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Biomedical subjects

C J Holmes

Publications and source records attributed to C J Holmes.

At least 73 records · Page 4Linked to original sources

Effect of freezing and microwave thawing on the stability of six antibiotic admixtures in plastic bags.

The stability of six antibiotics in intravenous fluids in polyvinyl chloride containers after freezing and microwave-thawing is reported. Tobramycin sulfate 160 mg, amikacin sulfate 1 g, ticarcillin disodium 3 g, clindamycin phosphate 300 mg, nafcillin sodium 1 g, and ampicillin sodium was also diluted in plastic bags of 0.9% sodium chloride injection 50 ml. For each antibiotic except ampicillin sodium, three bags were prepared and assayed immediately for antibiotic content. Two of the bags were frozen at -20 degrees C for 30 days and then thawed, one by exposure to room-temperature air and the other by microwave radiation. Each was assayed immediately and after 8 and 24 hours storage at room temperature. The third bag was not frozen, but was stored at room temperature and assayed at 8 and 24 hours. Five bags of ampicillin sodium were prepared-three in 0.9% sodium chloride, which were frozen at -20, -30, and -70 degrees C, and two in 5% dextrose, which were frozen at -30 and -70 degrees C. All ampicillin solutions were stored 30 days, assayed, microwave-thawed, and assayed again. All antibiotics except ampicillin retained 90% or more potency when microwave-thawed after storage at -20 degrees C for 30 days, and after subsequent storage at room temperature for 24 hours. Ampicillin sodium was stable in 0.9% sodium chloride when stored at -30 or -70 degrees C, microwave-thawed, and stored up to eight hours at room temperature. Ampicillin sodium was stable in 5% dextrose when stored at -70 degrees C and microwaved-thawed, but its potency declined to 70.5% after eight hours storage at room temperature.

Anti-Bacterial Agents↗

Potential hazards associated with microbial contamination of in-line filters during intravenous therapy.

The survival and multiplication of Enterobacter agglomerans, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa in 0.45- and 0.22-micrometer in-line filter sets during simulated infusions were studied to evaluate the ability of each filter type to prevent infusions of these bacteria into patients. Bacteria were found to proliferate in the upstream compartment of sets housing both filter porosities. None of the 0.22-micrometer in-line filters were penetrated by the test bacteria. In contrast, P. aeruginosa was observed to penetrate each 0.45-micrometer in-line filter examined within 12 h of continuous infusion. Tribe Klebsielleae organisms penetrated a proportion of the 0.45-micrometer filters usually between 48 and 72 h of infusion. In addition, the elution of endotoxin from gram-negative bacteria trapped in the filter set during infusion is reported. Collected infusion filtrate exhibited a trend of increasing endotoxin-like activity with an increasing duration of infusion. In the case of E. agglomerans, mean peak levels of approximately 65 pg of Escherichia coli endotoxin per ml were attained after 72 h. Other bacteria produced similar results, except mean peak levels ranged from 5 to 30 pg/ml. It was noted that endotoxin-like activity was not detected in filtrate eluted from contaminated filter sets during the initial 24 h of infusion. We conclude that to avoid potential hazards of bacterial penetration and endotoxin production during continuous use of in-line filter sets, the 0.22-micrometer filter type must be employed and replaced every 24 h.

Endotoxins↗

The application of a freeze-microwave thaw technique to central admixture services.

The establishment of a centralized, intravenous solution/admixture drug program in a hospital enhances the quality of patient care. Costs for personnel, equipment, and space have constrained the growth of such a service in the past. A method of preparation for admixture units, which capitalizes on the economics of volume and employs personnel at levels of training consistent with need, is proposed. This technique, utilizing freezing, long-term storage at -20 degrees C, and thawing by exposure in a microwave oven minutes before intended use, surmounts the real and perceived difficulties in many planned or existing admixture programs. A strong element of prospective quality control can be introduced. Where demand is insufficient to justify a separate activity, cooperative arrangements among hospitals will bring all the advantages of central admixture to each. It appears that reductions can be made in the pharmacy hours devoted to admixture. Waste of any unused, reconstituted drugs or prepared units that were not administered may be diminished. Thus, there may be substantial savings for existing admixture programs, if the technique described is adopted. The ultimate form of implementation in each institution, as always, is dependent upon the special "personality" of the hospital.

