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Biomedical subjects

S Smith

Publications and source records attributed to S Smith.

At least 307 records · Page 17Linked to original sources

Comparative expression of major histocompatibility complex (MHC) antigens on CD5+ and CD5- B cells in patients with chronic lymphocytic leukaemia (CLL)

The aim of this study was to investigate the expression of major histocompatibility complex (MHC) antigens on CD5+ and CD5- B cells of 13 patients with chronic lymphocytic leukaemia (CLL). This was carried out using a series of monoclonal antibodies (MAbs) against polymorphic and monomorphic class I and class II antigens, as well as to the transferrin receptor and assessed by flow cytometry and direct and indirect immunofluorescence. The expression of these molecules was assessed as mean fluorescent intensity (MFI). The results showed that cells from all 13 individuals expressed monomorphic class I antigens. The number of cases expressing polymorphic HLA-Bw6, -Bw4, -B7, -B27 and -A2 class I antigens on CD5- B cells was 11 (85%), 6(46%), 2(15%), 1(8%), 3 (23%), respectively, which was consistent with the expected population frequency distributions of these antigens. For each of the class I antigens on CD5+ and CD5- B cells, the ratio of the MFI was greater than 1 in 12 of 13 cases. For the transferrin receptor (CD71), this ratio was also almost always greater than 1. These results indicate that, unlike solid tumours where the loss or abnormal expression of class I and II antigens is a frequent event, the expression of class I antigens in CLL patients seems to be normal. This indicates that the loss of these antigens cannot provide the leukaemic cells with a selective advantage to escape immunological detection.

Antigens, Neoplasm↗

ErbB-2 protein in sera and tumors of breast cancer patients.

We compared levels of erbB-2 oncoprotein among three groups: Group I included 60 asymptomatic women; Group II had 51 women with benign breast biopsies; and Group III had 67 women with node-negative breast cancer. Serological levels of erbB-2 protein were measured in all participants; tumor levels were measured for Groups II and III. Forty-three percent of usable tumors (25/58), including three of seven lobular tumors, were erbB-2 positive. Tumor and blood oncoprotein levels were unrelated. Blood levels, however, were positively related to tumor volume, but only when the tumor had both a ductal carcinoma in situ (DCIS) component and an invasive component, suggesting a role for erbB-2 protein in progression of DCIS to invasive carcinoma. In Groups I and II serological levels of erbB-2 protein were directly related to age, and inversely related to having had a live birth. Therefore, a model that determined the threshold levels of serological erbB-2 positivity in Group III included age and nulliparity as independent variables. Only three of the 67 women (4.5%) in Group III were positive for serological erbB-2. In a multivariate model, with serological erbB-2 as the dependent variable, and in which the independent variables included Study Group, there was a statistical trend for younger women, in which Group III had the highest serological levels of erbB-2, followed by Group II, and then Group I. In women who were over the age of 50 years the trend was reversed; i.e., levels of erbB-2 tended to be lowest in Group III, followed by Group II, and finally Group I.

Age Factors↗

A randomized trial of a brief HIV risk reduction counseling intervention for women.

There is an urgent need for the development and implementation of effective and feasible behavioral HIV and STD interventions. The purpose of the present randomized controlled trial was to evaluate the effectiveness of a single-session, skill-based sexual risk reduction intervention for women. Participants were assessed at baseline and at 1 month and 3 months following the intervention on measures of AIDS knowledge, behavioral intentions, self-efficacy, and sexual risk behavior. Compared with women in an AIDS-education-only condition, women receiving the skill-based intervention reported significantly higher rates of condom use at 3-month follow-up. Results suggest that brief sexual risk reduction programs are feasible and effective within a community setting.

Adult↗

Facial changes in extraction and nonextraction patients.

