Use of a standardized-patient-based clinical performance examination as an outcome measure to evaluate medical school curricula.
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Biomedical subjects
Publications and source records attributed to A C Smith.
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A case of supernumerary tooth presenting in the nasal cavity is reported. The literature is reviewed for nasal and other unusual ectopic sites of tooth eruption and other possible diagnoses for calcified intranasal masses are discussed.
Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct developmental disorders caused by absence of paternal or maternal contributions of the chromosome region 15q11-q13, resulting from deletions, uniparental disomy (UPD), or rare imprinting mutations. Molecular cytogenetic diagnosis is currently performed using a combination of fluorescence in situ hybridisation (FISH), DNA polymorphism analysis, and DNA methylation analysis. Only methylation analysis will detect all three categories of PWS abnormalities, but its reliability in tissues other than peripheral blood has not been examined extensively. Therefore, we examined the methylation status at the CpG island of the small nuclear ribonucleoprotein associated polypeptide N (SNRPN) gene and at the PW71 locus using normal and abnormal lymphoblast (LB) cell lines (n = 48), amniotic fluid (AF) cell cultures (n = 25), cultured chorionic villus samples (CVS, n = 17), and fetal tissues (n = 18) by Southern blot analysis with methylation sensitive enzymes. Of these samples, 20 LB cell lines, three AF cultures, one CVS, and 15 fetal tissues had been previously diagnosed as having deletions or UPD by other molecular methods. Methylation status at SNRPN showed consistent results when compared with FISH or DNA polymorphism analysis using all cell types tested. However, the methylation pattern for PW71 was inconsistent when compared with other tests and should therefore not be used on tissues other than peripheral blood. We conclude that SNRPN, but not PW71, methylation analysis may be useful for diagnosis of PWS/AS on LB cell lines, cultured amniotic fluid, or chorionic villus samples and will allow, for the first time, prenatal diagnosis for families known to carry imprinting centre defects.
Thirty-nine Yucatan miniature swine were used in three fetal surgical experimental protocols. They involved antiarrhythmic administration, pacemaker implantation, and in-utero diagnosis of ventricular septal defect by intraoperative echocardiography. Because of problems encountered with surgical protocols in the initial stages, modifications were made to prevent fetal hypothermia and intraoperative mortality. These modifications included environmental temperature support, staple surgical techniques to reduce operative time, and development of fetal catheters designed to facilitate cannulation of small vessels. Postoperative care protocols were intensive and included antibiotics, analgesics, and supportive care designed to reduce discomfort and prevent abortion and sepsis. Thirty-seven of 39 sows survived the surgical procedures; experiments were performed on 117 fetuses. Twenty-two fetuses died either intraoperatively or postoperatively because of complications related to the experimental protocols. Modification of surgical and postsurgical protocols for these projects demonstrates the feasibility of using miniature swine as a model for fetal surgery, when their use was appropriate for anatomic and physiologic reasons.
This paper reviews the types of laser available for use in oral and maxillofacial surgery and discusses the indications, contraindications, advantages, disadvantages and potential hazards of their use. Preliminary reports of research projects into carbon dioxide laser penetration depth into mucosa and also results of treatment of a series of 20 patients with a variety of mucosal problems will be discussed.
Acute mitral regurgitation is a medical emergency that requires prompt, accurate diagnosis and urgent therapy. Although the use of echo Doppler imaging has been described in these patients, preliminary observations have suggested that color flow Doppler performed from the standard transthoracic windows may underestimate the severity of mitral insufficiency in this setting. The aim of this study was to compare transesophageal color Doppler quantitation of regurgitation with results obtained from standard transthoracic windows in patients with acute, severe mitral regurgitation. Two-dimensional echocardiography with pulsed, continuous, and color flow Doppler was performed by both transthoracic and transesophageal methods in 16 consecutive patients who were documented to have acute severe mitral insufficiency by catheterization. Transthoracic and transesophageal scans were reviewed by two blinded observers and assessed for the detection of mitral regurgitation by transthoracic pulsed wave (81%), continuous wave (100%), and color flow Doppler (81%) compared with transesophageal color flow imaging (100%; p = NS). Severity of mitral regurgitation was graded as none, mild, moderate, or severe on the basis of existing transthoracic pulsed wave and color flow criteria and compared with transesophageal color flow grading. At first examination patients were critically ill, with elevated pulmonary wedge pressures (mean 27 +/- 7 mm Hg) and V waves (mean 45 +/- 10 mm Hg). Fifteen of the patients underwent emergency surgery, and the overall hospital mortality rate was 12%. Maximal color flow jet areas were significantly greater on transesophageal scanning (mean 10.5 cm2) compared with transthoracic color jets (mean 2.3 cm2).(ABSTRACT TRUNCATED AT 250 WORDS)
The growth of colonies of Salmonella typhimurium derived from single immobilised cells was studied while subjected to constant and sinusoidally-varying temperatures. The bacteria grew in microbiological culture media adjusted to different pH and sodium chloride (NaCl) concentration and solidified with gelatin that was contained within a cassette formed between sheets of PVC film that allowed gaseous exchange. At pH 7.0 and 0.5% (w/v) NaCl and either 12 degrees C or 20 degrees C, S. typhimurium grew at a rate similar to that in liquid medium. The decrease in growth rate at 20 degrees C at a lower pH or higher NaCl concentration was greater in the case of immobilised cells than for cells in liquid medium. The change in the numbers of viable bacteria was measured with time under sinusoidally-varying temperatures between 4 and 22 degrees C and between 12 and 22 degrees C of period in the range 12 to 480 min. The experimental growth curves were compared with predictions based on isothermal growth in liquid medium. The discrepancies between experiment and prediction were greater for gels stressed by NaCl or pH than for gels at pH 7.0 and containing 0.5% (w/v) NaCl, consistent with the isothermal observations.
