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Biomedical subjects

D L Hamilton

Publications and source records attributed to D L Hamilton.

At least 19 recordsLinked to original sources

C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation.

HIF is a transcriptional complex that plays a central role in mammalian oxygen homeostasis. Recent studies have defined posttranslational modification by prolyl hydroxylation as a key regulatory event that targets HIF-alpha subunits for proteasomal destruction via the von Hippel-Lindau ubiquitylation complex. Here, we define a conserved HIF-VHL-prolyl hydroxylase pathway in C. elegans, and use a genetic approach to identify EGL-9 as a dioxygenase that regulates HIF by prolyl hydroxylation. In mammalian cells, we show that the HIF-prolyl hydroxylases are represented by a series of isoforms bearing a conserved 2-histidine-1-carboxylate iron coordination motif at the catalytic site. Direct modulation of recombinant enzyme activity by graded hypoxia, iron chelation, and cobaltous ions mirrors the characteristics of HIF induction in vivo, fulfilling requirements for these enzymes being oxygen sensors that regulate HIF.

2,2'-Dipyridyl↗

Varieties of groups and the perception of group entitativity.

Three studies examined perceptions of the entitativity of groups. In Study 1 (U.S.) and Study 2 (Poland), participants rated a sample of 40 groups on 8 properties of groups (e.g., size, duration, group member similarity) and perceived entitativity. Participants also completed a sorting task in which they sorted the groups according to their subjective perceptions of group similarity. Correlational and regression analyses were used to determine the group properties most strongly related to entitativity. Clustering and multidimensional scaling analyses in both studies identified 4 general types of groups (intimacy groups, task groups, social categories, and loose associations). In Study 3, participants rated the properties of groups to which they personally belonged. Study 3 replicated the results of Studies 1 and 2 and demonstrated that participants most strongly valued membership in groups that were perceived as high in entitativity.

Adult↗

The concentration-dependent effects of propofol on rat ventricular myocytes.

UNLABELLED: Whether propofol contributes a direct negative inotropic effect is controversial. Our principal aim in this study was to determine whether negative inotropic effects of propofol occur at clinically relevant concentrations. We constructed the concentration-response relationship for the negative inotropic effects on intact, isolated, stimulated rat ventricular myocytes. Contraction was measured as cell shortening by using an optical system. Propofol was applied as dilutions of the commercial preparation in physiological saline solution. The drug vehicle had a minimal effect on myocyte contractility. Propofol produced a concentration-dependent reduction in evoked contraction at concentrations greater than 5 microM. The maximum effect was observed at >100 microM, with the K(0.5) calculated to be 34.5 microM (95% CI, 21.8-54.7 microM). In further experiments, we investigated the relationship between changes in contractility and changes in Ca(2+) transient (measured by using fura-2 fluorescence) after the application of propofol. By using the shift in the relationship of the cell length to fura-2 fluorescence ratio in the relaxation phase of a contraction as an index of Ca(2+) response of the myofilaments, we demonstrated that some of the negative inotropic effect of propofol may be caused by a reduction in myofilament Ca(2+) sensitivity. We confirmed this by comparing the reduction in contractility in the presence of propofol with that caused by reducing the extracellular Ca(2+) concentration. We observed that, for a decrease in the fura-2 fluorescence ratio of 21%, propofol caused a 12% (95% CI, 2% to 22%) greater reduction in contractility than predicted from reducing the extracellular Ca(2+) concentration. However, the K(0.5) for the negative inotropic effect of propofol we observed is more than 80 times the 50% effective concentration value for anesthesia. The potential relevance of these findings for clinical use of propofol in humans is discussed. IMPLICATIONS: By using intact, isolated rat heart ventricle cells, we investigated the mechanisms and concentration dependence of the depressant effect of propofol on contractility of the heart. We conclude that direct effects of propofol on the heart are unlikely to be of significance at the clinical dosage usually given.

Anesthetics, Intravenous↗

Perceiving individuals and groups: expectancies, dispositional inferences, and causal attributions.

