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Biomedical subjects

J E Fischer

Publications and source records attributed to J E Fischer.

At least 37 records · Page 2Linked to original sources
PubMed2001

Infusion pump performance with vertical displacement: effect of syringe pump and assembly type.

OBJECTIVE: To evaluate the effect of different infusion pump models on continuity of drug delivery during vertical displacement of syringe pumps. DESIGN: Zero-drug delivery time (ZDDT), retrograde aspiration volume, and infusion bolus were recorded using the same syringe in three different models of syringe pump after lowering and elevating the pump. Compliance of each infusion assembly was measured using the occlusion release technique at 38 mmHg. RESULTS: Lowering the pump by 50 cm at an infusion rate of 1 ml/h resulted in ZDDT values ranging from 2.78 +/- 0.29 to 5.99 +/- 1.09 min. Elevating the syringe pump to its original position caused infusion boluses between 44.1 +/- 3.2 and 77.1 +/- 5.1 microl. The results demonstrated that there are large differences between syringe pump models (F = 66.8, df = 2/33, p < 0.0001) and between pumps of the same model (F = 21.3, df = 1/34, p < 0.0001). A similar pattern was found in retrograde aspiration volume and infusion bolus. CONCLUSION: All tested pumps led to clinically relevant flow irregularities during vertical displacement of the syringe pump. Thus, vertical displacement of any syringe pump connected to an infusion line delivering highly potent drugs at low infusion rates should be avoided. The variability across syringe pumps indicates that syringe pump design remains an area of potential further improvement for reducing the risk of adverse patient events.

Analysis of Variance↗
PubMed2001

Always flush the sampling port before flushing the arterial cannula in pediatric patients.

BACKGROUND: Blood sampling from arterial lines is a frequent event in anesthesia and critical care. To avoid clot formation, both the stopcock outlet and the cannula must be flushed after sampling. We investigated in a bench experiment whether fluid flow through the cannula is affected by the sequence of flushing procedures. METHODS: Continuity of fluid delivery from a vascular cannula was gravimetrically determined using two different flushing techniques with either a syringe pump flush system or a bag flush system. The procedures comprised first flushing the stopcock towards the cannula and then towards the stopcock sampling outlet or the reverse order. Experiments were repeated in triplicate and two sets for each flushing system at hydrostatic pressures of 37 mm Hg and 74 mm Hg. RESULTS: The main finding of the study was that flushing the stopcock towards the outlet after flushing the cannula resulted in considerable retrograde aspiration volumes and zero flow times, in particular in combination with syringe pump flush systems. At a hydrostatic pressure of 74 mm Hg, the observed zero flow time at the cannula tip amounted to (mean+/-SD) 0.1+/-0.01 min with the bag flush system and 7.7+/-0.5 min with the syringe pump flush system. The related retrograde aspiration volumes were 2.2+/-0.7 microl with the bag system and 30.0+/-2.0 microl with the syringe pump system. No backflow was recorded when the stopcock was first flushed to ambient pressure and then afterwards towards the cannula. CONCLUSION: Opening a flush system to ambient pressure affects the continuity of fluid delivery, particularly when using syringe pump flush systems. After blood sampling, the stopcock outlet should be flushed first followed by cannula flushing.

Blood Specimen Collection↗
PubMed2001

Long-term evaluation of extended thymectomy with anterior mediastinal dissection for myasthenia gravis.

BACKGROUND: Thymectomy for the treatment of myasthenia gravis (MG) is well established. The extent of resection, however, remains a source for debate. Outcomes for newer surgical techniques need to be compared to more extensive procedures. METHODS: A retrospective review was done of 64 consecutive patients who underwent transsternal thymectomy with extended anterior mediastinal dissection for MG between 1979 and 2000 and who were operated on by a single surgeon. RESULTS: Fifty-six patient charts were available, providing 58 operative procedures. Three patients had died of unrelated causes. The mean age of symptom onset was 36.0 +/- 2.5 years, with a mean duration of 3.3 +/- 0.5 years until surgery was undertaken. The mean length of follow-up was 6.8 +/- 0.8 years. Operative procedures were associated with a 10.3% major morbidity rate and no mortality. Drug-free remission was achieved in 50.0% of the patients, and symptoms were absent or improved in 76.8% of the patients. Patients followed up long-term (>10 years) achieved the greatest remission rate (71.4%) and symptomatic improvement (85.7%). After thymectomy, the mean dosages of prednisone and Mestinon decreased by 69.3% and 58.8%, respectively. CONCLUSIONS: Extended thymectomy provides excellent overall symptom improvement, which is enhanced over time. This review provides a basis for long-term comparison with other less invasive and perhaps less extensive procedures.

