Pharmacokinetics and effects of mannitol on hemodynamics, blood and cerebrospinal fluid electrolytes, and osmolality during intracranial surgery.

Fifteen patients who underwent surgery for intracranial tumors under general anesthesia were given mannitol (1 g/kg of body weight) over 30 min. Measurements of mannitol concentration, osmolality, and electrolytes were determined in blood and cerebrospinal fluid (CSF) samples collected over an 8-h period. Seven sets of hemodynamic observations and four sets of intracranial pressure (ICP) measurements were also made. Mannitol disappeared from plasma in a biexponential manner. The mean maximal plasma concentration was 5.91 mg/ml at the end of mannitol infusion and decreased to 0.58 mg/ml after 8 h. The plasma half-life for the distribution phase was 0.16 h and for the elimination phase was 2.44 h. The distribution volume was 17.0 L and total plasma clearance 87.4 ml/min. There were marked interindividual variations of mannitol concentration in the CSF. The mean CSF concentration at 8 h was 97.1 micrograms/ml, started to decline earlier in 10 of 12 patients, and never exceeded 12% of that in plasma. Osmolality in serum increased with a maximum at the end of mannitol infusion (from 292 +/- 7 mOsmol/kg to 310 +/- 14 mOsmol/kg; p < 0.01), whereas CSF osmolality was unchanged, thus giving rise to a positive blood-CSF osmotic gradient of at least 10 mOsmol/kg for about 30 min. At the end of the mannitol infusion, cardiac output and pulmonary capillary wedge pressure increased significantly, whereas the hematocrit decreased. ICP was observed in five patients for 45 min, and mannitol induced a mean reduction from 11 +/- 4 to 4 +/- 2 mm Hg (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Colonization with coagulase-negative staphylococci in two neonatal units.

Episodes of septicaemia due to coagulase-negative staphylococci (CNS) were more frequent in a level III than in a level II neonatal unit in Stockholm, Sweden. Colonization with CNS during the first 2 weeks of life was investigated in 10 infants from each unit. As the use of antibiotics differed between the two units, the aim was to correlate colonization and antimicrobial resistance patterns to antibiotic usage. Antimicrobial susceptibility of CNS to isoxazolylpenicillins, co-trimoxazole, erythromycin, clindamycin, chloramphenicol and gentamicin was determined. Selected isolates were typed with restriction endonuclease analysis of plasmid DNA and of genomic DNA. Infants were frequently colonized with multiple strains and species of CNS, and transmission of strains from patient to patient occurred within the unit. Qualitative and quantitative differences in antibiotic use were not correlated with colonization. The prevalence of resistant isolates, mostly of Staphylococcus haemolyticus, was higher in the level II unit with lower use of antibiotics. Staphylococcus epidermidis, which is generally more virulent, prevailed in the level III unit, where there were more severely ill children and invasive procedures were more frequently performed.

Pharmacokinetics of tetrahydroaminoacridine: relations to clinical and biochemical effects in Alzheimer patients.

The pharmacokinetics of tetrahydroaminoacridine (THA) was studied in patients suffering from Alzheimer's dementia. Single doses of the drug were administered by intravenous (15 mg), oral (50 mg) and rectal routes (25 mg). Pharmacokinetic parameters were related to clinical and biochemical effects in patients who, in a separate study, participated in a clinical trial of oral THA. The bioavailability of THA was low and varied considerably between subjects. Clinical improvement and occurrence of elevated liver enzymes correlated positively with drug bioavailability. Acetyl and butyryl cholinesterase activities in the plasma did not change following THA administration. Rectally administered THA had a higher bioavailability than orally administered THA in three subjects who were given the drug by both routes. These results indicate that a clinical trial of rectal THA would be justified as this administration route may improve resorption and diminish first-pass metabolism of the drug in the liver compared with oral administration.

Antibiotic susceptibility of Escherichia coli isolates from inpatients with urinary tract infections in hospitals in Addis Ababa and Stockholm.

