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Biomedical subjects

B Smith

Publications and source records attributed to B Smith.

At least 55 records · Page 3Linked to original sources

Nipple fluid carcinoembryonic antigen and prostate-specific antigen in cancer-bearing and tumor-free breasts.

PURPOSE: Mammograms and breast examinations are established methods for early breast cancer detection. Routine mammography screening reduces breast cancer mortality among women ages > or = 50 years, but additional screening methods are needed. We and others have found high levels of carcinoembryonic antigen (CEA) and prostate-specific antigen (PSA) in nipple aspirate fluids (NAFs), but the usefulness for these bio-markers for early breast cancer detection is unknown. PATIENTS AND METHODS: NAFs from one or both breasts of 388 women were analyzed for CEA, PSA, and albumin levels. The study included 44 women with newly diagnosed invasive breast cancers, 67 women with proliferative breast lesions (ductal and lobular carcinoma in situ and atypical ductal hyperplasia), and 277 controls without these breast lesions. Analyses were conducted using the log(10)-transformed CEA and PSA levels to normalize the distributions of these tumor markers. RESULTS: Nipple fluid CEAs are significantly higher for cancerous breasts than tumor-free breasts (median 1,830 and 1,400 ng/mL, respectively; P <.01). However, at 90% specificity of the assay (CEA = 11,750 ng/mL), the corresponding sensitivity for cancer detection is 32%. CEA levels are not significantly different for breasts with proliferative lesions compared with tumor-free breasts. Nipple fluid PSAs do not differ by tumor status. Analyses of NAF albumin-standardized CEAs and PSAs yield similar results. Nipple fluid CEA and PSA titers are correlated in the affected and unaffected breast of women with unilateral lesions. CONCLUSION: Nipple fluid CEAs are higher for breasts with untreated invasive cancers, but the test sensitivity is low. Nipple fluid PSA titers do not seem to be useful for breast cancer detection.

Adult↗

An extracorporeal membrane oxygenation-based approach to cardiogenic shock in an older population.

BACKGROUND: We investigated the efficacy of an integrated system of advanced supportive care based on extracorporeal membrane oxygenation (ECMO) in older patients with an estimated mortality of more than 90% to establish whether its use is justifiable. METHODS: Treatment was provided by cardiac surgeons and critical care physicians and included the following key elements: (1) ECMO, (2) early application of continuous venovenous hemofiltration, (3) inhaled nitric oxide, (4) maintenance of perfusion pressure with norepinephrine, (5) maintenance of pulmonary blood flow by ventricular filling with intravenous colloids, (6) avoidance of early postoperative anticoagulation, (7) frequent use of transesophageal echocardiography, and (8) low tidal volume ventilation. Demographic features, intraoperative details, postoperative course, ECMO weaning rate, morbidity, survival to hospital discharge, and the quality of life of survivors were recorded. RESULTS: Seventeen consecutive patients (median age, 69 years) with refractory cardiogenic shock were studied. The median duration of ECMO was 86 hours (20 to 201 hours). Eleven patients (65%) were successfully weaned from ECMO. Seven patients (41%) survived to discharge. The major causes of morbidity were bleeding and leg ischemia. All patients who survived to discharge were alive and well at follow-up (median, 21 months) and reported a satisfactory quality of life. CONCLUSIONS: An ECMO-based approach can be used with acceptable results in the treatment of refractory cardiogenic shock, even in older patients.

Aged↗

Composite stentless valve with graft extension for combined replacement of the aortic valve, root and ascending aorta.

OBJECTIVE: The composite mechanical valve conduit has been most commonly used for patients who require combined aortic valve, root, and ascending aorta replacement, but is limited, especially in the elderly, because of the need for long-term anticoagulation. We report the first consecutive series of patients in whom a composite stentless valve with graft extension, which does not require long-term anticoagulation, was performed. METHODS: Between April 1998 and July 2000, eight patients with severe aortic root and ascending aortic pathology underwent a combined aortic valve, root, and ascending aorta replacement with a Freestyle stentless porcine valve with a Hemashield graft extension. Mean age was 74 (range 56--82), three were males. Concomitant procedures included coronary artery bypass graft (CABG) alone (n=2), mitral valve replacement with atrial septal defect repair (n=1) and CABG with septal myomectomy (n=1). RESULTS: Operative mortality was zero. Median aortic cross-clamp and cardiopulmonary bypass times were 150 and 203 min, respectively. Two patients returned to the operating room for bleeding. Median blood transfusions and hospital length of stay were 4 units and 11 days, respectively. CONCLUSIONS: The composite stentless valve with graft extension is a reasonable alternative to a mechanical valve conduit for patients who require a combined aortic valve, root, and ascending aorta replacement, in whom anticoagulation is not desirable or contraindicated.

