Chaotic dynamics of graphene and graphene nanoribbons.

We study the chaotic dynamics of graphene structures, considering both a periodic, defect free, graphene sheet and graphene nanoribbons (GNRs) of various widths. By numerically calculating the maximum Lyapunov exponent, we quantify the chaoticity for a spectrum of energies in both systems. We find that for all cases, the chaotic strength increases with the energy density and that the onset of chaos in graphene is slow, becoming evident after more than 104 natural oscillations of the system. For the GNRs, we also investigate the impact of the width and chirality (armchair or zigzag edges) on their chaotic behavior. Our results suggest that due to the free edges, the chaoticity of GNRs is stronger than the periodic graphene sheet and decreases by increasing width, tending asymptotically to the bulk value. In addition, the chaotic strength of armchair GNRs is higher than a zigzag ribbon of the same width. Furthermore, we show that the composition of 12C and 13C carbon isotopes in graphene has a minor impact on its chaotic strength.

[Medical care unit -- a suitable instrument for ambulatory patient-adequate care and performance-related remuneration]. / Medizinisches Versorgungszentrum - geeignetes Instrument der ambulanten patientenadäquaten Versorgung und leistungsgerechten Vergütung.

BACKGROUND: The question of whether a medical care unit is an appropriate tool for outpatient care has been discussed for a long time. Our aim is to investigate whether the MCU is an effective instrument for outpatient care and adequate performance-related remuneration. MATERIAL AND METHODS: This retro- and prospective overview of the work included statements on legal foundations for medical care units, for reimbursement of services in medical care units, the development of medical care centres in Germany and a listing of the specific advantages and disadvantages of an MCU. This article focuses on the generally applicable facts and complements them with examples from general, visceral and vascular surgery. The main quantitative data on medical centre statistics come from different publications of the National Association of Statutory Health Insurance for Physicians. RESULTS: From a legal point of view the instrument MCU allows the participating of ambulatory and stationary care in the framework of medical care contracts. This has been especially extended for stationary applications, including the spectrum of possibilities that can contribute under certain circumstances for the provision of medical care in underdeveloped regions. Freelancers can benefit primarily from financial risk and minimising bureaucratic routine. The remuneration for services performed in the MCU is analogous to that of other ambulatory care providers. Basically, there are no disadvantages, but a greater design freedom and opportunities for the generation of aggregates are visible. The number of MCU in Germany has quadrupled in the last five years, indicating an establishment of an outpatient care landscape. MCU offers from the patient's perspective, providers and policy specific advantages and disadvantages. Indeed the benefits outweigh the disadvantages, but this is not yet verified by qualitative studies. CONCLUSION: The question of the appropriateness of medical care units as outpatient care instrumentation must be considered differentially. Under current conditions it appears suitable for ensuring the MCU and the supplement of care supply. Whether a value can be generated in the quality of care of patients, however, has to be examined separately, as there are no valid data so far. The same applies to economic assessments of costs and benefits from an economic perspective.

A new autosomal dominant syndrome of distinctive face showing ptosis and prominent eyes associated with cleft palate, ear anomalies, and learning disability.

We report on three patients from two families with apparently a novel clinical entity. The main features of which include unusual craniofacial dysmorphism with ptosis, prominent eyes, flat midface, Cupid's bow configuration of the upper lip, low-set, posteriorly rotated small ears, as well as conductive hearing loss, cleft palate, heart defect, and mild developmental delay. We suggest that this entity is an autosomal dominant disorder given the occurrence in a mother and daughter as well as in an unrelated boy.

Relevance of microbial coculture fermentations in biotechnology.

The purpose of this article is to review coculture fermentations in industrial biotechnology. Examples for the advantageous utilization of cocultures instead of single cultivations include the production of bulk chemicals, enzymes, food additives, antimicrobial substances and microbial fuel cells. Coculture fermentations may result in increased yield, improved control of product qualities and the possibility of utilizing cheaper substrates. Cocultivation of different micro-organisms may also help to identify and develop new biotechnological substances. The relevance of coculture fermentations and the potential of improving existing processes as well as the production of new chemical compounds in industrial biotechnology are pointed out here by means of more than 35 examples.

