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J Albanese

Publications and source records attributed to J Albanese.

At least 19 recordsLinked to original sources

Ionizing radiation alters Fas antigen ligand at the cell surface and on exfoliated plasma membrane-derived vesicles: implications for apoptosis and intercellular signaling.

Resident proteins that reside on the plasma membrane are continually exfoliated from the cell surface. Exfoliation is a selective, energy-dependent process that mediates intercellular communication. Ionizing radiation modulates the expression of many plasma membrane-bound growth regulators, including the "death" ligand, TNFSF6 (formerly known as FasL, CD95L). Here we report that ionizing radiation induces dose-dependent up-regulation of TNFSF6 on plasma membranes purified from SW620 cells, a TNFSF6-expressing colon cancer cell line. Serum-free medium conditioned by exposed and control cells was collected and exfoliated vesicles were obtained by ultracentrifugation. Western blot analysis of vesicles from unexposed cells and from cells treated with 10 Gy showed increased amounts of TNFSF6 compared to that on vesicles from unexposed cells. Cells treated with 4 Gy released vesicles having a low level of TNFSF6 on their surface relative to that on vesicles exfoliated from unexposed cells. When assayed for bioactivity, vesicles from unexposed cells induced the greatest level of apoptosis in TNFRSF6 (formerly known as FAS) receptor-bearing Jurkat cells (cell surviving fraction of 43.7 +/- 6.1; P < 0.05), followed by vesicles collected from cells treated with 4 Gy (79.6 +/- 2.6%; P < 0.05). Despite having a high level of TNFSF6 by Western analysis, vesicles collected from cells exposed to 10 Gy display minimal biological activity (77.9 +/- 3.2%; P < 0.05), suggesting that modification of the vesicle-associated ligand has occurred. Our results indicate that ionizing radiation increases the level of TNFSF6 exfoliated on extracellular vesicles. The data may provide a mechanism for abscopal and bystander effects after irradiation.

Adenocarcinoma↗

Biologically active Fas antigen and its cognate ligand are expressed on plasma membrane-derived extracellular vesicles.

Exfoliation of plasma membrane components is a directed process that consumes energy and requires active cell metabolism. Proteins involved in regulating the survival and proliferation of eukaryotic cells are released on exfoliated vesicles. We examine here whether the Fas receptor and its cognate ligand (FasL) are present on vesicles shed from high metastatic potential CX-1 cells and low metastatic potential MIP-101 cells and from HuT 78 cells, respectively. Rates of exfoliation at 2 hours and cumulative levels of extracellular vesicles in serum-free medium conditioned by CX-1 cells are increased by 1.8-fold and 1.6-fold, respectively, relative to that in medium conditioned by MIP-101 cells. Although vesicles shed from both cancer cell lines contain Fas antigen, the amount of Fas per vesicle and the percentage of vesicles containing Fas are increased for vesicles isolated from MIP-101 cells, relative to those from CX-1 cells, as determined by immunogold particle labeling and electron microscopy and by immunofluorescence microscopy and flow cytometry. Results of metabolic labeling with 35S-methionine indicate that Fas biosynthesis is reduced by up to 3.3-fold for CX-1 cells, relative to that of MIP-101 cells, consistent with the finding of decreased Fas on vesicles shed from the plasma membrane of CX-1 cells. Although mRNA for soluble Fas receptor is detectable in both cell lines, depletion of shed vesicles from serum-free medium by ultracentrifugation removes all detectable biological activity. FasL is detected on vesicles exfoliated from HuT 78 cells by immunoelectron microscopy and Western blot analysis. FasL-bearing vesicles induce apoptosis of Fas-expressing cancer cells at the same level as observed by treatment with monoclonal anti-Fas antibody. Furthermore, Fas-bearing extracellular vesicles from MIP-101 but not from CX-1 cells protect the CX-1 cell line from FasL-induced and anti-Fas-mediated apoptosis, indicating that Fas present on shed vesicles is biologically active. We conclude that the Fas antigen and its cognate ligand are exfoliated from the cell surface in a bioactive configuration. Exfoliation may provide a mechanism for long-range signal-directed apoptosis while maintaining Fas/FasL on a membrane surface.

Adenocarcinoma↗

Bilateral dissection of the internal carotid artery at the base of the skull due to blunt trauma: incidence and severity.

