in the presence of complement and human pooled sera containing high titers of strain-specific antibodies. Opsonophagocytosis of six other H. influenzae strains was also poor. Under the same conditions, opsonophagocytosis of Staphylococcus aureus was 90% +/- 5%, and opsonophagocytosis of C. albicans was 55% +/- 23%. About half of the number of H. influenzae bacteria associated with PMNs was internalized. Opsonophagocytosis of heat-killed H. influenzae d1 (41% +/- 20%) was higher than that of viable bacteria of the same strain (P < 0.05). This result suggests that the accessibility of epitopes on H. influenzae for opsonizing antibodies is better on killed than on viable bacteria. We conclude that viable nonencapsulated H. influenzae is poorly opsonophagocytized in the presence of strain-specific antibodies and complement.
This study was designed to compare the efficacy and serum concentrations of alfentanil given subcutaneously (SQ) or epidurally (EPID) for treatment of postoperative pain. Following abdominal surgery, patients (n = 12) were randomly assigned to receive double-blind SQ or EPID alfentanil over 24 h via the allocated route (1 mg along with 0.2 mg/h and 0.2-mg boluses on demand) and saline via the other route of administration using a patient-controlled analgesic (PCA) delivery system. Significantly less EPID alfentanil produced better quality analgesia and fewer side effects than SQ alfentanil. The fact that EPID analgesia was maintained with serum alfentanil concentrations less than those producing systemic analgesia confirms the spinal site of the EPID alfentanil action.
Bolus administration of high-dose thrombolytic agents has been reported for the treatment of acute pulmonary embolism. We describe the case of a 60-year-old woman who suffered a massive pulmonary embolism with cardiopulmonary arrest 21 h after an exploratory laparotomy. After 20 min of unsuccessful cardiopulmonary resuscitation (CPR), a bolus of 2,000,000 U of urokinase was injected via a peripheral vein. Ten minutes later, the circulatory system stabilized, and the patient survived without subsequent bleeding. In our opinion, bolus lysis made a definitive contribution to the success of the resuscitation. Several other case reports and small series showed successful treatment of pulmonary embolism during similar circumstances using high-dose bolus injection of thrombolytic agents. Mechanical thrombus fragmentation using a pulmonary artery catheter or pulmonary embolectomy has not been shown to be more successful during resuscitation. We conclude that bolus administration of thrombolytic agents during CPR for massive pulmonary thromboembolism may be an acceptable and successful technique, which also is available even in the community hospital setting.
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An epidemic of dengue fever occurred in Grande Comore island from March to May 1993. Dengue 1 virus has been isolated. The epidemic did not affect the other islands of the archipelago. No compound clinical picture, in particular hemorrhagic, was reported. A random sampling survey conducted towards the end of April showed that 26% of the population aged 5 years old or more had IgM dengue antibodies. The epidemic concerned essentially individuals under 45 years of age. The number of inhabitants of Grande Comore affected by the outbreak can be estimated between 56,000 and 75,000. The results of the sero-epidemiological survey allowed to find the serological scar of two previous epidemics of dengue: the first one around 1948, which may correspond with dengue 1, the other one in 1984, probably with dengue 2.
The ATB 32C (bioMerieux, Spain), AMS-YBC (Vitek System, bioMerieux, Spain) and API 20C (bioMerieux, Spain) systems were evaluated for their reliability in identifying 100 clinical yeast isolates. The ATB 32C, AMS-YBC and API 20C systems correctly identified 97%, 98% and 100% of the isolates respectively. There were no significant differences in incubation periods between ATB 32C and AMS-YBC systems. One isolate of Candida tropicalis was wrongly identified by the ATB 32C and the AMS-YBC systems. The Saccharomyces cerevisiae isolate was wrongly identified by the ATB 32C system while the AMS-YBC failed to identify it and a third isolate of Candida krusei was wrongly identified by the ATB 32C system. The overall accuracy and rapidity of the ATB 32C and AMS-YBC systems were sufficient to permit recommendation of either of these systems for routine use in the clinical microbiology laboratory, although the first system enjoys the advantages of having a wider data-base and the possibility of manual reading.
The authors report a case of protein losing gastropathy associated with cytomegalovirus. This form which is extremely rare in adults occurred alone after allogenic bone marrow transplantation and become apparent by a hypoalbuminaemia causing oedema of the lower limbs. Gastrocopy showed large red folds of approximately a centimetre covered in a whitish hypersecretion coating. Biopsy demonstrated active gastritis which appeared on a hypertrophic and hypersecretive gastritis. Outcome was favourable within 3 months without treatment.