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Biomedical subjects

S T Smith

Publications and source records attributed to S T Smith.

At least 37 records · Page 2Linked to original sources

Detection of numerical chromosome anomalies in interphase cells of ovarian carcinomas using fluorescence in situ hybridization.

Fluorescence in situ hybridization was used in interphase cells of 30 ovarian carcinomas to detect numerical changes in copy number of 13 different centromeres (1, 2, 3, 4, 6, 7, 8, 10, 11, 12, 17, 18, and X). Thirty-seven percent of samples (11/30) were near diploid and demonstrated only minor changes in centromere copy number, involving gain and/or loss of one or a few centromeres. The most common changes included loss of centromeres 4,6, 17, and 18 and gain of centromere 1. The remaining 63% of samples were hyperdiploid and demonstrated a general increase in copy number of most or all centromeres examined. Among these samples, the centromere of chromosome I was most often found to be at higher copy number. Centromeres that were less often at increased copy or deleted within the hyperdiploid samples include centromeres 4, 17, 18, and X. These results suggest that tumor-suppressor genes that are located on chromosomes 4, 6, 17, and 18 may be involved in the development and progression of ovarian cancer.

Adult↗

ERBB2 and chromosome 17 centromere studies of ovarian cancer by fluorescence in situ hybridization.

More than 26,000 new cases of ovarian cancer are identified each year in the United States, with almost 75% of these malignancies in advanced stages at the time of diagnosis. Early-stage disease has a cure rate of up to 90%, but the long-term survival rate of patients with advanced disease is 5-20%. At this time, there are no biomarkers that are effective indicators of early ovarian cancer. Recently, immunohistochemical and Southern blot studies have suggested that overexpression/amplification of the oncogene ERBB2 (HER2/neu) is associated with aggressive ovarian malignancies; however, some studies have not supported this conclusion. Because tumor cells are known to be highly heterogeneous, we used fluorescence in situ hybridization (FISH) to study individual ovarian cancer cells for HER2/neu amplification and chromosome 17 centromere copy number. Simultaneous multicolor cohybridization of HER2/neu and chromosome 17 centromere alpha-satellite probes were carried out on 43 ovarian cancer samples. Ten of the forty-three samples showed moderate to high amplification of HER2/neu, with varying numbers of chromosome 17 centromeres present. In some cells the amplified HER2/neu was dispersed throughout the nucleus, whereas in other cells the amplified oncogenes were clustered together. Within a sample there was heterogeneity in oncogene and centromere copy number. In this small study, we were unable to identify a specific clinical correlation. However, FISH is a powerful method for the study of oncogene amplification in tumor samples.

Adult↗

A geometric basis for measurement of three-dimensional eye position using image processing.

Polar cross correlation is commonly used for determination of ocular torsion from video images, but breaks down at eccentric positions if the spherical geometry of the eye is not considered. We have extended this method to allow three-dimensional eye position measurement over a range of +/- 20 deg by determining the correct projection of the eye onto the image plane of the camera. We also determine the orientation of the camera with respect to the eye, allowing eye position to be represented in appropriate head-fixed coordinates. These algorithms have been validated using both in vitro and in vivo measures of eye position.

Algorithms↗

"Inadvertent" thrombolytic administration in patients without myocardial infarction: clinical features and outcome.