Adolescent↗
PubMed2001

Use of angulated video-intubation laryngoscope in children undergoing manual in-line neck stabilization.

Laryngeal views obtained during direct laryngoscopy with and without manual in-line neck stabilization (MILNS) and during video-assisted intubation with MILNS using the angulated video-intubation laryngoscope were assessed in 100 paediatric patients (aged 0.25-17.3 yr). Visualization of the larynx (Cormack and Lehane score) as well as time taken for video-assisted tracheal intubation by six nurses and four resident anaesthetists not experienced in the technique were recorded. Cormack and Lehane scores were significantly worse during direct laryngoscopy when MILNS was applied. Video-assisted visualization of the larynx during MILNS produced scores, which were as good or better than those observed during direct laryngoscopy alone. Intubation times ranged from 19-75 s (mean 35 (SD 13.4); median 32).

Adolescent↗
PubMed2001

Muscle cachexia: current concepts of intracellular mechanisms and molecular regulation.

OBJECTIVE: To review present knowledge of intracellular mechanisms and molecular regulation of muscle cachexia. SUMMARY BACKGROUND DATA: Muscle cachexia, mainly reflecting degradation of myofibrillar proteins, is an important clinical feature in patients with severe injury, sepsis, and cancer. The catabolic response in skeletal muscle may result in muscle wasting and weakness, delaying or preventing ambulation and rehabilitation in these patients and increasing the risk for pulmonary complications. RESULTS: Muscle cachexia, induced by severe injury, sepsis, and cancer, is associated with increased gene expression and activity of the calcium/calpain- and ubiquitin/proteasome-proteolytic pathways. Calcium/calpain-regulated release of myofilaments from the sarcomere is an early, and perhaps rate-limiting, component of the catabolic response in muscle. Released myofilaments are ubiquitinated in the N-end rule pathway, regulated by the ubiquitin-conjugating enzyme E2(14k) and the ubiquitin ligase E3 alpha, and degraded by the 26S proteasome. CONCLUSIONS: An understanding of the mechanisms regulating muscle protein breakdown is important for the development of therapeutic strategies aimed at treating or preventing muscle cachexia in patients with severe injury, sepsis, cancer, and perhaps other catabolic conditions as well.

Cachexia↗
PubMed2001

Dantrolene reduces serum TNFalpha and corticosterone levels and muscle calcium, calpain gene expression, and protein breakdown in septic rats.

The effects of dantrolene on serum TNFalpha and corticosterone levels and on muscle calcium, calpain gene expression, and protein breakdown were studied in rats with abdominal sepsis induced by cecal ligation and puncture. Treatment of rats with 10 mg/kg of dantrolene 2 h before and 8 h after induction of sepsis reduced serum TNFalpha and corticosterone, muscle calcium levels, mRNA levels for m- and mu-calpain, and the muscle specific calpain p94, as well as total and myofibrillar protein breakdown rates, determined as release of tyrosine and 3-methylhistidine, respectively, from incubated extensor digitorum longus muscles. The results support the concept that increased calcium concentrations may be an important mechanism of sepsis-induced muscle protein breakdown. The data also indicate that other mechanisms, in addition to reduced muscle calcium concentrations such as decreased levels of TNFalpha and glucocorticoids, may contribute to the anti-catabolic effects of dantrolene during sepsis. The observations are important from a clinical standpoint because they suggest that the catabolic response in skeletal muscle during sepsis may be prevented by treatment with a calcium antagonist.