Emergency department-initiated tobacco control: a randomised controlled trial in an inner city university hospital.

OBJECTIVES: Emergency department (ED) patients show high smoking rates. The effects of ED-initiated tobacco control (ETC) on 7-day abstinence at 12 months were investigated. METHODS: A randomised controlled intention-to-treat trial (trials registry no.: ISRCTN41527831) was conducted with 1044 patients in an urban ED. ETC consisted of on-site counselling plus up to four telephone booster sessions. Controls received usual care. Analysis was by logistic regression. RESULTS: In all, 630 (60.7%) participants were males, the median age was 30 years (range 18-81) and the median smoking intensity was 15 (range 1-60) cigarettes per day. Overall, 580 study participants (55.6%) were unmotivated, 331 (31.7%) were ambivalent and 133 (12.7%) were motivated smokers. ETC (median time 30 (range 1-99) min) was administered to 472 (91.7% out of 515) randomised study participants. At follow-up, 685 study participants (65.6% of 1044) could be contacted. In the ETC group, 73 out of 515 (14.2%) in the ETC group were abstinent, whereas 60 out of 529 (11.3%) controls were abstinent (OR adjusted for age and gender = 1.31 (95% CI 0.91 to 1.89, p = 0.15). Stratified for motivation to change behaviour, the adjusted ORs for ETC versus usual care were OR = 1.00 (95% CI 0.57 to 1.76) in unmotivated smokers, respectively OR = 1.37 (95% CI 0.73 to 2.58) in ambivalent smokers and OR = 2.19 (95% CI 0.98 to 4.89) in motivated smokers, p for trend = 0.29. CONCLUSIONS: ETC, in the form of on-site counselling with up to four telephone booster sessions, showed no overall effect on tobacco abstinence after 12 months. A non-significant trend for a better performance of ETC in more motivated smokers was observed.

Motivation of trauma patients to stop smoking after admission to the emergency department.

Every smoker should be offered smoking cessation treatment when they present for clinical care. The Readiness to Change-Smokers (RTC-S) questionnaire and the Heidelberg Smoking History (HSH) are brief questionnaires that divide patients into three stages. The purpose of this study was to prospectively compare the performance of each questionnaire at identifying patients who will successfully quit smoking within one year of Emergency Department (ED) discharge. Out of 1292 injured ED patients nearly half (n = 599, 46.4%) were identified as current smokers. Both questionnaires were given to all 599 subjects, and used to divide patients into three stages. At 12-months postdischarge 306 patients (51.1%) were contacted to determine smoking status. Patients were similarly classified by both tests in only 36% of cases. Concordance between tests was poor (kappa = 0.33). The RTC-S classified fewer patients as ready to quit (A = 13% vs. 22.2%). At 12 month follow-up, 55 patients (17.9%) had stopped smoking. The HSH was more successful to predict quitters. Multivariate logistic regression with respect to smoking cessation resulted in significant impact of HSH (p = 0.024).

Trauma patients' desire for autonomy in medical decision making is impaired by smoking and hazardous alcohol consumption--a bi-national study.

This cross-sectional investigation studied the association between substance use and patients' desire for autonomy in medical decision making (MDM) in two trauma settings. A total of 102 patients (age 42.7 +/- 17.4 years, 70.6% male) admitted to an orthopaedic service in Warsaw, Poland, and 1009 injured patients (age 34.6 +/- 12.8 years, 62.3% male) treated in an emergency department in Berlin, Germany, were enrolled. Patients' desire for autonomy in MDM was evaluated with the Decision Making Preference Scale of the Autonomy Preference Index. Substance use (hazardous alcohol consumption and/or tobacco use) and educational level were measured. Linear regression techniques were used to determine the association between substance use and desire for autonomy in MDM. Substance use was found to be independently associated with a reduced desire by the patient for autonomy in medical decision making. No differences in patients' desire for autonomy were observed between the study sites. Empowerment strategies that encourage smokers or patients with hazardous alcohol consumption to participate in MDM may increase the effectiveness of health promotion and injury prevention efforts in this population.

