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Is it really myositis? A consideration of the differential diagnosis.

PURPOSE OF REVIEW: The idiopathic inflammatory myopathies are an important and treatable group of disorders. However, the potential toxicity associated with the immune therapeutic regimens used to treat these disorders may be significant; therefore, accurate diagnosis before such treatment is essential. The differential diagnosis is potentially large. Accurate diagnosis usually depends on a combination of careful clinical assessment in conjunction with detailed laboratory investigations. Muscle biopsy remains essential in achieving an accurate diagnosis that will then guide treatment. This review describes the diagnostic approach used. RECENT FINDINGS: There has been debate over the requirements for an accurate diagnosis of inflammatory myopathy (i.e., polymyositis and dermatomyositis). It is increasingly recognized that there can be clinical and muscle histopathologic overlap between the features of inflammatory myopathies and those of other muscle disorders, in particular, the genetic muscular dystrophies. Pathologic findings of inflammation and major histocompatibility complex upregulation, although typical of inflammatory myopathies, have been shown to occur in some muscular dystrophies, complicating the diagnostic process. Inclusion body myositis is much less responsive to immunotherapy and is now recognized as the most common acquired muscle disease in those older than 50 years of age. It is likely that genetic muscular dystrophies and inclusion body myositis account for some cases of apparently "treatment-resistant" myositis. SUMMARY: A thorough clinical assessment, including a detailed family history, complemented by electromyography and creatine kinase measurements, should be undertaken in any patient with presumed idiopathic inflammatory myopathy. In addition, a muscle biopsy remains essential in all cases. A precise tissue diagnosis confirming features of an active inflammatory process should be achieved before immunosuppressive treatment is commenced. An increasing array of immunocytochemical and histioenzymatic stains now allows a full analysis and will help to confirm or exclude virtually all the differential diagnostic possibilities considered in this review. Electron microscopy may also be valuable in selected cases. Close collaboration between clinicians and muscle pathologists is essential in allowing the most accurate interpretation of myopathologic findings in the clinical context.

Diagnosis, Differential↗

A three-dimensional multivariate model of passive human joint torques and articular boundaries.

OBJECTIVE: The development of a novel three-dimensional mathematical model of passive human joint torques that is of practical use, takes into account the complex non-linear interactions that exist between the moments generated by the various passive structures spanning the joint in question, and is applicable to all types of articular joints. DESIGN: Mathematical model validated by practical implementation. BACKGROUND: Previous models of passive human joint torques were predominantly one-dimensional and did not take into account the interactions of the various structural components. METHODS: Mathematical modelling is used in conjunction with repeated passive torque experiments on the right elbow joint of a healthy 29-year-old male. On the basis of the experimentally observed torque-angle data, the full set of articular model parameters characterizing the two-dimensional passive elastic torque function of the subject's right elbow joint could be determined. RESULTS: In addition to the passive elastic torque functions, the two-dimensional contour of the elbow joint's articular boundaries was also obtained. CONCLUSIONS: The present model is especially useful for assessing certain pathological conditions in any body joint investigated, and in addition is best suited for the inclusion in large-scale dynamic simulation models of the human neuromusculoskeletal system.

Journal Article↗

A review of educational developments with Brånemark osseointegrated oral implants in Australia and New Zealand 1992-1994. Part I: Treatment data for Australia and New Zealand.

This review should be read in conjunction with the Teams Day Conference review of 1992. This data further emphasises the trend in implant restoration that was becoming apparent at that time. However, the degree to which single tooth implant restorations now dominate clinical implant treatment is unprecedented. There is clear evidence of a progressive increase also in segmental and full arch bridgework, but minimal increase in overdenture restorations. The data also indicates that for the first time the number of males treated was greatest and that the maxilla was more frequently restored. This latter feature is no doubt closely linked with the emphasis given to single tooth restorations. This data, fully supports the inclusion of implant restoration into general and specialist dental practice.

Australia↗

A before-and-after study of driver stopping propensity at red light camera intersections.