Animals↗
PubMed2000

[Rational utilization of antibiotics in critically ill children].

BACKGROUND: The high risks associated with untreated infection in critically ill newborns or children lower the threshold for prescription of antibiotic treatment. Inappropriate use of antibiotic therapy promotes the emergence of resistant strains. This study had three aims: to identify sources of inappropriate antibiotic utilisation, to develop revised guidelines and to implement changes. METHODS: An observational study was performed in a tertiary, multidisciplinary, neonatal and paediatric intensive care unit (PICU) of a university teaching hospital during a 7-month period (456 admissions). Guidelines addressing one of the identified sources of inappropriate utilisation (prophylaxis following surgery) were developed according to published evidence and implemented, and the effect on prescription patterns was assessed during a second observation period. RESULTS: Patients received systemic antibiotics during 54.6% of all hospitalisation days. Antibiotics prescribed for suspected or proven infection were often continued 1-2 days beyond the intended duration. Prophylaxis accounted for 28% of all systemic antibiotics given, and postsurgical prophylaxis accounted for 14.6% of all exposure days. The literature search revealed little evidence to support this practice. After new guidelines were introduced with the aim of restricting surgical prophylaxis to a single dose prior to surgery, the rate of postsurgical prophylaxis dropped from 14.6 to 11.2% of all exposure days, accompanied by a significant decline in the overall exposure rate from 54.6 to 50.2% of all hospitalisation days. CONCLUSION: Several sources of inappropriate antibiotic utilisation were identified. These include failure to discontinue treatment and prolonged prophylaxis after surgery. Implementation of new guidelines reduced antibiotic utilisation.

Anti-Bacterial Agents↗
PubMed2000

Structure-activity studies including a Psi(CH(2)-NH) scan of peptide YY (PYY) active site, PYY(22-36), for interaction with rat intestinal PYY receptors: development of analogues with potent in vivo activity in the intestine.

Peptide YY (PYY) is a gut hormone that inhibits secretion and promotes absorption and growth in the intestinal epithelium. We have performed structure-activity studies with the active site, N-alpha-Ac-PYY(22-36)-NH(2), for interaction with intestinal PYY receptors. Investigation of aromatic substitutions at position 27 resulted in analogues that exhibited potent in vitro antisecretory potencies with N-alpha-Ac-[Trp(27)]PYY(22-36)-NH(2) exhibiting even greater potency than intact PYY. In vivo studies in dogs revealed that this analogue also promoted intestinal absorption of water and electrolytes during continuous intravenous and intraluminal infusion. Investigations carried out to identify features that would enhance stability revealed that incorporation of Trp(30) increased affinity for PYY receptors. A "CH(2)-NH" scan revealed that incorporation of reduced bonds at position 28-29 or 35-36 imparted greater receptor affinity. In general, disubstituted analogues designed based on the results of single substitutions exhibited good receptor affinity with N-alpha-Ac-[Trp(27),CH(2)-NH(35-36)]PYY(22-36)-NH(2) having the greatest affinity (IC(50) = 0.28 nM). Conservative multiple substitutions with Nle-->Leu and Nva-->Val also imparted good affinity. An analogue designed to encompass most of the favored substitutions, N-alpha-Ac-[Nle(24,28),Trp(30),Nva(31), CH(2)-NH(35-36)]PYY(22-36)-NH(2), exhibited a proabsorptive effect in dogs comparable to, but longer lasting than, that of intact hormone. Selected analogues also exhibited good antisecretory potencies in rats with N-alpha-Ac-[Trp(30)]PYY(22-36)-NH(2) being even more potent than PYY. However, the potencies did not correlate well with the PYY receptor affinity or the proabsorptive potencies in dogs. These differences could be due to species effects and/or the involvement of multiple receptors and neuronal elements in controlling the in vivo activity of PYY compounds. PYY(22-36) analogues exhibited good affinity for neuronal Y2 receptors but poor affinity for Y1 receptors. Also, crucial analogues in this series hardly bound to Y4 and Y5 receptors. In summary, we have developed PYY(22-36) analogues which, via interacting with intestinal PYY receptors, promoted potent and long-lasting proabsorptive and antisecretory effects in in vivo models. These compounds or analogues based on them may have useful clinical application in treating malabsorptive disorders observed under a variety of conditions.

