Colon cancer in a 16-year-old girl.
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Adenomatous Polyposis Coli↗
Biomedical subjects
M Thompson
Publications and source records attributed to M Thompson.
Chicken beta B1 crystallin: gene sequence and evidence for functional conservation of promoter activity between chicken and mouse.
The complete sequence was determined for the chicken beta B1-crystallin gene and 2.2 kbp of its 5' flanking region; the chicken gene was then compared to its rat ortholog. Although both have a 5' non-coding exon followed by 5 protein coding exons, the chicken gene is only 2.2 kbp while the rat gene is 13.6 kpb due to longer introns. The coding exons of the chicken beta B1-crystallin gene, like those of the rat and other beta-crystallin genes, each correspond to one of the four 'Greek key' motifs of the encoded protein. The only obvious similarity between the 5' flanking sequences of the chicken and rat beta B1-crystallin gene is associated with the TATA box. A CR1 repetitive element is present at positions -559 to -730 of the chicken beta B1-crystallin gene. In vivo footprinting using dimethyl sulfate/ligation mediated PCR showed that the PL-1 (-116/-102), PL-2 (-90/-76), OL-2 (-75/-68) and OL-1 (-125/-118) control elements identified previously (Roth et al. (1991) Mol. Cell. Biol. 11, 1488-1499) bind proteins within the chromatin of cultured embryonic chicken lens cells. Both -2448/+30 and -434/+30 promoter fragments from the chicken beta B1-crystallin gene directed lens-specific CAT gene expression in a copy number and position independent manner in transgenic mice. These data indicate that the structure and lens-specific expression of this gene are highly conserved although, like other crystallin genes, the 5' flanking sequences have diverged appreciably during evolution.
Amino Acid Sequence↗
Platinum anticancer drug binding to DNA detected by thickness-shear-mode acoustic wave sensor.
Nucleic acid has been attached to the electrodes of thickness-shear-mode acoustic wave devices to produce a biosensor for platinum-based drugs. The decreases in series resonant frequency for interactions of DNA with both cis- and transplatin are indicative of two distinct kinetic processes. The results of a kinetic analysis are interpreted in terms of nucleic acid binding of the hydrolysis products of the two drugs. Concentration-dependent decreases of series resonant frequency show that the limit of detection for the drugs is approximately 10(-7) M. Motional resistance changes for nucleic acid-drug interactions also convey information regarding the chemistry of the macromolecules at the interface.
Animals↗
Progressive hippocampal loss of immunoreactive GLUT3, the neuron-specific glucose transporter, after global forebrain ischemia in the rat.
Brain damage after global forebrain ischemia is worsened by prior hyperglycemia and ameliorated by antecedent hypoglycemia. To assess whether GLUT3, the neuron specific glucose transporter and its mRNA, are affected by cerebral ischemia, we investigated the hippocampal pattern of GLUT3 immunoreactivity and GLUT3 gene expression 1, 4 and 7 days after global forebrain ischemia in a rat 2-vessel occlusion model. We used a newly generated, specific, C-terminally directed polyclonal antiserum against GLUT3 to stain coronal frozen sections. Thionin staining and the microglial marker, OX42, indicated the extent of ischemic damage in hippocampus and correlated with GLUT3 loss. One day after ischemia, no significant change in hippocampal GLUT3 immunoreactivity was observed; by 4 days however, there was consistent and pronounced loss; and at 7 days the loss of GLUT3 staining was maximal. The greatest loss of GLUT3 staining was in the CA1 region, especially the strata oriens and radiatum of Ammon's horn. By contrast, GLUT3 staining was undiminished in the stratum lacunosum moleculare, in the mossy fibers of the lateral aspect of CA3 and in all but the inner-most portion of the molecular layer of the dentate gyrus, immediately adjacent to the granule cells. GLUT3 mRNA levels were not significantly altered at 24 hours and significantly declined at 4 and 7 days after ischemia in the CA1 pyramidal layer. These data are consistent with the pattern of neuronal loss and microglial activation in hippocampus. Loss of GLUT3 may affect the availability of glucose, and possibly the viability of ischemically damaged neurons.