Anti-Bacterial Agents↗

Activity of antibiotic admixtures subjected to different freeze-thaw treatments.

The freezing of antibiotic admixtures has been proposed as a potentially useful method by which the efficiency of admixture services might be improved. The time involved in thawing, however, has discouraged the implementation of this practice. This study describes a technique of thawing frozen antibiotic admixtures contained in minibags in commercially available microwave ovens. A quantitative microbiological agar gel diffusion assay was employed to determine the effect of such treatment on the antibiotic activity of the admixture. Admixtures containing cephalothin sodium, cefazolin sodium, cefamandole nafate, cefoxitin sodium, penicillin G potassium, ampicillin sodium, oxacillin sodium, carbenicillin disodium, and gentamicin sulfate in dextrose 5% solution were frozen at -20 degrees C for 30 days. The admixtures were assayed immediately before freezing, and again after either thawing technique: that is, upon exposure of the minibags to room temperature air or to microwave radiation. Assays were also performed 8 and 24 hours after thawing in order to assess antibiotic stability following each freeze-thaw treatment. It was discovered that, with the exception of ampicillin sodium, each of the antibiotics studied could be frozen and thawed as described without significant loss of activity, and were stable for 24 hours after thawing. The application of a freeze microwave-thaw technique to central admixture services can be seen as a cost-effective method of circumventing many of the problems associated with existing programs.

Anti-Bacterial Agents↗

The potential for contamination of intravenous infusions by airborne skin scales.

Skin scales may be attracted onto the surface of administration set connector needles before insertion into infusion containers. Viable microorganisms associated with skin scales may therefore gain access to the infusion by this route. A technique is described for creating an environment of airborne skin scales. This environment is used to examine the attraction of skin scales onto the surface of administration set connector needles and three other materials. After exposure, skin scales are found adhering to the surface of each material examined. The attraction of skin scales onto administration set connector needles is dependent on the time of exposure to the environment. Results suggest that intravenous infusions can be contaminated by this route when the infusion and administration set is assembled.

Air↗

Intravenous infusion bottle plugs as a source of microbial contamination.

A technique was described for the artificial contamination of the upper surface of intravenous infusion container plugs with viable micro-organisms. This technique was employed to assess the adequacy of decontamination of two designs of plug by the use of antiseptic swabbing. Results indicated that the MRC plug surface was more difficult to sterilize than that of the Travenol plug. The possibility of contamination of the infusion fluid during insertion of the giving-set needle was examined. Results indicated that there was a risk of contamination through the administration-set port of the MRC plug if swabbing was inadequate.

Bacillus megaterium↗

Periodic elevation of complement activation products in peritoneal dialysis effluent.

Peripheral white blood cells (WBCs) of chronic ambulatory peritoneal dialysis (CAPD) patients show a reduced expression of chemotactic receptors and a desensitization to chemotactic factor induced events. Chronic complement activation has been suggested as a cause of such phenomena, resulting from either uremia, the indwelling peritoneal catheter, and/or dialysis fluid stimulation. The presence of complement activation products in peritoneal dialysis effluent was assessed by longitudinal measurement of C3bi in eight patients over a 6 to 8 month period, while peritoneal polymorphonuclear leukocyte (PMN) and monocyte CR3 and C5a receptor expression was quantitated by flow cytometry. In six of eight patients, C3bi levels were stable over time and usually measured less than 5 micrograms/ml. Two other patients showed periodic elevation of C3bi, which was not associated temporally with peritonitis. Further study is required to identify the origin of such activated complement components within the peritoneal cavity. However, no correlation was found between dialysate C3bi levels and peritoneal PMN or monocyte expression of CR3 or C5a receptors. Furthermore, the incidence of peritonitis for the two individuals with elevated C3bi was discordant (1 episode/8 patient months vs. 0 episodes/32 patient months), suggesting little or no relationship between these parameters.