The purpose of this study was to determine if there are any differences in the posttreatment faces of patients treated nonextraction and those treated with premolar extraction in properly diagnosed and treated cases. The study was conducted in two parts. In Part 1, perceptions of 192 experienced general dentists and orthodontists were tested. Facial photos of 25 consecutively treated nonextraction patients and 25 consecutively treated four-premolar-extraction patients were shown to the study participants. They were asked if the patient was treated with the extraction of four premolars or without extractions. The mean score of the respondents was 54%, only slightly better than pure chance. In Part 2, profiles were evaluated based on cephalometric tracings. There was no significant difference between pretreatment and posttreatment profiles of the groups. The mean H-line values for both groups were within the desired esthetic range. It was concluded that experienced orthodontists and general dentists could not determine whether treatment was nonextraction or extraction by looking at the face alone. Also, there was no significant difference between the faces produced by the two types of treatments. Therefore, the avoidance of extracting premolars based on a fear of a significant detrimental effect on the face is unjustified when the case has been properly diagnosed and treated.

Adolescent↗

Reducing a peritoneal dialysis program's cost by changing from a vendor-provided to a program-provided system for general medical supplies: significant savings in CCPD.

An examination of the costs associated with outpatient chronic peritoneal dialysis prompted us to investigate the charges for general medical supplies used by patients on continuous ambulatory peritoneal dialysis (CAPD) and continuous cycling peritoneal dialysis (CCPD) in our hospital-owned, not-for-profit peritoneal dialysis program. The items used by patients to perform their dialysis exchanges and daily exit site care included 4 x 3 and 2 x 2 sterile gauze pads, antibacterial soap, masks, tape, and betadine swabsticks. The charges for these supplies when purchased from the dialysis vendor were compared with charges for the same items if purchased directly from hospital stores by the peritoneal dialysis program and then distributed to the patients. This initial analysis suggested a considerable savings if the peritoneal dialysis program provided the supplies. Based on this estimated savings, in July 1995, the peritoneal dialysis program changed from a vendor-provided to a program-provided system for general supplies used by CAPD and CCPD patients. This study examined the differences in charges expressed as $/patient-month for two periods: July 1994 to June 1995 (when all general medical supplies were provided by dialysis vendors directly to the CAPD and CCPD patients) and July 1995 to May 1996 (when the peritoneal dialysis program purchased general medical supplies from hospital stores and distributed these supplies directly to the patients). The median vendor charges for CAPD patients (n = 21 during 1994 to 1995 and n = 18 during 1995 to 1996) were not significantly different between the two periods. In fact, the charges were slightly higher during the 1995 to 1996 period ($1,264/patient-month v $1,193/patient-month during the vendor-provided period of July 1994 to June 1995, P = 0.67). The median vendor charges for patients on CCPD were significantly lower during the 1995 to 1996 period when the peritoneal dialysis program provided the general medical supplies used for CCPD ($1,110/patient-month v $1,389/patient-month during 1994 to 1995, P = 0.003). There were 30 CCPD patients during the 1994 to 1995 period and 27 patients on CCPD during 1995 to 1996. The total charges for CAPD and CCPD patients combined included dialysis vendor charges (dialysis solution, tubing, cycler rental) and charges from hospital stores. These total charges were lower in the July 1995 to May 1996 period when general medical supplies were purchased directly from hospital stores rather than from the dialysis vendors: $1,201/patient-month versus $1,360/patient-month (P = 0.03). The median hospital store charges rose slightly during the July 1995 to May 1996 period when supplies were purchased by the peritoneal dialysis program from hospital stores ($31/patient-month v $21/patient-month, P = 0.37, during the July 1994 to June 1995 period when general medical supplies were purchased directly from dialysis vendors). However, despite the rise in charges from hospital stores, an overall savings of $149/patient-month was achieved when the peritoneal dialysis program purchased and provided general medical supplies used by the peritoneal dialysis patients. This $149/patient-month equals $1,788 savings per dialysis year for each patient on peritoneal dialysis for that year. Significant savings in the cost of a chronic peritoneal dialysis program may therefore occur if less expensive sources for the general medical supplies used by CAPD and, especially, CCPD patients are found.

Contract Services↗

Effects of 14 d of covert substitution of olestra for conventional fat on spontaneous food intake.