Two experiments investigated differences in forming impressions of individual and group targets. Experiment 1 showed that when forming an impression of an individual, perceivers made more extreme trait judgments, made those judgments more quickly and with greater confidence, and recalled more information than when the impression target was a group. Experiment 2 showed that when participants were forming an impression of an individual, expectancy-inconsistent behaviors spontaneously triggered causal attributions to resolve the inconsistency; this was not the case when the impression target was a group. Results are interpreted as reflecting perceivers' a priori assumptions of unity and coherence in individual versus group targets.

Analysis of Variance↗

Anatomic, radiographic and physiologic comparisons of the internal carotid and maxillary artery in the horse.

The anatomy of the internal carotid and maxillary arteries was examined using angiography, subtraction angiography and arterial cast preparations in three horses. Subtraction angiography was superior to angiography in demonstrating the anatomy of the occipital, external ophthalmic, ethmoidal and palatine arteries. In three horses manipulation of the internal carotid and occipital arteries during angiography resulted in vasospasm which prevented filling of these vessels with contrast. Direct arterial blood pressure measurements of the maxillary artery impinging on the guttural pouches was measured in four anaesthetized and standing horses. Arterial pressure recordings from the maxillary artery indicate there is retrograde blood flow from contralateral vessels into the occluded arterial segment. Vasospasm prevented measurement of arterial pressure in the internal carotid artery.

Angiography↗

Concentration-dependent inotropic effects of halothane, isoflurane and sevoflurane on rat ventricular myocytes.

We have described the concentration-dependent inotropic effects of halothane, isoflurane and sevoflurane on rat ventricular cells and investigated the role of the sarcoplasmic reticulum (SR) in these inotropic actions. Single ventricular myocytes, isolated from rat hearts, were stimulated electrically at 1 Hz and contractions recorded optically. Cells were exposed to a range of concentrations of halothane, isoflurane or sevoflurane for a period of 1 min to determine the concentration-dependency of their inotropic actions. For each anaesthetic, the peak negative inotropic action was determined early during an exposure, and sustained negative inotropic action was measured at steady-state just before wash-off. In some experiments, cells were equilibrated with ryanodine 1 mumol litre-1 to investigate the role of the SR in these intropic effects. Halothane caused a concentration-dependent initial increase in contractions (to mean 130 (SEM 28)% at 10 mmol litre-1) followed by rapid onset of a negative inotropic effect (K0.5 0.34 mmol litre-1 for peak effect; K0.5 0.46 mmol litre-1 for sustained effect). Exposure to isoflurane induced a small potentiation of contractions in some cells, followed by a concentration-dependent decrease in contraction in all cells (K0.5 0.85 mmol litre-1 for peak effect; K0.5 1.92 mmol litre-1 for sustained effect); contractions recovered partially during a 1-min exposure. On wash-off, contractions were increased transiently above control. Sevoflurane caused a large initial decrease in contraction which then returned rapidly towards control (K0.5 0.2 mmol litre-1 for peak effect; K0.5 2.57 mmol litre-1 for sustained effect). In common with isoflurane, removal of sevoflurane caused a transient increase in contractions above control. After exposure to ryanodine, the positive inotropic effects of halothane and isoflurane did not occur, and recovery of contractions during exposure to isoflurane and sevoflurane was abolished as was the transient increase in contractions seen on wash-off, indicating that these effects were mediated via the SR. Halothane had the most potent sustained negative inotropic effect but there was little difference between the negative inotropic effects of isoflurane and sevoflurane at clinically relevant concentrations. At higher concentrations, sevoflurane caused a less potent negative inotropic effect than isoflurane. The SR plays a major role in the effects of all three anaesthetics. One possible mechanism underlying the initial potentiation of contraction by halothane (and isoflurane) may be sensitization of the Ca(2+)-induced Ca(2+)-release process of the SR.

Anesthetics, Inhalation↗

Effect of segregated early weaning on postweaning small intestinal development in pigs.