Aged↗

Examinations of chronic pain and affect relationships: applications of a dynamic model of affect.

Two studies of the relationship between pain and negative affect are presented in this article: a study of weekly fluctuations in pain and negative affect among those with arthritis and a study of daily fluctuations in pain and negative affect for participants with fibromyalgia. The roles of positive affect and mood clarity (or the ability to distinguish between different emotions) in modifying the size of the relationship between pain and negative affect were examined in both studies as a means of testing the predictions of a dynamic model of affect regulation. In both studies, the presence of positive affect reduced the size of the relationship between pain and negative affect. Also, for arthritis participants with greater mood clarity, there was less overlap in ratings of negative and positive affective states.

Adult↗

Prevalence, morbidity and management of adult asthma in South Australia.

This paper reviews asthma-related data obtained between 1987 and 1997 from self-report population surveys of adults in South Australia. A multistage, systematic, clustered area sample of adults (>15 years) was selected from a random sample of Australian Bureau of Statistics collector districts, and interviewed at home by trained health interviewers. The self-report prevalence of doctor-diagnosed asthma increased from 5.6% in 1987 to 12.2% in 1997. Morbidity measured as days lost from usual activities and nights awakened by asthma remained high, but hospitalization rates are trending down. The ownership of asthma action plans peaked in 1995 and has declined. The ownership of peak flow meters increased between 1992 and 1997, and the ownership of nebulisers remained constant. Evidence-based interventions are required to improve asthma management.

Adult↗

Method for simultaneous epicardial and endocardial mapping of in vivo canine heart: application to atrial conduction properties and arrhythmia mechanisms.

INTRODUCTION: It has been suggested that the three-dimensional structure of the atria may be crucial in arrhythmogenesis; however, previous in vivo atrial activation mapping studies have been limited to either endocardial or epicardial approaches. METHODS AND RESULTS: To investigate the role of endocardial and epicardial structures and their interaction in atrial conduction and arrhythmias, we used five epicardial plaques and two intra-atrial balloon arrays to record a total of 368 unipolar electrograms from the entire epicardial and endocardial surface of both atria. During regular 1:1 pacing from the right atrial appendage, right atrial endocardial activation spread considerably faster than epicardial (total activation time 45+/-12 msec vs 60+/-19 msec, respectively [mean +/- SD]; P < 0.05), pointing to preferential conduction over structures like the crista terminalis and pectinate muscles. No such differences were noted in the left atrium. Transseptal spread occurred via discrete anterior and posterior pathways, causing separate breakthroughs in anterior and posterior atrial regions, respectively. Dissociation between septal pathways played a role in reentry during vagal atrial fibrillation. In 2 of 4 dogs with atrial fibrillation associated with congestive heart failure, single macroreentrant circuits involving endocardial and epicardial components were revealed during the arrhythmia. CONCLUSION: We conclude that activation mapping using simultaneous recording from both epicardial and endocardial surfaces provides potentially important insights into the mechanisms of atrial conduction and arrhythmogenesis.

Activation Analysis↗

A double-blind study to evaluate the safety of recombinant human hemoglobin in surgical patients during general anesthesia.

OBJECTIVE: To evaluate recombinant human hemoglobin (rHb1.1) in patients undergoing surgery involving general anesthesia; examine rHb1.1 for toxicity, including renal dysfunction and hypertension; and measure plasma concentrations of rHb1.1 over time. DESIGN: Prospective, double-blinded, randomized, placebo-controlled study. SETTING: University medical center hospital. PARTICIPANTS: Eighteen patients having surgery under general anesthesia. INTERVENTIONS: One of 4 escalating doses of rHb1.1 or normal saline (control) was administered by continuous infusion to patients receiving general anesthesia for elective surgical procedures. Total rHb1.1 doses ranged from 4.7 to 25.6 g. MEASUREMENTS AND MAIN RESULTS: Clinical and laboratory data, including vital signs monitoring, hematology (white blood cell and reticulocyte count, hemoglobin, hematocrit, erythrocyte sedimentation rates, and coagulation values), renal function (serum creatinine and blood urea nitrogen), hepatic function (mean and indirect bilirubin), pancreatic function (serum amylase and lipase), and antibodies (IgG and IgM) to Escherichia coli protein, were collected at specified intervals for 7 days after infusion of rHb1.1. No serious adverse events occurred. The most frequently observed clinical event occurred during the first 24 hours after infusion and was primarily associated with surgery and anesthetic administration. A slightly higher incidence of hypertension, symptoms suggestive of pyrogenicity, mildly elevated total and indirect bilirubin, and elevated pancreatic enzymes was observed in rHb1.1 treatment groups when compared with control. Hypertension resolved within 7 hours, and laboratory values returned to normal levels by day 7. CONCLUSION: Although the elevations in pancreatic enzymes seen in some rHb1.1-treated patients remain unexplained, the safety profile of rHb1.1 appears to be acceptable. These results support the continued clinical evaluation and development of rHb1.1.