Adult↗

Detection and mapping of abnormal brain structure with a probabilistic atlas of cortical surfaces.

PURPOSE: We have devised, implemented, and tested a technique for creating a comprehensive probabilistic atlas of the human cerebral cortex, based on high-dimensional fluid transformations. The goal of the atlas is to detect and quantify subtle and distributed patterns of deviation from normal cortical anatomy, in a 3D brain image from any given subject. METHOD: Given a 3D MR image of a new subject, a high-resolution surface representation of the cerebral cortex is automatically extracted. The algorithm then calculates a set of high-dimensional volumetric maps, fluidly deforming this surface into structural correspondence with other cortical surfaces, selected one by one from an anatomic image database. The family of volumetric warps so constructed encodes statistical properties of local anatomical variation across the cortical surface. Additional strategies are developed to fluidly deform the sulcal patterns of different subjects into structural correspondence. A probability space of random transformations, based on the theory of anisotropic Gaussian random fields, is then used to encode information on complex variations in gyral and sulcal topography from one individual to another. A complete system of 256(2) probability density functions is computed to reflect the observed variability in stereotaxic space of the points whose correspondences are found by the warping algorithm. Confidence limits in stereotaxic space are determined for cortical surface points in the new subject's brain. RESULTS: Color-coded probability maps are generated, which highlight and quantify regional patterns of deformity in the anatomy of new subjects. These maps indicate locally the probability of each anatomic point being as unusually situated, given the distributions of corresponding points in the scans of normal subjects. 3D MRI volumes are analyzed, from subjects with clinically determined Alzheimer disease and age-matched normal subjects. CONCLUSION: Applications of the random fluid-based probabilistic atlas include the transfer of multisubject 3D functional, vascular, and histologic maps onto a single anatomic template, the mapping of 3D atlases onto the scans of new subjects, and the rapid detection, quantification, and mapping of local shape changes in 3D medical images in disease and during normal or abnormal growth and development.

Aged↗

Automated image registration: I. General methods and intrasubject, intramodality validation.

PURPOSE: We sought to describe and validate an automated image registration method (AIR 3.0) based on matching of voxel intensities. METHOD: Different cost functions, different minimization methods, and various sampling, smoothing, and editing strategies were compared. Internal consistency measures were used to place limits on registration accuracy for MRI data, and absolute accuracy was measured using a brain phantom for PET data. RESULTS: All strategies were consistent with subvoxel accuracy for intrasubject, intramodality registration. Estimated accuracy of registration of structural MRI images was in the 75 to 150 microns range. Sparse data sampling strategies reduced registration times to minutes with only modest loss of accuracy. CONCLUSION: The registration algorithm described is a robust and flexible tool that can be used to address a variety of image registration problems. Registration strategies can be tailored to meet different needs by optimizing tradeoffs between speed and accuracy.

Algorithms↗

Enhancement of MR images using registration for signal averaging.

PURPOSE: With the advent of noninvasive neuroimaging, a plethora of digital human neuroanatomical atlases has been developed. The accuracy of these atlases is constrained by the resolution and signal-gathering powers of available imaging equipment. In an attempt to circumvent these limitations and to produce a high resolution in vivo human neuroanatomy, we investigated the usefulness of intrasubject registration for post hoc MR signal averaging. METHOD: Twenty-seven high resolution (7 x 0.78 and 20 x 1.0 mm3) T1-weighted volumes were acquired from a single subject, along with 12 double echo T2/proton density-weighted volumes. These volumes were automatically registered to a common stereotaxic space in which they were subsampled and intensity averaged. The resulting images were examined for anatomical quality and usefulness for other analytical techniques. RESULTS: The quality of the resulting image from the combination of as few as five T1 volumes was visibly enhanced. The signal-to-noise ratio was expected to increase as the root of the number of contributing scans to 5.2, n = 27. The improvement in the n = 27 average was great enough that fine anatomical details, such as thalamic subnuclei and the gray bridges between the caudate and putamen, became crisply defined. The gray/white matter boundaries were also enhanced, as was the visibility of any finer structure that was surrounded by tissue of varying T1 intensity. The T2 and proton density average images were also of higher quality than single scans, but the improvement was not as dramatic as that of the T1 volumes. CONCLUSION: Overall, the enhanced signal in the averaged images resulted in higher quality anatomical images, and the data lent themselves to several postprocessing techniques. The high quality of the enhanced images permits novel uses of the data and extends the possibilities for in vivo human neuroanatomy.

