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Biomedical subjects

C J Holmes

Publications and source records attributed to C J Holmes.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effect of two-chambered bicarbonate lactate-buffered peritoneal dialysis fluids on peripheral blood mononuclear cell and polymorphonuclear cell function in vitro.

Low pH, high osmolality, increasing glucose concentration, and glucose degradation products (GDP) formed during heat sterilization of conventional peritoneal dialysis (PD) fluids have been shown to have a detrimental effect on cells involved in peritoneal host defense. The two-chambered PD fluid bag in which glucose at pH approximately 3 is separated from a bicarbonate (25 mmol/L)-lactate (15 mmol/L) buffer during heat sterilization permits PD fluids with lower GDP to be delivered to the patient at neutral pH. To establish the possible benefit of two-chambered bag PD fluids on peripheral blood mononuclear cell (PBMC) and polymorphonuclear (PMN) cell function, we compared conventional 1.5% Dianeal (1.5%D) with 1.5% two-chambered bag bicarbonate-lactate (1.5%D-B), and conventional 4.25% Dianeal (4.25%D) with 4.25% two-chambered bag bicarbonate-lactate (4.25%D-B). Furthermore, to study the effect of the sterilization process on PBMC and PMN function, we compared filter-sterilized 4.25%D (4.25%D-F) with 4.25%D and 4.25%D-B. PBMC were harvested by Ficoll-Hypaque separation, and 2.5 x 10(6) cells in RPMI were incubated with an equal volume of the test fluids for 4 hours, pelleted, and resuspended in RPMI containing 10 ng endotoxin for a further 20 hours. Tumor necrosis factor alpha (TNF-alpha) production by endotoxin-stimulated PBMC was not significantly different (P = 0.10) between 1.5%D-B and 1.5%D, but was significantly higher (P = 0.01) with 4.25%D-B compared with 4.25%D. PBMC exposed to filter-sterilized fluid (4.25%D-F) showed significantly higher endotoxin-stimulated TNF-alpha production compared with 4.25%D (P = 0.02), but was not significantly different from 4.25%D-B (P = 0.40). PMN were harvested by Ficoll-Hypaque separation and 10 x 10(6) cells incubated with test fluids for 30 minutes. After incubation, phagocytosis (phagocytosis index) was determined by the uptake of 14C-labeled Staphylococcus aureus, oxidative burst by reduction of ferricytochrome C to ferrocytochrome C on stimulation with PMA, and enzyme release by measurement of endotoxin-stimulated bactericidal/permeability increasing protein (BPI). Bicarbonate-lactate two-chambered fluids of similar osmolality and glucose concentration conferred a significant improvement in phagocytosis (P = 0.02 for 1.5%D-B and P < 0.001 for 4.25%D-B). Oxidative burst and BPI release were significantly higher in 4.25%D-B compared with 4.25%D (P < 0.001). Filter-sterilized 4.25%D-F conferred a significant improvement in phagocytosis and oxidative burst compared with 4.25%D (P < 0.001) or 4.25%D-B (P < 0.001). Furthermore, conventional 4.25%D was associated with significantly lower BPI release compared with 4.25%D-F (P = 0.01). GDP's acetaldehyde and 5-HMF were analyzed in 4.25%D-B, 4.25%D, and 4.25%D-F. Acetaldehyde was below the lower limit (0.79 ppm) of the standard curve in 4.25%D-B and 4.25%D-F fluids but was detected (3.76 to 5.12 ppm) in all of the 4.25%D fluids. Relative levels of 5-HMF in the 4.25%D-B (0.032 to 0.041 Abs @ 284 nm) and 4.25%D (0.031 to 0.036 Abs @ 284 nm) were similar. The lowest levels (0.001 Abs @ 284 nm) were observed in the filter-sterilized 4.25%D-F. The beneficial effects of two-chambered bicarbonate lactate-buffered PD fluids on PBMC and PMN function are probably related to reduction of GDP from heat sterilization of glucose in a separate chamber at a lower pH. This improvement in biocompatibility could have a beneficial affect on peritoneal defenses.

Bicarbonates↗
PubMed1997

A three-dimensional multimodality brain map of the nemestrina monkey.