Adult↗

Risk of neurovascular injury with limited-open carpal tunnel release: defining the "safe-zone".

Limited-open carpal tunnel release was performed in ten cadaver arms using the "Safeguard" system. The "Safeguard" guide was intentionally placed off of the longitudinal middle/ring finger axis, either in 15 degrees of radial deviation or 15 degrees of ulnar deviation. Despite the errant placement, carpal tunnel release was performed without damage to any neurovascular structure. The proximity of neurovascular structures to the middle/ring finger axis was measured in all ten cadaver specimens. From this, a "safe-zone" was defined for endoscopic or limited-open carpal tunnel release. The "safe-zone" expands when surgery is performed from distal to proximal. The area of the "safe-zone" is greatest when a protective guide is placed between the bursal sac of the carpal canal and the flexor retinaculum.

Cadaver↗

Educational benefits of student self-marking of short-answer questions.

A pilot study was undertaken to evaluate the feasibility and reliability of undergraduate medical student selfmarking of degree written examinations, and to survey student opinion regarding the process. The correlation between student and faculty staff scores for individual questions and the total examination was high (correlation coefficient ranged from 0.77 to 0.91: p < 0.001). There were no significant differences between the mean student and mean faculty staff scores for individual questions or the total examination: 98% (97199) of student scores fell within ± 15% of the faculty staff score, with 92% (91199) of students falling within ± 10%. Although the approach was demonstrated to be reliable, students generally failed to acknowledge the potential value of self-marking in terms of feedback and as a learning opponunity, and found the process stressful.

Journal Article↗

Characteristics of 15,314 hypertensive patients at high coronary risk. The VALUE trial. The Valsartan Antihypertensive Long-term Use Evaluation.

Valsartan is an orally active, selective antagonist of the angiotensin II-1 (AT1) receptor developed for the treatment of hypertension. The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) Trial of Cardiovascular Events in Hypertension is a double-blind, randomized prospective, parallel group study designed to compare the effects of valsartan with those of the calcium-antagonist amlodipine on the reduction of cardiac morbidity and mortality. Patients with essential hypertension, aged 50 years and older, and at particularly high risk of coronary events were enrolled. 18,119 patients were screened and 15,314 patients in 31 countries were randomized mainly between January 1998 and December 1999. These hypertensives had a mean blood pressure of 154.7/87.5 mmHg at the time of their randomization to blinded medication. The population comprises both genders (men 57.6%), Caucasians (89.1%), mean age 67.2 years, mean body mass index 28.6 kg/m2, coronary heart disease (45.8%), high cholesterol (33.0%), type 2 diabetes mellitus (31.7%) and smokers (24.0%). More than 92% of the randomized participants had been treated for high blood pressure for at least 6 months when screened for the study. The randomized population is now being treated (goal blood pressure < 140/90 mmHg) in adherence with the protocol until at least 1450 patients experience primary cardiac endpoint defined as clinically evident or aborted myocardial infarction, hospitalization for heart failure or death caused by coronary heart disease.

Aged↗

Quality of life in asthma: a comparison of community and hospital asthma patients.