STUDY OBJECTIVES: Increasing pressure to deliver thrombolytic agents quickly to patients with suspected myocardial infarction (MI), along with expanded indications, may contribute to inappropriate administration of these agents, with potentially catastrophic results. We sought to identify the extent to which MI is ruled out in patients given thrombolytic therapy for acute MI and to characterize the clinical course and outcome in such patents. METHODS: We studied 609 consecutive patients admitted to the CCU of an urban teaching hospital who were treated with thrombolytic agents for suspected acute MI between January 1986 and December 1993. In 35 (5.7%), MI was ruled out on the basis of persistently normal serum creatine kinase-MB isoenzyme levels. Hospital course and alternative diagnoses were established by means of chart review and database inquiry. RESULTS: Patients in whom MI was ruled out were similar to those with MI with regard to baseline demographic and clinical features. Presenting ECGs in patients without MI were less likely to show Q waves (43 versus 64%, P < .02) but more likely to show left ventricular hypertrophy (26 versus 7%, P = .001) and nonspecific ST-segment and T-wave changes (54 versus 32%, P < .01) compared the ECGs of MI patients. Transient ST-segment elevation was detected in 51%. Hospital complications of patients without MI were similar to those of MI patients. No patient in whom MI was ruled out sustained a major hemorrhage. Final diagnoses of patients without MI included unstable angina (n = 20, 57%) undefined chest pain (n = 8, 17%) pericarditis (n = 3), pancreatitis (n = 2), esophagitis (n = 1), and aortic dissection (n = 1). Two patients died, one of aortic dissection and another of pericarditis. CONCLUSION: In a consecutive series of CCU patients in whom MI was ruled after thrombolysis, we found no demographic or presenting clinical features to distinguish them from patients in whom MI was diagnosed. Transient ST-segment elevation potentially justifying thrombolytic therapy was present in more than half of the patients in whom MI was ruled out but may have represented transient coronary occlusion, coronary spasm, or other manifestations of unstable angina. In this study, patients in whom MI was ruled out had a high incidence of coronary disease and risk of in-hospital complications similar to that of patients with acute MI. Our findings support the rationale and safety of policies to rapidly and aggressively administer thrombolytic agents in the emergency department.

Aged↗

Three-view radiographic assessment of heterotopic ossification after acetabular fracture surgery.

A random sample of 100 patients who had operative treatment for a fracture of the acetabulum, an otherwise normal appearing hip joint, and at least one year of follow-up were analyzed to assess heterotopic ossification (HO) and its relationship to hip motion. The extent of HO was graded in a blinded fashion according to the Brooker classification, which relies solely on the anteroposterior (AP) view, as well as a modified classification using three radiographic views (AP pelvis, internal, and external Judet oblique views). For each patient, range of motion of the affected hip was compared with that of the contralateral normal limb. There were 16 cases with disagreement between the two methods. As opposed to the Brooker method, the modified classification provided an accurate correlation with the actual hip range of motion.

Acetabulum↗

GABAA receptor-mediated responses in the ventromedial nucleus of the hypothalamus of female and male neonatal rats.

Perinatal exposure of the developing brain to gonadal steroids during a limited critical period induces permanent, organizational differences in neural structures between male and female animals. These differences are believed to underlie the manifestation of sexually dimorphic behaviors. Gamma-aminobutyric acid type A (GABAA) receptors expressed in the ventromedial nucleus (VMN) of the hypothalamus appear to be a key component underlying the expression of sexually dimorphic, and GABAA-mediated transmission within the VMN is critical for the expression of sexual behavior in female, but not male, rats. Here we report that analysis of VMN neurons from neonatal rats revealed significant sex-specific differences in GABAA receptor channel properties. Specifically, GABAA-mediated currents elicited by direct agonist application decayed more rapidly in VMN neurons from females than from males. Kinetic differences became more pronounced during the first 2 weeks of postnatal development. Analysis of small, spontaneous inhibitory postsynaptic currents recorded in intact slices indicated a trend towards slower responses in neurons from males than females, but the differences in decay kinetics were not significant. Sex-specific differences in GABAA receptor kinetics may arise from activation of receptors not receiving synaptic contacts in the slice preparation or may become apparent at intact synapses under conditions of increased activity and evoked release.

Adenosine Triphosphate↗

A conserved region of engrailed, shared among all en-, gsc-, Nk1-, Nk2- and msh-class homeoproteins, mediates active transcriptional repression in vivo.

