Correction to: 18F-Fluciclovine (18F-FACBC) PET imaging of recurrent brain tumors.

The article 18F-Fluciclovine (18F-FACBC) PET imaging of recurrent brain tumors written by Laure Michaud, B. J. Beattie, T. Akhurst, M. Dunphy, P. Zanzonico, R. Finn, A. Mauguen, H. Schöder, W. A. Weber, A. B. Lassman, R. Blasberg.

18F-Fluciclovine (18F-FACBC) PET imaging of recurrent brain tumors.

PURPOSE: The aim of our study was to investigate the efficacy of 18F-Fluciclovine brain PET imaging in recurrent gliomas, and to compare the utility of these images to that of contrast enhanced magnetic resonance imaging (MRI) and to [11C-methyl]-L-methionine (11C-Methionine) PET imaging. We also sought to gain insight into the factors affecting the uptake of 18F-FACBC in both tumors and normal brain, and specifically to evaluate how the uptake in these tissues varied over an extended period of time post injection. METHODS: Twenty-seven patients with recurrent or progressive primary brain tumor (based on clinical and MRI/CT data) were studied using dynamic 18F-Fluciclovine brain imaging for up to 4 h. Of these, 16 patients also had 11C-Methionine brain scans. Visual findings, semi-quantitative analyses and pharmacokinetic modeling of a subset of the 18F-Fluciclovine images was conducted. The information derived from these analyses were compared to data from 11C-Methionine and to contrast-enhanced MRI. RESULTS: 18F-Fluciclovine was positive for all 27 patients, whereas contrast MRI was indeterminate for three patients. Tumor 18F-Fluciclovine SUVmax ranged from 1.5 to 10.5 (average: 4.5 ± 2.3), while 11C-Methionine's tumor SUVmax ranged from 2.2 to 10.2 (average: 5.0 ± 2.2). Image contrast was higher with 18F-Fluciclovine compared to 11C-Methionine (p < 0.0001). This was due to 18F-Fluciclovine's lower background in normal brain tissue (0.5 ± 0.2 compared to 1.3 ± 0.4 for 11C-Methionine). 18F-Fluciclovine uptake in both normal brain and tumors was well described by a simple one-compartment (three-parameter: Vb,k1,k2) model. Normal brain was found to approach transient equilibrium with a half-time that varied greatly, ranging from 1.5 to 8.3 h (mean 2.7 ± 2.3 h), and achieving a consistent final distribution volume averaging 1.4 ± 0.2 ml/cc. Tumors equilibrated more rapidly (t1/2ranging from 4 to 148 min, average 57 ± 51 min), with an average distribution volume of 3.2 ± 1.1 ml/cc. A qualitative comparison showed that the rate of normal brain uptake of 11C-Methionine was much faster than that of 18F-Fluciclovine. CONCLUSION: Tumor uptake of 18F-Fluciclovine correlated well with the established brain tumor imaging agent 11C-Methionine but provided significantly higher image contrast. 18F-Fluciclovine may be particularly useful when the contrast MRI is non-diagnostic. Based on the data gathered, we were unable to determine whether Fluciclovine uptake was due solely to recurrent tumor or if inflammation or other processes also contributed.

Imaging skeletal muscle volume, density, and FDG uptake before and after induction therapy for non-small cell lung cancer.

AIM: To assess whether changes in body composition could be assessed serially using conventional thoracic computed tomography (CT) and positron-emission tomography (PET)/CT imaging in patients receiving induction chemotherapy for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: CT-based skeletal muscle volume and density were measured retrospectively from thoracic and lumbar segment CT images from 88 patients with newly diagnosed and untreated NSCLC before and after induction chemotherapy. Skeletal muscle 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) uptake was measured from PET/CT images from a subset of patients (n=42). Comparisons of each metric before and after induction chemotherapy were conducted using the non-parametric Wilcoxon signed-rank test for paired data. The association between clinical factors and percentage change in muscle volume was examined using univariate linear regression models, with adjustment for baseline muscle volume. RESULTS: Following induction chemotherapy, thoracic (-3.3%, p=0.0005) and lumbar (-2.6%, p=0.0101) skeletal muscle volume were reduced (adiposity remained unchanged). The proportion of skeletal muscle with a density <0 HU increased (7.9%, p<0.0001), reflecting a decrease in skeletal muscle density and skeletal muscle FDG uptake increased (10.4-31%, p<0.05). No imaging biomarkers were correlated with overall survival. CONCLUSION: Changes in body composition can be measured from routine thoracic imaging. During chemotherapy skeletal muscle volume and metabolism are altered; however, there was no impact on survival in this retrospective series, and further validation in prospective, well-controlled studies are required.