Between January 1, 1992 and December 31, 1996, a total of 1095 head trauma vicims were admitted in our intensive care unit. If CT scans demonstrated ischemic brain lesions, arteriography to visualize supraaortic vessels was performed. Carotid artery dissection was observed in ten patients (0.91%) and was bilateral in eight patients (0.73%). In the bilateral carotid artery dissection (BCAD) group, there were five women and three men, with a mean age of 35.2 years (range: 17 to 54 years). Injuries resulted from traffic accidents in seven patients and a fall in one patient. Upon admission, six patients presented with alteration of consciousness and three with hemiplegia or hemiparesia, associated with aphasia in two cases. In two other cases, hemiplegia occurred 24 hr and 13 days after the accident. All patients had brain infarction, which was unilateral in five cases and bilateral in three cases. The severity of lesions was graded on the basis of arteriographic findings as follows: Type I, wall involvement without significant stenosis or dilation; Type II, arterial dissection with stenosis >70% (Type IIA) or dilatation >50% (Type IIB) and the normal diameter of the proximal or distal internal carotid artery; and Type III, thrombosis of the internal carotid artery. Lesions were asymmetrical in six patients, including two with Type II and III lesions and four with Type I and II lesions, and symmetrical in two patients, including one with bilateral Type III lesions and one with bilateral Type II lesions. Surgery was performed in two patients with Type II lesions, including one case associated with contralateral carotid thrombosis. The intrapetrous carotid artery was exposed by an ear-nose-throat (ENT) surgeon and repaired by interposition grafting. Follow-up in these two surgical cases was 28 and 31 months. In the remaining six cases, medical treatment was performed. Outcome in nonsurgical cases was variable: death in two cases at 31 and 43 days after the accident, severe permanent hemiplegia in two cases, and minimal or no sequels in two cases. Following blunt trauma, arteriography of supraaortic vessels should be performed to detect BCAD in any patient with immediate or delayed neurologic symptoms that cannot be explained by CT-scan findings. To better understand the natural course of these lesions and define the indications for surgery, we propose a three-grade classification according to arteriographic findings. If surgery is undertaken, vein grafting should be performed following resection of the carotid artery lesions.

Adult↗

Preservation of humidity and heat of respiratory gases in spontaneously breathing, tracheostomized patients.

BACKGROUND: Ventilation with endotracheal intubation bypasses the upper airway and the normal heat and moisture exchanging process of inspired gases. A continuous loss of moisture and heat occurs and predisposes patients to serious airway damage. We therefore prospectively studied one heated humidifier system, one cold humidifier system and one heat and moisture exchanger in spontaneously breathing, tracheostomized intensive care unit patients to determine the ability to preserve patients' heat and water. METHODS: Following a randomized order, 10 patients were spontaneously ventilated for 24-h periods with the Nam 35 humidifier (Europe Medical, France, a cold water humidifier), the heat and moisture exchange Trach-Vent (Gibeck, Sweden), and the Aerodyne humidifier (Kendall USA). In each patient, during the inspiration phase, the following measurements were performed: mean values of temperature and relative humidity of inspired gases. The absolute humidity was calculated. Values were obtained in each patients after 40 min and 24 h. RESULTS: The Trach-Vent filter and the Aerodyne humidifier had better humidification and thermic capacities than the Nam 35 humidifier (P < 0.001). With the Nam 35 humidifier, no patient had temperature of inspired gas > 29 degrees C. Concerning absolute humidity of inspired gases, the Nam 35 humidifier achieved a lower performance than the other two tested systems (P < 0.001). CONCLUSION: In spontaneously breathing, tracheostomized intensive care unit patients, the Trach-Vent heat and moisture exchanger and the Aerodyne heated system achieved satisfactorily preservation of heat and humidity of inspired gases.

Body Temperature↗

Early plasma membrane events occurring in ultraviolet-B-induced apoptosis.

Whereas nonsolar ultraviolet C radiation primarily affects nuclei (i.e., where it is absorbed by nucleic acids) of eukaryotic cells, ultraviolet radiation of long (320-380 nm) wavelengths (ultraviolet A) and intermediate (290-320 nm) wavelengths (ultraviolet B) primarily affects lipid membranes. We have previously demonstrated that ultraviolet B irradiation alters the surface architecture of human B cells and impairs expression of an erythroid growth factor on their surface and on extracellular vesicles. Here, we examined the effects of ultraviolet B irradiation on the capacity of Chinese hamster ovary cells to undergo the process of exfoliation, and on the capacity of Chinese hamster ovary cells transfected with flt3/flk2 cDNA to express the cytokine flt3/flk2. Our results indicate that the rate of release of shed vesicles from untransfected Chinese hamster ovary cells is decreased after one to two h, at a time when there is electron microscopic evidence for retention of vesicles at the cell surface. These changes at the cell surface precede all other apparent morphological changes (including DNA condensation in the nucleus, swelling of the mitochondria and appearance of apoptotic bodies). Furthermore, plasma membranes and shed extracellular vesicles from ultraviolet B irradiated Chinese hamster ovary cells that have been transfected with flt3/flk2 cDNA fail to express the protein.