We conducted a double-blind, placebo-controlled, within-subject crossover study to investigate the effects of covert substitution of olestra, a non-energy-containing fat replacer, for conventional fat on food selection and energy intake in lean and obese men and women. Fifty-one subjects [BMI (kg/m2): 19-36; age: 25-63 y] were studied during two 14-d treatment periods (olestra and placebo), with a 7-d washout between feeding periods. During the intervention periods all foods were provided to the subjects. The aim was to produce a 10% dilution of total energy intake by replacing conventional triacylglycerol with olestra. To accomplish this, subjects were required to consume core foods providing 20-35 g olestra (depending on estimated energy needs) or the same foods containing placebo triacylglycerol. Additional items could be selected from foods that varied in macronutrient composition. When the two treatment periods were compared, total energy intake was 8% lower and fat intake 11% lower during the olestra period than during the placebo treatment period (P < 0.0001). Overall, subjects compensated for 15% of the fat and 20% of the total energy replaced by olestra. In absolute terms, subjects consumed 32% of total energy from fat during the placebo period and 27% of total energy from fat during the olestra period. Neither carbohydrate nor protein intake (g/d) differed between periods. The results did not differ as a function of BMI (lean compared with obese) or sex. Over a 2-wk period, covert substitution of olestra for conventional fat led to reductions in dietary fat intake and total energy intake in all subjects.

Adult↗

Defining multiple sclerosis disease activity using MRI T2-weighted difference imaging.

Serial brain MRI scanning is widely used for assessing multiple sclerosis disease activity in the evaluation of new therapies. Traditionally, the net change in T2-weighted lesion volume between paired scans has been used as a measure of disease progression and as a secondary endpoint in definitive clinical trials. However, as the net change in T2-weighted lesion volume reflects only the difference between new and resolved T2-weighted lesions, this measure significantly under-represents the total T2-weighted lesion activity. Difference images produced by subtracting labelled T2-weighted lesion volumes from serial registered T2-weighted scans allows separate measurements of individual volumes of new and resolving T2-weighted lesions, which may reflect underlying disease activity more sensitively. We generated T2-weighted differences images to define T2-weighted lesion changes over 1 year for 19 patients with relapsing multiple sclerosis. The mean new T2-weighted lesion volume change was three times greater than the mean net T2-weighted lesion volume change over the study period. New T2-weighted lesion volumes were more strongly correlated with T1-weighted gadolinium-enhancing lesion volumes (r = 0.72, P = 0.001) than were the net T2-weighted lesion volume changes (r = 0.45, P = 0.01). Baseline T2-weighted lesion volume was more highly correlated with new T2-weighted lesion volumes (r = 0.89, P < 0.0001) than with net T2-weighted lesion change (r = 0.47, P < 0.001). There was a trend for patients who showed sustained clinical progression over the year to have a greater new T2-weighted lesion volume than those who did not. This difference was not seen with net T2-weighted lesion volume change. T2-weighted lesion difference images should provide an additional and sensitive tool for monitoring disease activity in multiple sclerosis. Independent definition of new and resolving T2-weighted lesion volumes also offers the potential for discrimination of the relative effects of experimental therapies on new inflammatory activity from the effects on oedema resolution and lesion repair.

Adult↗

Satisfaction with outpatient geriatric evaluation and management (GEM).

The purpose of this study was to evaluate high-risk older adults' satisfaction with outpatient geriatric evaluation and management (GEM). Community-dwelling Medicare beneficiaries (n = 522) age 70 years and older who had a high probability of repeated admission to hospitals (Pra > .40) were randomly assigned to receive either usual care or GEM for six months. Despite the stresses imposed by outpatient GEM (e.g., new relationships with providers, frequent office visits and changes in treatments), the mean satisfaction scores of the recipients of GEM were 9% higher than those of the recipients of usual care (4.31 vs 3.96, p < .001). The primary physicians of GEM recipients were also highly satisfied with GEM care.

Aged↗

The successful use of pronuclear embryo transfers the day following oocyte retrieval.