Artifacts↗

Analyzing functional brain images in a probabilistic atlas: a validation of subvolume thresholding.

PURPOSE: The development of structural probabilistic brain atlases provides the framework for new analytic methods capable of combining anatomic information with the statistical mapping of functional brain data. Approaches for statistical mapping that utilize information about the anatomic variability and registration errors of a population within the Talairach atlas space will enhance our understanding of the interplay between human brain structure and function. METHOD: We present a subvolume thresholding (SVT) method for analyzing positron emission tomography (PET) and single photon emission CT data and determining separately the statistical significance of the effects of motor stimulation on brain perfusion. Incorporation of a priori anatomical information into the functional SVT model is achieved by selecting a proper anatomically partitioned probabilistic atlas for the data. We use a general Gaussian random field model to account for the intrinsic differences in intensity distribution across brain regions related to the physiology of brain activation, attenuation effects, dead time, and other corrections in PET imaging and data reconstruction. RESULTS: H2(15)O PET scans were acquired from six normal subjects under two different activation paradigms: left-hand and right-hand finger-tracking task with visual stimulus. Regional region-of-interest and local (voxel) group differences between the left and right motor tasks were obtained using nonparametric stochastic variance estimates. As expected from our simple finger movement paradigm, significant activation (z = 6.7) was identified in the left motor cortex for the right movement task and significant activation (z = 6.3) for the left movement task in the right motor cortex. CONCLUSION: We propose, test, and validate a probabilistic SVT method for mapping statistical variability between groups in subtraction paradigm studies of functional brain data. This method incorporates knowledge of, and controls for, anatomic variability contained in modern human brain probabilistic atlases in functional statistical mapping of the brain.

Adult↗

Estimation of brain compartment volume from MR Cavalieri slices.

PURPOSE: Recent theory has been developed to estimate volume from a systematic sample of tissue slices of a given thickness and to predict the corresponding error. Our goal was to check the error prediction formulas by resampling and to determine the minimum number of MR slices required to estimate the volumes of the cerebrum and of the compartments of gray matter (GM) and white matter (WM) with prescribed errors. METHOD: Our working data set comprised the GM and WM segmentations obtained from a paradigmatic high signal-to-noise ratio 3D spoiled GRASS MR volume data set for a single healthy human subject. The data were classified using a fuzzy clustering minimum distance algorithm. We thereby obtained a stack of 183 serial coronal slices of 1 mm thickness encompassing the whole cerebrum. Empirical resampling was carried out using the corresponding data vectors, and the theoretical error predictors were thereby checked for slice thicknesses of 1, 3, 9, and 27 mm, with a distance of 45 mm between slice midplanes. RESULTS: Irrespective of slice thickness, a minimum of 3, 5, and 10 slices provided estimates of the true total volume of GM and WM in the cerebrum with coefficients of error (CEs) of 10, 5, and 3%, respectively, where CE(V)% = 100 x SE(V)/V. For the cerebrum, a minimum of two, three, and four slices were required for CEs of the same precision. CONCLUSION: In combination with high signal-to-noise ratio and enhanced tissue contrast, Cavalieri slices are the most appropriate for MRI, they supply unbiased and highly efficient volume estimates of brain compartments. For a given number of slices, CE(V) decreases rapidly when the slices are thicker than the gaps between them; when the slices are thinner than the gaps, then CE(V) is similar to that in the situation when the slice thickness is zero.

Brain↗