Randomized comparative study of ampicillin/sulbactam vs. ceftriaxone for treatment of soft tissue and skeletal infections in children.

In a prospective study 105 children hospitalized with soft tissue infection, 11 children with suppurative arthritis and 9 children with osteomyelitis were treated with either parenterally administered ampicillin/sulbactam or ceftriaxone. Treatment was randomized using a computer-generated table in a 2:1 fashion: 84 patients received ampicillin/sulbactam and 41 patients received ceftriaxone. Organisms isolated from wound site or blood cultures included Staphylococcus aureus (33), Streptococcus pyogenes (19), Haemophilus influenzae (9) including 4 beta-lactamase-positive organisms, Streptococcus pneumoniae (5), Neisseria gonorrhoeae (3) and 9 other organisms. Clinical and bacteriologic response was satisfactory in 100% of the ampicillin/sulbactam-treated patients and in 93% of the ceftriaxone-treated patients. Two patients with S. aureus infections treated with ceftriaxone had a delayed response and required change in therapy to parenterally administered oxacillin. Ampicillin/sulbactam represents a potentially useful single agent for the treatment of cellulitis and bone or joint infections in pediatric patients.

Reliability of polymerase chain reaction in the detection of human immunodeficiency virus infection in children.

During a 3-year period we followed 128 human immunodeficiency virus (HIV) antibody-positive children ages 6 days to 11 years clinically and with an HIV diagnostic panel consisting of antibody (by enzyme-linked immunosorbent assay and confirmed by indirect fluorescence assay or Western blot), p24 antigen detection, HIV isolation from peripheral blood culture and molecular detection of HIV nucleic acids by polymerase chain reaction (PCR). The PCR procedure included 30 cycles of amplification using two separate gag primer pairs (SK38/39 and SK101/145), followed by detection with probes to areas amplified (SK19 and SK102). Results of PCR were available within 48 hours and were sensitive (97%) and specific (100%). PCR should be obtained on all children exposed perinatally, and aggressive management should be undertaken for those found to be positive.

Effects of lithium on open field behavior in "stressed" and "unstressed" rats.

Rats were tested for 3 min per day, for 4 successive days, in an open field apparatus, 20 min after injection of either lithium chloride (2 mEq/kg) or physiological saline. In the first experiment, the open field was illuminated with moderate white light for some rats (stress condition) and dim red light for others (non-stress condition). In the second experiment, some rats received an electric foot shock 5 h before each open field test (stress condition) and others received no foot shock (non-stress condition). In both experiments, lithium significantly reduced rearing behavior in the stressed, but not the unstressed, rats. Lithium also reduced horizontal locomotion, but this effect appeared in both stressed and unstressed rats. In the second experiment, defecation was measured, and it was found that lithium-treated rats defecated less than saline-treated rats in the first session, but not in subsequent sessions, due to habituation which occurred for the saline rats.

Teaching dietetic interns to write for lay and professional audiences.

The University of Iowa Hospitals and Clinics Dietetic Internship Program has developed a series of workshops and assignments to enhance the writing skills of interns. Three workshops cover basic writing skills, development of materials for the lay public, and basic elements of journalistic writing for professional audiences. The interns received a variety of assignments throughout the year to build competencies learned in these workshops. Evaluation forms have been developed to make assessing the assignments easier for the instructors and to give feedback to the interns. Evaluation reports from interns and graduates indicate that the program is effective and appreciated.

A computerized dietary order entry system.

The Dietary Order Entry System is a computerized system which instantaneously communicates orders/messages from the patient care units to the floor diet offices. The system also produces up-to-date management reports such as diet lists and diet census at pre-determined times and on demand. Dietary and nursing personnel believe it is an extremely beneficial system in terms of both increased accuracy of data and time savings in transmission of information. We believe that improved patient care will result from this improved method of diet ordering.