Animals↗
Selective coagulation necrosis of canine adventitia and media induces extracellular matrix accumulation without neointima formation.
Endothelial cell injury, the disruption of the internal elastic membrane and medial damage represent important stimuli for the development of a neointima. It is unclear whether selective adventitial and medial injury also induce neointima formation. Incremental argon laser energies (11.4-180 J/cm2) were applied to the external surface of dog femoral arteries to evaluate the vascular repair of acute adventitial or medial necrosis without injury of the intima. The animals were sacrificed either one hour after the initial procedure or after an 8 week follow up period for histologic examination. Acute, and mild to moderate necrosis of the arterial wall was found above 50 J/cm2. Ablation of the internal elastic membrane or mural thrombi was not detected. Eight weeks after photocoagulation with laser energies above 50 J/cm2, a significant increase in mean wall thickness of the media was observed. The medial thickening was characterised by an accumulation of extracellular matrix and a loss of smooth muscle cells. Necrosis of adventitia and media resulted in arterial wall thickening without neointima formation. It is concluded that, in dogs, an acute, selective injury of adventitia and media stimulates the production of extracellular matrix and not the proliferation of cells. Smooth muscle cell migration and subsequently neointima formation are induced by viable smooth muscle cells when blood-borne stimuli are available.
Analysis of Variance↗
Computerized three-dimensional activation mapping study of spontaneous ventricular arrhythmias during acute myocardial ischemia in dogs. Evidence against macroreentrant mechanism.
This study was undertaken to investigate the activation patterns of spontaneous ventricular arrhythmias during acute myocardial ischemia in dogs. In 14 open-chest dogs, the left anterior descending coronary artery was occluded for 2 hours. Three-dimensional activation maps were derived from 240 bipolar sites by insertion of 60 plunge needle electrodes into both ventricles and the septum. Global ventricular activation sequences were displayed in five planes in 10 dogs, whereas the high density regional activation maps of the anterior wall were displayed in four layers in 4 dogs. Three-dimensional activation maps of 95 sinus beats, 82 premature ventricular complexes (PVCs), and 210 beats of ventricular tachycardia (VT) were analyzed. Sinus beats had a uniform activation pattern with total ventricular activation times measuring 42 +/- 4 ms and 67 +/- 8 ms during baseline and ischemia, respectively (P < .05). The PVCs and VTs originated from the subendocardial and intramural layers, and activation patterns invariably suggested focal excitation. Macroeentry was not operative because (1) the breakthrough sites were always remote from the latest activation areas; (2) there was no electrical activity bridging the gap between the termination of a beat and initiation of the subsequent beat; and (3) impulse conduction was not sufficiently delayed to reexcite the area of impulse origin even though functional conduction block was frequently present. In high-density regional activation maps, fragmented activity spanning the diastolic interval was never found. In conclusion, spontaneously occurring PVCs and VTs during acute myocardial ischemia in dogs display focal excitation with no evidence of macroreentry.
Animals↗
The changing workload of a surgical unit with a vascular interest.
OBJECTIVES: To examine the changing relationship between general and vascular surgical workload on a vascular "firm", over a 6-year period. DESIGN: Retrospective review. SETTING: Leicester Royal Infirmary and Professorial Surgical Unit, U.K. 1987-1992. METHOD: Analysis of audit of all surgical admissions. Relation of vascular surgery to general surgery. RESULTS: There has been a slight decrease (5%) in the number of general surgical elective admissions. Overall, the number of general surgical admissions, both elective and emergency, show a slight increase of about 3%. In contrast the number of vascular admissions increased by 42%. Of the general surgical procedures carried out 75.9% were either minor or intermediate, whereas 92.5% of vascular procedures were coded as major or higher. There has been a three times increase in the number of carotid endarterectomies, a similar increase in the number of the femorodistal bypass grafts and a halving of the number of major amputations. There has also been a five times increase in the number of angioplasties carried out. CONCLUSIONS: Our figures show the progressive, rapid increase in vascular surgical workload, compared to general surgery, and the need for the continued expansion of vascular surgery as a speciality.
