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Biomedical subjects

N Wallace

Publications and source records attributed to N Wallace.

At least 19 recordsLinked to original sources

Strategic leukocyte depletion reduces pulmonary microvascular pressure and improves pulmonary status post-cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) precipitates inflammation that causes marked pulmonary dysfunction. Leukocyte filtration has been proposed to reduce these deleterious effects. Other studies show an improvement with aprotinin. We proposed that a combination of these two therapies would synergistically improve pulmonary outcomes. Two hundred and twenty-five patients participated in a randomized prospective study comparing pulmonary microvascular function and pulmonary shunt fraction postcoronary artery bypass grafting (CABG). The study group underwent leukocyte depletion with aprotinin during the procedure. Pulmonary microvascular function was assessed by pulmonary microvascular pressure (PMVP), a measure of pulmonary capillary edema, and pulmonary function was evaluated by comparing pulmonary shunt fractions. Elevated PMVP and increased pulmonary shunting compromise pulmonary performance. The leukocyte-depleted group had significantly reduced PMVP and pulmonary shunt fraction for at least the first 24 hours postbypass. The combination of strategic leukocyte filtration and aprotinin therapy can effectively reduce postoperative decline in pulmonary function. Cardiopulmonary bypass precipitates a variety of inflammatory effects that can cause marked pulmonary dysfunction to the point of respiratory failure, necessitating prolonged mechanical ventilation. Leukocyte filtration has been investigated previously and appears to be beneficial in improving pulmonary outcome by preventing direct neutrophil-induced inflammatory injury. Recent studies of leukocyte reduction profiles suggest that leukoreduction via leukofiltration is short lived with filter saturation occurring 30-45 minutes after onset of filtration. This phenomenon may explain the limited utility observed with higher risk patients. These patients typically require longer pump runs, so leukocyte reduction capability is suboptimal at the time of pulmonary vascular reperfusion. To more effectively protect the lung from reperfusion injury, leukocyte filtration can be delayed so that reduction of activated neutrophils is maximal at the time of pulmonary vascular reperfusion. It is, thus, conceivable that a timely use of arterial line leukoreducing filters may improve, more substantially, pulmonary function postbypass. Two hundred and twenty-five isolated coronary revascularization patients participated in this prospective, randomized trial. The patients received moderately hypothermic CBP alone (control group: n = 110) or combined with leukocyte depletion, initiated 30 minutes before crossclamp release, with filters placed in the bypass circuit (study group: n = 115). All patients also received full Hammersmith aprotinin dosing during the operation. Pulmonary microvascular pressures were lower in the study group at three hours postbypass, and continued to fall until 24 hours postbypass. In contrast, the control group measured a rise in PMVP and a continued plateau throughout 24 hours postbypass (p < 0.028). The calculated pulmonary shunt fraction also was reduced significantly throughout the study interval, with the greatest reduction occurring approximately three to six hours post-CPB (p < 0.002). Shunt fractions eventually converged at 24 hours postbypass. Outcome measures included hospital charges and length of stay, which were also markedly reduced in the treatment group. Increasing PMVPs are a direct reflection of pulmonary capillary edema, which, in conjunction with increased pulmonary shunt ratio, lead to an overall worsening of pulmonary function. Intraoperative strategic leukocyte filtration combined with aprotinin treatment improves post-CPB lung performance by reducing significantly the reperfusion inflammatory response and its sequelae. These benefits are manifested by reductions in ventilator times, hospital stay and patient morbidity.

Aged↗

Intraoperative treatment strategy to reduce the incidence of postcardiopulmonary bypass atrial fibrillation.

PURPOSE: Postcardiopulmonary bypass atrial fibrillation remains a constant complication associated with coronary revascularization, the incidence of which occurs from 20% to 35%. Previous studies have addressed this problem in the postoperative setting utilizing pharmacological agents, but the results have been variable. The purpose of this study was to evaluate a novel intraoperative strategy to reduce the incidence of postcardiopulmonary bypass atrial fibrillation. We theorized that leukocyte depletion by filtration with the addition of aprotinin would reduce the systemic inflammatory effects of bypass and reduce the incidence of atrial fibrillation. METHODS: One hundred and twenty-two patients participated in this randomized study. Only isolated primary coronary revascularization procedures on cardiopulmonary bypass were included. The control group (n=55) received standard moderate hypothermic blood cardioplegia cardiopulmonary bypass. The treatment group (n=65) received similar cardiopulmonary bypass with the addition of strategic leukocyte depletion with Pall Biomedical Products (East Hills, NY) leukodepletion filters and full-dose aprotinin. RESULTS: The intraoperative addition of leukocyte depletion by filtration with aprotinin reduced the incidence of postcardiopulmonary bypass atrial fibrillation by 72%. The incidence.of atrial fibrillation in the control group was 27% (15 of 55). In contrast, the occurrence of atrial fibrillation in the treated group was only 7.6% (5 of 65) (p<0.025). CONCLUSIONS: This novel intraoperative treatment strategy of both mechanical (leukocyte filtration) and pharmacological (aprotinin) intervention appears to markedly reduce the incidence of postcardiopulmonary bypass atrial fibrillation. To our knowledge, this is the first study to combine these two treatment strategies. A previous study has noted a decline in atrial fibrillation with aprotinin in the animal model, but not to the extent observed in our study. The beneficial effects of the reduction of atrial fibrillation include reduced risk of emboli formation and the incidence of ischemia in the heart, lung and brain. In addition, a decrease in length of hospital stay, recovery time and overall cost occurred.

