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Biomedical subjects

Patricia Smith

Publications and source records attributed to Patricia Smith.

15 recordsLinked to original sources

Microstructure and chemical composition of primary teeth in children with Down syndrome and cerebral palsy.

This study was designed to test the hypothesis that prenatal growth insults leave permanent signs in the developing primary teeth that can be identified in later life. To test this hypothesis we examined exfoliated and extracted lower second primary molars of children with Down syndrome (DS) and cerebral palsy (CP). Teeth of children with no adverse medical history were used as a control group. Informed consent of parents and children was obtained in all cases. On each tooth two thin sections were cut, one bisecting the mesial cusps and one bisecting the distal cusps. Using a light microscope, the width of prenatal enamel and postnatal enamel was measured on each section at standardized locations from the dentin-enamel junction (DEJ) with the neonatal line used to distinguish between prenatal and postnatal enamel. Chemical analysis of each section was carried out using an energy dispersive spectrophotometer (ESR). The Ca/P ratios of enamel and dentin for each cusp were calculated and intercusp and intergroup differences analysed using non-parametric statistical tests. The results showed that significantly less enamel was laid down prenatally in DS and CP teeth than in the control group and that the enamel of the mesial cusps in these groups was less highly mineralised than that of the controls. The results also showed that in DS teeth growth and mineralisation of all cusps was affected. Based on these findings we propose that analysis of exfoliated deciduous teeth in developmentally challenged children may help in identifying the onset and severity of growth insults in utero and its impact on later development.

Amelogenesis↗

Clinical profile and early surgical complications in the Cornea Donor Study.

PURPOSE: The Cornea Donor Study was designed to investigate the safety and efficacy of older donor corneal tissue compared with younger donor tissue in recipient eyes at moderate risk to the graft from progressive endothelial failure. Baseline patient data, including indications for transplant, intraoperative complication rates, and early postoperative complication rates are described herein. METHODS: This study was a multicenter prospective, double-masked, controlled clinical trial. RESULTS: Fuchs dystrophy was the most common indication for corneal transplantation (61%). Intraoperative complications occurred in 33 (3%) patients. A persistent epithelial defect was the most commonly reported postoperative complication, occurring in 92 patients (8%). CONCLUSION: Intraoperative and postoperative complication rates were low. There was no apparent association between donor or recipient age and either intraoperative or early postoperative complication rates.

Adult↗

Prospective testing of the Brisbane Postnatal Depression Index.

BACKGROUND: Over 50 percent of women have one or more risk factors for postnatal depression during pregnancy or in the perinatal period, but only 10 to 15 percent become clinically depressed. The objective of this study was to prospectively test the Brisbane Postnatal Depression Index (referred to here as Index), to validate a theoretical index that was developed earlier, and to establish whether the index could be introduced as a clinically useful method to detect women who may be at risk for developing postnatal depression. METHODS: Antenatally, women were asked about social support and about personal and family history of mental illness, including postnatal depression. Responses were scored according to predefined ratings on the Index. In the postnatal wards, 353 women were recruited and their scores for "blues," social support, feelings about the baby, and satisfaction with the birth process were added. Sixteen weeks after hospital discharge, women were asked to complete the Edinburgh Postnatal Depression Scale. The Brisbane Index was validated by the number of women scoring more than 12 on the Edinburgh Postnatal Depression Scale at 16 weeks postpartum who were correctly predicted by a score of more than 6 on the Index. Sensitivity, specificity, positive predictive value, and negative predictive value for the Index, using >6 as a cutoff point, were calculated. "Ease of use" was assessed informally with participants and staff responsible for administration and scoring the instrument. RESULTS: Compared with results from the derivation study, prospective testing of the index showed an improvement in sensitivity from 36.3 to 47.5 percent and a small decrease in specificity, but no improvement on the positive predictive value from 39.8 to 39.6 percent. CONCLUSION: The Brisbane Postnatal Depression Index was validated in a prospective sample, but its sensitivity and specificity require improvement before introduction as a measure of prediction.

Adult↗

Rat cytomegalovirus-accelerated transplant vascular sclerosis is reduced with mutation of the chemokine-receptor R33.

