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Biomedical subjects

J E Fischer

Publications and source records attributed to J E Fischer.

At least 55 records · Page 3Linked to original sources
PubMed2000

Use of antibiotics in pediatric intensive care and potential savings.

OBJECTIVE: Minimizing unwarranted prescription of antibiotics remains an important objective. Because of the heterogeneity between units regarding patient mix and other characteristics, site-specific targets for reduction must be identified. Here we present a model to address the issue by means of an observational cohort study. SETTING: A tertiary, multidisciplinary, neonatal, and pediatric intensive care unit of a university teaching hospital. PATIENTS: All newborns and children present in the unit (n = 456) between September 1998 and March 1999. Reasons for admission included postoperative care after cardiac surgery, major neonatal or pediatric surgery, severe trauma, and medical conditions requiring critical care. METHODS: Daily recording of antibiotics given and of indications for initiation. After discontinuation, each treatment episode was assessed as to the presence or absence of infection. RESULTS: Of the 456 patients 258 (56.6%) received systemic antibiotics, amounting to 1815 exposure days (54.6%) during 3322 hospitalization days. Of these, 512 (28%) were prescribed as prophylaxis and 1303 for suspected infection. Treatment for suspected ventilator-associated pneumonia accounted for 616 (47%) of 1303 treatment days and suspected sepsis for 255 days (20%). Patients were classified as having no infection or viral infection during 552 (40%) treatment days. The average weekly exposure rate in the unit varied considerably during the 29-week study period (range: 40-77/100 hospitalization days). Patient characteristics did not explain this variation. CONCLUSION: In this unit the largest reduction in antibiotic treatment would result from measures assisting suspected ventilator-associated pneumonia to be ruled out and from curtailing extended prophylaxis.

Anti-Bacterial Agents↗
PubMed2000

Institutional and individual learning curves for focused abdominal ultrasound for trauma: cumulative sum analysis.

OBJECTIVE: To evaluate both institutional and individual learning curves with focused abdominal ultrasound for trauma (FAST) by analyzing the incidence of diagnostic inaccuracies as a function of examiner experience for a group of trauma surgeons performing the study in the setting of an urban level I trauma center. SUMMARY BACKGROUND DATA: Trauma surgeons are routinely using FAST to evaluate patients with blunt trauma for hemoperitoneum. The volume of experience required for practicing trauma surgeons to be able to perform this examination with a reproducible level of accuracy has not been fully defined. METHODS: The authors reviewed prospectively gathered data for all patients undergoing FAST for blunt trauma during a 30-month period. All FAST interpretations were validated by at least one of four methods: computed tomography, diagnostic peritoneal lavage, celiotomy, or serial clinical evaluations. Cumulative sum (CUSUM) analysis was used to describe the learning curves for each individual surgeon at target accuracy rates of 85%, 90%, and 95% and for the institution as a whole at target examination accuracy rates of 85%, 90%, 95%, and 98%. RESULTS: Five trauma surgeons performed 546 FAST examinations during the study period. CUSUM analysis of the aggregate experience revealed that the examiners as a group exceeded 90% accuracy at the outset of clinical examination. The level of accuracy did not improve with either increased frequency of performance or total examination experience. The accuracy rates observed for each trauma surgeon ranged from 87% to 98%. The surgeon with the highest accuracy rate performed the fewest examinations. No practitioner demonstrated improved accuracy with increased experience. CONCLUSIONS: Trauma surgeons who are newly trained in the use of FAST can achieve an overall accuracy rate of at least 90% from the outset of clinical experience with this modality. Interexaminer variations in accuracy rates, which are observed above this level of performance, are probably related more to issues surrounding patient selection and inherent limitations of the examination in certain populations than to practitioner errors in the performance or interpretation of the study.

Abdominal Injuries↗
PubMed2000

Experience and endocrine stress responses in neonatal and pediatric critical care nurses and physicians.