Aprotinin↗

Effect of virginiamycin on ruminal fermentation in cattle during adaptation to a high concentrate diet and during an induced acidosis.

The objective of Exp. 1 was to compare the effects of virginiamycin (VM; 0, 175, or 250 mg x animal(-1) x d(-1)) and monensin/tylosin (MT; 250/ 90 mg x animal(-1) x d(-1)) on ruminal fermentation products and microbial populations in cattle during adaptation to an all-concentrate diet. Four ruminally cannulated, Holstein steers were used in a 4x4 Williams square design with 21-d periods. Steers were stepped up to an all-concentrate diet fed at 2.5% of BW once daily. Ruminal pH, protozoal counts, and NH3-N and VFA concentrations generally were unaffected by VM or MT. Mean counts of Lactobacillus and Streptococcus bovis were lower (P<.05) for VM-treated compared with control or MT-treated steers. Both VM and MT prevented the increase in Fusobacterium necrophorum counts associated with increasing intake of the high-concentrate diet observed in the control. The objective of Exp. 2 was to compare the effects of VM and MT on ruminal pH, L(+) lactate and VFA concentrations, and F. necrophorum numbers during carbohydrate overload. Six ruminally cannulated Holstein steers were assigned randomly to either the control, VM (175 mg/d), or MT (250 + 90 mg/d) treatments. Acidosis was induced with intraruminal administration of a slurry of ground corn and corn starch. The VM and MT premixes were added directly to the slurry before administration. Carbohydrate challenge induced acute ruminal acidosis (pH was 4.36 and L (+) lactate was 19.4 mM) in controls by 36 h. Compared with the controls, steers receiving VM or MT had higher (P<.05) ruminal pH, and the VM group had a lower (P<.05) L (+) lactate concentration. Fusobacterium necrophorum numbers initially increased in VM- and MT-administered steers. In the control steers, F. necrophorum was undetectable by 36 h. Virginiamycin seemed to control the growth of ruminal lactic acid-producing bacteria and, therefore, has the potential to moderate ruminal fermentation in situations that could lead to rapid production of lactic acid.

Acidosis↗

Effects of tylosin on concentrations of Fusobacterium necrophorum and fermentation products in the rumen of cattle fed a high-concentrate diet.

OBJECTIVE: To determine effects of tylosin on ruminal concentrations of Fusobacterium necrophorum and fermentation products in cattle during rapid adaptation to a high-concentrate diet. ANIMALS: 6 steers fitted with ruminal cannulas. PROCEDURE: Steers were assigned randomly to 2 treatment groups and switched from a 0 to an 85% concentrate diet during a 4-day period. Cattle received this diet, with or without tylosin (90 mg/steer/d), for 4 weeks. Samples of ruminal contents were collected daily beginning 2 days before the treatment protocol and in the first week of concentrate feeding. Four subsequent samples were collected at weekly intervals. Concentration of F. necrophorum in samples was determined, using the most-probable-number technique. Ruminal pH and concentrations of volatile fatty acids (VFA), lactate, and ammonia also were determined. All steers received both treatments separated by 4 weeks (cross-over design), during which time they were fed alfalfa hay only. RESULTS: In control steers, concentration of F. necrophorum increased in response to the high-concentrate diet. Tylosin-fed steers had lower concentrations of F. necrophorum than control steers at all times during concentrate feeding. However, ruminal pH and concentrations of lactate, VFA, and ammonia did not differ between treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: Tylosin caused a significant reduction in ruminal concentrations of F. necrophorum during rapid adaptation to a high-concentrate diet but had no effect on fermentation products. The reduction in ruminal concentration of F. necrophorum helps explain the reduction in prevalence of hepatic abscesses reported in tylosin-fed feedlot cattle.

Ammonia↗

Biochemical and ribotypic comparison of Actinomyces pyogenes and A pyogenes-like organisms from liver abscesses, ruminal wall, and ruminal contents of cattle.