This study compares the quality of life of a community sample of people with asthma in South Australia, using population norms, people suffering from other chronic diseases, and a sample of asthma patients from two hospital clinics. A representative population survey was performed by trained interviewers in spring 1995 of 3001 respondents aged > or = 15 years. A physician's diagnosis of current asthma was reported by 299 (9.9%). The hospital clinic sample had a physician's diagnosis and lung function evidence of asthma (n = 293). All completed the SF-36 health survey. Standardized SF-36 scores, adjusted for age, sex, and social class, were significantly lower for respondents with asthma, compared with population norms, across all subscales of the SF-36 (p < 0.05). Physical component summary (PCS) and mental component summary (MCS) scores were not significantly different in people in the community sample with asthma from scores in people with diabetes and arthritis. PCS and MCS scores did not differ for those with similar symptom frequency in the community and hospital asthma samples, except that hospital patients with frequent symptoms had significantly lower MCS scores (p < 0.01). Asthma has a major impact on the health-related quality of life in the community, comparable to other chronic diseases. The SF-36 performs uniformly in asthma in different situations.

Adolescent↗

Asthma care by nurse practitioners in the United States.

PURPOSE: To survey nurse practitioners (NPs) in the United States on their level of input to asthma care prior to enrolling in The National Asthma and Respiratory Training Centre (NARTC) specialist asthma education program in the UK. DATA SOURCES: Responses of 134 (66%) of the 202 NPs who self-selected for enrollment in the NARTC program on a preliminary questionnaire. CONCLUSIONS: Nearly all (133 or 99%) currently work with asthmatics and 122 (91%) prescribe asthma drugs. Only 92 (69%) measure peak flow(PF), 84 (63%) check inhaler technique, 76 (57%) teach use of a home PF meter and diary, and 63 (47%) provide written self-management plans on any regular basis. Many have not established follow-up procedures (56 or 42%), or evaluated their asthma management practices (55 or 41%). IMPLICATIONS FOR PRACTICE: Successful asthma management requires correct medication, systematic follow-up, patient education, and self-management. Specialist asthma training should encourage practitioners to combine effective drug usage with a long-term preventative approach.

Asthma↗

The role of exon 5 in fibroblast collagenase (MMP-1) substrate specificity and inhibitor selectivity.

Interstitial collagen is degraded by members of the matrix metalloproteinase (MMP) family, including MMP-1. Previous work has shown that the region of MMP-1 coded for by exon 5 is implicated both in substrate specificity and inhibitor selectivity. We have constructed a chimeric enzyme, the exon 5 chimera, consisting primarily of MMP-1, with the region coded for by exon 5 replaced with the equivalent region of MMP-3, a noncollagenolytic MMP. Unlike MMP-3, the exon 5 chimera is capable of cleaving type I collagen, but the activity is only 2.2% of trypsin-activated MMP-1. 'Superactivation' of the chimera has no discernible effect, suggesting that the salt bridge formed in 'superactive' MMP-1 is not present. The kinetics for exon 5 chimera cleavage of two synthetic substrates display an MMP-3 phenotype, however, cleavage of gelatin is slightly impaired as compared to the parent enzymes. The K(iapp) values for the exon 5 chimera complexed with synthetic inhibitors and N-terminal TIMP-2 also show a more MMP-3-like behaviour. However, the k(on) values for N-terminal TIMP-1 and N-terminal TIMP-2 are more comparable to those for MMP-1. These data show that the region of MMP-1 coded for by exon 5 is involved in both substrate specificity and inhibitor selectivity and the structural basis for our findings is discussed.

Amino Acid Sequence↗

Estrogen priming modulates autoreceptor-mediated potentiation of dopamine uptake.

The ability of a physiological dose of estrogen (estradiol benzoate, estrogen: 10 microgram 48 and 24 h prior) to modulate autoreceptor-mediated changes in dopamine transport properties was investigated in a synaptosomal preparation prepared from the nucleus accumbens of ovariectomized rats. Quinpirole (1-100 microM)-mediated potentiation of [3H]dopamine uptake was attenuated in synaptosomes from estrogen-primed animals. Haloperidol (10 microM) inhibited basal uptake and effectively prevented quinpirole potentiation of uptake in both ovariectomized and estrogen-primed samples. The ability of selective protein phosphatase inhibitors to modulate autoreceptor-mediated potentiation of dopamine uptake was also examined. Pretreatment with protein phosphatase 2B (deltamethrin, cypermethrin) or protein phosphatase 1 (tautomycin) inhibitors attenuated basal and quinpirole-potentiated dopamine uptake in ovariectomized but not estrogen-primed tissue. These data suggest that autoreceptor-mediated activation of dopamine transport can be regulated by physiological doses of estrogen and implicate a role for protein phosphorylation in autoreceptor-mediated potentiation of dopamine uptake.

Animals↗