Animals↗

A prospective evaluation of the use of femoral venous catheters in critically ill adults.

OBJECTIVE: To determine the rate of complications following the use of femoral catheters in adults. DESIGN: Prospective survey of major and minor complications. SETTING: A mixed medical/surgical intensive care unit (ICU) in a university hospital. PATIENTS: Eighty consecutive patients admitted to the ICU who underwent right femoral venous catheterization over a 13-month period. INTERVENTIONS: Patients were carefully monitored for mechanical, infectious, and thrombotic complications. On catheter removal, a lower extremity bilateral phlebographic examination was performed in each patient. MEASUREMENTS AND MAIN RESULTS: There were 80 polyurethrane catheters inserted for a mean duration of 8.8 +/- 4.4 (SD) days. Catheters were inserted by interns or residents (75%) or by critical care fellows (25%). Minor complications consisted of arterial puncture (15%), local hematoma (4.4%), local bleeding (3%), and local inflammation (5%). After insertion, 17% of catheter tips were in the right atrium, 13% in the abdominal vena cava, 63% in the thoracic inferior vena cava (correct position), and 8% in aberrant abdominal intravascular positions. After repositioning, 80% of catheter tips were in the thoracic inferior vena cava. One patient developed a catheter-related bacteremia. Catheter-related sepsis were seen in three (3.7%) patients and catheter colonization in 11 (13.7%) patients. No patient had clinical signs of deep vein thrombosis or pulmonary embolism. Bilateral phlebography was performed in 70 patients at the time of catheter removal and was normal in 45 (64%) patients. Fibrin sleeves were seen in 11 (15.7%) patients. Lower extremity deep vein thrombosis developed in 24 (34%) patients. Six (8.5%) patients had femoral vein thrombosis (common femoral vein in two patients, and superficial femoral vein in four patients). Eighteen (25.7%) patients developed popliteal vein or posterior tibial vein thrombosis that was either bilateral (n = 16) or homolateral (n = 2) to the femoral catheter. CONCLUSIONS: Based on the data from this study, we conclude that femoral vein catheterization with a polyurethane catheter is associated with an 8.5% frequency rate of femoral vein thrombosis. Thrombosis in the popliteal vein or posterior tibial vein is higher (25.7%), but is homolateral to the catheter with only a 2.8% frequency rate. Infectious complications are low and similar to those of other central venous routes. Given the acceptable rate of clinically important complications, femoral venous catheterization offers an attractive alternate site of insertion to the jugular and subclavian veins for central venous access in the critically ill.

Adult↗

High-yield purification of cytochrome aa3 and cytochrome caa3 oxidases from Bacillus subtilis plasma membranes.

When grown in aerated shaking culture, Bacillus subtilis expresses two different haem A-containing terminal oxidases: cytochrome aa3-quinol oxidase and cytochrome caa3 oxidase. This paper describes a high-yield conventional procedure for purifying the two haem A-containing oxidases from the same aerobic culture of Bacillus subtilis. Yields of close to 40% of the total haem A are achieved and about 6 mg of each of the purified oxidases is obtained from 4 litres of liquid culture. Both of the purified enzymes have two subunits, with apparent molecular masses of 71.6 kDa and 34.3 kDa for the cytochrome caa3 oxidase, and 67.6 kDa and 37.2 kDa for aa3-quinol oxidase. These features are in agreement with the sequence data for the corresponding structural genes in the aa3 and caa3 operons of B. subtilis. Some spectral and enzymic features of the two purified oxidases are reported that are consistent with the inclusion of both of these enzymes as members of the cytochrome oxidase superfamily.

Bacillus subtilis↗

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↗

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↗

beta-Endorphin and blood pressure in multiple trauma victims.

In addition to pain and stress, endogenous opiates and in particular beta-endorphin could be involved in the modulation of cardiovascular parameters. Several studies have thus shown increases in plasma beta-endorphin levels in the course of septic or hypovolemic shock. Our study involving 44 multiple trauma patients indicates that even in the absence of any hemodynamic disorders, there is a correlation between systolic blood pressure and plasma beta-endorphins. These results argue in favor of the existence of feedback between systolic blood pressure and plasma beta-endorphins.

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↗

Monitoring of pefloxacin serum concentrations in intensive care unit patients: comparison of a new immunoassay with high-performance liquid chromatography.