A three-dimensional multimodality computerized map of the nemestrina monkey brain was created with serial sectioning and digital imaging techniques. An adult female Macaca nemestrina (pigtail macaque) weighing 7.2 kg was used in constructing this atlas. CT, PET, and MRI were performed on the monkey before the specimen's head was frozen and cryoplaned. Closely spaced (50 microns) images of the specimen blockface were then digitally acquired and modified to produce whole head and brain-only 3D image sets. The resulting data sets were organized into a digital volume and repositioned into a stereotaxic coordinate system defined by Horsley and Clark in 1908 [7]. Orthogonal images were obtained by digitally resampling the volume in order to produce a full set of coronal, sagittal, and horizontal images. Stereotaxic reference grids were applied to each image indicating the A/P, M/L, or Ho position within the digital volume. Specific anatomic structures were outlined from the cryosection data set and 3D surface models reconstructed. Structural labels indicating nuclei, tracts, and other neuroanatomical features were incorporated into coronally sliced cryosection images spaced at 500 microns. The CT, PET, and MRI data sets were reconstructed into a digital volume and coregistered to the cryosection volume. All images constructed from this 3D map are available for public access via the internet using an anonymous file transfer protocol (FTP) and the World Wide Web (http:@www.loni.ucla.edu). The foremost advantage of this digital map is an integrated multimodality three-dimensional representation of the Macaca nemestrina brain, which is not possible with traditional atlases.

Animals↗
PubMed1996

In vitro effects of bicarbonate and bicarbonate-lactate buffered peritoneal dialysis solutions on mesothelial and neutrophil function.

The inclusion of bicarbonate in the formulation of peritoneal dialysis solutions may avoid the in vitro impairment of certain cell functions seen with acidic lactate-based fluids. The supranormal physiological levels of HCO3- and PCO2 inherent in such formulations may, however, not be biocompatible. This study compared the in vitro biocompatibility of a pH 5.2 lactate-based formulation with formulations containing either 40 mM lactate at pH 7.4, 38 mM HCO3- at pH 6.8 (PCO2 at approximately 240 mm Hg) or 7.4 (PCO2 at approximately 60 mm Hg), and 25 mM HCO3- plus 15 mM lactate at pH 6.8 (PCO2 at approximately 160 mm Hg) or 7.4 (PCO2 at approximately 40 mm Hg). Significant release of lactate dehydrogenase or decreases in ATP content by human peritoneal mesothelial cells (HPMC) and human peripheral polymorphonuclear leukocytes (PMN) after a 30-min exposure to each test solution was only seen with the pH 5.2 lactate-based fluid. The ATP content of HPMC exposed to this fluid returned to control levels after 30 min of recovery in M199 control medium but showed a trend toward decreasing ATP content at 240 min. Similarly, interleukin (IL)-1 beta-induced IL-6 synthesis by HPMC was also only significantly reduced by the pH 5.2 lactate solution. PMN chemiluminescence was unaffected by 30-min exposure to all test solutions except for the pH 5.2 lactate formulation. Staphylococcus epidermidis phagocytosis was reduced to between 46 to 57% of control with all test solutions except the pH 5.2 lactate solution, which further suppressed the chemiluminescence response to 17% of control. These data suggest that short exposure to supranormal physiological levels of HCO3- and PCO2 does not impair HPMC or PMN viability and function. Furthermore, neutral pH lactate-containing solutions show equivalent biocompatibility to bicarbonate-based ones.

Adenosine Triphosphate↗
PubMed1996

Informatics and computational neuroanatomy.

Rapid and convenient access to digital image archives, as well as archive-based computational tools, are fundamental to many hypothesis-driven investigations of brain anatomy and function in health and disease. The complexity and density of brain image data requires the design of intelligent tools which allow scientific and clinical data, collected at numerous research centers, to be compared, integrated, and disseminated. We describe our results in the development of image data navigational tools, a World Wide Web repository of image analysis software, and strategies to represent populations of brain image data involving atlas descriptions of its variance.

Algorithms↗
PubMed1995

GABAergic neurons in the rat pontomesencephalic tegmentum: codistribution with cholinergic and other tegmental neurons projecting to the posterior lateral hypothalamus.