Abdominal Pain↗
Myocardial temperatures during in vivo endocardial Nd:YAG laser irradiation.
To determine safety and efficacy of neodymium:YAG laser irradiation of the endocardium, temperatures at both the epicardium and the endocardium were recorded for thermal damage evaluation. A total of 48 coagulation lesions were created at power settings of 20 and 30 W in 20 open chest dogs by transcatheter endocardial laser irradiation. Tissue temperatures were monitored by epicardial thermography (Tepi), and by endocardial thermocouples at the catheter tip (Tprox) and 4 mm below the endocardial surface (Tdist). In group I the optical fiber extended 1 mm from the catheter and irradiation times ranged from 3 to 60 sec. Tepi reached > or = 57 degrees after a weighted average of 5 sec of laser irradiation (n = 44). In group II the fiber was retracted 1 mm from the catheter tip, and irradiation times were 100 to 150 sec. Tepi reached > or = 57 degrees C after a weighted average of 30 sec (n = 4). Blood vessels were recognized as heat sinks until coagulation occurred. Lesion volume showed a proportional increase with total delivered energy. From the observed timeframes in epicardial temperature rise it is suggested that total direct light absorption at the epicardium was the main contribution to Tepi, and the Nd:YAG laser can efficiently create transmural lesions. The epicardial temperatures remained below 80 degrees C in combination with the constant movement of the epicardial wall suggested safety from thermal damage to the ambient organs.
Animals↗
Need for more career counseling.
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Career Choice↗
Responses to endothelins-1, -2, and -3 and sarafotoxin 6c after ischemia/reperfusion in isolated perfused rat heart: role of vasodilator loss.
Coronary constrictor actions of endothelin-1 (ET-1) are enhanced after myocardial ischemia/reperfusion (I/R), possibly owing to enhanced ETA-receptor-mediated constriction and/or loss of the opposing ETB-receptor-mediated vasodilatation. We examined the actions of ET-1, ET-2, and ET-3 and the selective ETB-receptor agonist sarafotoxin 6c (Sx6c) after I/R in perfused rat heart. To examine the effects of a loss of ETB-receptor-mediated vasodilatation on coronary constrictor responses to ET-1, we used repeated doses of Sx6c to desensitize ETB receptors. After I/R, the coronary constrictor effects of all three ETs were enhanced, whereas their initial vasodilator effects were inhibited. The pure coronary dilator effect of Sx6c observed in control hearts was also inhibited after I/R. After desensitization of ETB receptors, the coronary constrictor action of ET-1 was enhanced by an amount equivalent to the vasodilatation that had been lost. This enhancement of constriction was not as marked as that noted after I/R, suggesting that the enhanced coronary constrictor action of ET-1 after I/R is not simply due to loss of opposing ETB-receptor-mediated vasodilatation and that other mechanisms are involved. The most likely explanation is upregulation of functional ETA receptors after I/R because ETB-receptor stimulation did not cause coronary constriction in this preparation. The vasoconstrictor enhancement therefore is likely to be the combined effect of receptor upregulation and vasodilator loss.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Building an empowered work team.
A work team taps into each member's unique talents, which allows valuable skills to be shared across medical units. As a result, continuous quality improvement efforts were more objective and systematic; leadership skills were gained, both individually and jointly. The obstacles encountered, stakeholders' responses and the team's productivity analysis are described.
Humans↗
Modafinil, d-amphetamine and placebo during 64 hours of sustained mental work. I. Effects on mood, fatigue, cognitive performance and body temperature.