Differential activation of TRAIL-R1 and -2 by soluble and membrane TRAIL allows selective surface antigen-directed activation of TRAIL-R2 by a soluble TRAIL derivative.

TNF-related apoptosis-inducing ligand (TRAIL) is a typical member of the tumor necrosis factor (TNF) ligand family that is expressed as a type II membrane protein (memTRAIL) and signals apoptosis via the death domain-containing receptors TRAIL-R1 and -2. Soluble recombinant derivatives of TRAIL (sTRAIL) are considered as novel tumors therapeutics because of their selective apoptosis inducing activity in a variety of human tumors but not in normal cells. Using antagonistic antigen-binding fragment (Fab) preparations of TRAIL-R1- and TRAIL-R2-specific antibodies, we demonstrate in this study that TRAIL-R1 becomes activated by both the soluble and the membrane-bound form of the ligand, whereas TRAIL-R2 becomes only activated by memTRAIL or soluble TRAIL secondarily cross-linked by antibodies. Furthermore, we show that the restricted signal capacity of sTRAIL can be readily converted into a fully signal competent memTRAIL-like molecule, i.e. a TRAIL-R2 stimulating ligand, by genetic fusion to an antibody derivative that allows antigen-dependent 'immobilization' of the fusion protein to cell surfaces. We conclude that antibody targeting-dependent activation can be used to design selective therapeutics derived of those ligands of the TNF family that are biologically inactive in their soluble form.

No association of antibodies to glutamic acid decarboxylase and diabetic complications in patients with IDDM.

OBJECTIVE: To evaluate the association of antibodies to glutamic acid decarboxylase (GAD-ab) and diabetic complications (neuropathy, retinopathy, and nephropathy) in patients with insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: We examined the prevalence of GAD-ab (immunoprecipitation assay) and islet cell antibodies (ICAs) (indirect immunofluorescence) in a representative sample of IDDM patients (n = 146) with different disease duration (2-52 years, median 13.2 years). Of all patients characterized for the existence of diabetic complications, 56 of 146 had peripheral neuropathy, 24 of 142 had autonomic neuropathy, 67 of 141 had retinopathy, and 39 of 146 had nephropathy. RESULTS: GAD-ab (> 2 SD) were detected more frequently than ICA (> 5 Juvenile Diabetes Foundation units) in IDDM patients of different disease duration (GAD-ab+ 37% [54 of 146] vs. ICA+ 22% [32 of 146], P = 0.011; diabetes duration less than median: GAD-ab+ 47% vs. ICA+ 23%, P = 0.0046; diabetes duration greater than median: GAD-ab+ 27% vs. ICA+ 22%, P > 0.05). For GAD-ab and for ICA, respectively, no difference was observed in frequency of positivity or titers between patients with or without diabetic complications. CONCLUSIONS: Both GAD-ab and, to a lesser extent, ICA persist for a long time in several individuals. This persistence is not related to diabetic neuropathy or any other diabetic complication.

Stimulation of endothelial adenosine A1 receptors enhances adhesion of neutrophils in the intact guinea pig coronary system.

OBJECTIVE: The primary aim was to determine the action of pathophysiologically relevant adenosine concentrations (0.1-1 microM) on adhesion of neutrophils to coronary endothelium. Further aims were to evaluate the nature and localisation of the adenosine receptor involved, and to assess the effect of endogenous adenosine. METHODS: Adhesion was studied in isolated perfused guinea pig hearts by determining the number of cells emerging in the coronary effluent after intracoronary bolus injections of 600,000 neutrophils prepared from guinea pig or human blood. The system was characterised by the use of the proadhesive stimulus thrombin. RESULTS: A 5 min infusion of adenosine (0.1-0.3 microM) or the A1 receptor agonist N6-cyclopentyladenosine (CPA, 0.01 microM) significantly increased adhesion from about 20% (control) to 30%. This effect was prevented by the A1 receptor antagonist dipropyl-8-cyclopentylxanthine (DPCPX, 0.1 microM). It was not diminished by cessation of adenosine infusion 90 s prior to neutrophil injection. At a higher concentration of adenosine (1 microM), adhesion did not seem to be enhanced. However, coinfusion of the A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine (DMPX, 0.1 microM) with 1 microM adenosine unmasked the A1 action, adhesion rising to 39%. Adenosine had a quantitatively identical effect on adhesion of human neutrophils. Total ischaemia of 15 min duration raised adhesion of subsequently applied neutrophils to 35%. This effect was completely blocked by DPCPX, as well as by ischaemic preconditioning (3 x 3 min). Preconditioning raised initial postischaemic coronary effluent adenosine from about 0.8 microM to 1.5 microM. CONCLUSIONS: The findings suggest a bimodal participation of adenosine in the development of postischaemic dysfunction by an endothelium dependent modulation of neutrophil adhesion. Stimulation occurs via endothelial A1 receptors at submicromolar adenosine levels, whereas cardioprotection by adenosine may in part relate to the use of pharmacologically high concentrations of adenosine or enhanced endogenous production after preconditioning.