This paper reports a before-and-after study which evaluated the impacts of installing and operating red light cameras at two "T" and one "X" signalized intersections on driver stopping propensity upon the onset of amber. Rather than using video cameras, a special purpose data logger working in conjunction with loop sensors was used to gather traffic parameters, vehicle stopping/crossing movements, and signal phases. Logistic modeling was employed to model the revealed stopping/crossing decisions of non-platoon vehicle drivers in response to the onset of amber with traffic, situational and behavioral variables, including their interactions. The results indicate that the variable Cam_Inst that gathered the impacts of red light camera (RLC) installation on driver decision-making at signalized intersection was significant at 5% level only for the camera approach model of the cross-intersection. The significance of Cam_Inst was undermined for the camera approaches at the T-intersections by the inclusion of a significant two-order variable defining the interaction of Cam_Inst with distance from the stop-line. One may, thus, infer that RLC has a fixed-quantum effect at the cross-intersection, but an accentuated effect with distance at the two T-intersections. Lastly, the effects of a RLC at an intersection on the stopping decision at the non-camera approaches were minimal.

Automobile Driving↗

Variability in thrombolytic practice in Oregon.

STUDY OBJECTIVE: To examine current thrombolytic protocols in Oregon emergency departments with regard to variations in patient evaluation, inclusion and exclusion criteria, initiation of therapy, and available thrombolytic agents. DESIGN: Telephone survey of ED head nurses. SETTING: All acute-care hospital EDs in Oregon. TYPE OF PARTICIPANTS: Of 70 acute-care hospitals contacted, 67 (96%) were included: 61 (87%) have a written ED protocol for thrombolytic agent use. METHODS: Telephone survey of written thrombolytic protocols, with comparison of groups using Kruskal-Wallis test (P less than .05). MEASUREMENTS AND MAIN RESULTS: The primary modes of initiating thrombolytic therapy are at the emergency physician's discretion (32%). after private physician consultation (24%), through the use of an agreement developed by the emergency physicians in conjunction with cardiologists or internists (22%), or after cardiologist or internist consultation (22%). ECG interpretation before drug administration is most often performed by the emergency physician (41%), cardiologist or internist (28%), private physician (6%), or computer (10%). Both tissue plasminogen activator (tPA) and streptokinase are available at 50 hospitals (75%); tPA is used exclusively in ten (15%) and streptokinase in seven (10%) other hospitals. tPA and streptokinase are approved for ED use in 43 (72%) and 46 (81%), respectively, of the hospitals at which these agents are available. In these, the ED is the most frequent site of administration of tPA in only 28 (65%) and of streptokinase in 33 (72%) hospitals; tPA and streptokinase are kept in the ED in only 23 (53%) and 23 (50%) of these hospitals, respectively. There was a significant correlation between thrombolytic administration in the ED and the number of full-time emergency physicians and American Board of Emergency Medicine diplomates. CONCLUSION: Thrombolytic protocols are highly variable in Oregon EDs.

Bed Occupancy↗

[Role of bovine respiratory syncytial virus in the aetiology of viruspneumonia in calves and yearlings ("pinkengriep") (author's transl)].

The clinical picture of "pinkengriep", an enzootic form of bronchopneumonia in young cattle, is described. In addition to cough, conjunctivitis and a soporous state, accelerated respiration initially is an outstanding clinical symptom. In some cases, symptoms of fog fever appear during the second stage of the disease. In the autumn of 1973 and that of 1974, a total number of 292 animals with "pinkengriep" were serologically examined for known respiratory virus infections and Chlamydia. Complement fixation tests showed that there was significant increase in antibodies to respiratory syncytial virus in 76 per cent of the animals studied. In the case of para-influenza virus 3, virus diarrhoea virus, the adenoviruses of the antigen groups 1, 2 and 3, those of the antigen groups 4 to 10 inclusive and Chlamydia, these proportions were 48, 13, 12, 11 en 10 per cent respectively. On the other hand, symptoms of infection with infectious bovine rhinotracheitis virus were absent in the herds studied. These findings suggest a possible role of bovine respiratory syncytial virus in "pinkengriep".

Animals↗

Correlates of quantitative measurement of BK polyomavirus (BKV) DNA with clinical course of BKV infection in renal transplant patients.