The engrailed homeoprotein is a dominantly acting or 'active' transcriptional repressor both in cultured cells and in vivo. When retargeted via a homeodomain swap to the endogenous fushi tarazu gene (ftz), it actively represses it, resulting in a ftz mutant phenocopy. We have mapped functional regions of engrailed using this in vivo repression assay. In addition to a region containing an active repression domain identified in cell culture assays (K. Han and J. L. Manley (1993) EMBO J. 12, 2723-2733), we find that two evolutionarily conserved regions contribute to activity. The one of these that does not flank the HD is particularly crucial to repression activity in vivo. We find that this domain is present not only in all engrailed-class homeoproteins but also in all known members of several other classes, including goosecoid, Nk1, Nk2 and msh. Thus engrailed's active repression function in vivo is dependent on a highly conserved interaction that was established early in the evolution of the homeobox gene superfamily. We further show using rescue transgenes that the widely conserved in vivo repression domain is required for the normal function of engrailed in the embryo.

Amino Acid Sequence↗

Skeletal repair by in situ formation of the mineral phase of bone.

A process has been developed for the in situ formation of the mineral phase of bone. Inorganic calcium and phosphate sources are combined to form a paste that is surgically implanted by injection. Under physiological conditions, the material hardens in minutes concurrent with the formation of dahllite. After 12 hours, dahllite formation was nearly complete, and an ultimate compressive strength of 55 megapascals was achieved. The composition and crystal morphology of the dahllite formed are similar to those of bone. Animal studies provide evidence that the material is remodeled in vivo. A novel approach to skeletal repair is being tested in human trials for various applications; in one of the trials the new biomaterial is being percutaneously placed into acute fractures. After hardening, it serves as internal fixation to maintain proper alignment while healing occurs.

Animals↗

The human ocular torsion position response during yaw angular acceleration.

Recent results by Wearne [(1993) Ph.D. thesis] using the scleral search-coil method of measuring eye position indicate that changes in ocular torsion position (OTP) occur during yaw angular acceleration about an earth vertical axis. The present set of experiments, using an image processing method of eye movement measurement free from the possible confound of search coil slippage, demonstrates the generality and repeatability of this phenomenon and examines its possible causes. The change in torsion position is not a linear vestibulo-ocular reflex (LVOR) response to interaural linear acceleration stimulation of the otoliths, but rather the effect is dependent on the characteristics of the angular acceleration stimulus, commencing at the onset and decaying at the offset of the angular acceleration. In the experiments reported here, the magnitude of the angular acceleration stimulus was varied and the torsion position response showed corresponding variations. We consider that the change in torsion position observed during angular acceleration is most likely to be due to activity of the semicircular canals.

Acceleration↗

Gender risk for anaphylactoid reaction to radiographic contrast media.

BACKGROUND: Female predominance has been reported previously in series of anaphylaxis cases; however, no definite precedent has been established for greater risk of anaphylactoid reaction caused by contrast media infusion on the basis of gender. OBJECTIVE: This study was designed to determine whether greater risk for anaphylactoid reaction caused by intravenous contrast media infusion exists in association with female gender. METHODS: Rates of anaphylactoid and severe anaphylactoid reaction, according to gender, were determined in a sample of 5264 consecutive patients receiving conventional radiocontrast media during performance of computed tomography. RESULTS: Of 80 adverse reactions caused by contrast media infusion, 73 (1.39%) were classified as anaphylactoid in nature. Among 5191 patients who received intravenous contrast media without experiencing an anaphylactoid reaction, there were 2642 male patients (51%) and 2549 female patients (49%); reactors included 22 male patients and 51 female patients (odds ratio = 2.40, 95% confidence interval = 1.42-4.10, p < 0.0005). Female patients also comprised 21 of 22 cases of severe anaphylactoid reaction (odds ratio = 21.77, 95% confidence interval = 3.13-435.12, p < 0.0005). CONCLUSION: Greater risk for anaphylactoid and severe anaphylactoid reaction exists in association with female gender. Further studies are needed to identify mechanisms that can explain this risk. The importance of these findings for cost-effective use of lower osmolality contrast media need to be determined.

Anaphylaxis↗

Inserting the Ftz homeodomain into engrailed creates a dominant transcriptional repressor that specifically turns off Ftz target genes in vivo.

