Biomedical subjects

D Olson

Publications and source records attributed to D Olson.

At least 37 records · Page 2Linked to original sources

PubMed1996

Sedation of critically ill patients during mechanical ventilation. A comparison of propofol and midazolam.

Propofol (P) and midazolam (M) are frequently given by continuous infusion for sedation in critically ill, mechanically ventilated patients. We compared these drugs with regard to: (1) time-to-awaken; (2) reproducibility of bedside assessments of level of sedation; (3) time-to-sedation; and (4) change in oxygen consumption (V O2) from awake to sedated state. Seventy-three patients were prospectively randomized to receive either P (n=37) or M (n=36). Wake-up times after stopping the drug were assessed by blinded and unblinded observers, by asking patients to perform simple tasks. Times to sedate were assessed by consensus agreement among nurses and investigators. Demographics and APACHE II scores were not different between P and M. The P group had a significantly narrower range of wake-up times with a higher likelihood of waking in less than 60 min. Blinded versus unblinded observations had excellent correlation. Average time to sedate and decrease in V O2 were not different. We conclude that in this patient population: (1) both P and M achieved optimal sedation in a large fraction of patients when administered by specified dosing protocols; (2) P had a faster, more reliable, wake-up time; (3) assessments of time-to-awaken were objective and reproducible; (4) time to sedation was not significantly different; (5) V O2 decreased similarly with both.

APACHE↗

PubMed1996

Administration of low-dose dopamine to nonoliguric patients with sepsis syndrome does not raise intramucosal gastric pH nor improve creatinine clearance.

Tissue hypoxia resulting from regional blood flow abnormalities and oxygen extraction defects may underlie the pathogenesis of multiple system organ failure (MSOF) in sepsis. Low-dose dopamine (LDD) is widely employed to enhance splanchnic perfusion although data to support this approach are lacking. We assessed the effect of LDD on surrogate markers of renal and gastric perfusion. Sixteen nonoliguric mechanically ventilated patients with sepsis syndrome received LDD (3 micrograms/kg/min) or placebo in a double-blind crossover design experiment. Hemodynamics, gastric intramucosal pH (pHi) urine volumes, urinary sodium excretion, and cimetidine-corrected creatinine clearance were compared. Mortality for the group was 63%. LDD caused a significant increase in urine volume (88 +/- 58 to 115 +/- 70 ml/h, p = 0.02, 95% confidence interval for change 4.7 to 49 ml/h), but no significant change in any other parameter. We conclude that use of LDD results in diuresis but does not improve other markers of renal or gut perfusion. These data do not support the use of LDD to reduce risk of progression to MSOF in sepsis.

Adult↗

PubMed1996

Xenobiotic metabolism enzyme gene expression in human bronchial epithelial and alveolar macrophage cells.

Human bronchial epithelial cells (BEC), a primary defense against inhaled materials, are the progenitor cells for bronchogenic carcinomas and have important metabolic capabilities. We used reverse transcriptase-polymerase chain reaction (RT-PCR) to identify xenobiotic metabolism enzymes expressed in primary BEC and alveolar macrophages (AM) of non-smoking volunteers. Cytochromes P450 (CYP) 1A1, 1B1, 2B7, 2E1, and 4B1 and microsomal epoxide hydrolase (mEH) were expressed in BEC but not AM. CYP2F1 was expressed in BEC, but it was expressed at barely detectable levels or not at all in AM. NADPH oxidoreductase (NADPH OR), microsomal glutathione transferase (GST 12), glutathione transferase mu, phenol sulfotransferase (PST), thermolabile phenol sulfotransferase (TL PST), and the clara cell-specific gene, CC10 were expressed in both BEC and AM. CYP3A4 and glucuronosyl transferases-1 and 2 were not expressed in either BEC or AM. In contrast to primary BEC, of the genes evaluated, the immortalized human bronchial epithelial cell line BEP2D constitutively expressed only CYP1A1, CYP2E1, NADPH OR, glucuronosyl transferase 1, GST 12, GST mu, PST, TL PST, and CC10. The loss of xenobiotic metabolism enzyme gene expression in the BEP2D cell line may result from either reduced exposure to inducing agents, or loss of differentiative characteristics in culture. It is clear from the data comparing BEC and AM that there are important intertissue differences in expression of xenobiotic metabolism enzymes.

Base Sequence↗

PubMed1995

A technique for porcine hepatocyte harvest and description of differentiated metabolic functions in static culture.