BK virus-allograft nephropathy (BKVAN) is an increasingly recognized complication after kidney transplantation. Quantitative tests have been advocated to monitor patients, but data demonstrating their efficacy are relatively limited. We developed a real-time PCR assay to quantitate BK virus loads in the setting of renal transplantation, and we correlated the BK virus load with clinical course and with the presence of BK virus in renal biopsy specimens. BK virus loads were measured in urine, plasma, and kidney biopsy samples in three clinical settings: (i) patients with asymptomatic BK viruria, (ii) patients with active BKVAN, and (iii) patients with resolved BKVAN. Active BKVAN was associated with BK viremia greater than 5 x 103 copies/ml and with BK viruria greater than 107 copies/ml in all cases. Resolution of nephropathy led to resolution of viremia, decreased viruria levels, and disappearance of viral inclusions, but low-level viral DNA persisted in biopsy specimens even for patients whose viruria was cleared. All but one patient in the resolved BKVAN group carried a urinary viral load below 107 copies/ml. Viral loads in patients with asymptomatic viruria were generally lower but in some cases overlapped with levels more typical of BKVAN. One patient with asymptomatic viruria and with a viral load overlapping values seen in BKVAN had developed nephropathy by the time of follow-up. In conclusion, serial measurement of viral loads by quantitative PCR is a useful tool in monitoring the course of BK virus infection. The results should be interpreted in conjunction with the clinical picture and biopsy findings.

BK Virus↗

Defining a metabolic phenotype in the brain of a transgenic mouse model of spinocerebellar ataxia 3.

Many of the spinocerebellar ataxias (SCAs) are caused by expansions of CAG trinucleotide repeats encoding abnormal stretches of polyglutamine. SCA3 or Machado-Joseph disease (MJD) is the commonest dominant inherited ataxia disease, with pathological phenotypes apparent with a CAG triplet repeat length of 61-84. In this study a mouse model of SCA3 has been examined which was produced using a human yeast artificial chromosome containing the MJD gene with a CAG triplet expansion of 84 repeats. These mice have previously been shown to possess a mild progressive cerebellar deficit. NMR-based metabolomics/metabonomics in conjunction with multivariate pattern recognition identified a number of metabolic perturbations in SCA3 mice. These changes included a consistent increase in glutamine concentration in tissue extracts of the cerebellum and cerebrum and spectra obtained from intact tissue using magic angle spinning (1)H-NMR spectroscopy. Furthermore, these profiles demonstrated metabolic abnormalities were present in the cerebrum, a region not previously implicated in SCA3. As well as an increase in glutamine both brain regions demonstrated decreases in GABA, choline, phosphocholine and lactate (representing the summation of lactate in vivo, and postmortem glycolysis of glucose and glycogen). The metabolic changes are discussed in terms of the formation of neuronal intranuclear inclusions associated with SCA3. This study suggests high-resolution (1)H-NMR spectroscopy coupled with pattern recognition may provide a rapid method for assessing the phenotype of animal models of human disease.

Animals↗

Chitosan microspheres in PLG films as devices for cytarabine release.

Cytarabine was included in chitosan microspheres and several of these microspheres were embedded in a poly(lactide-co-glycolide) (PLG) film to constitute a comatrix system, to develop a prolonged release form. Chitosan microspheres, in the range of 92+/-65 microm, having good spherical geometry and a smooth surface incorporating cytarabine, were prepared. The cytarabine amount included in chitosan microspheres was 43.7 microg of ara-C per milligram microsphere. The incorporation efficiency of the cytarabine in microspheres was 70.6%. Total cytarabine release from microspheres in vitro was detected at 48 h. Inclusion of cytarabine-loaded microspheres in poly(lactide-co-glycolide) film initiated a slower release of the drug and, in this way, the maximum of cytarabine released (80%) took place in vitro at 94.5 h. Comatrices, with 8.7 mg of cytarabine, signifying a dose of 34.5 microg/kg, were subcutaneously implanted in the back of rats. Maximum plasma cytarabine concentration was 18.5+/-1.5 microg/ml, 48 h after the device implantation and the drug was detected in plasma for 13 days. The histological studies show a slow degradative process. After 6 months of implantation, most of the microspheres of the matrix seemed to be intact, the comatrix appeared surrounded by conjunctive tissue and small blood vessels and nerve packets were detected in the periphery of the implant.

Animals↗

Optimizing DREAR and SnB parameters for determining Se-atom substructures.