OBJECTIVE: Critical care is a working environment with frequent exposure to stressful events. High levels of psychological stress have been associated with increased prevalence of burnout. Psychological distress acts as a potent trigger of cortisol secretions. We attempted to objectify endocrine stress reactivity. DESIGN: Observational cohort study during two 12-day periods in successive years. SETTING: A tertiary multidisciplinary neonatal and pediatric intensive care unit (33 beds). SUBJECTS: One hundred and twelve nurses and 27 physicians (94% accrual rate). INTERVENTIONS AND MEASUREMENTS: Cortisol determined from salivary samples collected every 2 hrs and after stressful events. Participants recorded the subjective perception of stress with every sample. Endocrine reactions were defined as transient surges in cortisol of >50% and 2.5 nmol/L over the baseline. MAIN RESULTS: During 7,145 working hours, we observed 474 (12.5%) endocrine reactions from 3,781 samples. The mean cortisol increase amounted to 10.6 nmol/L (219%). The mean occurrence rate of endocrine reactions per subject and sample was 0.159 (range, 0-0.43). Although the mean raw cortisol levels were lower in experienced team members (>3 yrs of intensive care vs. <3 yrs, 4.1 vs. 4.95 nmol/L, p < .001), professional experience failed to attenuate the frequency and magnitude of endocrine reactions, except for the subgroup of nurses and physicians with >8 yrs of intensive care experience. A high proportion (71.3%) of endocrine reactions occurred without conscious perception of stress. Unawareness of stress was higher in intensive care nurses (75.1%) than in intermediate care nurses (51.8%, p < .01). CONCLUSIONS: Stress-related cortisol surges occur frequently in neonatal and pediatric critical care staff. Cortisol increases are independent of subjective stress perception. Professional experience does not abate the endocrine stress reactivity.

Adult↗
PubMed2000

Interleukin-1beta induces complement component C3 and IL-6 production at the basolateral and apical membranes in a human intestinal epithelial cell line.

In previous studies, stimulation of cultured enterocytes with IL-1beta resulted in production of IL-6 and complement component C3. The cellular mechanisms of these responses in the enterocyte are not fully understood. We tested the hypothesis that IL-1beta-induced C3 and IL-6 production is differentially regulated at the apical and basolateral membranes of the enterocyte. Caco-2 cells (a transformed human colonic carcinoma cell line) were grown in a 2-chamber system to full differentiation. The cells were treated with IL-1beta either at the apical or basolateral membrane, and C3 and IL-6 mRNA levels and release of C3 and IL-6 into the apical and basal chambers were determined. The release of C3 was greatest into the basal chamber regardless of whether the cells were stimulated at the apical or basolateral membrane. In contrast, the production of IL-6 was greatest at the cell membrane that was stimulated with IL-1beta. Stimulation of the Caco-2 cells with IL-1beta resulted in increased mRNA levels for C3 and IL-6 with no major differences noted when the cells were treated at the apical or basolateral membrane. The results suggest that enterocyte production and release of at least some acute phase proteins and cytokines are differentially regulated at the apical and basolateral membrane of the enterocyte after stimulation with IL-1beta.

Acute-Phase Reaction↗
PubMed2000

IL-1beta induction of NF-kappaB activation in human intestinal epithelial cells is independent of oxyradical signaling.

IL-1beta stimulation of cultured epithelial cells induces the degradation of IkappaBalpha and the consequent nuclear translocation of NF-lambdaB, a critical proinflammatory transcription factor in the mucosal host immune response. The role of reactive oxygen intermediates, serine protease activity, and tyrosine kinase activity in the activation of NF-kappaB is weakly conserved across various cell lineages and has not been defined in human enterocytes, a major target of oxidant stress in sepsis, thermal injury, and hemorrhagic shock. We report here that in Caco-2BBe cells, a transformed human colon cancer cell line with features of small intestinal epithelial cells in culture, exposure to oxidant stress (hydrogen peroxide 1-10 mM) did not induce NF-kappaB activation. Similarly, scavenging of free radicals and oxidants by pyrrolidine dithiocarbamate and dimethyl sulfoxide did not block IL-1beta-induced IkappaBalpha degradation and NF-kappaB activation. Genistein, a nonspecific tyrosine kinase inhibitor, also had no effect on IL-1beta-mediated effects on NF-kappaB. Serine protease inhibition by tosyl-lysine-chloromethylketone and tosyl-phenylalanine-chloromethylketone inhibited IkappaBalpha degradation and NF-kappaB activation stimulated by IL-1beta. Our data highlight the strong divergence between epithelial and mononuclear cells in the signal transduction pathways relating IL-1beta stimulation and NF-kappaB nuclear translocation.