The effect of segregated early weaning (SEW) on postweaning small intestinal development was investigated in SEW and control (CON) pigs. Small intestines were collected from a total of 15 pigs killed at 11 (preweaning), 15 (3 d postweaning), and 34 d of age. At 3 d postweaning, the SEW and CON pigs had shorter villi (P<.01), deeper crypts (P<.01), and reduced (P<.01) ratios of villus height:crypt depth (V:C) compared with preweaning. Weaning also reduced specific activities of lactase (P<.01) in duodenum and ileum and alkaline phosphatase (ALP) (P<.05) in duodenum and jejunum. Sucrase activity in the three regions of the small intestine marginally decreased in both groups at 3 d postweaning. The mucosal protein:DNA ratio in duodenum and jejunum increased (P<.05) in SEW and CON pigs at 3 d postweaning compared with preweaning pigs. The SEW and CON treatments resulted in differences in postweaning gut development. At 15 d of age in SEW pigs, the mucosal protein:DNA ratio in duodenum and jejunum were 20 and 25.5% (P<.05) less, respectively, than those in CON pigs. However, at 34 d, these ratios in duodenum, jejunum, and ileum were 43.5 (P<.05), 24.3, and 32.9% (P<.05) greater, respectively, in SEW pigs than in CON pigs. Longer villi, shorter crypts (P<.01), and higher V:C ratios (P<.01) in jejunum and ileum were observed in SEW pigs vs CON pigs at 34 d of age. The specific activities of lactase in duodenum (P<.01) and jejunum (P<.05) and of ALP in duodenum (P<.01) were higher in SEW pigs. Sucrase activity in duodenum, jejunum, and ileum was 21.7, 46.3 (P<.05), and 11.2% greater in SEW pigs at 34 d of age. These results demonstrate differences in postweaning gut development between SEW and CON pigs. Furthermore, the number of intraepithelial lymphocytes in jejunum was greater (P<.001) in 34-d-old SEW pigs compared with CON pigs. Microscopy revealed a thick mucus coating over epithelial cells in the ileum of 34-d-old CON pigs that was not apparent in the SEW pigs. These observations are consistent with reduced pathogen exposure associated with SEW. We suggest that segregated early weaning advances postweaning gut maturation, which is consistent with improved growth and feed efficiency observed in SEW pigs.

Animals↗

Droperidol-ondansetron combination versus droperidol alone for postoperative control of emesis after total abdominal hysterectomy.

STUDY OBJECTIVES: To investigate the hypothesis that the combination of ondansetron and droperidol would be more effective than droperidol alone in reducing nausea and vomiting. DESIGN: Randomized, doubleblind study. SETTING: Magee-Womens Hospital, Pittsburgh, Pennsylvania. PATIENTS: 160 healthy, ASA physical status I and II, female patients scheduled for total abdominal hysterectomy. INTERVENTIONS: After induction of anesthesia with propofol, Group 1 received intravenous (i.v.) droperidol 1.25 mg plus i.v. ondansetron 4 mg. Group 2 received i.v. droperidol plus i.v. saline. MEASUREMENTS AND MAIN RESULTS: The complete response (no emesis, no rescue) for Group 1 was 36 of 80 patients (45%) versus 30 of 80 patients (38%) in Group 2 (p = 0.21). In Group 1, 42 of 80 patients (53%) required rescue antiemetic as compared with 44 of 80 patients (55%) in Group 2 (p = 0.43). There were 72 total rescues in Group 1 versus 73 in Group 2, (p = 0.24). Mean time until first rescue was 578 +/- 429 minutes in Group 1 and 418 +/- 354 minutes in Group 2, (p = 0.03). In Group 1, 81 % (34/42) were rescued for nausea only versus 90% (39/44) of Group 2 (p = 0.16). In Group 1, 21% of patients (17/80) had at least one emetic episode versus 34% (27/80) of Group 2 patients (p = 0.05). There were 31 emetic episodes in Group 1 versus 72 episodes in Group 2. (p = 0.02). Mean time to the first emetic episode was 699 +/- 403 minutes in Group 1 and 616 +/- 376 minutes in Group 2, (p = 0.23). CONCLUSION: For patients undergoing total abdominal hysterectomies, the addition of ondansetron to droperidol increases the time until first rescue and reduces the number of emetic episodes, as well as the percentage of patients, having at least one emetic episode.