The determination of the anomalous scattering substructure is the first essential step in any successful macromolecular structure determination using the multiwavelength anomalous diffraction (MAD) technique. The diffE method of calculating difference Es in conjunction with SnB has had considerable success in determining large Se-atom substructures. An investigation of the parameters used in both the data-reduction and error-analysis routines (DREAR) as well as the SnB phasing process itself was undertaken to optimize these parameters for more efficient use of the procedure. Two sets of selenomethionyl S-adenosylhomocysteine hydrolase MAD data were used as test data. The elimination of all erroneously large differences prior to phasing was found to be critical and the best results were obtained from accurate highly redundant intensity measurements. The high-resolution data collected in the typical MAD experiment are sufficient, but the inclusion of low-resolution data below 20 A improved the success rate considerably. Although the best results have been obtained from single-wavelength peak anomalous diffraction data alone, independent SnB analysis of data measured at other wavelengths can provide confirmation for questionable sites.

Computer Simulation↗

Double-antibody radioimmunoassay of serum insulin: effect of use of hormone-depleted human serum.

Human serum can be depleted of insulin and growth hormone by treatment with dextran-coated charcoal or by dialysis, or both. Inclusion of such hormone-depleted serum in the standard curve of a double-antibody radioimmunoassay for immunoreactive insulin more nearly mimics the conditions under which an unknown human serum sample is assayed. Compared to the usual standard curve in which serum albumin is the only protein, the addition of hormone-depleted serum can cause an increase (by an average 64% under the conditions we used) in the absolute value for apparent insulin in serum. The effect of hormone-depleted serum should be tested in the standard curves of double-antibody radioimmunoassays and included routinely in these standard curves if it changes the results. When used in conjunction with an eventual reference standard for human insulin, this modification of the insulin assay may make the measured values of human serum insulin from different laboratories more comparable.

Blood↗

[Study on the perinatal infection caused by Chlamydia trachomatis].

OBJECTIVE: Study on the frequency and outcome of chlamydia trachomatis (CT) infection of the pregnant women and their babies. METHODS: Two hundred and seventy eight pregnant women and their 79 infants were studied with McCoy cell culture, polymerase chain reaction (PCR) and DNA sequence analysis. Isolation of CT was performed in McCoy cell culture, and iodine-stained glycogen-positive inclusions were considered to be positive. CT DNAs were extracted by modified NaI method. Two sets of primers derived from CT common plasmid and major outer membrane protein genes were used in the PCR. Dideoxy-mediated chain-termination method was used for DNA sequence analysis. RESULTS: 10.8% (30/278) of the cervical cultures were positive for CT, while the positive rate by PCR was 14.0% (39/278). The vertical transmission rate of CT was 55.0% (11/22). The sequences of DNA amplified from a maternal-infant pair were matched perfectly. The incidence of puerperal endometritis in CT positive women was 28.6%, much higher than 8.1% in those CT negative mothers. Neonatal conjunctivitis and pneumonia in group of CT positive mothers were 45.0% and 30.0%, respectively, much higher than 18.3% and 8.3%, respectively, in that of CT negative mothers (P < 0.05). CONCLUSION: Perinatal infection caused by CT is very common in China.

Chlamydia Infections↗

Incremental cost-effectiveness of incorporating oestriol evaluation in Down syndrome screening programmes.

As screening for Down syndrome becomes increasingly sophisticated, it is important to evaluate the newer technologies in terms of their cost-effectiveness. One recent addition to Down syndrome screening programmes is maternal serum unconjugated oestriol (uE3), especially when used in conjunction with maternal serum alpha-fetoprotein and human chorionic gonadotropin. Using assumptions used in a California proposal to justify an expanded screening programme for Down syndrome, we calculated both the average and the incremental cost-effectiveness of adding uE3. Using the base case assumptions, including an $8 fee for the uE3, the incremental cost-effectiveness of adding uE3 to the proposed California programme is $119,100 per case detected, a value that compares favourably with other Down syndrome screening programmes. The sensitivity analysis supports this conclusion over a wide range of assumptions. However, because of the uncertainty with some key data, it is still too early to fully support the inclusion of uE3 in Down syndrome screening programmes.

Adult↗

Detection and quantification of Listeria monocytogenes by 5'-nuclease polymerase chain reaction targeting the actA gene.