Effects of chronic treatment with adrenaline or propranolol on platelet function and c-AMP levels in the rat.

Most of our knowledge about the modulation of platelet function by catecholamines is based on observations of acute in vitro actions. Little is known about the effects of chronically elevated or reduced adrenergic stimulation of the platelets. We therefore treated rats for 8 weeks with either adrenaline or the beta-blocker propranolol. Adrenaline (0.5 mg.kg-1.d-1) continuously administered from subcutaneously implanted osmotic mini pumps caused an increase in the sensitivity of the platelets towards ADP as stimulating agent. In contrast, chronic application of propranolol (10 mg.kg-1.d-1) via the drinking water led to a reduction in platelet aggregability. For animals treated with adrenaline, in accordance with the results of the aggregation experiments, the levels of c-AMP found in platelet rich plasma were reduced, both basally (by 33%) and after stimulation of platelet adenylate cyclase with prostaglandin E1 (by 39%). For the propranolol treated animals, the basal c-AMP concentrations remained unchanged. The levels of c-AMP attained after stimulation with prostaglandin E1 were diminished to a similar extent as for the adrenaline treated animals (by 38%). Although the in vitro addition of adrenaline to platelet rich plasma causes a beta-adrenoceptor mediated inhibition of platelet aggregation in the rat, the simulation seen after chronic adrenaline exposure in vivo, which is associated with decreases in both basal and stimulated c-AMP levels, suggests a functional preponderance of alpha-adrenoceptors over beta-adrenoceptors on the rat platelets. Although intraplatelet metabolic changes (blockade of stimulated c-AMP formation) after chronic application of propranolol should have resulted in enhancement of platelet aggregability, an inhibition of aggregation was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Preischaemic as well as postischaemic application of a calcium antagonist affords cardioprotection in the isolated guinea pig heart.

OBJECTIVE: The aim was to answer the following questions: (1) Does treatment with calcium antagonists have to be begun before ischaemia or is postischaemic application also protective? (2) When applied before ischaemia, do calcium antagonists have to depress preischaemic cardiac function in order to elicit protection? (3) Is cardioprotection a matter of improved reflow or do the agents influence the degree of oxidative injury during reperfusion? METHODS: Isolated working guinea pig hearts underwent ischaemia (15 min) and reperfusion (15 min). The calcium antagonist gallopamil was given either before (0.1 nM and 1 nM) or after ischaemia (0.1 nM) during early reperfusion (first 5 min). Recovery was defined as postischaemic compared to preischaemic external heart work, expressed in percent. Oxidative stress was assessed by the release of glutathione (GSH). Lactate release served as a measure of the ischaemic challenge. The ability of gallopamil to scavenge oxygen radicals directly was investigated in an in vitro chemiluminescence assay. RESULTS: Pump function of control hearts recovered to only 28% after reperfusion. Pretreatment with 0.1 and 1 nM gallopamil improved recovery to the same extent (48.7% and 43.4%, respectively); however, postischaemic application of 0.1 nM gallopamil afforded equal protection (45.4% recovery). Only the higher concentration of 1 nM gallopamil depressed preischaemic external heart work (by 11%). During earliest reperfusion (1-5 min), release of GSH only tended to be lower in treated hearts. During the subsequent minutes of reperfusion (5-15 min), release of GSH was significantly less in hearts postischaemically treated with 0.1 nM gallopamil (40 pmol.min-1 v 940 pmol.min-1 for controls). In contrast, ischaemia-induced lactate release did not differ between the groups. Gallopamil did not scavenge reactive oxygen species in vitro. CONCLUSIONS: Short term postischaemic application of the calcium antagonist gallopamil is almost as effective at restoring pump function as preischaemic application which, in turn, does not have to depress preischaemic cardiac function in order to elicit protection. A reduction of oxidative stress during reperfusion seems to contribute to the beneficial effects of postischaemic application of gallopamil, but a direct oxygen radical scavenging activity of gallopamil is not involved.