The Engrailed homeodomain protein is an 'active' or dominant transcriptional repressor in cultured cells. In contrast, the Fushi Tarazu homeodomain protein is an activator, both in cultured cells and in Drosophila embryos, where it activates several known target genes, including its own gene. This auto-activation has been shown to depend on targeting to a fushi tarazu enhancer by the Fushi Tarazu homeodomain. We combined Fushi Tarazu targeting and Engrailed active repression in a chimeric regulator, EFE. When EFE is ubiquitously expressed, it overrides endogenous Fushi Tarazu and causes a fushi tarazu mutant phenotype. Normal Fushi Tarazu target genes are affected as they are in fushi tarazu mutants. One such target gene is repressed by EFE even where Fushi Tarazu is not expressed, suggesting that the repression is active. This is confirmed by showing that the in vivo activity of EFE depends on a domain that is required for active repression in culture. A derivative that lacks this domain, while it cannot repress the endogenous fushi tarazu gene, can still reduce the activity of the fushi tarazu autoregulatory enhancer, suggesting that it competes with endogenous Fushi Tarazu for binding sites in vivo. However, this passive repression is much less effective than active repression.

Animals↗

External fixation and limited internal fixation for complex fractures of the tibial plateau.

Twenty-one complex fractures of the tibial plateau in twenty patients were treated with closed reduction, interfragmental screw fixation of the articular fragments, and application of a unilateral half-pin external fixator. The average duration of external fixation was twelve weeks (range, three to twenty weeks). The fixator was left in situ until the fracture had united in all but two patients. All of the fractures healed. The complications with this technique were attributable primarily to the proximal half-pins of the external fixator. Seven patients needed antibiotics for an infection at a pin site, and two had septic arthritis that necessitated arthrotomy and débridement. The average duration of follow-up was thirty-eight months. The range of motion of nineteen of the twenty-one knees was at least a 115-degree arc. Laxity was evident in seven knees, but no patient complained of instability of the knee. Radiographs showed malalignment of more than 6 degrees in three knees compared with the normal, contralateral knee and evidence of post-traumatic osteoarthrosis in five knees. The Iowa knee score, determined for nineteen patients, averaged 87 points (range, 55 to 100 points). The SF-36 general health survey demonstrated that most patients had function close to that of age-matched controls. We concluded that external fixation with limited internal fixation is a satisfactory technique for the treatment of selected complex fractures of the tibial plateau.

Adult↗

Effect of phonophoresis with dexamethasone on adrenal function.

One of the side effects of corticosteroid ingestion and inhalants is suppression of the adrenal glands. Phonophoresis of topically applied corticosteroids is commonly used to treat musculoskeletal inflammatory conditions. The purpose of this study was to determine whether phonophoresis with dexamethasone sodium phosphate affected adrenal function. The subjects included 28 male volunteers (mean = 25.3 years, SD = 6.4) who received phonophoresis to the left shoulder every other day for 2 weeks. Subjects were randomly assigned to one of four groups, including a control group (N = 8), an ultrasound group (N = 8), a .33% dexamethasone group (N = 7), and a ultrasound with .33% dexamethasone group (N = 5). Adrenal function was assessed by 24-hour urinary-free cortisol (microgram cortisol/g creatinine) collected two days prior to and following the phonophoresis treatments. A nonparametric analysis of variance using a split plot factorial design was calculated for ranked urinary-free cortisol scores and found no significant (p > 0.05) differences in urinary-free cortisol levels between the four groups and between the four collection days, and there were no significant (p > 0.05) interactions exhibited between group and collection day. This study suggests that phonophoresis with dexamethasone sodium phosphate, using common clinical parameters, does not cause dexamethasone sodium phosphate to become systemic in large enough quantities to impair adrenal function.

Administration, Topical↗

Elevated risk of anaphylactoid reaction from radiographic contrast media is associated with both beta-blocker exposure and cardiovascular disorders.