AIMS: The aim of this study was to develop a 5'-nuclease polymerase chain reaction (PCR) for the rapid detection and quantification of Listeria monocytogenes. METHODS AND RESULTS: Specific primers and a fluorogenic probe were designed, which target a specific sequence of the actA gene encoding for a protein involved in the actin filament assembly. The PCR system was highly sensitive and specific for L. monocytogenes (inclusivity, 100%; exclusivity, 100%), which was determined using 46 L. monocytogenes and 28 non-L. monocytogenes strains. Detection limits of 10(4) cfu ml(-1) after 35 cycles and 10(2) cfu ml(-1) after 45 cycles were achieved by PCR in both real-time and end-point fluorescence measurement modes. Linear calibration lines were obtained in the range from 10(2) to 10(9) cfu ml(-1) for three L. monocytogenes strains in real-time PCR with 45 cycles. CONCLUSIONS: The developed 5'-nuclease PCR of the actA gene provides a new target for the rapid detection and quantification of L. monocytogenes. SIGNIFICANCE AND IMPACT OF THE STUDY: In conjunction with enrichment or with an appropriate quantitative sample preparation technique, the method is suitable for food safety applications.

Bacterial Proteins↗

A postmarketing, open-label study to evaluate the tolerability and effectiveness of replacing standard-formulation doxazosin with doxazosin in the gastrointestinal therapeutic system formulation in adult patients with hypertension.

BACKGROUND: The antihypertensive doxazosin works to decrease perivascular muscular tone, causing vasodilatation and hence a decrease in peripheral vascular resistance. To prevent the sharp decrease in blood pressure (BP), syncope, and other postural effects that may occur at the beginning of therapy with this drug, the dose must be adjusted. A new formulation, doxazosin gastrointestinal therapeutic system (GITS), allows slow release of the active agent so therapeutic serum levels are reached within 24 hours, rendering dose adjustment unnecessary and eliminating any first-dose effects. OBJECTIVES: The goals of this study were to evaluate the tolerability and effectiveness of (1) using doxazosin in the standard and new GITS formulations in adult patients with hypertension who either had uncontrolled or newly diagnosed disease, and (2) replacing standard-formulation doxazosin with doxazosin in the GITS formulation. METHODS: This was a postmarketing, open-label, noncomparative, multicenter clinical study covering primary care patients diagnosed with essential uncontrolled arterial hypertension (AHT). Subjects could be patients who were undergoing drug therapy before enrollment or those diagnosed with AHT and/or treated for the disease for the first time on entering the study. The study covered a period of 6 to 9 months, divided into 2 phases. Phase 1 involved a minimum of 3 and maximum of 6 months of treatment with standard-formulation doxazosin. Phase 2 commenced with the changeover from standard-formulation doxazosin to the GITS formulation and lasted 12 weeks. The principal study variables included BP and the development of adverse events (AEs). At every visit, the patients were asked by an investigator whether they had suffered any AEs since the previous contact. RESULTS: Of the total of 4,512 patients initially enrolled, 3537 (78.4%) completed the study. A total of 285 patients were excluded for failing to comply with the inclusion criteria, leaving 4,227 patients for analysis. In most instances, premature withdrawal from the study (16.3% [690/4,227]) was due to loss to follow-up (37.2% [257/690]), followed by the development of AEs (27.8% [192/690]). Fifty-nine percent (2,493/4,226) of patients analyzed were men and 41.0% (1,733/4,226) were women (sex data not recorded for 1 patient), with a mean age of 62.4 years (SD, 10.6). Among the patients participating, 54.8% (2,316/4,227) presented with some type of associated disease. The percentage of patients undergoing monotherapy was 70.7% (2,987/4,227); the remainder (29.3% [1,240/4,227]) underwent a combined-therapy regimen using another antihypertensive drug in conjunction with doxazosin. The mean initial systolic and diastolic BPs were 160 +/- 10.63 mm Hg and 95.26 +/- 7.21 mm Hg, respectively. Reduction in systolic BP was 20.9 mm Hg in phase 1 and 3.8 mm Hg in phase 2. In the case of diastolic BP, the reduction was 13.3 mm Hg in phase 1 and 2.6 mm Hg in phase 2. The percentage of patients with controlled disease was 47.9% (1,891/3,949) by the end of phase 1 and 63.4% (2,242/3,537) by the end of phase 2. A total of 322 (7.6%) patients presented with 343 AEs. 37 (0.9%) of which were deemed severe (0.6% in phase 1 and 0.3% in phase 2). Limitations included the following: (1) the design of this study did not allow comparison of the 2 formulations regarding effectiveness or tolerability: (2) the patients who remained in the study after phase 1 were those less susceptible to toxicity from doxazosin; and (3) it is probable that the nonresponders were more likely to drop out of the study. CONCLUSIONS: Doxazosin in the standard formulation was effective and well tolerated for the purpose of lowering BP. Patients who tolerated the standard formulation also tolerated the switch to the GITS formulation. Finally, this substitution did not negatively impact the effectiveness of treatment of AHT.