ACE-inhibition prevents postischemic coronary leukocyte adhesion and leukocyte-dependent reperfusion injury.

OBJECTIVE: Polymorphonuclear leukocytes (PMN), retained in the microvascular bed, can contribute to postischemic myocardial reperfusion injury. Since a beneficial effect of ACE-inhibition on reperfusion injury has been reported, we investigated the impact of cilazaprilat on PMN dependent reperfusion injury in isolated guinea pig hearts. METHODS: Hearts (n = 5 per group) were subjected to 15 min of ischemia. Immediately thereafter, a bolus of PMN was injected into the coronary system. External heart work (EHW) and total cardiac nitric oxide release were measured. For microscopic evaluation, hearts received rhodamine 6G labelled PMN after ischemia, were arrested 5 min later and further perfused with FITC dextran (0.1%). Localization of retained PMN was assessed by fluorescence microscopy. Leukocyte activation was studied by FACS analysis of the adhesion molecule CD11b before and after coronary passage of the PMN. The ACE-inhibitor cilazaprilat (Cila, 2 microM) and the NO-synthase inhibitor nitro-L-arginine (NOLAG, 10 microM) were used to modulate nitric oxide formation of the heart. RESULTS: Postischemic EHW recovered to 67 +/- 5% (controls) and 64 +/- 6% (Cila) of the preischemic value. Addition of PMN severely depressed recovery of EHW (39 +/- 2%) and NO release (39 +/- 6% of the preischemic value). Simultaneously, ischemia led to a substantial increase in postcapillary PMN adhesion (from 21 +/- 5 to 172 +/- 27 PMN/mm2 surface) and CD11b-expression of the recovered PMN (3-fold). Cila attenuated postischemic PMN adhesion (83 +/- 52 PMN/mm2) and activation of PMN, whereas it improved recovery of work performance (64 +/- 4%) and NO release (65 +/- 4%) in the presence of PMN. Conversely, NOLAG increased PMN adhesion (284 +/- 40 PMN/mm2) and myocardial injury. We conclude that ACE-inhibition prevents leukocyte dependent reperfusion injury mainly by inhibition of postcapillary leukocyte adhesion. The effect may be mediated by NO, given the proadhesive effect of NOLAG.

Isolation, identification, and continuous culture of coronary endothelial cells from guinea pig hearts.

Viable and homogeneous endothelial cells were obtained from isolated guinea pig hearts by application of a special perfusion technique of the coronary system with an isotonic collagenase-trypsin solution and subsequent purification of the dissociated cells by Percoll density gradient centrifugation. The coronary endothelial cells were grown in tissue culture for periods up to 7 months. Serial passage proved to be possible. During logarithmic growth, generation time was found to be 18 h; it could be reduced to 16 h by addition of thrombin to the culture medium. Light, phase contrast and scanning electron microscopy as well as autoradiography revealed that cultured coronary endothelial cells grew as strict monolayers of closely apposed, polygonal large cells. By scanning electron microscopy, it could be demonstrated that the morphology of the cultured cells changes characteristically during attachment of the cells to their substratum. The changes observed were very similar to those of proliferating endothelial cells of isolated coronary vessels kept in organ culture. According to transmission electron microscopy studies, cultured coronary endothelial cells proved to contain only an extremely small number of Weibel-Palade bodies. Nucleoside phosphorylase (EC 2.4.2.5.) and 5'-nucleotidase (EC 3.1.3.5.) were identified in freshly isolated as well as in cultured endothelial cells. Their specific and total activities proved to be much higher than in myocardial tissue, thus indicating a prominent role of nucleotide metabolism in the coronary endothelium.