A retrospective analysis of results from 114 initiated in-vitro fertilization cycles utilizing pronuclear embryo transfer is presented. Patients were unselected for age or infertility criteria, constituted a continuous series and were grouped according to response to stimulation (Group 1, ideal; Group 2, suboptimal) or ovarian reserve (Group 3, poor). At 16-18 h post-insemination, embryos were scored for alignment of pronuclei and nucleoli and the appearance of the cytoplasm, generating an embryo score (ES). Transfers were performed 24-26 h post-insemination using two to six embryos with the highest ES. A corrected score was calculated (total score/number of embryos; CS). A total of 114 initiated cycles resulted in 97 oocyte retrievals with 38 clinical pregnancies (39%; 15% implantation). Pregnancy rates were significantly different between the three groups; 37 pregnancies in Group 1 (55% clinical pregnancy; 20% implantation), none in Group 2 and one in Group 3 (6%; 2% implantation: P < 0.001). The ES of transferred embryos correlated with groups. There was a strong correlation between CS and implantation and delivery rates. CS >15 resulted in a 28% implantation; 65% delivery rate. CS <14 resulted in four pregnancies, one delivered. The data show that oocyte quality and pronuclear embryo morphology are related to implantation and that pronuclear embryos can be successfully selected for embryo transfer.

Abortion, Spontaneous↗

Effects of the novel high-affinity 5-HT(1B/1D)-receptor ligand frovatriptan in human isolated basilar and coronary arteries.

The contractile actions of the novel high-affinity 5-hydroxytryptamine (5-HT(1B/1D)) ligand, frovatriptan (formerly VML 251/SB-209509) were investigated in human isolated basilar and coronary arteries in which the endothelium had been removed. Basilar arteries were obtained post mortem, and coronary arteries were obtained from patients undergoing heart transplant (recipient) or from donor hearts that were not suitable for transplant. Frovatriptan was a potent contractile agent in isolated basilar artery with a -log mean effective concentration (EC50) value of 7.86 +/- 0.07 and intrinsic activity of 1.25 +/- 0.10 relative to 5-HT (n = 4). Frovatriptan was 8.5-fold more potent than sumatriptan, which produced a -log EC50 value of 6.93 +/- 0.09 and intrinsic activity 11.1 +/- 0.08 relative to 5-HT (n = 4). In coronary arteries, frovatriptan produced contraction with -log EC50 values of 7.38 +/- 0.12 and 7.81 +/- 0.2 in recipient (n = 7) and donor (n = 3) arteries, respectively. The relative degree of contraction of frovatriptan was lower than that of 5-HT, with relative intrinsic activities of 0.42 +/- 0.06 and 0.40 +/- 0.09, respectively. Sumatriptan produced contraction of human recipient and donor arteries with -log EC50 values (intrinsic activity) of 6.57 +/- 0.13 (0.79 +/- 0.27; n = 6) and 7.35 (1.41; n = 2), respectively. Furthermore, marked bell-shaped responses were apparent for frovatriptan in coronary arteries, with relaxation occurring at concentrations >6 microM in some tissues. In contrast, no bell-shaped concentration-response curves were apparent for sumatriptan or 5-HT. Threshold concentrations for frovatriptan-induced contractions were also different between basilar (>2 nM) and coronary arteries (>20 nM). No separation of threshold activity was observed with sumatriptan or 5-HT. These data show that frovatriptan produces constriction of human isolated basilar and coronary arteries. However, frovatriptan produces a complex pharmacologic response in the coronary artery, with threshold contractile activity requiring approximately 10-fold greater concentrations of agonist than in the basilar artery. Frovatriptan also shows a differential pharmacologic profile compared with sumatriptan in coronary arteries, with reversal of tone predominating at high concentration.

Basilar Artery↗

Assessment of asthma severity in adults with asthma treated by family practitioners, allergists, and pulmonologists.

OBJECTIVES: Accurate measurement of asthma severity is critical for research evaluating asthma health outcomes. There are, however, no widely accepted asthma severity measures. A severity-of-asthma score, which is based on self-reported information, was previously developed and validated in subjects recruited from pulmonary and allergy subspecialty practices. The purpose of this study was to validate the severity-of-asthma score in subjects treated by family practice physicians and to compare asthma severity in subjects treated by family practitioners (n = 150) with those seen by allergists (n = 217) and pulmonologists (n = 384). METHODS: The study was an ongoing panel study of adults with asthma. Subjects were a random sample of board-certified family practice, allergy, and pulmonary physicians. Each physician registered patients with asthma aged 18 to 50 years. Of 869 subjects registered, 751 (86%) completed structured telephone interviews. The family practice panel was recruited approximately 3 years after the subspecialty panel. RESULTS: In the family practice subjects, the severity-of-asthma score demonstrated internal consistency (Cronbach's alpha 0.76) and concurrent validity, correlating strongly with asthma-specific quality of life, SF-36 General Health and Physical Functioning scales, and subject-perceived asthma severity. After controlling for demographic characteristics, a 5-point score increment was associated with increased emergency department visits, urgent physician visits, and restricted activity days. The mean severity score was highest in the pulmonary group (11.8 +/- 6.3), followed by the allergy (10.3 +/- 5.3) and family practice (9.3 +/- 5.5) groups. CONCLUSIONS: The severity-of-asthma score was a valid measure in generalist-treated subjects. Asthma severity varied significantly by physician specialty.