Adenocarcinoma↗
PubMed2000

Activation of NF-kappaB varies in different regions of the gastrointestinal tract during endotoxemia.

The transcription nuclear factor-kappaB (NF-kappaB) regulates a large number of genes involved in the inflammatory response to sepsis and endotoxemia. We recently found that NF-kappaB is activated in the jejunal mucosa during endotoxemia, but the response of NF-kappaB in other parts of the gastrointestinal tract is not known. We hypothesized that NF-kappaB is differentially activated in different regions of the gastrointestinal tract during endotoxemia. NF-kappaB DNA binding activity was determined by electrophoretic mobility shift assay in mucosa of the stomach, jejunum, ileum, and colon from endotoxemic and saline-injected mice. Cytoplasmic levels of the NF-kappaB inhibitory proteins IkappaB-alpha and IkappaB-beta were determined by Western blot analysis. Endotoxemia increased NF-kappaB activity in mucosa of stomach, jejunum, and ileum, with jejunum responding to smaller doses of endotoxin than the other parts of the gastrointestinal tract. NF-kappaB DNA binding activity was not induced in colonic mucosa, even following administration of high doses of endotoxin. IkappaB-alpha and IkappaB-beta levels decreased in jejunal mucosa of endotoxin injected mice, concomitant with activation of NF-kappaB. The results suggest that during endotoxemia, NF-kappaB is activated in mucosa of stomach and small intestine, but not in colon, and that the jejunum is particularly sensitive to endotoxin.

Animals↗
PubMed1999

Lactate is an unreliable indicator of tissue hypoxia in injury or sepsis.

High blood lactate concentration (hyperlactacidaemia) in trauma or sepsis is thought to indicate tissue hypoxia and anaerobic glycolysis even when blood pressure, cardiac output, and urine output are within clinically acceptable ranges. However, mechanisms of lactate generation by well-oxygenated tissues have received little attention. Within cells, oxidative and glycolytic energy production can proceed in separate, independent compartments. In skeletal muscle and other tissues, aerobic glycolysis is linked to ATP provision for the Na+-K+ pump, the activity of which is stimulated by epinephrine. In injured patients, hypokalaemia may reflect increased Na+,K+-ATPase activity. We propose that increased blood lactate often reflects increased aerobic glycolysis in skeletal muscle secondary to epinephrine-stimulated Na+,K+-ATPase activity and not anaerobic glycolysis due to hypoperfusion. The hypothesis explains why hyperlactacidaemia often neither correlates with traditional indicators of perfusion nor diminishes with increased oxygen delivery. When other variables have returned to normal, continued attempts at resuscitation based on elevated blood lactate may lead to unnecessary use of blood transfusion and inotropic agents in an effort to increase oxygen delivery and lactate clearance.

Cell Hypoxia↗
PubMed1999

Complement component C3 production in IL-1beta-stimulated human intestinal epithelial cells is blocked by NF-kappaB inhibitors and by transfection with ser 32/36 mutant IkappaBalpha.

BACKGROUND: Recent studies suggest that interleukin-1beta (IL-1beta) stimulates the production of the acute phase protein complement component C3 in human intestinal epithelial cells. The transcription factor NF-kappaB activates different genes involved in the response to cytokines. It is not known if IL-1beta-induced C3 production in the enterocyte is regulated by NF-kappaB. MATERIALS AND METHODS: Cultured Caco-2 cells, a human intestinal epithelial cell line, were treated with one of the NF-kappaB inhibitors, tosyl-lys-chloromethylketone (TLCK), genistein, or pyrrolidine dithiocarbamate (PDTC), or with N-acetyl-leu-leu-norleucinal (LLnL), a proteasome inhibitor known to block the degradation of Ikappabeta, the cytosolic inhibitor of NF-kappaB. Following this treatment, the Caco-2 cells were stimulated with IL-1beta, and C3 levels in the culture medium were measured after 24 h by ELISA. C3 mRNA levels were determined after 4 h by Northern blot analysis. In other experiments, Caco-2 cells were transfected with a mutant IkappaBalpha in which serines 32 and 36 were substituted by alanine. This mutation prevents IkBalpha phosphorylation and subsequent NF-kappaB nuclear translocation. After transfection, the cells were stimulated with IL-1beta, and C3 levels in the culture medium were measured after 24 h. Cytosolic IkappaBalpha was determined by Western blot analysis. RESULTS: TLCK, genistein, and LLnL each inhibited IL-1beta-induced C3 production in a dose-dependent fashion. These responses were associated with decreased C3 mRNA levels. In contrast, PDTC did not influence C3 production or C3 mRNA in the Caco-2 cells. Transfection of the Caco-2 cells with the Ser 32/36 mutant IkBalpha resulted in maintained IkappaBalpha levels and decreased IL-beta-induced C3 production. CONCLUSIONS: IL-1beta-stimulated C3 production in the enterocyte may be regulated by NF-kappaB.