Characterization of different soluble TNF receptor (TNFR80) derivatives: positive influence of the intracellular domain on receptor/ligand interaction and TNF neutralization capacity.

Different soluble human TNFR80 derivatives, a solubilized form of the complete TNFR80, the TNFR80 extracellular domain, a secretory TNFR80 mutant (TR80TM-) with a deleted transmembrane region, and a TNFR80 immunoadhesin were produced in insect cells and characterized side by side with a recombinant human TNFR60 extracellular domain with respect to TNF binding affinity and neutralization of TNF bioactivity. The construct TR80TM- and the solubilized complete TNFR80 revealed a similar TNF binding and neutralization capacity, which was superior to the monovalent TNFR80 extracellular domain and comparable to the bivalent TNFR80 immunoadhesin, already known as a potent TNF antagonist. Determination of ligand off rate constants of the various receptor constructs by surface plasmon resonance revealed a correlation of low off rates with a high TNF neutralization capacity. We propose that the high TNF binding and neutralization capacity of the solubilized complete TNFR80 and TR80TM- in comparison with the monovalent extracellular TNR80 domain is due to a noncovalent self-aggregation of the receptors via their intracellular domain. This finding suggests that efficient soluble TNF antagonists can be derived from TNFR themselves without the need of construction of TNFR Ig Fc fusion proteins.

A bivalent immunoadhesin of the human interferon-gamma receptor is an effective inhibitor of IFN-gamma activity.

We describe here the bioengineering of a bivalent IFN-gamma-RFc immunoadhesin consisting of the extracellular domain of the human IFN-gamma receptor alpha chain (IFN-gamma-R) fused to a human IgG1 Fc region (encoding hinge, CH2 and CH3 domain) that was efficiently expressed as a covalently linked homodimer in insect cells and purified in a one-step purification procedure. The IFN-gamma-RFc fusion protein exerted a 3-fold higher ligand binding affinity in binding competition studies in vitro compared with the monovalent extracellular IFN-gamma-R domain. In addition, the in vitro antagonistic activity of IFN-gamma-RFc, as determined by inhibition of IFN-gamma-induced virus protection and HLA-DR expression, was more than 30-fold higher in comparison with the monovalent soluble receptor. The described IFN-gamma-R immunoadhesin is a potential therapeutic reagent to interfere with the disease-promoting activities of IFN-gamma in several autoimmune diseases.

The function of neutrophils isolated by a magnetic antibody cell separation technique is not altered in comparison to a density gradient centrifugation method.

Most comparative studies on neutrophil (PMN) isolation techniques have shown either activation or functional impairment of the cells due to the different separation processes. We have established a preparation method for PMN from human whole blood employing iron tagged, magnetizable antibodies against the cell surface antigen CD15. The aim of our study was to test whether this magnetic separation (MACS) alters cellular functions of PMN in comparison to a conventional density gradient technique (Percoll). The purity, cell yield, and pre-activation of the cells were evaluated. The latter was assessed by quantifying the expression of the integrin CD11b using flow cytometry. Furthermore, as functional tests, cell morphology and the oxidative burst reaction were investigated. We have shown that the use of 'magnetic' antibodies leads to highly purified PMN (> 99% of isolated leukocytes), while there is still contamination by eosinophils (about 6%) after Percoll separation. Platelet contamination was about the same in both procedures (approx. one platelet per two PMN). The basal expression of CD11b and, hence, neutrophil activation, was significantly lower and the upregulation of CD11b in response to FMLP was more pronounced after magnetic separation, as compared to density gradient centrifugation. The MACS technique did not lead to polarisation of PMN, nor did it affect the oxidative burst. This study suggests that magnetic separation is a simple, time-saving technique, yielding highly purified and functionally intact PMN.