Effective nutrition education program for medical students.

The existing nutrition education luncheon program at the University of Iowa Hospitals is an effective method of teaching clinical dietetics to third-year medical students. The development of a Nutrition Reference Handbook has made a significant impact on attendance at the luncheons, which is voluntary, and has become an integral part of the program.

Beta-endorphin and components of depression as powerful discriminators between joggers and sedentary middle-aged men.

UNLABELLED: This study identifies the relative importance of resting plasma beta-endorphin, used as a marker of perceived stress, and components of non-clinical depression that discriminate between physically active joggers and sedentary men. The profiles of joggers (n = 10) and sedentary (n = 10) middle-aged men (40-60 yr) were compared. The jogger group had been running about 20 miles per week for at least 3 yr. RESULTS: as expected, the joggers exhibited greater physical fitness, but lower circulating beta-endorphin (measured with the subjects at rest). The joggers also exhibited greater emotional stability (Eysenck scores), and lower depression (MMPI Scale 2 scores). In addition, the joggers had lower scores on MMPI subscales of depression: subjective depression, physical malfunctioning, mental dullness, and brooding. Multivariate discriminant function analyses showed that subjective depression, beta-endorphin, and physical malfunctioning were powerful discriminators between the jogger and sedentary groups. IN CONCLUSION: (1) subjective depression appeared to be the MMPI component of depression that most powerfully discriminated between joggers and sedentary middle-aged men in this study. (2) Lower beta-endorphin may be an adaptation to exercise training and was related to greater emotional stability and lower depression, especially lower subjective depression. (3) The lower beta-endorphin in the jogger group may be related to lower perceived stress in the joggers, relative to the sedentary group.

Susceptibility of Haemophilus influenzae type b to ampicillin-sulbactam.

Seventy-five strains of Haemophilus influenzae type b, including 45 beta-lactamase-positive strains, were tested by MIC and time kill studies for susceptibility to ampicillin-sulbactam at various ratios. beta-Lactamase-negative strains were inhibited by lower concentrations of ampicillin-sulbactam than beta-lactamase-positive organisms. beta-Lactamase-negative strains showed a decrease in CFU per milliliter by a factor of 10(4) after a 24-h incubation with ampicillin-sulbactam. beta-Lactamase-positive isolates showed an initial decrease by a factor of up to 10(2) CFU per milliliter, but by the end of incubation these isolates grew to approximately the same cell density as the antibiotic-free control regardless of ampicillin-sulbactam ratios. Caution should be exercised in the use of this combination in treatment of meningitis, in which a high bacterial density is commonly encountered.

A postdischarge adverse drug reaction capture mechanism using medical record technicians.

This article describes a system of adverse drug reaction (ADR) reporting implemented at WJB Dorn Veterans Affairs (VA) Hospital, Columbia, South Carolina, which involves reviewing all inpatient charts by medical record technicians for possible ADRs and notifying the chief pharmacist for investigation. Cases are assigned to a clinical or staff pharmacist who completes an ADR data collection form. All ADR forms are presented to and reviewed by the pharmacy and therapeutic committee where a decision is made on whether to forward the ADR to the U.S. Food and Drug Administration via the VA Central Office for compilation. In the program's second quarter of 1990, ADR reporting increased approximately fivefold.

Quantitation of N,N,N',N'-tetrakis (2-hydroxypropyl)-ethylenediamine in plasma by gas chromatography.

A wide-bore capillary gas chromatographic method with nitrogen-selective thermionic detection is described for the quantitative analysis of N,N,N',N'-tetrakis (2-hydroxypropyl)ethylenediamine (Quadrol) in plasma. N,N,N',N'-tetrakis (2-hydroxybutyl)ethylenediamine is used as an internal standard. Rat or human plasma samples (0.5 ml) are mixed with internal standard, adjusted to alkaline pH and subjected to a single extraction with dichloromethane. Quadrol recovery from plasma typically exceeds 90%. The method is linear over the range 1.0-50 micrograms/ml. The working detection limit is 0.5 microgram/ml and the analysis time is under 7 min. The procedure has been used to obtain plasma concentration versus time data for the evaluation of Quadrol pharmacokinetics in rats.