Serum quinolone concentrations are not routinely measured in clinical practice. However, in order to optimize quinolone treatment, monitoring of serum concentrations could sometimes be useful particularly in critically ill patients. A new enzyme-linked immunosorbent assay (ELISA) that permits direct determination of pefloxacin in serum is described. To validate this new assay, pefloxacin concentrations were measured in 314 serum samples from 74 intensive care unit patients treated with pefloxacin (400 mg i.v. twice daily). Reference concentrations were obtained by reverse phase high-performance liquid chromatography (HPLC) with spectrofluorometric detection. Results showed that concentrations measured by ELISA correlated very well with those by HPLC (r = 0.957; y = 1.03 and x -0.15). In this population, the concentrations found by ELISA varied between individuals (Cmin = 0.70-39 micrograms/ml; Cmax = 5.2-40 micrograms/ml). However, 86% of the measured Cmax and Cmin levels were adequate for optimal pefloxacin therapy. Only 11% of Cmin and 14% of Cmax were below the optimal values (i.e., 2 and 8 micrograms/ml, respectively). These results suggest that despite the large therapeutic index of pefloxacin, monitoring of its serum concentrations using a rapid ELISA technique may be useful for optimal antimicrobial treatment of certain intensive care unit patients.

Adolescent↗

Right ventricular end-systolic pressure-volume relation during propofol infusion.

The effects of propofol on right ventricular function were studied in 11 ICU patients who needed sedation for acute respiratory failure or neurological diseases. Right ventricular function was studied using a thermodilution method at patients' bedside. Right ventricular ejection fraction (RVEF), cardiac output (CO), right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV), right ventricular end-systolic pressure (RVESP) and pulmonary capillary wedge pressure (PCWP) were obtained from a modified Swan-Ganz catheter. Calculation of right ventricular end-systolic pressure-volume relation (ESPVR) allowed to assess changes in right ventricular inotropic state. A baseline ESPVR was obtained before propofol infusion: RVESP = 0.21 RVESV + 2.4, r = 0.83, P < 0.0001. Then, patients were given an induction dose of 1 to 2.5 mg.kg-1 propofol over 1 min followed by a continuous infusion of 3 mg.kg-1.h-1. During propofol infusion heart rate, mean arterial pressure, PCWP, CO, systemic vascular resistance and RVEF significantly decreased. No change in RVEDV and RVESV was observed. ESPVR was significantly altered with a dramatic decrease in the slope of the relation: RVESP = 0.12 RVESV + 6.9 (P < 0.001 from baseline). Dobutamine was used in five patients with clinically significantly cardiac dysfunction and restored the slope of the ESPVR to the baseline value: RVESP = 0.22 RVESV + 6.3 (NS from baseline). In the study patients, propofol altered the inotropic state of the right ventricle.

Anesthesia, Intravenous↗

Contrasting effects of vecuronium and succinylcholine on the renal microcirculation in rodents.

We assessed the effects of succinylcholine and vecuronium on renal function and on the renal microcirculation in a rodent model. Vecuronium (0.02 mg/kg followed by 0.2 mg.kg-1 x h-1) caused a significant decrease of 16.1% +/- 3.87% in inulin clearance from 0.92 +/- 0.07 to 0.71 +/- 0.05 mL.min-1 x gKW-1 (gram of kidney weight), and a decrease in para-aminohippuric acid clearance by 21.6% +/- 4.69% from 1.58 +/- 0.26 to 1.31 +/- 0.20 mL.min-1 x gKW-1 (P < 0.05), whereas succinylcholine (0.45 mg/kg followed by 2 mg.kg-1 x h-1) altered neither. The effect of these muscle relaxants was also determined on the renal microcirculation in separate experiments using videomicroscopy. Succinylcholine (n = 10; 10(-10) to 10(-6) M) and its parent compound, acetylcholine (n = 10, 10(-10) to 10(-6) M) used as a control, caused a significant vasodilation from baseline diameter in the interlobular, afferent, and efferent arterioles. The vasodilation caused by succinylcholine was significantly less than that observed with acetylcholine. Atropine blocked the response to succinylcholine, indicating the latter has a muscarinic effect. In contrast, vecuronium caused a significant, selective vasoconstriction from baseline diameter in the preglomerular vessels, but not in the postglomerular vessels. The vasoconstriction caused by vecuronium was significantly different than the vasodilation caused by succinylcholine. The preglomerular vasoconstriction observed with vecuronium may contribute to the decrease in renal plasma flow and glomerular filtration rate observed experimentally. The choice of a neuromuscular blocking drug can therefore have the potential to influence renal function by altering the renal microcirculation.