Gentamicin, tobramycin, and sisomicin disc susceptibility tests. Revised zone standards for interpretation.

Studies were undertaken to reevaluate interpretive zone standards for gentamicin and tobramycin disc tests. Disc tests with an investigational aminoglycoside, sisomicin, were also evaluated. The data suggest modification of zone standards for gentamicin disc tests to R (resistant) less than or equal to 12 mm and S (susceptible) greater than or equal to 16 mm. Currently recommended standards for tobramycin disc tests (R less than or equal to 12 mm and S greater than or equal to 15 mm) were found to be satisfactory. For 10-microgram sisomicin discs, zone standards of R less than or equal to 12 mm and S greater than or equal to 15 mm were also appropriate. Although gentamicin is structurally similar to sisomicin, it was less active against Pseudomonas aeruginosa. The activity spectrum of sisomicin against the collection of 470 bacterial isolates studied more nearly resembled that of tobramycin. Data analysis suggested that tobramycin disc tests might be used to predict susceptibility to sisomicin. However, these two drugs differ in their susceptibilities to aminoglycoside-inactivating enzymes produced by some resistant strains. In those institutions where such strains are endemic, the class concept of disc testing may not be applicable.

Reassessment of the "class" concept of disk susceptibility testing. Cephalothin disks versus minimal inhibitory concentrations with eleven cephalosporins.

Reassessment of the "class" concept of disk susceptibility testing. Cephalothin disks versus minimal inhibitory concentrations with eleven cephalosporins. Am J Clin Pathol 70: 909--913, 1978. Studies were carried out to determine whether susceptibility or resistance to 11 cephalosporins could be predicted reliably from the results of tests with a single cephalothin disk. The cephalosporins were tested with a microdilution technic and with a standardized disk test. Strains susceptible to a cephalothin disk were predictably susceptible to all other cephalosporins. However, 2--12% of the strains were resistant to cephalothin disks but were susceptible to the more active parenteral drugs cefoxitin, cephamandole, cefuroxime, and BL-S786. Because of differences in antimicrobial activities, the cephalosporins could be divided into three subgroups for purposes of susceptibility testing: one subgroup includes the majority of cephalosporins and may be represented by tests with cephalothin, the second subgroup inclues three active parenteral drugs (cephamandole, cefuroxime, and BL-S786) and may be represented by tests with cefuroxime, and the third subgroup consists of cefoxitin, a cephamycin with a unique broad spectrum of activity. Until the drugs in the second and third subgroups are released for general therapeutic use, the practice of testing only one cephalosporin disk appears to be a reasonably reliable procedure.

Optimal cefotaxime dosing for gram-negative bacteremia: effective trough serum bactericidal titers and drug concentrations 8 and 12 hr after 1- or 2-gm infusions.

Thirteen adult patients (47-81 yr) with gram-negative bacteremia and normal (less than or equal to 1.5 mg/dl) serum creatinines were treated with 1 or 2 gm of cefotaxime every 8 or 12 hr. The infecting organisms were Escherichia coli (9 strains), Klebsiella pneumoniae (2 strains), and one isolate of Salmonella enteritidis and Serratia marcescens. All patients recovered without any serious sequelae. The range of MICs for cefotaxime and desacetyl-cefotaxime were 0.015-0.25 micrograms/ml and 0.015-4.0 micrograms/ml, respectively. The MBC values for cefotaxime and desacetyl-cefotaxime were identical to the MIC values except for two strains. The trough levels of cefotaxime varied from 65.9 to 1.1 micrograms/ml. The serum concentration of desacetyl-cefotaxime varied from 84 to less than 1.0 microgram/ml. All corresponding trough serum inhibitory activities (SIA) were greater than or equal to 1:32. Comparisons of calculated and directly measured serum bactericidal activity (SBA) and SIA results suggest an additive and occasional synergistic benefit of the cefotaxime desacetyl metabolite. This study supports the clinical efficacy and cost-effectiveness of 8- and 12-hr dosing intervals for cefotaxime against bacteremic gram-negative strains having the usual high susceptibility (MICs, less than or equal to 0.25 micrograms/ml) to the newer cephalosporins.