Biomedical subjects
Publications and source records attributed to A Shafer.
IMPLICATIONS: Patients who receive sedation occasionally divulge thoughts that they would not usually express. This report describes a sedated patient who threatened to murder two family members. Immediate consultation with an attorney and psychiatrist is recommended when the anesthesiologist may be required to breach patient confidentiality to warn potential victims.
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The regulation of gene expression by the tetracycline system has attracted a high level of interest in the recent past. However, expression of secreted proteins has not been evaluated precisely. In this study, we constructed two versions of a one-plasmid system containing the elements necessary for the regulation of gene expression. The regulatable elements and the selectable marker (Neor) were set up in two different configurations, pTRIN31 and pTRIN76. With these two regulatable versions, the levels of protein expression after transfection into the NIH/3T3 cell line were measured by insertion of three different genes encoding the secreted proteins (hGH, ApoE3, hGM-CSF). The maximum levels of gene expression obtained with the pTRIN76-derived plasmids were 100ng/24h/106 cells for hGH, 427ng/24h/106 cells for ApoE3 and 108ng/24h/106 cells for hGM-CSF. For the pTRIN31-derived plasmids the maximum levels were 2.7ng/24h/106 cells for hGH and 47ng/24h/106 for ApoE3. Both plasmids give rise to an expression of the transfected gene that can be tightly regulated by three different molecules: tetracycline, minocycline and doxycycline. The levels of the secreted proteins are below the detectable level when the reporter genes are repressed. This repression is reversible within 48h after the regulator has been removed from the medium.
OBJECTIVE: Evaluate vancomycin prescribing patterns in a tertiary-care hospital before and after interventions to decrease vancomycin utilization. DESIGN: Before/after analysis of interventions to limit vancomycin use. SETTING: 420-bed academic tertiary-care center. INTERVENTIONS: Educational efforts began August 10, 1994, and involved lectures to medical house staff followed by mailings to all physicians and posting of guidelines for vancomycin use on hospital information systems. Active interventions began November 15, 1994, and included automatic stop orders for vancomycin at 72 hours, alerts attached to the medical record, and, for 2 weeks only, computer alerts to physicians following each vancomycin order. Parenteral vancomycin use was estimated from the hospital pharmacy database of all medication orders. Records of a random sample of 344 patients receiving vancomycin between May 1, 1994, and April 30, 1995, were reviewed for an indication meeting published guidelines. RESULTS: Vancomycin prescribing decreased by 22% following interventions, from 8.5 to 6.8 courses per 100 discharges (P<.05). The estimated proportion of vancomycin ordered for an indication meeting published guidelines was 36.6% overall, with no significant change following interventions. However, during the 2 weeks that computer alerts were in place, 60% of vancomycin use was for an approved indication. CONCLUSIONS: Parenteral vancomycin prescribing decreased significantly following interventions, but the majority of orders still were not for an indication meeting published guidelines. Further improvement in the appropriateness of vancomycin prescribing potentially could be accomplished by more aggressive interventions, such as computer alerts, or by targeting specific aspects of prescribing patterns.
OBJECTIVE: To describe the various complications that have been reported with use of midazolam for sedation in the intensive care unit (ICU). DATA SOURCES: Publications in scientific literature. DATA EXTRACTION: Computer search of the literature. SYNTHESIS: Sedation is required in the ICU in order for patients to tolerate noxious stimuli, particularly mechanical ventilation. Under- and oversedation can lead to complications. To sedate patients in the ICU, midazolam is commonly administered via titrated, continuous infusions. Cardiorespiratory effects tend to be minimal; however, hypotension can occur in hypovolemic patients. Prolonged sedation after cessation of the midazolam infusion may be caused by altered kinetics of the drug in critically ill patients or by accumulation of active metabolites. In addition, paradoxical and psychotic reactions have been rarely reported. Tolerance and tachyphylaxis may occur, particularly with longer-term infusions (> or = 3 days). Benzodiazepine withdrawal syndrome has also been associated with high dose/long-term midazolam infusions. Compared with propofol infusions, midazolam infusions have been associated with a decreased occurrence of hypotension but a more variable time course for recovery of function after the cessation of the infusion. Lorazepam is a more cost-effective choice for long-term (> 24 hrs) sedation. CONCLUSION: Continuous infusion midazolam provides effective sedation in the ICU with few complications overall, especially when the dose is titrated.