In vitro activity of moxalactam alone and in combination with penicillin against common meningeal pathogens.

Moxalactam demonstrated marked activity against beta-lactamase-positive and -negative Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis by both standard minimal inhibitory concentration testing and growth curve studies. Moxalactam was ineffective against S. pneumoniae partially susceptible to penicillin G. Moxalactam (5 micrograms/ml) and penicillin (1 microgram/ml) in combination were indifferent to each other's antibacterial activity, exerting neither synergism nor antagonism against these organisms.

Nitrate analysis by capillary gas chromatography.

A microanalytical gas chromatographic (GC) method for the analysis of nitrate in rat urine is described. The method involves the conversion of nitrate to nitromesitylene and quantitation using 3,4-dimethylnitrobenzene as an internal standard. The nitroaromatics were separated on a wide-bore capillary column and detected with a nitrogen-phosphorus thermionic detector. The method exhibited linearity over the range of 1.0 to 1000 microM nitrate, and the detection limit was 0.5 microM nitrate (200-microliters sample). The coefficient of variation (CV) range for intra-day precision was 2.2 to 5.8% (20 microM level) and 3.1 to 6.5% (200 microM level). Inter-day CVs ranged from 2.0 to 6.1% for the samples tested. The average recovery was 77% (20 microM level) and 80% (20 microM level). The accuracy of the GC method compared favorably with results obtained from a standard colorimetric nitrate assay. Interference by urinary chloride was eliminated by pretreatment of samples with saturated silver acetate. Both processed and unprocessed samples were stable for at least 60 days at -15 degrees C. The procedure was used to measure urinary nitrate in rats fed a custom low-nitrate diet.

Susceptibility of Haemophilus influenzae type b to cefaclor and influence of inoculum size.

Cefaclor appeared to be an effective antibiotic against both beta-lactamase-positive and beta-lactamase-negative strains of Haemophilus influenzae type b when tested with 10(5) colony-forming units per ml. With inocula in excess of 10(6) colony-forming units per ml, these organisms were neither inhibited nor killed at concentrations of 400 micrograms/ml. This inoculum effect was also demonstrated in time-kill curve studies.

Promotion of wound collagen formation in normal and diabetic mice by quadrol.

The rate of collagen deposition in implanted polytetrafluoroethylene (PTFE) tubing in non-diabetic and streptozotocin-induced (STZ) diabetic mice was measured during 14 days post-wounding. At the time of implantation, test groups received injections of either Quadrol [N,N,N',N'-tetrakis(2-hydroxypropyl)ethylenediamine], glucan, or buffer in an area adjacent to the wound site. The accumulation of collagen in the implants of Quadrol-treated non-diabetic animals was more than 200% above control on days 8 to 11 and was 50% above control on day 14. In Quadrol-treated STZ-diabetic mice, the collagen accumulation gradually increased from 50% above control on day 8 to 200% above control on day 14. Treatment with glucan increased the collagen accumulation in normal mice 200 to 300% above control from days 8 to 11 respectively and then 30% above control on day 14. Collagen accumulation in the implants of the glucan-treated STZ-diabetic mice was similar to the control group. These results indicate that Quadrol promotes in vivo collagen synthesis and that Quadrol may be effective as a stimulator of wound healing in diabetic and non-diabetic animals.

Resolution of diastereomers of N,N,N',N'-tetrakis(2-hydroxypropyl)ethylenediamine (quadrol) by reversed-phase high-performance liquid chromatography.

Quadrol, N,N,N',N'-tetrakis(2-hydroxypropyl)ethylenediamine, has been recently observed to display biological activity. It is an immunostimulant and has been implicated as a potentially useful agent in accelerated wound healing. Quadrol exists as a mixture of four unique diastereomers, each of which may, upon further investigation, display differences in biological activity. This paper describes an high-performance liquid chromatographic procedure (both analytical and prep) for the separation of the Quadrol diastereomers. Gas-liquid chromatography and NMR data are presented which corroborate the high-performance liquid chromatographic results. This procedure may be used to obtain pure Quadrol diastereomers, to monitor the progress of Quadrol synthesis from propylene oxide and ethylenediamine or to develop a quantitative assay for Quadrol diastereomers.