Adult↗

Haemopericardium: a rare fatal complication of attempted subclavian vein cannulation. A report of two cases.

This paper describes two otherwise unrelated cases of fatal haemopericardium resulting directly from attempted cannulation of the right subclavian vein. Although this is an extremely rare complication, it is essential that all physicians involved in establishing central venous access are aware of the danger of causing this condition, and how the use of a careful technique of insertion can minimize the risk.

Adult↗

Tick bite anaphylaxis in Australia.

Tick bite anaphylaxis has rarely been reported. It may follow the bite of any of the different tick life cycle forms, is related to the release of salivary juices, and may range from mild itch to severe wheeze or shock. Data obtained suggest that it is more common and potentially life threatening than tick paralysis, which is more widely reported. Emergency physicians should recognise this possibility following a tick bite and be prepared to give treatment such as adrenaline rapidly. Patients should be referred to an allergist after recovery.

Adolescent↗

Effect of propofol for induction and ondansetron with or without dexamethasone for the prevention of nausea and vomiting after major gynecologic surgery.

STUDY OBJECTIVES: To test the hypothesis that for major gynecologic surgery the combination of propofol for induction, ondansetron, and dexamethasone would be a more effective antiemetic combination than propofol for induction, ondansetron, and saline; and to determine if a propofol induction of anesthesia improved our previously reported results when thiamylal was the induction drug. DESIGN: Double-blind, randomized study. SETTING: Magee-Womens Hospital, Pittsburgh, Pennsylvania. PATIENTS: 80 healthy ASA physical status I, II, and III female inpatients scheduled for major gynecologic surgery. INTERVENTIONS: After induction of anesthesia with propofol, Group 1 received intravenous (IV) ondansetron 4 mg and saline, and Group 2 received IV ondansetron 4 mg followed by IV dexamethasone 20 mg. MEASUREMENTS AND MAIN RESULTS: For Group 1 and Group 2, respectively, no emesis and no rescue occurred in 15 (37.5%) and 21 (52.5%) patients (p = 0.13); emesis occurred in 7 (17.5%) Group 1 patients and 5 (12.5%) Group 2 patients, rescue antiemetic 23 (57.5%) Group 1 patients and 19 (47.5%) Group 2 patients. Nausea was reported by 31 (77.5%) Group 1 patients and 30 (75%) Group 2 patients. CONCLUSIONS: The hypothesis that the addition of dexamethasone to the propofolondansetron combination would significantly reduce postoperative nausea and vomiting (PONV) was not confirmed. A propofol induction of anesthesia resulted in a comparable incidence of PONV when compared with our previously reported results using thiamylal for induction of anesthesia for women having major gynecologic operations.

Adolescent↗

Target entitativity: implications for information processing about individual and group targets.

It is hypothesized that perceptions of entitativity (i.e., seeing social targets as possessing unity and coherence) have important implications for how one organizes information about, and forms impressions of, individual and group targets. When perceivers expect entitativity, they should form an integrated impression of the target, resulting in on-line judgments. However, when perceivers expect little entitativity, they should not process target-relevant information in an integrative fashion, resulting in memory-based judgments. Although many factors affect perceptions of entitativity, the current study focused on expectations of similarity and behavioral consistency. It was predicted that in general, perceivers expect greater entitativity for individual than group targets. However, when explicitly provided with similar expectancies of entitativity, information processing would be similar for both individual and group targets. Two experiments supported these predictions, using recall, memory-judgment correlation, and illusory correlation measures.

Adult↗

Resolving the apparent discrepancy between the incongruency effect and the expectancy-based illusory correlation effect: the TRAP model.