A high level of antimicrobial resistance of bacteria has been detected at the Tikur Anbessa Hospital (TAH), Addis Ababa, for many years. In contrast, at the Karolinska Hospital (KH), Stockholm, the level of resistance is low. Reported are the results of an investigation of the correlation between antibiotic usage and the antimicrobial resistance rates of Escherichia coli isolates from patients with urinary tract infections in these hospitals. At TAH the strains of E. coli isolated were considerably more resistant to all seven antibiotics tested. The level of multiresistance was 63% at TAH and 7% at KH. There were no significant differences in the total amount of antibiotics used in the two hospitals, except for antituberculosis agents. The strain biotypes and antibiograms, together with the length of patients' hospitalization before a positive urine culture was obtained, suggest that the majority of the strains from TAH were of nosocomial origin.

Antibiotic susceptibility of Escherichia coli isolates from inpatients with urinary tract infections in hospitals in Addis Ababa and Stockholm

A high level of antimicrobial resistance of bacteria has been detected at the Tikur Anbessa Hospital (TAH), Addis Ababa, for many years. In contrast, at the Karolinska Hospital (KH), Stockholm, the level of resistance is low. Reported are the results of an investigation of the correlation between antibiotic usage and the antimicrobial resistance rates of Escherichia coli/isolates from patients with urinary tract infections in these hospitals

At TAH the strains of E. coli isolated were considerably more resistant to all seven antibiotics tested. The level of multiresistance was 63 per cent at TAH and 7 per cent at KH. There were no significant differences in the total amount of antibiotics used in the two hospitals, except for antituberculosis agents. The strain biotypes and antibiograms, together with the length of patients' hospitalization before a positive urine culture was obtained, suggest that the majority of the strains from TAH were of nosocomial origin(AU)

Antibiotic susceptibility of escherichia coli isolates from inpatients with urinary tract infections in hospitals in Addis Ababa and Stockholm

A high level of antimicrobial resistance of bacteria has been detected at the Tikur Anbessa Hospital (TAH), Addis Ababa, for many years. In contrast, at the Karolinska Hospital (KH), Stockholm, the level of resistance is low. Reported are the results of an investigation of the correlation between antibiotic usage and the antimicrobial resistance rates of Escherichia coli isolates from patients with urinary tract infections in these hospitals. At TAH the strains of E. coli isolated were considerably more resistant to all seven antibiotics tested. The level of multiresistance was 63% at TAH and 7% at KH. There were no significant differences in the total amount of antibiotics used in the two hospitals, except for antituberculosis agents. The strain biotypes and antibiograms, together with the length of patients' hospitalization before a positive urine culture was obtained, suggest that the majority of the strains from TAH were of nosocomial origin

Use of mannitol during neurosurgery: interpatient variability in the plasma and CSF levels.

An i.v. infusion of mannitol was given over 15 min to 12 patients before they underwent intracranial surgery under general anesthesia. Samples of blood, CSF and urine were taken over 4 h. Mannitol disappeared from plasma in a bi-exponential manner. The mean maximal plasma concentration was 4.08 mg/ml at 15 min, and at 4 h it had declined to 0.53 mg/ml. The mean distribution rate constant was 11.2 h-1, corresponding to a plasma distribution half-life of 0.11 h. The mean elimination rate constant was 0.41 h-1, the plasma half-life was 2.2 h, the central distribution volume was 16.3 l, and total plasma clearance was 100.4 ml/min. The mean concentration of mannitol in CSF during the 4 h period increased up to 0.10 mg/ml. There were marked interindividual differences in the concentration ratio blood/CSF, and the CSF concentration varied 7.5 fold between patients. Optimal use of mannitol during neurosurgery requires further prolonged study of its pharmacokinetics.

Effect of detergent on kinetic Jaffé-method assay of creatinine.

Using isotope dilution-mass spectrometry as reference method, we show that the kinetic Jaffé method for determination of serum creatinine sometimes produces results that are much too high. Such falsely increased values were obtained in about 10% of the sera collected for routine determination of creatinine, and were most common when certain types of collecting tubes were used. The interferences could be overcome by use of detergent in the reaction mixture.

Use of isotope dilution--mass spectrometry for accuracy control of different routine methods used in clinical chemistry.