Adult↗

Retinopathy in newly presenting non-insulin-dependent (type 2) diabetic patients.

One hundred and twenty-nine (97 M, 32 F) previously untreated non-insulin-dependent diabetic patients were studied. Meal and glucose (75 g) tolerance tests were performed on two separate days with glucose, C-peptide and insulin levels estimated during each with the inclusion of growth hormone during the meal test. In addition glycosylated haemoglobin (HbA1) and plasma creatinine levels were determined. Clinical evaluation included detailed ophthalmological examination following mydriasis. Differences between retinopaths (n = 21) and non-retinopaths (n = 108) were FPG 13.7 vs 11.6 (mmol/l) (p less than 0.01); HbA1: 12.9 vs 11.3 (%) (p less than 0.01); BMI: 25.2 vs 29.4 (kg/m2) (p less than 0.001); age 56.8 vs 52.4 (yr) (ns); creatinine: 91.2 vs 88.4 (mumol/l) (ns); systolic blood pressure: 152.4 vs 143.9 mmHg (ns); diastolic blood pressure 87.9 vs 87.7 mmHg (ns); fasting growth hormone: 4.6 +/- 0.9 vs 2.4 +/- 0.3 (mU/1) (p less than 0.01). Multivariate logistic analysis however revealed that systolic blood pressure in conjunction with the insulin response gave the most significant correlation with retinopathy. No significant correlation was observed with age, sex, diastolic blood pressure, creatinine, family history or smoking. The effect of disease duration could not be evaluated. B-cell function appears central to microvascular complications in non-insulin dependent diabetes mellitus.

Blood Glucose↗

Synergistic effects of pesticides and metals on the fibrillation of alpha-synuclein: implications for Parkinson's disease.

Aggregation of alpha-synuclein has been implicated in the formation of proteinaceous inclusions in the brain (Lewy bodies, Lewy neurites) that are characteristic of neurodegenerative diseases, such as Parkinson's disease (PD) and dementia with Lewy bodies (DLBs). The etiology of PD is unknown, but recent work has shown that except in rare cases, there appears to be no direct genetic basis. However, several studies have implicated environmental factors, especially pesticides and metals. Here we show that certain pesticides and metals induce a conformational change in alpha-synuclein and directly accelerate the rate of formation of alpha-synuclein fibrils in vitro. In addition, the simultaneous presence of metal and pesticide led to synergistic effects on the rate of fibrillation. We propose a model in which environmentalfactors in conjunction with genetic susceptibility may form the underlying molecular basis for idiopathic PD.

Aluminum Chloride↗

Protein binding and antimicrobial activity of ceftriaxone: comparative assessments by gradient plate technique and time-kill study.

In conjunction with initial bactericidal rate measurements, this study evaluated the impact of protein binding on the antimicrobial activity of ceftriaxone employing the gradient plate technique. Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923 were employed as test organisms. At various albumin concentrations (0 to < or = 16% w/v), the effects of albumin binding were estimated by the shift in concentration-responses (via initial bactericidal rate) and the distance of inhibition zone (DIZ) on gradient agar plates. Supplementation with 4% albumin reduced the antimicrobial activity of ceftriaxone against E. coli as suggested by the similar 1.5-fold shift in both initial bactericidal rate and DIZ when compared to those with no albumin. As with S. aureus, the inclusion of albumin increased the initial bactericidal rate but the DIZ assessments showed a reduction in antimicrobial activity. The reason for the difference observed on the initial bactericidal effect between the two species is unknown. However, the similar patterns of change in the DIZ data at increasing albumin concentrations from 0 to 4% for both organisms suggest consistency and reproducibility of the gradient plate technique. This technique appears to be an attractive alternative for the assessment of the effect of protein binding on antibiotics.

Albumins↗