The incongruency effect and the expectancy-based illusory correlation effect seem contradictory because they describe apparently contrasting consequences of previously held expectancies: better recall of incongruent than congruent items but overestimation of congruent items. This article resolves this dilemma by presenting a model that is able to simultaneously predict both of these effects. The Twofold Retrieval by Associative Pathways (TRAP) model adopts the encoding assumptions of person memory models but distinguishes between two different retrieval processes, exhaustive and heuristic, hypothesized to underlie recall and frequency estimation, respectively. Experiment 1 showed that expectancy-based illusory correlation effects and incongruency effects are compatible in that they were produced simultaneously. Experiments 2 and 3 tested and rejected alternative explanations for the obtained pattern of results.

Adult↗

Perceiving persons and groups.

This article analyzes the similarities and differences in forming impressions of individuals and in developing conceptions of groups. In both cases, the perceiver develops a mental conception of the target (individual or group) on the basis of available information and uses that information to make judgments about that person or group. However, a review of existing evidence reveals differences in the outcomes of impressions formed of individual and group targets, even when those impressions are based on the very same behavioral information. A model is proposed to account for these differences. The model emphasizes the role of differing expectancies of unity and coherence in individual and group targets, which in turn engage different mechanisms for processing information and making judgments. Implications of the model are discussed.

Ego↗

Droperidol/ondansetron combination controls nausea and vomiting after tubal banding.

The antiemetic activity of droperidol is attributed to antagonizing the dopaminergic neurons of the chemoreceptor trigger zone. Ondansetron is a serotonin (5HT) receptor antagonist at both peripheral and central 5-HT3 receptor sites with no known action on dopamine-mediated activity. We hypothesized that the combination of these two antiemetics would be more effective than droperidol alone. Women with ASA classified physical status I or II, scheduled for laparoscopic tubal banding, participated in a randomized double-blind clinical trial using a standardized anesthesia regimen. Within 15 min after induction of anesthesia, Group 1 (n = 60) received IV droperidol 1.25 mg and ondansetron 4 mg and Group 2 (n = 60) received IV droperidol 1.25 mg and saline. Before surgery and during recovery at 1, 2, and 24 h, emetic episodes, nausea, pain, drowsiness, medications taken, and adverse events were recorded. The complete response (no emesis, no rescue) for Group 1 was 55 of 60 (91.6%) versus 47 of 60 (78.3%) in Group 2 (P = 0.04). No patient needed rescue antiemetic medication in Group 1, whereas 5 of 60 (8.3%) patients were rescued in Group 2 (P = 0.03). There were seven emetic episodes in five patients in Group 1 and 30 emetic episodes in 12 patients in Group 2 over the 24-h study period (P = 0.03). The time to the first emetic episode was more than twice as long for Group 1 than Group 2 (P = 0.03) and total nausea scores were lower in Group 1 than Group 2 (P = 0.01). The droperidol/ondansetron combination was significantly superior to droperidol in complete response, time to and number of emetic episodes, and the incidence and severity of nausea in women having tubal banding.

Antiemetics↗

Self-stereotyping and social context: the effects of relative in-group size and in-group status.

In 2 laboratory experiments, the tendency to stereotype oneself in terms of one's group membership as a function of the social context was examined. Experiment 1 examined the effects of relative in-group size on self-stereotyping. The results confirmed the prediction that minority members are more likely than majority members to stereotype themselves. Experiment 2 examined the interactive impact of relative in-group size and in-group status. As predicted, a high (relative to a low) status of the in-group increased self-stereotyping primarily for minority members, but not for majority members. Moreover, analyses of the differences in perceived in-group and out-group homogeneity suggest that the in-group homogeneity effect should also be interpreted in terms of self-stereotyping processes. Finally, the interplay between cognitive and motivational determinants of self-stereotyping is discussed as well as a possible distinction between self-stereotyping effects on individual level versus group level self-representations.

Adult↗