Serum from patients was pooled, filtered, dispensed and frozen. The serum pool obtained was used for accuracy control in twenty-one participating laboratories in the Stockholm area. Mean values (state of art values) were obtained for creatinine, cholesterol, glucose, urea and uric acid. These values were compared with values obtained with highly accurate reference methods, based on isotope dilution--mass fragmentography. The most marked difference was found in the case of determination of creatinine. It is suggested that immediate access to such a well-defined human serum might decrease the need for conventional interlaboratory control programmes.

Evaluation of three clinical chemical routine methods for the determination of serum uric acid, by mass fragmentography.

A mass fragmentographic method for assay of serum uric acid was developed and used as a reference method to evaluate the accuracy of different routine methods used in clinical chemistry. [1,3-15N2]Uric acid was added to the serum sample and the mixture was subjected to ion-exchange chromatography. After conversion to the tetra-trimethylsilyl derivative the purified mixture was analyzed by combined gas chromatography-mass spectrometry using a multiple ion detector. Within-series imprecision of the reference method as calculated by means of relative standard deviation was 0.6%. The small difference between calculated and found value obtained in different recovery experiments could be explained by this degree of imprecision. In a comparison between results obtained with the reference method and different routine methods, a significant difference was observed only when using an uricase-oxygen consumption method.

Toward absolute methods in clinical chemistry: application of mass fragmentography to high-accuracy analyses.

We review recently developed reference methods based on mass fragmentography (specific ion monitoring) with use of isotope-labeled internal standard, for determination of cholesterol, triglycerides, urea, glucose, cortisol, progesterone, and testosterone. With an optimal ratio between standard and material to be determined, the relative standard deviation of these methods, based on duplicate determinations, is between 1.3 and 2.7%. The very high specificity of the methods, in combination with the fact that the ratio between labeled and unlabeled molecules is determined with a high degree of accuracy, makes it likely that the most significant errors in the methods are related to errors in pipetting. The possibility is discussed that these methods might be developed into "absolute" or "definitive" methods by subjecting each individual step in the determination to a detailed analysis with respect to possible error. We also discuss some of the consequences of the different reference methods on the choice of routine methods.

The use of mass fragmentography in the evaluation of routine methods for glucose determination.

A highly specific and accurate mass fragmentographic reference method for determination of serum glucose is described. A fixed amount of hepta-deuterated glucose is added to a fixed amount of serum. The mixture is lyophilized, converted into the penta-trimethylsilyl-methyloxime derivative and subjected to analysis with a combined gas chromatograph - mass spectrometer equipped with a MID-unit (multiple ion detector). The amount of unlabeled glucose was determined from the ratio between recordings at m/e 319 and 323. The two ions used correspond to the base peak in the mass spectrum of derivative of unlabeled and hepta-deuterium labeled glucose, respectively. The relative standard deviation of the method was 1.9%. The method was compared with different enzymatic methods based on the hexokinase reaction and the glucose oxidase reaction. Of the different methods tested, a glucose oxidase method with determination of maximal rate of consumption of oxygen gave results most close to the results of the reference method.

Determination of serum urea by mass fragmentography.

A mass fragmentographic method of high accuracy for determination of serum urea is described. A fixed amount of [15N2]urea is added to a fixed amount of serum, then the urea is converted into 5,5-diallyl barbituric acid by coupling with diallyl malonic acid diethyl ester. The barbiturate is then transferred from an alkaline water phase into an organic phase containing methyl iodine by ion-pair extraction using tetrabutyl ammonium as the positive counterion. The amount of urea is determined from the ratio between the recordings at m/e 236 and m/e 238 obtained after analysis with a combined gas chromatograph-mass spectrometer equipped with an MID-unit (multiple-ion detector). The two ions used correspond to the molecular peak in the mass spectrum of the methyl derivative of unlabeled and labeled 5,5-diallyl barbituric acid, respectively. The relative standard deviation of the method was 3.6%. A comparison between the mass fragmentographic method and a routine method for determination of serum urea based on the urease-Berthelot reaction gave a high correlation (r = 0.99) and a regression coefficient of 0.95.