BACKGROUND: A case-control study, with both retrospective and concurrent subject selection, was performed (1) to determine whether greater risk for anaphylactoid reaction from contrast media associated with beta-blocker exposure reflects presence, or is independent of underlying cardiovascular disorder; and (2) to characterize further the risk of anaphylactoid reaction from contrast media in patients with cardiovascular disorders and patients with asthma. METHODS: Adverse reactions from intravenous contrast media were recorded in accordance with quality assurance guidelines. Anaphylactoid reactions were classified as mild to moderate (urticaria/angioedema), severe (stridor, bronchospasm, or hypotension), or major and life-threatening (hypotension with or without the need for subsequent hospitalization). Medical records from reactors were compared with those from matched (gender, age, date, and type of contrast study) controls who received conventional contrast media without adverse reaction. RESULTS: Of 34,371 intravenous contrast media procedures performed, 122 anaphylactoid reactions were recorded. The risk of anaphylactoid reaction was significantly associated with asthma (odds ratio [OR], 8.74; 95% confidence interval [CI], 2.36 to 32.35; P = .0012). The risk of bronchospasm was associated with beta-blocker exposure (OR, 3.73; 95% CI, 1.18 to 11.75; P = .025) and with asthma (OR, 16.39; 95% CI, 4.30 to 62.46; P = .0001). The risk of major and life-threatening reaction was associated with the presence of cardiovascular disorder (OR, 7.71; 95% CI, 1.04 to 57.23; P = .046). Among patients with severe reactions, the risk of hospitalization was elevated by the presence of cardiovascular disorder (P = .001), exposure to beta-blockers (OR, 7.67; 95% CI, 1.79 to 32.85; P = .029), or asthma (OR, 20.7; 95% CI, 1.21 to 355.55; P = .065). Although beta-blocker exposure and the presence of cardiovascular disorder were highly associated (chi 2 = 49, P < .001), a greater risk of bronchospasm with severe reaction was observed in nonasthmatic patients with cardiovascular disorders receiving beta-blockers (OR, 15.75; P = .023). Among reactors with asthma, receiving beta-blockers, or with a cardiovascular disorder, 60.8% (31/51) experienced severe anaphylactoid reactions, compared with 35.2% (25/71) of patients without these risk factors (OR, 3.62; P = .005). CONCLUSIONS: beta-Blocker exposure and cardiovascular disorder are both statistically significant risk factors for severe anaphylactoid reaction from contrast media. Thus, patients receiving beta-adrenergic blockers and patients with asthma, on the basis of greater risk for bronchospasm, and patients with cardiovascular disorders, on the basis of elevated risk of major and life-threatening reaction, are appropriate target populations for risk reduction measures before receiving intravenous infusion of contrast media.

Adrenergic beta-Antagonists↗

Social desirability of personality items as a predictor of endorsement: a cross-cultural analysis.

Earlier studies using specialized instruments confirmed a positive relation between a personality item's desirability and its endorsement outside North America, but allowed for few conclusions about the strength of the relationship in non-Western societies and offered no explanations for the observed correlations. In Study 1 of this investigation, university students from Turkey (a country rich in non-Western cultural elements) were found to be as likely as their U.S. counterparts to describe themselves in socially desirable terms. Furthermore, the strength of the relationship between desirability and endorsement did not depend on their level of exposure to the English language or to Western concepts. Study 2 indicated that socially desirable traits were also the most common among students in Turkey (paralleling results with U.S. samples), in support of desirable traits' prevalence as an explanation for the desirability-endorsement correlation.

Adult↗

Estimation of uterine volume with ultrasound in women with endometrial carcinoma.

In calculating uterine volume with ultrasound, it is necessary to calculate the volume of a parallelogram containing the uterus or to assume a specific shape for the uterus. The objective of this study was to determine how much (what percentage) of the parallelogram was actually occupied by the uterus without assuming any specific shape for the uterus. Overall, the volume of the uterus occupies 63% of the volume of the parallelogram. The uterus occupies a greater percentage of smaller parallelogram volumes than larger ones. The data also suggest that the concomitant presence of myomata may be responsible for the positive intercept of the regression line and therefore for the finding that small uteri occupy more than 63% of the parallelogram volume.

Adult↗