Adolescent↗

Increased sialylation of oligosaccharides on IgG paraproteins--a potential new tumour marker in multiple myeloma.

AIMS: To investigate whether changes in carbohydrate structure of IgG are related to malignancy and stage of disease in myeloma and monoclonal gammopathy of uncertain significance (MGUS). METHODS: 61 patients were studied at diagnosis: 14 with MGUS, nine with stage I multiple myeloma, 11 with stage II, 21 with stage III, and five with solitary plasmacytoma. IgG was extracted from serum by protein G affinity chromatography. Oligosaccharides were cleaved from the protein backbone enzymatically by N-glycosidase F. Oligosaccharide analysis was performed by high pressure anion exchange chromatography with pulsed electrochemical detection (HPAE-PED). RESULTS: Up to 15 oligosaccharide peaks were identified in three major fractions: neutral, monosialylated, and disialylated. Patients with myeloma showed an increase in the proportion of sialylated oligosaccharides in comparison with patients with MGUS. The ratio of neutral to sialylated oligosaccharides (N:S) was reduced at all stages of myeloma compared with MGUS: MGUS, 11.35; myeloma stage I, 7.6 (p = 0.047); stage II, 5.20 (p = 0.035); stage III, 3.60 (p = 0.0002); plasmacytoma, 7.5 (p = 0.046). The N:S ratio was independent of paraprotein concentration (r = 0.05). CONCLUSIONS: The ratio of neutral to sialylated oligosaccharides may act as a new marker of malignancy in IgG paraproteinaemia and warrants further investigation.

Aged↗

Postmodernity and a hypertensive patient: rescuing value from nihilism.

Much of postmodern philosophy questions the assumptions of Modernity, that period in the history of the Western world since the Enlightment. These assumptions are that truth is discoverable through human reason; that certain knowledge is possible; and furthermore, that such knowledge will provide a basis for the ineluctable progress of Mankind. The Enlightenment project is underwritten by the conviction that knowledge gained through the scientific method is secure. In so far as biomedicine inherits these assumptions it becomes fair game for postmodern deconstruction. Today, perhaps more than ever, plural values compete, and contradictory approaches to health, for instance, garner support and acquire supremacy through consumer choice and media manipulation rather than evidence-based science. Many doctors feel a tension between meeting the needs of the patient face to face, and working towards the broader health needs of the public at large. But if the very foundations of medical science are questioned, by patients, or by doctors themselves, wherein lies the value of their work? This paper examines the issues that the anti-foundationalist thrust of postmodernism raises, in the light of a case of mild hypertension. The strict application of medical protocol, derived from a nomothetic, statistical perspective, seems unlikely to furnish value in the treatment of an individual. The anything goes, consumerist approach, however, fares no better. The author argues that whilst value cannot depend on any rationally predetermined parameters, it can be rescued, and emerges from the process of the meeting with the patient.

Antihypertensive Agents↗

How to pass the MRCP (UK) examination--ask a successful candidate!

Recently successful MRCP (UK) candidates were asked to rate the value of clinical experience, reading, practice with past or simulated examination papers and commercially organised courses as preparation for parts 1 and 2 of the examination. With respect to part 1, practice with past and simulated papers was unanimously felt to be of crucial importance with examination-focused reading helpful. Clinical experience was deemed irrelevant and commercially organised courses a matter of individual choice. For part 2, clinical experience was felt to be of fundamental importance but needed to be practised in an 'examination atmosphere'. Both general reading and practice with past and simulated papers were judged helpful and commercially organised courses were perceived to be of more value than for part 1. Trainees should be advised to seek advice on examination preparation from both 'authoritative sources' and their recently successful colleagues.