OBJECTIVE: To isolate Actinomyces pyogenes and A pyogenes-like (APL) organisms from the ruminal wall and ruminal contents of cattle and compare them with isolates from liver abscesses from the same animals, using ribosomal DNA restriction fragment length polymorphism analysis or ribotyping. PROCEDURE: Specimens of liver abscesses, ruminal walls, and ruminal contents were collected from 59 cattle at slaughter. All beta-hemolytic, pinpoint colonies that were gram positive, pleomorphic rod-shaped, and catalase negative, and that hydrolyzed casein and gelatin were presumptively identified as A pyogenes and were characterized biochemically, using an identification kit. The isolates that resembled A pyogenes but fermented mannitol or raffinose, or both, were called APL organisms. Isolates from the ruminal wall and ruminal contents were compared with liver abscess isolates from the same animal by use of ribotyping. RESULTS: Actinomyces pyogenes and APL organisms were isolated more frequently from the ruminal wall than from ruminal contents. Ruminal isolates of A pyogenes and APL had biochemical characteristics similar to those of the isolates from liver abscesses. Among 6 sets of isolates (4 A pyogenes and 2 APL), 2 isolates from liver abscesses had ribopatterns identical to the corresponding ruminal wall isolates. Also, the APL organisms isolated from the ruminal content matched with the corresponding liver abscess isolates for both sets of specimens tested. CONCLUSIONS: The ruminal wall may be the niche for A pyogenes and APL organisms in the rumen. The genetic similarity, on the basis of ribotyping among isolates from liver abscesses, the ruminal wall, and ruminal contents of the same animal suggests that A pyogenes and APL organisms that cause liver abscesses originate from the rumen.

Abscess↗

Motor unit behavior in canine motor neuron disease.

Hereditary canine spinal muscular atrophy (HCSMA) is an autosomally dominant disease of motor neurons that shares many pathological features with human motor neuron disease. A particularly striking feature of the affected, accelerated phenotype (homozygous HCSMA) is that profound weakness develops before appreciable motor neuron cell death occurs (Cork et al., 1989a), implying that motor unit functional defects occur initially. The purpose of this study was to identify the site of these defects and characterize their nature. In most young homozygotes (2-3 months postnatal), motor neurons were encountered that could support orthodromic action potential propagation to the muscle but did not activate muscle fibers. The tetanic forces of innervated motor units in young homozygotes tended to be smaller than those in closely age-matched clinically normal animals. In older homozygotes (approximately 4.5 months, postnatal), all motor neurons sampled were capable of activating muscle fibers, but many motor units displayed abnormal behavior including an inability to sustain force output during high frequency activation. Motor units exhibiting tetanic failure also showed proportionately greater twitch potentiation than nonfailing units of similar unpotentiated twitch amplitude. Tetanic failure and large potentiation tended to occur in motor units that possessed the slowest contraction speeds. These results indicate that motor neuron functional defects in HCSMA appear initially in the most distal parts of the motor axon and involve defective neurotransmission. The possible roles of distal nerve degeneration, motor terminal sprouting, and synaptic transmission in causing these deficits are considered.

Action Potentials↗

Comparison of four commercially available rapid enzyme immunoassays with cytotoxin assay for detection of Clostridium difficile toxin(s) from stool specimens.

Rapid (2.5- to 3.5-h) enzyme immunoassays (EIAs) for the detection of Clostridium difficile toxins have been developed. We report the results of simultaneous testing of 700 fresh stool specimens by the tissue culture cytotoxin assay and four EIAs (Bartels Prima System C. difficile Toxin A EIA, Cambridge Biotech Cytoclone A+B EIA, Meridian Diagnostics Premier C. difficile Toxin A EIA, and TechLab C. difficile Tox-A Test EIA). In cases of disagreement, culturing for toxigenic C. difficile was performed. A total of 61 (8.7%) specimens from 46 patients were positive for C. difficile toxin. The sensitivity of the cytotoxin assay was 87%, and that of culture was 93%. In comparison with the cytotoxin assay results, the sensitivity and specificity of the EIAs were as follows: Bartels, 87 and 96%; Cambridge, 89 and 99%; Meridian, 87 and 98%; and TechLab, 87 and 95%, respectively. In comparison with the cytotoxin assay plus toxigenic culture results, the sensitivity and specificity of the EIAs were as follows: Bartels, 84 and 97%; Cambridge, 85 and 99%; Meridian, 79 and 98%; and TechLab, 80 and 96%, respectively. The EIAs varied in positive predictive values (PPVs). A high PPV was seen with the Cambridge EIA (96%); lower PPVs were seen with the TechLab (64%), Bartels (72%), and Meridian (80%) EIAs because of high false-positive rates. The negative predictive values (98 to 99%) were excellent with all EIAs. Results were indeterminant with 0.3% of the samples by the Meridian EIA and 3% by all the other EIAs. Although the EIAs were less sensitive than the cytotoxin assay, they provide same-day results and may be useful in laboratories without tissue culture facilities.