Modafinil is an alerting substance that is considered safer than amphetamine with fewer side effects. Although modafinil has been used successfully to treat narcolepsy, relatively little is known about its ability to ameliorate fatigue and declines in mental performance due to sleep deprivation (SD) in a normal population. Forty-one military subjects received either 300 mg of modafinil, 20 mg of d-amphetamine, or placebo on 3 separate occasions during 64 hours of continuous cognitive work and sleep loss. Three drug treatments were given: at 23.30 hours and 05.30 hours during the first and second SD nights, respectively, and once at 15.30 hours during the third day of continuous work. Subjective estimates of mood, fatigue and sleepiness, as well as objective measures of reaction time, logical reasoning and short-term memory clearly showed better performance with both modafinil and amphetamine relative to placebo. Both modafinil and amphetamine maintained or increased body temperature compared to the natural circadian cycle observed in the placebo group. Also, from subject debriefs at the end of the study, modafinil elicited fewer side-effects than amphetamine, although more than the placebo group. Modafinil appears to be a good alternative to amphetamine for counteracting the debilitating mood and cognitive effects of sleep loss during sustained operations.
Journal Article↗
Cold dry air-induced rhinitis: effect of inhalation and exhalation through the nose.
Ten subjects with a history of cold air-induced nasal symptoms participated in a randomized two-period crossover study to evaluate the occurrence and magnitude of the reaction induced by inhalation and exhalation of cold dry air through the nose. The protocol involved breathing of either warm moist or cold dry air for 45 min at resting breathing rates. The nasal response was quantified by determining the amount of produced secretions as well as by measuring histamine and N-alpha-p-tosyl-L-arginine methyl (TAME) esterase activities in recovered nasal lavage fluids. Symptom scores were obtained. Warm moist air did not increase symptoms nor did it result in any significant changes in secretions or mediator levels. Compared with baseline, cold dry air induced significant rhinorrhea and increased both secretion weights (9.6 +/- 1.3 vs. 28.1 +/- 6.5 mg; P = 0.01) and the levels of histamine (3.9 +/- 1.2 vs. 10.6 +/- 2.7 ng/ml; P = 0.02) and TAME esterase activity (3.1 +/- 0.8 vs. 7.0 +/- 2.0 counts.min-1.10(-3); P = 0.01). We conclude that bidirectional nasal breathing of cold dry air results in a reaction that is qualitatively similar to that induced when air is only inhaled through the nose and exhaled through the mouth.
Adult↗
Psychological sequelae of torture and trauma in Chilean and Salvadorean migrants: a pilot study.
Torture has existed since the earliest times, usually as public punishment prior to death. Today it is predominantly used in secret with the aim of destroying the individual's personality. The effects of torture include severe physical and psychological sequelae which have only recently come under scrutiny. In recent years many Chilean and El Salvadorean migrants have left their countries after being tortured and severely traumatised as a result of organised violence. The aim of this study was to pilot an investigation into the psychological sequelae of torture. Subjects were 30 Chileans and El Salvadoreans classified into three groups: torture, trauma and non-torture/trauma migrants. It was found to be feasible to access and interview survivors from a clinical research perspective without causing additional psychological morbidity. The subjects were interviewed and administered three scales: the Post-Traumatic Stress Disorder Scale, SCL-90-R, and the Impact of Event Scale. The results from the scales and the descriptive data presented indicate some support for the hypothesis that torture survivors show higher levels of PTSD, psychosomatic impairment and stress response disturbance than the trauma and non-torture/trauma groups. Methodological issues are discussed. The strengths and limitations of this preliminary study are considered in relation to future research.
Adult↗
A comparative study of genetic variation at five VNTR loci in three ethnic groups of Houston, Texas.