The present study was undertaken to determine the frequency and distribution of GABAergic neurons within the rat pontomesencephalic tegmentum and the relationship of GABAergic cells to cholinergic and other tegmental neurons projecting to the hypothalamus. In sections immunostained for glutamic acid decarboxylase (GAD), large numbers of small GAD-positive neurons (approximately 50,000 cells) were distributed through the tegmentum and associated with a high density of GAD-positive varicosities surrounding both GAD-positive and GAD-negative cells. Through the reticular formation, ventral tegmentum, raphe nuclei, and dorsal tegmentum, GAD-positive cells were codistributed with larger cells, which included neurons immunostained on adjacent sections for glutamate, tyrosine hydroxylase (TH), serotonin, or choline acetyltransferase (ChAT). In sections dual-immunostained for GAD and ChAT, GABAergic neurons were seen to be intermingled with less numerous cholinergic cells (approximately 2,600 GAD+ to approximately 1,400 ChAT+ cells in the laterodorsal tegmental nucleus, LDTg). Retrograde transport of cholera toxin (CT) was examined from the posterior lateral hypothalamus, where a major population of cortically projecting neurons are located. A small number of GABAergic cells were retrogradely labeled, representing a small percentage of all the GABAergic neurons (approximately 1%) and of all the hypothalamically projecting neurons (approximately 6%) in the tegmentum. The double-labeled GAD+/CT+ cells were commonly found ipsilaterally within 1) the deep mesencephalic reticular field, codistributed with putative glutamatergic projection neurons; 2) the ventral tegmental area, substantia nigra compacta, and retrorubral field, codistributed with dopaminergic projection neurons; 3) dorsal raphe, codistributed with serotonergic projection neurons; and 4) laterodorsal and pedunculopontine tegmental nuclei, codistributed with and in similar proportion to cholinergic projection cells (20-30% in LDTg). Acting as both projection and local neurons, the pontomesencephalic GABAergic cells would have the capacity to modulate the influence of the "ascending reticular activating system" and its chemically specific constituents upon cortical activation.

Acetylcholine↗
PubMed1995

Hemodialyzer performance: biological indices.

In the last decade there has been a rapid increase in the number of biological indices that could potentially be used as measures of hemodialyzer or membrane biocompatibility. Consequently, it has become more challenging for all of those involved in renal replacement therapy to evaluate the relative merits of one membrane versus another when faced with their ever increasing variety of parameters. This review attempts to summarize the current array of biological parameters described in the literature as indices of biocompatibility and provide a critique of their utility. Emphasis is placed on measures of activation of the plasma cascade systems, complement, coagulation, and kinin as primary indices of biocompatibility. Additional information on neutrophil, monocyte, platelet, lymphocyte and natural killer (NK) cell effects may provide further insight into blood-membrane mediated interactions although many of these may parallel plasma cascade systems activation. The importance of good statistical design and analysis is emphasized to ensure meaningful interpretation of any study.

Biocompatible Materials↗
PubMed1995

A longitudinal in vitro antimicrobial evaluation of two silver polymer surface treatments for peritoneal dialysis catheters.

The oligodynamic effect of silver has been utilized in medicine for many decades. This study evaluated the antimicrobial properties of two silver polymer surface treatments over 9 months to assess their usefulness for chronic percutaneous access. Silicone catheters were either dip-coated with micronized silver oxide in a silicone matrix (AgX) or impregnated with silver using an ion beam deposition process (Spire Argent I). Four-inch (10-cm) segments were shaken continuously in 10 mL minimum essential media (MEM) with 2% fetal bovine serum (FBS) at 25 degrees C. The medium was replaced weekly. Monthly eluate samples were assayed for Ag+ concentration using ICP atomic emission spectroscopy. Bimonthly, segments were removed, placed in fresh medium inoculate with 10(5) colony-forming units (cfu)/mL Staphylococcus aureus ATCC 25923 and quantitated over 24 hours for bacterial survival/growth. Relative to control catheters, there was a mean log10 reduction of S. aureus of 4.4 with AgX and 1.7 with Spire Argent I persisting over the 9-month study period. Silver ion elution followed a biphasic pattern with both coatings establishing a steady state of 0.2 ppm at 4 months. These data suggest that the test surface coatings employed will deliver long-term oligodynamic activity when implanted percutaneously.