Bacterial Proteins↗

Adult spinal motoneurons remain viable despite prolonged absence of functional synaptic contact with muscle.

Several rat medial gastrocnemius (MG) motor axons were allowed to regenerate into normally innervated muscle. Under these conditions, synapse formation is known to be prevented by the existence of the original innervation of the host muscle. A study was made of the ability of the implanted spinal motoneurons to acquire and retrogradely transport horseradish peroxidase (HRP) injected into the host muscle at various postoperative intervals. HRP-labeled MG motoneurons on the implanted side were observed at postoperative intervals as long as 290 days. A comparison of the number of labeled MG motoneurons on the implanted side versus the number on the unoperated, control side indicated no significant differences. At all investigated postoperative intervals except the earliest (7 DPO), a significant decrease in the mean MG motoneuron soma cross-sectional area was observed relative to the unoperated, control side. Analysis of labeled motoneuron size distributions showed that postoperative atrophy of larger, presumably alpha, motoneurons occurred at a significantly faster rate than in smaller, presumably gamma, motoneurons. These results demonstrate that axotomized adult spinal motoneurons survive and remain viable for prolonged periods when denied the opportunity to reinnervate muscle but do so in an atrophied state. The results indicate further that alpha and gamma motoneurons differ quantitatively in their responses to peripheral axotomy.

Animals↗

Axotomy-like changes in cat motoneuron electrical properties elicited by botulinum toxin depend on the complete elimination of neuromuscular transmission.

The electrical properties of cat medial gastrocnemius (MG) spinal motoneurons were studied 14-21 d following injection of type A botulinum toxin (BTX) into the MG muscle. Treated MG muscles were atrophic, displayed pronounced fibrillation activity, and were markedly but not completely paralyzed. MG motoneuron electrical properties from animals with the highest MG muscle-twitch forces (greater than 20 gm) appeared normal, while motoneuron properties from animals with the lowest MG muscle-twitch forces (less than 10 gm) exhibited axotomy-like changes, though these changes were less pronounced than after axotomy itself. No changes in the axonal conduction velocity were observed, however. Motoneuron connectivity with MG muscle fibers was determined following intracellular stimulation of MG motoneurons by averaging EMG signals from 3 or 4 pairs of recording electrodes inserted into the BTX-treated MG muscles. Normal electrical properties were observed among motoneurons in which detectable EMG activity linked to the intracellular stimulation pulse was observed. The level of this connectivity, however, indicated that a relatively small number of muscle fibers were activated by individual motoneuron action potentials. Axotomy-like changes of electrical properties were observed in MG motoneurons that could not be associated with detectable EMG activity in the BTX-treated MG muscle following repeated trials of intracellular stimulation. These results indicate that the existence of effective neuromuscular transmission at a small number of motor terminals is sufficient to prevent the appearance of axotomy-like changes in motoneuron electrical properties, and that the absence of such transmission at all motor terminals is associated with the appearance of axotomy-like changes. The results suggest that the effects of axotomy itself on motoneuron properties may be based upon the loss or elimination of a potent interaction between muscle and motoneurons normally mediated by neuromuscular transmission.

Animals↗

Using creative arts to help children cope with altered body image.

A specific aspect of development to be considered when planning expressive activities for hospitalized children is the potential and actual effects of hospitalization and illness on their developing body image. Therapeutic activities which address this stressful issue can be an integral part of the care of pediatric patients. This manuscript highlights several categories of expressive activities to help illustrate the way in which these activities can be used individually and with groups of children for therapeutic intervention when dealing with body image issues. Case studies are presented.

Art Therapy↗

Having a bone marrow test: a child's perspective.

This article describes the process involved in developing a slide/tape show about bone marrow tests for school-aged, hematology/oncology patients and their families. Patient's concerns about bone marrow tests are reviewed. Techniques involved in developing a slide/tape show with the assistance of a pediatric hematology patient, including planning, organization and production are discussed.

Audiovisual Aids↗

Group education after myocardial infarction: Is it effective?

An analysis of the results of a study of a group of post-infarction patients who had received group instruction concerning the nature of myocardial infarction, compared with patients not so instructed, is presented. Contrary to expectation, anxiety levels as measured by the Catel IPTA Anxiety Scale were significantly higher in patients who experienced group education. Regardless of this finding, patients were subjectively appreciative of education.

Adult↗