The ob gene product, leptin, has been shown in several studies to be involved in weight control and recombinant leptin recently has entered clinical trials to treat obesity. The leptin receptor (OB-R/B219) is expressed in a variety of protein isoforms not only in the central nervous system, but also in reproductive, and hematopoietic tissues. We reported recently that the OB-R/B219 was associated with a variety of hematopoietic lineages as well as the small fraction of cells containing the long-term reconstituting hematopoietic stem cells. Herein we report that leptin significantly stimulates the proliferation and differentiation of yolk sac cells and fetal liver cells and stimulates directly hematopoietic precursors. Leptin alone can increase the number of macrophage and granulocyte colonies, and leptin plus erythropoietin act synergistically to increase erythroid development. These data show that leptin has a significant, direct effect on early hematopoietic development and can stimulate the differentiation of lineage-restricted precursors of the erythrocytic and myelopoietic lineages. These observations along with a recent report strongly support our previous hypothesis that leptin has an unanticipated important role in hematopoietic and immune system development.
The expression of leptin and its receptors was examined by reverse transcriptase-polymerase chain reaction and immunofluorescence in granulosa and cumulus cells of pre-ovulatory follicles and in meiotically mature oocytes obtained from women undergoing in-vitro fertilization. Leptin concentrations were measured in newly aspirated follicular fluids and in maternal serum before and after the administration of an ovulatory dose of human chorionic gonadotrophin. The findings demonstrate leptin expression at the mRNA and protein levels by granulosa and cumulus cells, and the presence of leptin in mature human oocytes. While an association between follicular leptin concentration and embryo development was not observed, a post-ovulatory increase in serum leptin concentration was associated with implantation potential. The results are discussed with respect to possible roles of leptin in early human development.
We sought to compare self-assessment of preoperative anxiety levels and selection of worst fears by surgical patients with the assessments made by the anesthesia and surgery residents providing intraoperative care for those patients. One hundred inpatients at a Veterans Affairs hospital (Group 1) and 45 patients at a University hospital (Group 2) were asked to complete a brief questionnaire; the residents were asked to complete the same questionnaire. Group 1 results showed that median patient visual analog scale (VAS) scores were lower for anxiety about anesthesia compared to surgery (16 vs 22, P < or = 0.05). Anesthesia resident VAS scores were higher than patient or surgery resident scores. Neither type of resident was able to predict their individual patient's VAS score (Kendall's tau). The fear chosen with the greatest incidence by Group 1 patients and residents was "whether surgery would work". A significant number of residents (34%, anesthesia or surgery, P < or = 0.05) matched their patient's fear choice. Residents commonly chose fears related to their specialty (e.g., anesthesia residents chose anesthesia-related fears more often than surgery residents, 50% vs 28%, P < or = 0.001). In Group 2, residents demonstrated an improved ability to predict patient scores. For instance, both surgery and anesthesia residents were able to predict individual University patient VAS scores (P < or = 0.01). The fear chosen with the greatest frequency by Group 2 patients was "pain after the operation". Sixty percent of anesthesia residents matched their patients' fear choice (P < or = 0.001). This study indicates a variable ability of anesthesia and surgery residents to predict patient anxiety and fear which may be due, in part, to difficulty in understanding a Veterans Affairs hospital patient population.