Attitude of Health Personnel↗

Abnormal oxygen uptake kinetic responses in women with type II diabetes mellitus.

Persons with type II diabetes mellitus (DM), even without cardiovascular complications have a decreased maximal oxygen consumption (VO2 max) and submaximal oxygen consumption (VO2) during graded exercise compared with healthy controls. We evaluated the hypothesis that change in the rate of VO2 in response to the onset of constant-load exercise (measured by VO2-uptake kinetics) was slowed in persons with type II DM. Ten premenopausal women with uncomplicated type II DM, 10 overweight, nondiabetic women, and 10 lean, nondiabetic women had a VO2 max test. On two separate occasions, subjects performed 7-min bouts of constant-load bicycle exercise at workloads below and above the lactate threshold to enable measurements of VO2 kinetics and heart rate kinetics (measuring rate of heart rate rise). VO2 max was reduced in subjects with type II DM compared with both lean and overweight controls (P < 0.05). Subjects with type II DM had slower VO2 and heart rate kinetics than did controls at constant workloads below the lactate threshold. The data suggest a notable abnormality in the cardiopulmonary response at the onset of exercise in people with type II DM. The findings may reflect impaired cardiac responses to exercise, although an additional defect in skeletal muscle oxygen diffusion or mitochondrial oxygen utilization is also possible.

Adult↗

The locus of tumor necrosis factor-alpha action in lung inflammation.

The pulmonary host response to infection and inflammation appears, at least in part, to be compartmentalized from the systemic host response. Tumor necrosis factor-alpha (TNF-alpha) has been implicated in lung inflammation and injury, but its site(s) of action has not been clearly defined. To investigate this, transgenic mice (surfactant apoprotein C promotor/soluble TNF receptor type II-Fc fusion protein ([SPCTNFRIIFc] mice) were generated in which TNF-alpha was selectively antagonized in the distal lung through tissue-specific expression of sTNFRIIFc, a soluble TNF inhibitor. The lung inflammatory response in these mice to pulmonary challenge with Micropolyspora faeni antigen or lipopolysaccharide (LPS) was compared with the response of wild-type mice, wild-type mice treated with recombinant sTNFRIIFc intravenously, and type I TNF-receptor knockout mice. Recruitment of polymorphonuclear leukocytes (PMN) to the lung after challenge with M. faeni antigen was essentially abolished in the TNFRI knockout mice and markedly reduced in the SPCTNFRIIFc mice. Wild-type mice given sTNFRIIFc intravenously in amounts resulting in lung concentrations similar to those in SPCTNFRIIFc mice also showed significantly reduced lung PMN recruitment, whereas those given doses that achieved such concentrations in the blood but low levels in the lung did not. In contrast, PMN recruitment to the lung following aerosol challenge with LPS was reduced significantly in the TNFRI knockout mice and in mice given high-dose sTNFRIIFc intravenously, but was not reduced significantly in SPCTNFRIIFc mice. Thus, inhibition of PMN recruitment in response to M. faeni antigen correlated largely with the extent of intrapulmonary inhibition of TNF-alpha, whereas the response to LPS correlated best with the extent of extrapulmonary inhibition of TNF-alpha. These studies indicate that TNF-alpha may act at different loci to mediate lung inflammation, with the site of action depending in part on the nature of the inflammatory stimulus, and that SPCTNFRIIFc mice provide a tool by which the locus of TNF action can be addressed.

Administration, Intranasal↗

Evaluating dental office ergonomic. Risk factors and hazards.

Concerns about ergonomic risk factors have been growing among health care and other workers. The authors undertook a study to determine the presence of certain ergonomic risk factors in typical tasks performed by dentists and dental hygienists. They further investigated--by means of electromyography and goniometry--the force, frequency and duration of the task. The study suggests that when a task's duration, force and frequency are accounted for, scaling, polishing, flossing and probing activities do not represent exposure to high ergonomic risk.

Crowns↗