Animals↗

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↗

Kinetic and ligand binding evidence for two heme A-based terminal oxidases in plasma membranes from Bacillus subtilis.

Detergent-solubilized plasma membranes from Bacillus subtilis have been characterized for their cytochrome oxidase content. Triton X-100-solubilized membranes show high O2 turnover with ascorbate plus TMPD. Reduced-oxidized difference spectroscopy of ascorbate-TMPD-reduced membranes reveals the presence of cytochrome c and cytochrome a. An additional, b-type cytochrome appears when the membranes are reduced with dithionite. Time-resolved difference spectra taken during reduction by ascorbate-TMPD reveal two kinetic forms of heme A-containing cytochromes. There is a high-turnover form that is rapidly reduced upon anaerobiosis, and a second type which is only slowly reduced upon anaerobiosis. The slowly reduced oxidase is distinguished by an alpha-band blue-shifted to 600 nm relative to the 603-nm position observed for high-turnover oxidase. Addition of CO to ascorbate-TMPD-reduced membranes gives a spectrum typical of ferrocytochrome a3-CO, and the intensity corresponds to the total ferrocytochrome a3 concentration. Photolysis of ascorbate-TMPD-reduced, CO-bound membranes indicates that both species are photosensitive with similar rates of recombination. Addition of CO to dithionite-reduced membranes shows an additional CO reactive center that has a spectrum characteristic of cytochrome o. Cyanide blocks complete reduction of high-turnover oxidase by ascorbate plus TMPD, but does not appear to effect slowly reduced oxidase. These results indicate the presence of two different types of cytochrome aa3 oxidase in plasma membranes of B. subtilis.

Ascorbic Acid↗

Effect of bolus doses of midazolam on intracranial pressure and cerebral perfusion pressure in patients with severe head injury.

We have studied the effects of bolus doses of midazolam 0.15 mg kg-1 i.v. on intracranial pressure (ICP), mean arterial pressure (MAP) and cerebral perfusion pressure (CPP) in 12 patients with severe head injury (Glasgow Coma Scale score < or = 6). The study was performed in patients aged 17-44 yr who were sedated (phenoperidine 20 micrograms kg-1 h-1) and paralysed (vecuronium 2 mg h-1). Midazolam reduced MAP from 89.0 mmHg to 75.0 mmHg (P < 0.0001), while CPP decreased from 71.0 mmHg to 55.8 mmHg (P < 0.0001). During the study, CPP decreased to less than 50 mmHg in four patients. Midazolam induced small, non-significant changes in ICP. However, when control ICP was less than 18 mmHg (n = 7 patients), an increase in ICP was observed. The remaining five patients (control ICP > or = 18 mmHg) exhibited a slight decrease in ICP. These findings suggest that bolus administration of midazolam should be performed with great caution in patients with severe head injury, especially when ICP is less than 18 mmHg.

Adolescent↗

A non-comparative study of the efficacy and tolerance of cefepime in combination with amikacin in the treatment of severe infections in patients in intensive care.

Patients in intensive care units (ICUs) are at increased risk of developing nosocomial infections. This is of special concern in the immunocompromised patient, particularly with regard to multiresistant pathogens. We evaluated the effectiveness of cefepime 2 g bd in combination with amikacin 7.5 mg/kg bd for the treatment of severe bacterial infection in 118 ICU patients, including 113 patients with nosocomial lower respiratory tract infections (LRTI) (mean age, 51 years). Ninety-six per cent (108/113) of the LRTI patients required respiratory assistance and 12% (14/113) had associated septicaemia/bacteraemia. Eighty-four per cent (95/113) had clinical signs of sepsis and 35% (39/113) had features of septic shock. The mean Simplified Acute Physiologic Score (SAPS) was 12 at inclusion. Seventy-nine patients with LRTI were clinically and bacteriologically evaluable. The causative pathogens were representative of those usually isolated in ICUs: Staphylococcus aureus (19%); Pseudomonas aeruginosa (14%); and Klebsiella, Enterobacter and Serratia spp. (17%). The clinical cure rate was 86% (68/79) while the pathogen eradication rate was 91% (107/117). Of the patients with associated septicaemia/bacteraemia, 89% (8/9) of the pathogens were eliminated. Cefepime-amikacin combination therapy was well tolerated; two patients discontinued treatment due to rashes. Combination therapy with cefepime 2 g bd and amikacin 7.5 mg/kg bd appears safe and effective for the treatment of nosocomial pneumonia in patients hospitalized in ICUs. Further comparative controlled studies are justified.

Adolescent↗