Animals↗
PubMed2000

Pertussis toxin sensitization alters the pathogenesis of subsequent respiratory syncytial virus infection.

Evidence suggests that both host and viral factors influence disease severity after infection with respiratory syncytial virus (RSV). To characterize the effects of pertussis toxin (PT) sensitization on subsequent RSV infection, BALB/c mice were treated with PT parenterally before RSV challenge. Priming with purified and detoxified PT before RSV challenge increased postchallenge weight loss and mortality. PT priming changed the kinetics, location, and composition of the cellular infiltrate in the lung but altered neither antibody responses nor virus titers. Passive transfer of PT-sensitized splenocytes produced similar responses. Priming with purified, but not genetically detoxified, PT propagated a modest type 2 cytokine response to RSV antigens. However, anti-interleukin-4 treatment before RSV challenge failed to abrogate the effects of PT priming. These data confirm that the preexisting immune environment can change virus-specific immunity and provide both a model for study of RSV disease and evidence that noninfectious immunomodulators may impact pathogen-specific immunity.

Animals↗
PubMed2000

Induction of the stress response in vivo decreases nuclear factor-kappa B activity in jejunal mucosa of endotoxemic mice.

BACKGROUND: Results of previous studies suggest that the stress response protects cells and tissues by regulating proinflammatory mediators. The transcription factor nuclear factor-kappa B (NF-kappa B), normally sequestered in the cytoplasm by its inhibitory protein, I kappa B, regulates many genes involved in inflammatory responses to critical illness. Endotoxemia is associated with increased NF-kappa B activity in intestinal mucosa, but the effect of the stress response on endotoxin-induced NF-kappa B activation in intestinal mucosa is not known. HYPOTHESIS: Induction of the stress response inhibits NF-kappa B DNA binding activity in jejunal mucosa during endotoxemia. METHODS: The stress response was induced in mice by hyperthermia (42 degrees C) or injection with sodium arsenite (10 mg/kg). After 2 to 5 hours, mice were injected with endotoxin (lipopolysaccharide, 12.5 mg/kg) or a corresponding volume of sterile saline. One hour later, jejunal mucosa was harvested for preparation of nuclear and cytoplasmic extracts. RESULTS: Mucosal levels of heat shock protein-72 increased after hyperthermia or treatment with sodium arsenite, consistent with induction of the stress response. The increase in NF-kappa B DNA binding activity and decrease in I kappa B-alpha levels seen after endotoxin injection were inhibited by previous induction of the stress response. CONCLUSION: The protective effects of the stress response in vivo might, at least in part, be due to inhibited NF-kappa B activation.

Animals↗
PubMed2000

Diagnostic potential of neutrophil elastase inhibitor complex in the routine care of critically ill newborn infants.

UNLABELLED: It has been suggested that determination of the neutrophil elastase alpha1-proteinase inhibitor complex (E-alpha1PI) improves the diagnosis of bacterial infection in newborns. We evaluated the use of E-alpha1PI measurements in 143 newborns, consecutively admitted to a tertiary intensive care unit, employing a new random access assay and a sampling procedure that minimises post-collection artefacts. The 95% range for noninfected newborns was 20-110 microg/l up to the 5th day of life and 20-85 microg/l thereafter. The sensitivity as to the diagnosis of culture-proven bloodstream infection was 80% for E-alpha1PI, 86% for the immature to total neutrophil ratio, 64% for C-reactive protein and 37% for the total white blood cell count. The corresponding specificity amounted to 97%, 85%, 85% and 86%, respectively. E-alpha1PI increases preceded elevations of C-reactive protein by 18 h. Like C-reactive protein, E-alpha1PI levels did not distinguish between bloodstream infection and non-bacterial inflammatory responses. Results of E-alpha1PI became available within 1 h of collection and usually 2-3 h before manual leucocyte counts. CONCLUSION: Determination of neutrophil elastase alpha1-proteinase inhibitor levels yields diagnostic advantages comparable to those of manual differential counts but provide faster turnaround times.