Current bioartificial liver devices are based on the use of a large mass of hepatocytes exhibiting differentiated metabolic function. The pig has become a source of interest for the acquisition of such cells-however, harvesting a large mass of highly viable cells has met with difficulty. This study describes a technique for harvesting large quantities of hepatocytes at viabilities greater than 90% and also describes several features documenting differentiated function. Pigs, 6 to 10 kg body weight, underwent in situ two-step whole liver perfusion (ethylene glycol tetraacetic acid and collagenase) and ex vivo cell harvest. Harvests yielded an average of 19.5 billion cells with an average viability of 94.6%. Hepatocytes were then entrapped in type I collagen (3 x 10(5) cells/well) and cultured in serum-free media for 5 days. Pig hepatocytes produced stable amounts of albumin and maintained cytochrome P-450 and glucuronidation activity over 5 days, as shown by the metabolism of lidocaine and 4-methylumbelliferone. These data indicate that pig hepatocytes can be harvested with high yields and can retain viability and differentiated function over at least 5 days of culture, and therefore should prove to be an excellent source of hepatocytes for bioartificial liver devices.

Animals↗

PubMed1995

Expression of relB is required for the development of thymic medulla and dendritic cells.

Dendritic cells (DC) derived from bone marrow are critical in the function of the immune system, for they are the primary antigen-presenting cells in the activation of T-lymphocyte response. Their differentiation from precursor cells has not been defined at a molecular level, but recent studies have shown an association between expression of the relB subunit of the NF-kappa B complex and the presence of DC in specific regions of normal unstimulated lymphoid tissues. Here we show that relB expression also correlates with differentiation of DC in autoimmune infiltrates in situ, and that a mutation disrupting the relB gene results in mice with impaired antigen-presenting cell function, and a syndrome of excess production of granulocytes and macrophages. Thymic UEA-1+ medullary epithelial cells from normal mice show striking similarities to DC and, interestingly, these cells are also absent in relB mutant mice. Taken together, these results suggest that relB is critical in the coordinated activation of genes necessary for the differentiation of two unrelated but phenotypically similar cells (DC and thymic UEA-1+ medullary epithelial cells) and is therefore a candidate for a gene determining lineage commitment in the immune system.

Amino Acid Sequence↗

PubMed1995

PMA-induced down-regulation of the receptor for alpha 2-macroglobulin in human U937 cells.

Transcription and expression of the urokinase (uPA) receptor (uPAR) are strongly stimulated by PMA. As for uPAR, the expression of alpha 2-MR is regulated by PMA in U937 cells. Ligand blotting experiments with the 39 kDa receptor-associated protein RAP, a ligand for alpha 2-MR, indicated that alpha 2-MR levels first increased and then decreased after PMA treatment. FACscan as well as immunoblotting analysis with alpha 2-MR-specific antibodies showed an identical trend: alpha 2-MR levels increased within the first day of treatment with PMA, decreased at later times, and totally disappeared by three days of treatment. The effect of PMA was not due to transcriptional down-regulation, as the alpha 2-MR mRNA level did not decrease at later times. Sensitivity of U937 cells to uPA-saporin, a toxin conjugate that reguires binding to uPAR for killing activity, was also markedly decreased. These results suggest that uPAR-mediated endocytosis depends on alpha 2-MR expression.

Base Sequence↗

PubMed1995

Congenital cytomegalovirus infection as a result of nonprimary cytomegalovirus disease in a mother with acquired immunodeficiency syndrome.

A pregnant woman with acquired immunodeficiency syndrome had nonprimary cytomegalovirus (CMV) viremia and died of complications from Pneumocystis carinii pneumonia and CMV sinusitis and pneumonitis. A boy was delivered by cesarean section at 34 weeks of gestation as the mother's health deteriorated and fetal distress developed. The infant died soon after delivery of interstitial pneumonitis and hyaline membrane disease with invasive CMV disease that affected the kidneys, adrenal glands, and placenta; the CMV strains from the mother and neonate were identical.

AIDS-Related Opportunistic Infections↗

PubMed1995

In vivo administration of CD4-specific monoclonal antibody: effect on provirus load in rhesus monkeys chronically infected with the simian immunodeficiency virus of macaques.

Since monoclonal antibodies (MAb) specific for CD4 are potent inhibitors of HIV and SIV replication in vitro, we explored their potential usefulness in vivo as an AIDS therapy. The anti-CD4 MAb 5A8 binds to domain 2 of the CD4 molecule and inhibits virus replication and virus-induced cell fusion at a postvirus binding step. Administration of this MAb to normal rhesus monkeys coats all circulating and lymph node CD4 cells and induces neither CD4 cell clearance nor measurable immunosuppression. In the present study, monkeys chronically infected with the simian immunodeficiency virus of macaques (SIVmac) had stable levels of SIVmac provirus in PBMC prior to treatment as measured by a quantitative polymerase chain reaction technique. Six infected monkeys treated with anti-CD4 MAb demonstrated a significant decrease in SIVmac provirus level after 9 days. Of these monkeys, 3 had > 800 CD4 cells/microliter and developed strong antimouse Ig responses that prevented further treatment. The remaining 3 monkeys had < 800 CD4 cell/microliter and failed to develop antimouse Ig antibody responses. When treatment was continued for 12-21 days in these monkeys, a sustained or further decrease in SIVmac provirus load occurred over the extended treatment period. Four monkeys that received a control MAb of irrelevant specificity for 9-22 days showed either no significant change or a transient increase in SIVmac provirus. Thus, the passive administration of anti-CD4 MAb may exert a specific antiviral effect in controlling immunodeficiency virus infection in vivo.