The effect of fluctuating temperatures on microbial growth is important in the passage of foods from production to consumption. Suspensions of Salmonella typhimurium have been subjected to sinusoidally time-varying temperatures of periods from 60 to 240 min between 4 degrees and 22 degrees C, that is within and below the growth temperature range. The suspensions were prepared with two concentrations of sodium chloride and adjusted to two different values of pH. The change in the numbers of viable bacteria was measured with time and the experimental growth curves and average generation times compared with predictions based on isothermal growth data. Generally, the experimental average generation times exceeded the predictions by not more than 10%. In enumerating viable bacteria in the suspensions containing 3.5% (w/v) sodium chloride it was necessary to use sodium chloride in the diluent and recovery medium in order to recover the bacteria quantitatively.
Water activity is a method of preservation that can affect microbial growth in foods and that may fluctuate during their processing, distribution and storage. Sucrose has been used to change the water activity of microbiological culture media. Suspensions of Salmonella typhimurium LT2 in the exponential phase of growth have been subjected to step changes in sucrose concentration at 20 degrees C. The changes in the numbers of viable bacteria were measured with time and the experimental growth curves compared with predictions based on growth data obtained at constant sucrose concentrations. Steps down in sucrose concentration showed some apparent loss of viability after the step followed by growth at a rate close to the expected value. Steps up in sucrose concentration resulted in a greater apparent loss of viability after the step and either growth or the inducement of lag, depending on the final concentration of sucrose. A series of small steps up in sucrose concentration to 45% (w/v) was able to sustain growth where it was not possible by inoculation directly into this concentration. Improved recovery of bacteria subject to osmotic stress was possible with a medium containing sodium chloride.
PURPOSE: To evaluate the acute hemodynamic effects of ibopamine (IBO), captopril (CAP) and placebo (PLA) in patients with severe congestive heart failure at rest. METHODS: Twelve male patients in sinus rhythm with dilated cardiomyopathy and NYHA class IV were studied with Swan-Ganz hemodynamics. Drugs were given in a blinded fashion. Rest, 30 min and every hour for 5 h measurements were made after oral ingestion of 100 mg IBO, 25 mg CAP or PLA. Prior to the study, patients were on diuretics as the only medication for at least 48 h. Comparisons were made with analysis of variance of repeated measurements and Duncan's multiple comparisons procedure. RESULTS: Significant increase in cardiac index and stroke volume index and reduction in systemic vascular resistance were observed with IBO and CAP for 2 h after ingestion. IBO however increased right and left filling pressures in the first hour after its administration. Ventricular tachycardia occurred in 2 patients 1 h after IBO administration. CONCLUSION: Both IBO and CAP improved hemodynamic parameters in the first two hours after oral ingestion in patients with dilated cardiomyopathy in class IV.
We are currently developing fetal models of congenital heart disease in Yucatan miniature swine for pharmacologic, diagnostic, and interventional methods used to treat cardiac arrhythmias and ventricular septal defect. Fifty-four fetuses from 12 pregnant sows were included in this study. Eleven were fetuses between 76 and 88 days of gestation (early gestation fetuses). A second population of 43 fetuses were between 96 and 110 days of gestation (late gestation fetuses). Erythrocyte, leukocyte, serum electrolyte, enzyme, lipid, carbohydrate, and metabolite values were measured. Complete serum protein profiles were also obtained by electrophoresis. Significant differences could be shown between the sows and fetuses and between the early and late gestation fetuses in all of the categories studied, though not for every parameter. This study provides a large normal database for development of Yucatan miniature swine as an animal model in the rapidly expanding field of fetal medicine.
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The development of non-surgical techniques for the relief of malignant low bileduct obstruction has cast doubt on the best way of relieving jaundice, particularly in patients fit for surgery whose life expectancy is more than a few weeks. We did a randomised prospective controlled trial comparing endoscopic stent insertion and surgical biliary bypass in patients with malignant low bileduct obstruction. 204 patients were randomised (surgery 103, stent 101); 3 subsequently proved to have benign disease and were excluded, leaving 101 surgical and 100 stented patients for assessment. Technical success was achieved in 94 surgical and 95 stented patients, with functional biliary decompression obtained in 92 patients in both groups. In stented patients, there was a lower procedure-related mortality (3% vs 14%, p = 0.01), major complication rate (11% vs 29%, p = 0.02), and median total hospital stay (20 vs 26 days, p = 0.001). Recurrent jaundice occurred in 36 stented patients and 2 surgical patients. Late gastric outlet obstruction occurred in 17% of stented patients and 7% of the surgical group. Despite the early benefits of stenting there was no significant difference in overall survival between the two groups (median survival: surgical 26 weeks; stented 21 weeks; p = 0.065). Endoscopic stenting and surgery are effective palliative treatments with the former having fewer early treatment-related complications and the latter fewer late complications.