Base Sequence↗
PubMed1999

Flexner and the whole-time system: the second Flexner report and the whole-time system in American academic surgery.

BACKGROUND: Reform in medical education started in the mid 19th century and continued through the early decades of the 20th century. Both Carnegie and Rockefeller foundation monies were applied to the process of attempting to improve medical education. The University of Cincinnati College of Medicine, associated with a municipal hospital and a municipally owned university, offered a model for improvements in medical education in other municipal hospitals. The attempt to institute the "whole-time" ("full-time" salaried, "University") system, and restructure the University of Cincinnati College of Medicine along radical lines hitherto unknown in much of the country and in particular to the city of Cincinnati, disturbed the relationship of the College of Medicine with the community and echoes to this day. The tensions between the "University-salaried" professors of clinical surgery and the practitioners attempting to practice at the institution have abated but remain unresolved. CONCLUSION: The history of the establishment of the full-time chairs, including the Christian R. Holmes Chair of Surgery, led to a rethinking of the role that the full-time system might play in American medical education.

Education, Medical↗
PubMed1999

Vaccination with pertussis toxin alters the antibody response to simultaneous respiratory syncytial virus challenge.

Many bacterial toxins, including pertussis toxin (PT), exert potent adjuvant effects on antibody synthesis to coadministered antigens. In these studies, we examined whether locally or peripherally administered PT similarly altered the antibody isotype selection to replicating virus after intranasal (inl) challenge. Mice primed intramuscularly with PT and inl with respiratory syncytial virus (RSV) produced RSV-specific antibodies of the IgG2a isotype at a level similar to that of unprimed controls, with some increase in IgG1 production. Mice primed inl with both PT and RSV showed elevated RSV-specific IgG1, increased serum IgE levels, and increased interleukin (IL)-4 in lung supernatants. Splenocytes from these animals produced increased IL-4 when stimulated in vitro with RSV or PT antigens after infection. These results suggest that PT can influence the local production of IL-4 to alter the humoral and cellular immune responses to viral infection as well as to coadministered antigens.

Administration, Intranasal↗
PubMed1999

Sepsis stimulates release of myofilaments in skeletal muscle by a calcium-dependent mechanism.

Sepsis is associated with a pronounced catabolic response in skeletal muscle, mainly reflecting degradation of the myofibrillar proteins actin and myosin. Recent studies suggest that sepsis-induced muscle proteolysis may reflect ubiquitin-proteasome-dependent protein breakdown. An apparently conflicting observation is that the ubiquitin-proteasome pathway does not degrade intact myofibrils. Thus, it is possible that actin and myosin need to be released from the myofibrils before they can be ubiquitinated and degraded by the proteasome. We tested the hypothesis that sepsis results in disruption of Z-bands, increased expression of calpains, and calcium-dependent release of myofilaments in skeletal muscle. Sepsis induced in rats by cecal ligation and puncture resulted in increased gene expression of micro-calpain, m-calpain, and p94 and in Z-band disintegration in the extensor digitorum longus muscle. The release of myofilaments from myofibrillar proteins was increased in septic muscle. This response to sepsis was blocked by treating the rats with dantrolene, a substance that inhibits the release of calcium from intracellular stores to the cytoplasm. The present results provide evidence that sepsis is associated with Z-band disintegration and a calcium-dependent release of myofilaments in skeletal muscle. Release of myofilaments may be an initial and perhaps rate-limiting component of sepsis-induced muscle breakdown.