This study examined four variables (sense of control, perceived social support, degree of achievement motivation, and experienced satisfaction) hypothesized to mediate or buffer adolescents from the negative impact of academic and social stressors. The subjects were 61 high school students enrolled in a college preparatory setting with high academic standards and 63 of their parents. Students and parents were asked to rate student responses to stress that is related to both academic and nonacademic activities. Student-reported Control, Support, and Achievement Motivation were found to be strongly related to reported stress levels, although only Control and Achievement were entered in the full model of a stepwise regression analysis. Differences in the sample in terms of boarding versus day-student status, as well as differences between male and female student reports were examined.
Narrative plays a key role in medical education and knowledge, via the case history, the case presentation, or even the patient's chart. Hospitalization for elective surgery provides the structure for a discrete story in a person's life. The details make the story unique for each patient. By analyzing themes and content of narratives obtained from patients and medical trainees, the reader gains insight into the realms of patients' and residents' lives. We believe that even anesthesiologists, who work at the procedure-oriented end of the spectrum of patient care, can benefit from a narrative approach to understanding the patient's perspective. An unanticipated reward of the study is the therapeutic benefit that some of the patients express in their narratives. Patients write that they hope future patients will benefit ("Use this information to the betterment of anyone in need & etc" [patient 15]) or physicians and nurses will improve their interactive skills (patient 09). Perhaps physicians may share the rewards of narrative creation that patient 10 expresses when he triumphantly exclaims, "EUREKA!!! ... I hope you learn something from it (as I have from remembering it)." Patients can provide medical personnel not only with signs and symptoms, but also with insight into the human aspects of the medical process. Reading or writing narratives about such processes may enhance physicians' understanding of their patients' experiences.
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The biological activities of bovine growth hormone (bGH) were studied in a transgenic mouse model system. The following experimental design was used: (1) in-vitro mutagenesis of the bGH gene; (2) expression of the mutated gene in cultured mouse cells under transcriptional regulation of the mouse metallothionein I promoter; (3) binding studies of the mutated and wild-type protein to mouse liver membrane preparations; (4) generation of transgenic mice which express the mutant hormone; and (5) growth rate analysis of transgenic mice. Removal of the alanine +1 codon from the bGH gene or a substitution of serine for cysteine 189 does not affect the ability of the mutant protein to influence transgenic mouse growth. Also, mutations which increase the hydrophobicity within the bGH alpha helix 3 region (amino acid residues 109-126) do not alter the enhanced growth rate in transgenic mice which express these mutated bGH proteins.
Acute anxiety reactions have been reported following antagonism of benzodiazepine-induced sedation. In this study, the level of sedation and anxiety was assessed in 30 patients randomly assigned to receive either saline or flumazenil (a benzodiazepine antagonist) after midazolam sedation according to a double-blind protocol. Carefully titrated doses of flumazenil, 0.8 +/- 0.2 mg (mean +/- SD), effectively reversed residual midazolam-induced sedation without producing significant changes in the patients' level of anxiety. In addition, plasma epinephrine, norepinephrine, vasopressin, and beta-endorphin concentrations were measured in a subset of patients (n = 5) from each group. The levels of these stress hormones did not acutely change following flumazenil (or saline). These results indicate that flumazenil, 0.6-1.0 mg iv, can antagonize midazolam sedation without producing acute anxiety or evidence of a stress response.
The perioperative effects of administering sedative and analgesic drugs prior to outpatient surgery were evaluated. One hundred fifty adult outpatients were randomly assigned to one of six study groups according to a double-blind protocol design. Patients were given placebo (saline) or midazolam (5 mg im) 30-60 min prior to surgery, and then either placebo, oxymorphone (1 mg iv), or fentanyl (100 micrograms iv) 3-5 min prior to a standardized anesthetic technique. Preoperatively, midazolam premedication was associated with a significantly lower anxiety level (37 +/- 29 mm vs. 50 +/- 32 mm, P less than 0.05), higher sedation level (254 +/- 136 mm vs. 145 +/- 109 mm, P less than 0.01), worsening of psychomotor skill (5 +/- 5 vs. 2 +/- 2 dots missed, P less than 0.01; midazolam vs. placebo), and impaired recall abilities. In addition, use of midazolam did not prolong the discharge time. Compared to control patients, those who received fentanyl had a decreased incidence of intraoperative airway difficulties such as coughing (28% vs. 0%, P less than 0.01). Although use of opioids increased the incidence of postoperative nausea (42% vs. 18%, P less than 0.01) and vomiting (23% vs. 2%, P less than 0.01; opioid vs. no opioid), average recovery times were not affected by opioid administration. Oxymorphone use was associated with a lower incidence of pain at home compared with that following fentanyl (46% vs. 74%, P less than 0.05). Finally, preoperative administration of both midazolam and fentanyl or oxymorphone prior to a standardized methohexital-nitrous oxide anesthetic technique did not adversely affect recovery after outpatient surgery.