Catheters, Indwelling↗
PubMed1994

Distribution of cholinergic, GABAergic and serotonergic neurons in the medial medullary reticular formation and their projections studied by cytotoxic lesions in the cat.

As part of a larger study concerning the role of neurons in the medial medullary reticular formation in sleep-wake states, the distribution and projections of cholinergic, GABAergic and serotonergic neurons were studied within the lower brainstem of the cat. Cells were plotted with the aid of an image analysis system through the medullary reticular formation and raphe in adjacent sections immunostained for choline acetyltransferase, glutamic acid decarboxylase and serotonin. Immunostained fibres and varicosities were examined and quantified by microdensitometry in regions of the medulla, pons and upper spinal cord in normal and quisqualate-injected animals to assess the loss of local and distant projections following cytotoxic destruction of neurons in the medial medullary reticular formation. Choline acetyltransferase-immunoreactive neurons are unevenly and sparsely distributed, though none the less in significant numbers (estimated at approximately 9080 in total), through the medial medullary reticular formation, and are present in all tegmental fields, including the gigantocellular (approximately 3700) and magnocellular (approximately 1760) rostrally and the ventral (approximately 3240) and paramedian (approximately 380) caudally, and are absent in the midline raphe. Glutamic acid decarboxylase-immunoreactive neurons are more evenly and densely distributed in large numbers (estimated at approximately 18,720) through the medial medullary reticular formation, being present in the gigantocellular (approximately 5960), magnocellular (approximately 8260), ventral (approximately 2280) and paramedian (approximately 2220) tegmental fields, and are also numerous within the raphe magnus and pallidus-obscurus nuclei (approximately 3880). Serotonin-immunoreactive cells are sparse in the medial medullary reticular formation (estimated to total approximately 1540), where they are mainly located in the magnocellular tegmental field (approximately 1340), and are concentrated in larger numbers within the raphe nuclei (approximately 8060). Cholinergic varicose fibres were moderately densely distributed through the medial medullary reticular formation, as well as through more distant lateral, rostral and caudal brainstem and upper spinal regions. After cytotoxic lesions focussed in the gigantocellular and magnocellular tegmental fields, a loss of approximately 55% of the cholinergic neurons in the medial medullary reticular formation was associated with a minor decrease (approximately 35% in optical density measures) of local cholinergic fibres. Small and variable reductions in varicose fibres (and their optical density measures) were detected in distant structures (including the pontine lateral, gigantocellular and subcoerular tegmental fields and the caudal spinal trigeminal nucleus), that were none the less correlated with the number of intact medial medullary cholinergic cells, suggesting that these cells may project to distant brainstem targets, in addition to providing a minor proportion of the local cholinergic innervation of the medial medullary reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Importance of cholinergic, GABAergic, serotonergic and other neurons in the medial medullary reticular formation for sleep-wake states studied by cytotoxic lesions in the cat.

Previous evidence has suggested that neurons in the medial medullary reticular formation play a critical role in the modulation of forebrain and spinal cord activity that occurs during the sleep-waking cycle and particularly in association with the state of paradoxical sleep. The importance of these neurons, including cholinergic, serotonergic and GABAergic cells [Holmes C. J. et al. (1994) Neuroscience 62, 1155-1178] for sleep-wake states was investigated after their destruction with the neurotoxin quisqualic acid injected into the medullary gigantocellular and magnocellular tegmental fields in cats. To assess the effects of the neuronal loss, polygraphic recording and behavioural observations were performed in baseline and for three weeks after the lesion, and the changes in these measures were correlated with the volume of destruction of medullary regions and the numbers of chemically identified cells within those regions. Following the cytotoxic lesions, which affected approximately 60% of the medullary gigantocellular and magnocellular tegmental fields, there was a significant reduction in the amount of paradoxical sleep (to a mean of 64% of baseline) during the first postlesion week, that recovered variably across cats in the second and third weeks. There was little to no change in the amount or organization of waking and slow wave sleep. The individually variable amounts of postlesion paradoxical sleep were correlated positively with the number of surviving cholinergic cells, negatively with the number of surviving serotonergic cells and positively with the ratio of surviving cholinergic or GABAergic cells to serotonergic cells. The most marked effect of the lesion was a substantial increase in the amplitude of the nuchal electromyogram during slow wave sleep (to 198%) and paradoxical sleep (to 378% of baseline in the first postlesion week). The increase in muscle tone was associated with movements of the head, neck or limbs during paradoxical sleep. Although, in some cats, the abnormal neck muscle tone decreased with time, limb movements continued to occur during paradoxical sleep for the duration of the experiment. The ratio of the total number of remaining cholinergic or GABAergic cells to serotonergic cells correlated negatively with the increased muscle tone and/or movements. It was concluded that the neurons of the medial medullary reticular formation contribute to, but are not necessary for, the generation of paradoxical sleep, and have particular importance for the regulation of muscle tone and inhibition of movement during this state.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