Animals↗

PubMed1995

Effect of cooling on oxygen consumption in febrile critically ill patients.

Hyperthermic critically ill patients are commonly cooled to reduce their oxygen consumption (VO2). However, no previous studies in febrile humans have measured VO2 during cooling. We cooled 12 febrile, critically ill, mechanically ventilated patients while measuring VO2 and CO2 production (VCO2) by analysis of inspired and expired gases. All patients were mechanically ventilated for hypoxemic, hypercapneic, or shock-related respiratory failure and had a mean APACHE II score of 22.4 +/- 7.7. As temperature was reduced from 39.4 +/- 0.8 to 37.0 +/- 0.5 degrees C, VO2 decreased from 359.0 +/- 65.0 to 295.1 +/- 57.3 ml/min (p < 0.01) and VCO2 decreased from 303.6 +/- 43.6 to 243.5 +/- 37.3 ml/min (p < 0.01). The respiratory quotient (RQ) did not change significantly, and calculated energy expenditure decreased from 2,481 +/- 426 to 1,990 +/- 33 kcal/day (p < 0.01). In 7 patients with right heart catheters, cardiac output decreased from 8.4 +/- 3.2 to 6.5 +/- 1.8 L/min (p < 0.01) as the oxygen extraction fraction also tended to decrease from a mean of 28.2 +/- 6.8 to 23.4 +/- 4.7% (p = 0.12) during cooling. Accordingly, cooling the febrile patient unloads the cardiorespiratory system and, in situations of limited oxygen delivery or hypoxemic respiratory failure, may thus facilitate resuscitation and minimize the potential for hypoxic tissue injury.

APACHE↗

PubMed1995

Factors contributing to the stability of social relationships between individuals with mental retardation and other community members.

Stability of social relationships may be an important indicator of lifestyle quality. Fourteen community members identified as being in long-term, socially stable relationships with one or more individuals with mental retardation provided answers to a quantitatively oriented questionnaire and participated in a more open-ended qualitative interview. In general, results indicated that the stability of the relationships was influenced by (a) the community members having previously served as staff members to the individuals with mental retardation, (b) their willingness to overcome logistical barriers that might otherwise have impeded their friendships, (c) their perception that the relationships included reciprocal social support, and (d) other idiosyncratic variables.

Activities of Daily Living↗

PubMed1994

Protease nexin-1-urokinase complexes are internalized and degraded through a mechanism that requires both urokinase receptor and alpha 2-macroglobulin receptor.

After binding to its receptor (uPAR), active cell-surface urokinase (uPA) is not internalized while the complex formed by uPA with plasminogen activator inhibitor type 1 (PAI-1) is internalized and degraded. Internalization and degradation require binding to uPAR and subsequently an interaction with the alpha 2-macroglobulin receptor (alpha 2-MR). To analyze the generality of this mechanism, we studied the internalization of uPA by recombinant protease nexin-1 (rPN-1), an inhibitor of thrombin, uPA, and plasmin. 125I-uPA.rPN-1 complexes bound specifically to uPAR; internalization occurred efficiently, and its time course was essentially the same as for uPA.PAI-1. Internalization required binding to uPAR since it could be blocked by the anti-uPAR monoclonal antibodies, by the uPAR antagonist amino-terminal fragment of uPA, and by the removal of uPAR by the treatment of cells with phosphatidylinositol-specific phospholipase C. As for uPA.PAI-1, the internalization of uPA.rPN-1 also required alpha 2-MR, since it could be inhibited by the 39-kDa alpha 2-macroglobulin receptor/low density lipoprotein receptor-associated protein, a ligand for the alpha 2-MR. Finally, we show by ligand blot analysis that the uPA.rPN-1 complex, like uPA.PAI-1 but unlike free uPA, bound specifically to both uPAR and alpha 2-MR.

Amyloid beta-Protein Precursor↗

PubMed1994

The association of swallowing dysfunction and aspiration pneumonia.