Following the technique of Southern blot restriction fragment length polymorphisms (RFLP) analysis, we generated a database of DNA profiles at five Variable Number of Tandem Repeats loci (D1S7, D2S44, D4S139, D10S28, and D17S79) for 669 individuals of three major ethnic populations (Caucasians, Blacks, and Hispanics) of Houston, Texas. Analysis of fragment sizes at these loci within each sample, as well as their fixed-bin analyses, reveal that the assumptions of independence of allelic occurrences within and between loci are valid for this database. Fixed-bin allele frequency tables, therefore, are the best descriptors of this database for conservative forensic calculations. Finally, we demonstrate that this regional database from Houston, Texas, does not yield any meaningfully different forensic inference than the one obtained from the National database of the respective ethnic groups.
Alleles↗
Comparison of nuclear area measurements carried out on normal and dysplastic oral smears.
We previously showed that quantitative cytology can help to detect oral cancer, not only at initial presentation but also in patients with unstable mucosa in whom recurrence has been detected prior to detection of a clinically obvious cancer. This has been due principally to the presence of a reduction in cytoplasmic area for Papanicolaou-stained cells and abnormal DNA distributions in Feulgen-stained nuclei collected from histologically confirmed dysplastic lesions. Furthermore, Feulgen-stained nuclei in oral smears that display abnormal DNA profiles appear to be larger than those in clinically normal smears, although an increase in nuclear area (NA) in Papanicolaou-stained smears is not always apparent. The aims of this study were to compare the mean NA values recorded for cells in Feulgen-stained smears with the values recorded for cells in Papanicolaou-stained smears collected from a selection of normal and abnormal sites to determine which of these smears produced mean NA values that correlated most closely with their DNA distributions. Forty patients with histologically confirmed epithelial dysplasia or invasive carcinoma and 20 patients with clinically normal mucosa were included in the study. NA values were obtained using image analysis. The mean NA values were obtained from the Feulgen-stained smears were significantly elevated when compared with mean NA values obtained from Papanicolaou-stained smears of dysplastic lesions and invasive carcinoma and for clinically normal smears collected from these patients. This elevation in mean nuclear size, for Feulgen-stained smears, correlated closely with DNA distribution.
Cell Nucleus↗
Low-molecular-weight heparin versus aspirin and dipyridamole after femoropopliteal bypass grafting.
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Anastomosis, Surgical↗
Didanosine compared with continuation of zidovudine in HIV-infected patients with signs of clinical deterioration while receiving zidovudine. A randomized, double-blind clinical trial. The Bristol-Myers Squibb AI454-010 Study Group.
OBJECTIVE: To determine the benefits of switching to didanosine compared with continuing zidovudine among patients infected with human immunodeficiency virus (HIV) who have previously used zidovudine and have signs of clinical deterioration. DESIGN: Randomized, double-blind, two-armed, parallel, comparative clinical trial with a blinded, compassionate crossover provision at 12 weeks. SETTING: Outpatient clinics at 19 tertiary care medical centers. PATIENTS: 312 patients infected with HIV who had received zidovudine for 6 months or more, had CD4 cell counts of 300/mm3 or less, and had signs of clinical deterioration within 12 weeks before study entry. INTERVENTION: Peroral didanosine tablets (600 mg/d adjusted for weight, "high dose") or zidovudine capsules (600 mg/d). MEASUREMENTS: Primary study end points were death, a new acquired immunodeficiency syndrome (AIDS)--defining event, or the combination of two new or recurrent HIV-related diagnoses with a 50% decrease in CD4 cells. RESULTS: Switching to didanosine was associated with fewer end points than continuing zidovudine (relative risk [RR] for zidovudine:didanosine = 1.5; 95% Cl, 1.1 to 2.0). This benefit was consistent across subgroups of patients with either AIDS-related complex or AIDS and was most apparent among those with a CD4 count at entry of 100/mm3 or more (RR = 2.2; Cl, 1.1 to 4.4). CONCLUSIONS: This study shows a positive treatment effect for switching from zidovudine to didanosine among patients with either AIDS-related complex or AIDS and validates the common practice of using clinical signs or a decrease in the CD4 count as an indication for changing therapy.
AIDS-Related Complex↗