The role of plasma in the transfer of Escherichia coli cytokine-inducing substances across high-flux cellulosic membranes.

It has been previously reported that the presence of plasma in the blood side compartment of cellulosic membranes enhances the transfer of cytokine-inducing substance (CIS) present in the dialysate compartment. This apparent enhancement could either be a result of (1) improved membrane permeability to CIS, (2) transfer of plasma components to the dialysate compartment thereby causing dissaggregation of CIS with subsequent backtransfer to the blood compartment, or (3) improved detection of transferred CIS resulting from carryover of plasma from the blood compartment to the mononuclear cell incubation step. An in vitro dialysis model was used to determine which of the above mechanisms were involved in this phenomenon. Results showed that enhanced detection of CIS could not be attributed to improved detection resulting from carryover plasma. Both addition of plasma to the dialysate compartment of pre-exposure of membranes to plasma resulted in enhanced transfer of CIS in a fashion similar to that seen when plasma was added to the blood compartment. These observations suggest that the transfer of Escherichia coli culture filtrate-derived CIS across cellulosic membranes is enhanced on exposure to 10% plasma because of alterations in the permselectivity of the membrane.

Blood↗
PubMed1993

Relationship between frequent episodes of peritonitis and altered immune status.

A 60-year-old Native American diabetic female patient had a history of nine episodes of peritonitis (both relapsing and persistent) during the year that she was treated with continuous ambulatory peritoneal dialysis (CAPD). At the start of CAPD the patient had an inverted CD4 to CD8 ratio that decreased from 0.97 to 0.50 in 1 year. This finding was due to a decrease in CD4+ cells and an increase in CD8+ cells that were also positive for CD57 (Leu-7) and HLA-DR (Ia) antigen, suggesting a state of activation. The serology indicated a cytomegalovirus immunoglobulin G titer of 1:2,048. The patient also had significantly increased natural killer cells. These alterations suggest the presence of a chronic viral infection that may have caused the patient to be immunosuppressed, thereby predisposing her to repeated episodes of peritonitis.

CD4-CD8 Ratio↗
PubMed1993

Dialyzer reprocessing using heat. Scientific and technical considerations.

Reprocessing of used dialyzers with chemical disinfectants is practiced commonly in the United States and in some areas of Western Europe. Concern over residual toxic or allergenic agents has encouraged the search for other practical methods to disinfect or sterilize used hemodialyzers. The use of moist heat has been proposed as an attractive alternative to chemical disinfection, as the effectiveness of moist heat in inactivating microorganisms is well established and, inherently, should be less toxic than chemical means. However, despite the initial appeal of heat reprocessing, validation and maintenance procedures necessary to ensure a reproducible heat cycle are likely to be burdensome with the currently available hardware. This paper discusses the potential requirements for and barriers to implementation of a dialyzer reprocessing system using heat.

Hot Temperature↗
PubMed1993

Characteristics of peripheral and peritoneal lymphocytes from continuous ambulatory peritoneal dialysis patients.

The role of peritoneal lymphocytes in host immunity for continuous ambulatory peritoneal dialysis (CAPD) patients is just beginning to be understood. CAPD therapy increases the proportion of peritoneal lymphocytes, most of which demonstrate signs of activation. There are decreased peritoneal T cells and increased peritoneal B cells as compared to the patients' peripheral blood. When studies examine immunophenotypes of peripheral and peritoneal lymphocytes over time, no significant changes are found. Although changes in peritoneal lymphocyte subsets occur during peritonitis episodes, there are no changes in peripheral blood lymphocytes. The purpose of this article is to provide a brief review of research that has studied lymphocytes in CAPD patients.

Humans↗