The medical literature has emphasized that aspiration of gastric contents or oral bacteria is a common cause of aspiration pneumonia. Swallowing disorders have been implicated in this disease but not studied at the time that aspiration pneumonia was diagnosed. A significant difference was found in the incidence of videofluoroscopically confirmed oropharyngeal swallowing problems in a group of patients diagnosed with aspiration pneumonia (AP) when compared with patients with nonaspiration pneumonia (NAP). Six of the 9 patients in the AP group aspirated during the videofluoroscopic evaluation and 2 others were considered to be at risk for aspiration. None of the 7 NAP patients demonstrated swallowing problems or aspiration. A significant difference in oral transit time also occurred between the two groups. Liquid was found to have a significantly faster oral transit time than paste or a cookie. Pharyngeal transit times were not found to be significantly different. Although there were only a small number of patients who met the criteria for this pilot study, a strong association was found between swallowing dysfunction and aspiration pneumonia.

Adult↗

PubMed1994

Model curriculum for physician training in emergency ultrasonography.

A model curriculum for the implementation and training of physicians in emergency medicine ultrasonography is described. Widespread use of limited bedside ultrasonography by emergency physicians will improve diagnostic accuracy and efficiency, increase the quality of care, and prove to be a cost-effective technique for the practice of emergency medicine.

Curriculum↗

PubMed1994

Building a children's health network: city-wide computer linkages among heterogeneous sites for pediatric primary care.

For many infants and children in our cities, quality of care and health status outcomes suffer due to poor continuity and coordination among ambulatory care sites. Despite proximity to technologically-advanced secondary and tertiary institutions, primary care services for children are fragmented, multiple-site use is common, and data flow among providers serving the same patients is primitive. Preventive and acute health care is often incomplete or redundant, and aggregate information for public health purposes is insufficient. This paper focuses on the development of a city-wide computer-based pediatric health care network to improve provider decision-making and follow-through, parent role in their children's care, and community-wide data. A process of building consensus for a regional system is presented, addressing issues of establishing a uniform data base, coordination among heterogeneous institutions, system development, confidentiality, and integration with public health reporting and planning functions.

Child↗

PubMed1994

Babesia equi erythrocytic stage continuously cultured in an enriched medium.

Babesia equi was continuously cultured through 90 passages in an enriched chemically defined basal medium (HL-1) supplemented with 20% fetal bovine serum and serum replacement factors, including lipid-rich bovine serum albumin, bovine insulin, and human transferrin. Cryopreservation and subsequent recovery of B. equi were easily achieved. Inoculation of a splenectomized and an intact horse with cultured infected erythrocytes resulted in parasitemias and B. equi in vitro reisolation from both animals. In vitro forms of the parasite resembled in vivo forms. After establishment, parasitemias of 10-15% were commonly observed.

Animals↗

PubMed1993

Cloning of an inflammation-specific phosphatidyl inositol-linked form of murine vascular cell adhesion molecule-1.

Vascular cell adhesion molecule-1 (VCAM1) is a member of the immunoglobulin (Ig) superfamily which interacts with the integrin very late antigen-4 (VLA4). The VCAM1/VLA4 interaction mediates both adhesion and signal transduction and is thought to play an important role in inflammatory and immune responses in vivo. VCAM1 cDNAs cloned from mouse, rat, rabbit, and human libraries contain six, seven, or eight extracellular Ig-like domains generated by alternate splicing, but to date shorter forms have not been found. We have cloned a novel cDNA encoding only the three N-terminal domains of murine VCAM1 followed by a unique C-terminal tail generated by alternate splicing of a previously undescribed exon. This truncated form of murine VCAM1 (3D-VCAM1) is expressed in COS cells as a functional adhesion molecule which is lost from the cell surface following treatment with phosphatidylinositol-specific phospholipase C. 3D-VCAM1 is found only in endotoxin-treated but not control murine and rat tissues. Thus in rodents alternate splicing of the VCAM1 gene generates a unique truncated inflammation-specific phosphatidylinositol-linked form of VCAM1.

Alternative Splicing↗

PubMed1993

Blindness secondary to prostate cancer.

We report a case of blindness, secondary to hormone-refractory prostate cancer, occurring 7 years after the diagnosis of metastatic prostate cancer and 3.5 years after the clinical onset of the hormone-refractory state. Prolonged suppression of the disease with chemotherapy may have contributed to the unusual clinical findings. We discuss the role of supportive care in the management of prostate cancer.

Adenocarcinoma↗

PubMed1993

The p53-mdm-2 autoregulatory feedback loop.

The p53 protein can bind to a set of specific DNA sequences, and this may activate the transcription of genes adjacent to these DNA elements. The mdm-2 gene is shown here to contain a p53 DNA-binding site and a genetically responsive element such that expression of the mdm-2 gene can be regulated by the level of wild-type p53 protein. The mdm-2 protein, in turn, can complex with p53 and decrease its ability to act as a positive transcription factor at the mdm-2 gene-responsive element. In this way, the mdm-2 gene is autoregulated. The p53 protein regulates the mdm-2 gene at the level of transcription, and the mdm-2 protein regulates the p53 protein at the level of its activity. This creates a feedback loop that regulates both the activity of the p53 protein and the expression of the mdm-2 gene.

Animals↗