Cohort Studies↗
PubMed2000

Objectifying psychomental stress in the workplace--an example.

BACKGROUND: Psychomental stress is a major source of illness and reduced productivity. Data objectifying physiological stress responses are scarce. We studied salivary cortisol levels in a highly stressful environment, the pediatric critical care unit. The aim was to identify targets for organizational changes, to implement these changes and to assess their impact on cortisol levels. DESIGN: Repeated measurements observational cohort study (before and after intervention). SUBJECTS: 84 nurses working in two independent teams (A and B) in a 19 bed pediatric intensive care unit. Between study periods team A experienced a major exchange of experienced staff while the turnover rate in team B remained average. MEASUREMENTS AND INTERVENTIONS: Salivary cortisol samples were collected every 2 h and after stressful events. Nurses in study period I showed elevated cortisol levels at the beginning of the late shift, interpreted as an anticipatory stress reaction. To ease conditions during the early part of the late shift (conflicting tasks, noise and crowding), we postponed the afternoon ward round, limited non-urgent procedures and introduced a change in visiting hours. The early shift, which was not affected by the intervention, served as control. MAIN RESULTS: Both crude and adjusted analysis revealed a decrease of cortisol levels at the beginning of the late shift in team B (p = 0.0009), but not in team A (p = 0.464). The control situation showed no difference between teams and study periods. INTERPRETATION: We demonstrated reduced cortisol secretions in one team following organizational changes, which was probably overridden by the disruption of social coherence in the second team.

Adult↗
PubMed2000

Adrenal crisis presenting as hypoglycemic coma.

An 18-month-old male infant presented with hypoglycemic coma and clinical signs of bronchopneumonia. He was suspected of suffering from septic shock. The patient progressed to irreversible multiple organ failure before the diagnosis of adrenal crisis was established. Plasma levels of ACTH and cortisol remained undetectable. Renin and aldosterone were normal. An autopsy failed to demonstrate any adrenal gland cortical tissue. Immunohistochemical staining demonstrated the presence of all pituitary hormones except ACTH, establishing the diagnosis of isolated ACTH deficiency. Intensive care clinicians should consider adrenal crisis in non-diabetic children with hypoglycemia and rapid circulatory deterioration.

Adrenal Cortex↗
PubMed2000

Delay of extubation in neonates and children after cardiac surgery: impact of ventilator-associated pneumonia.

OBJECTIVE: This study was undertaken to determine the delay of extubation attributable to ventilator-associated pneumonia (VAP) in comparison to other complications and complexity of surgery after repair of congenital heart lesions in neonates and children. METHODS: Cohort study in a pediatric intensive care unit of a tertiary referral center. All patients who had cardiac operations during a 22-month period and who survived surgery were eligible (n = 272, median age 1.3 years). Primary outcome was time to successful extubation. Primary variable of interest was VAP Surgical procedures were classified according to complexity. Cox proportional hazards models were calculated to adjust for confounding. Potential confounders comprised other known risk factors for delayed extubation. RESULTS: Median time to extubation was 3 days. VAP occurred in 26 patients (9.6%). The rate of VAP was not associated with complexity of surgery (P = 0.22), or cardiopulmonary bypass (P = 0.23). The adjusted analysis revealed as further factors associated with delayed extubation: other respiratory complications (n = 28, chylothorax, airway stenosis, diaphragm paresis), prolonged inotropic support (n = 48, 17.6%), and the need for secondary surgery (n = 51, 18.8%; e.g., re-operation, secondary closure of thorax). Older age promoted early extubation. The median delay of extubation attributable to VAP was 3.7 days (hazards ratio HR = 0.29, 95% CI 0.18-0.49), exceeding the effect size of secondary surgery (HR = 0.48) and other respiratory complications (HR = 0.50). CONCLUSION: VAP accounts for a major delay of extubation in pediatric cardiac surgery.

Analysis of Variance↗