Stable, oxygen-resistant cell lines (O2R) were isolated from P19 and P19H22 (APRT hemizygote) mouse embryonic carcinoma cells by serial exposures of increasing durations to 95% O2. Neurally differentiated progeny were also oxygen-resistant. P19O2R exhibited reduced oxygen-mediated micronucleation and a 10- to 20-fold reduction of the forward mutation rate at the HPRT locus in 20% O2. P19H22O2R cells showed reduced frequencies of colonies resistant to 2,6-diaminopurine. The modal karyotype of P19O2R was identical to that of a nonmodal karyotype present in the parental line [39,X,-Y, add(14)]. There was no evidence of enhanced resistance to ionizing radiation. We conclude that this general approach, when applied to pluripotent embryonic stem cells, has the potential to lead to the synthesis of antimutator strains of mice.
OBJECTIVES: To identify primary care patients' and physicians' beliefs, attitudes, preferences, and expectations regarding discussions of end-of-life medical care, and to identify factors limiting the quality and frequency of these discussions. DESIGN: Descriptive study using audiotaped, structured, qualitative interviews. SETTING: Ambulatory care clinics and offices at eight medical centers in six states. PARTICIPANTS: Forty-three primary care physicians and 47 ambulatory outpatients. RESULTS: The patients expressed strong feelings about having end-of-life discussions early in their medical courses while they were competent. They desired straightforward and honest discussions and were less concerned than the physicians about damaging hope. The patients wanted their physicians to play central roles in discussions and both the patients and the physicians noted the impact of the patient-physician relationship on these discussions. The patients desired information focusing more on expected outcomes than on medical processes. The physicians expressed feelings of ambiguity when their desire to save lives clashed with their belief that aggressive life-sustaining treatments were futile. The physicians described their roles in end-of-life discussions in five major categories; lifesaver, neutral scientist, guide, counselor, and intimate confidant. The physicians considered living wills excellent "icebreakers" for starting discussions but of limited utility otherwise. CONCLUSIONS: Patients prefer end-of-life discussions earlier and with greater honesty than physicians may perceive. These discussions are inseparably linked with the patient-physician relationship. Physicians can better address patients' desires in end-of-life discussions by altering their timing, content, and delivery.
To express high levels of proteins encoded by transfected DNA constructs in a variety of cultured cells, including neuronal cells, the activities of nine different promoters were evaluated using Escherichia coli beta-galactosidase (beta-gal) (LacZ) as a reporter gene. These nine promoters were categorized into three distinct groups (high, intermediate, and low expresser), in terms of the levels of beta-gal expression. An expression vector containing the cytomegalovirus enhancer and the chick beta-actin promoter (high expresser) showed the highest levels of expression, followed by vectors containing the cytomegalovirus promoter/enhancer and the SV40 promoter/enhancer (intermediate expresser). The rest of the promoters (thymidine kinase, adenovirus, murine proliferative sarcoma virus, nerve growth factor receptor, Rous sarcoma and mouse mammary tumor virus, and beta-amyloid precursor protein) expressed low levels of beta-gal. These results were consistent for eight different cell types. A particularly attractive model is the stem cell, P19; cultures differentiating into progeny consisting predominantly of cholinergic neurons could be readily transfected with expression vectors using liposomes and expressed beta-gal without significant morphologic changes of the differentiated neurons. The systems should be useful for the study of promoters and various expressed proteins, including those involved in axonal transport.
The beta amyloid peptide which accumulates within the brains of patients with Alzheimer's disease (AD) is proteolytically derived from a precursor protein (beta PP). We established and characterized four stably transformed human neuroblastoma cell lines which conditionally expressed a partial beta PP fusion protein (amino-17 residues+carboxyl-99 residues; S beta C). Conditional expression of S beta C was achieved using a tetracycline-responsive promoter system. Expression of this fusion protein in one of the cell lines resulted in pronounced cytotoxicity. Addition of n6,O2'-dibutyryl adenosine 3',5'-cyclic monophosphate and/or fetal bovine serum to the culture medium of this cell line further elevated the level of S beta C expression and enhanced the associated cytotoxicity. Conditioned medium, acquired from cells expressing S beta C, was not cytotoxic. These findings suggest that modulation of beta PP expression and/or metabolism can have cytotoxic consequences. This is the first report of cytotoxic effects mediated by conditional expression of a beta PP derivative. This immortal cell line provides a unique opportunity to screen for complementary DNAs which suppress this toxicity. Such cDNAs could help elucidate the processes underlying S beta C mediated cytotoxicity which in turn could further our understanding of the pathogenesis of AD and could also provide additional candidate genes for various forms of familial AD.
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