One hundred and twenty patients undergoing elective operations were randomly assigned to receive anesthesia with either thiopental, 4 mg/kg-isoflurane, 0.2-3%-nitrous oxide, 60-70% (control) or propofol, 2 mg/kg-propofol infusion, 1-20 mg/min-nitrous oxide, 60-70% (propofol). Although anesthetic conditions were similar during the operation, differences were noted in the recovery characteristics. For non-major (superficial) surgical procedures, the times to awakening, responsiveness, orientation, and ambulation were significantly shorter in the propofol group (4 +/- 3, 5 +/- 4, 6 +/- 4, and 104 +/- 36 min) than in the control group (8 +/- 7, 9 +/- 7, 11 +/- 9, and 142 +/- 61 min, respectively). In addition, less nausea and vomiting (20 vs. 45%) and significantly less psychomotor impairment was noted in the non-major propofol (vs. control) group. Following major abdominal operations, recovery characteristics did not differ between propofol and control groups. Delayed emergence (greater than 20 min), significant psychometric impairment, and a high overall incidence of postoperative side effects (55-60%) were noted in both drug treatment groups. The authors conclude that propofol-nitrous oxide compares favorably to thiopental-isoflurane-nitrous oxide for maintenance of anesthesia during short outpatient procedures. However, for major abdominal operations, propofol anesthesia does not appear to offer any clinically significant advantages over a standard inhalational anesthetic technique.
The pharmacokinetic and pharmacodynamic properties of propofol were studied in 50 surgical patients. Propofol was administered as a bolus dose, 2 mg/kg iv, followed by a variable-rate infusion, 0-20 mg/min, and intermittent supplemental boluses, 10-20 mg iv, as part of a general anesthetic technique that included nitrous oxide, meperidine, and muscle relaxants. For a majority of the patients (n = 30), the pharmacokinetics of propofol were best described by a two-compartment model. The propofol mean total body clearance rate was 2.09 +/- 0.65 1/min (mean +/- SD), the volume of distribution at steady state was 159 +/- 57 l, and the elimination half-life was 116 +/- 34 min. Elderly patients (patients older than 60 yr vs. those younger than 60 yr) had significantly decreased clearance rates (1.58 +/- 0.42 vs. 2.19 +/- 0.64 l/min), whereas women (vs. men) had greater clearance rates (33 +/- 8 vs. 26 +/- 7 l.kg-1.min-1) and volumes of distribution (2.50 +/- 0.81 vs. 2.05 +/- 0.65 l/kg). Patients undergoing major (intraabdominal) surgery had longer elimination half-life values (136 +/- 40 vs. 108 +/- 29 min). Patients required an average blood propofol concentration of 4.05 +/- 1.01 micrograms/ml for major surgery and 2.97 +/- 1.07 micrograms/ml for nonmajor surgery. Blood propofol concentrations at which 50% of patients (EC50) were awake and oriented after surgery were 1.07 and 0.95 microgram/ml, respectively. Psychomotor performance returned to baseline at blood propofol concentrations of 0.38-0.43 microgram/ml (EC50). This clinical study demonstrates the feasibility of performing pharmacokinetic and pharmacodynamic analyses when complex infusion and bolus regimens are used for administering iv anesthetics.