Actin Cytoskeleton↗
PubMed1999

Prospective, randomized comparison of epidural versus parenteral opioid analgesia in thoracic trauma.

OBJECTIVE: To evaluate systemic versus epidural opioid administration for analgesia in patients sustaining thoracic trauma. SUMMARY BACKGROUND DATA: The authors have previously shown that epidural analgesia significantly reduces the pain associated with significant chest wall injury. Recent studies report that epidural analgesia is associated with a lower catecholamine and cytokine response in patients undergoing elective thoracotomy compared with patient-controlled analgesia (PCA). This study compares the effect of epidural analgesia and PCA on pain relief, pulmonary function, cathechol release, and immune response in patients sustaining significant thoracic trauma. METHODS: Patients (ages 18 to 60 years) sustaining thoracic injury were prospectively randomized to receive epidural analgesia or PCA during an 18-month period. Levels of serum interleukin (IL)-1beta, IL-2, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) were measured every 12 hours for 3 days by enzyme-linked immunosorbent assay. Urinary catecholamine levels were measured every 24 hours. Independent observers assessed pulmonary function using standard techniques and analgesia using a verbal rating score. RESULTS: Twenty-four patients of the 34 enrolled completed the study. Age, injury severity score, thoracic abbreviated injury score, and length of hospital stay did not differ between the two groups. There was no significant difference in plasma levels of IL-1beta, IL-2, IL-6, or TNF-alpha or urinary catecholamines between the two groups at any time point. Epidural analgesia was associated with significantly reduced plasma levels of IL-8 at days 2 and 3, verbal rating score of pain on days 1 and 3, and maximal inspiratory force and tidal volume on day 3 versus PCA. CONCLUSIONS: Epidural analgesia significantly reduced pain with chest wall excursion compared with PCA. The route of analgesia did not affect the catecholamine response. However, serum levels of IL-8, a proinflammatory chemoattractant that has been implicated in acute lung injury, were significantly reduced in patients receiving epidural analgesia on days 2 and 3. This may have important clinical implications because lower levels of IL-8 may reduce infectious or inflammatory complications in the trauma patient. Also, tidal volume and maximal inspiratory force were improved with epidural analgesia by day 3. These results demonstrate that epidural analgesia is superior to PCA in providing analgesia, improving pulmonary function, and modifying the immune response in patients with severe chest injury.

Adolescent↗
PubMed1999

Implementation of a clinical pathway decreases length of stay and cost for bowel resection.

OBJECTIVE: To examine the effect of a clinical pathway for small and large bowel resection on cost and length of hospital stay. SUMMARY BACKGROUND DATA: Clinical pathways are designed to streamline patient care delivery and maximize efficiency while minimizing cost. Theoretically, they should be most effective in commonly performed procedures, in which volume and familiarity are high. METHODS: A clinical pathway to assist in the management of patients undergoing bowel resection was developed by a multidisciplinary team and implemented. Data about length of stay and cost was collected for all patients undergoing bowel resection 1 year before and 1 year after pathway implementation. Three groups were compared: patients undergoing bowel resection in the year prior to pathway implementation (prepathway), patients in the year after pathway implementation but not included on the pathway (nonpathway), and patients included in the pathway (pathway). RESULTS: The mean cost per hospital stay was $19,997.35 +/- 1244.61 for patients in the prepathway group, $20,835.28 +/- 2286.26 for those in the nonpathway group, and $13,908.53 +/- 1113.01 for those in the pathway group (p < 0.05 vs. other groups). Mean postoperative length of stay was 9.98 +/- 0.62 days (prepathway), 9.68 +/- 0.88 days for (nonpathway), and 7.71 +/- 0.37 days (pathway) (p < 0.05 vs. other groups). CONCLUSIONS: Implementation of the pathway produced significant decreases in length of stay and cost in the pathway group as compared to the prepathway group. These results support the further development of clinical pathways for general surgical procedures.

Costs and Cost Analysis↗