Cytomegalovirus (CMV) infection accelerates transplant vascular sclerosis (TVS) and chronic rejection (CR) in both human and animal solid organ transplantation models. The host/viral mechanisms involved in this process are unclear. We examine the role of the rat CMV (RCMV)-encoded chemokine-receptor R33 in the development of TVS using a rat heart transplantation/CR model. F344 heart grafts were transplanted heterotopically into Lewis recipients. The ability of RCMV lacking the R33 gene (RCMV-Deltar33) to accelerate CR/TVS (neointimal index, NI) was compared to wild-type (WT) RCMV. Allograft recipients were infected with 1 x 10(5) pfu RCMV or RCMV-Deltar33 on postoperative day (POD) 1. Grafts from RCMV-Deltar33-infected recipients demonstrated an accelerated time to allograft CR compared to grafts from uninfected recipients (POD = 56 vs. 90), this was slower than that seen in grafts from WT-RCMV-infected recipients (POD = 45). Similarly, the degree of graft TVS formation at terminal rejection in RMCV-Deltar33 infected recipients was more severe than uninfected recipients (NI = 63 vs. 45), yet not as severe as in WT-RCMV infected recipients (NI = 83). In parallel, RCMV-Deltar33 failed to induce vascular smooth muscle cell (SMC) migration in vitro, whereas WT-RCMV induced substantial migration. The RCMV-encoded chemokine-receptor r33 is critical for RCMV-accelerated TVS/CR and vascular SMC migration.

Animals↗

Recombinant human leptin in women with hypothalamic amenorrhea.

BACKGROUND: Disruptions in hypothalamic-gonadal and other endocrine axes due to energy deficits are associated with low levels of the adipocyte-secreted hormone leptin and may result in hypothalamic amenorrhea. We hypothesized that exogenous recombinant leptin replacement would improve reproductive and neuroendocrine function in women with hypothalamic amenorrhea. METHODS: Eight women with hypothalamic amenorrhea due to strenuous exercise or low weight were studied for one month before receiving recombinant human leptin and then while receiving treatment for up to three months. Six control subjects with hypothalamic amenorrhea received no treatment and were studied for a mean (+/-SD) of 8.5+/-8.1 months. RESULTS: Luteinizing hormone (LH) pulsatility, body weight, ovarian variables, and hormone levels did not change significantly over time in the controls and during a one-month control period before recombinant leptin therapy in the treated subjects. In contrast, recombinant leptin treatment increased mean LH levels and LH pulse frequency after two weeks and increased maximal follicular diameter, the number of dominant follicles, ovarian volume, and estradiol levels over a period of three months. Three patients had an ovulatory menstrual cycle (P<0.05 for the comparison with an expected rate of spontaneous ovulation of 10 percent); two others had preovulatory follicular development and withdrawal bleeding during treatment (P<0.05). Recombinant leptin significantly increased levels of free triiodothyronine, free thyroxine, insulin-like growth factor 1, insulin-like growth factor-binding protein 3, bone alkaline phosphatase, and osteocalcin but not cortisol, corticotropin, or urinary N-telopeptide. CONCLUSIONS: Leptin administration for the relative leptin deficiency in women with hypothalamic amenorrhea appears to improve reproductive, thyroid, and growth hormone axes and markers of bone formation, suggesting that leptin, a peripheral signal reflecting the adequacy of energy stores, is required for normal reproductive and neuroendocrine function.

Adult↗

New approach to quantifying developmental variation in the dentition using serial microtomographic imaging.

Dental morphogenesis and cellular differentiation are expressed in the fully formed tooth by the topography of the dentin-enamel junction and outer enamel surface. These boundaries can be differentiated using a variety of imaging systems. In this study, we used serial microCT imaging to provide accurate 3D reconstructions of developing lower human second deciduous molars. These were used to quantify the volume of enamel and dentin of individual cusps in relation to basal crown height. As growth and differentiation proceed apically, the spatial orientation of cusp tips and their bases were used to estimate their order of initiation and coalescence. We found that the order of coalescence differed from the order of initiation. We also found that dentin cusp height and volume as well as rate and quantity of enamel apposition varied along mesio-distal and bucco-lingual axes, and were independent of order of initiation and duration of growth. These results demonstrate that the potential for variation in crown size and form is maintained throughout development. We propose that the microCT model developed in this study constitutes a new approach for the investigation of developmental variation and its contribution to phylogenetic variation expressed in crown form and size.

Dental Enamel↗

Evidence of amelogenesis imperfecta in an early African Homo erectus.

The teeth of the Homo erectus child (Garba IV) recovered from Melka Kunture Ethiopia and dated to 1.5 Ma are characterized by generalized enamel dysplasia, reduced enamel radio-opacity, and severe attrition. This combination of features is found in a large group of hereditary, generalized enamel dysplasias known as amelogenesis imperfecta (AI). SEM studies carried out on epoxy replicas of teeth from the Garba IV child, confirmed that the defects noted were developmental and not due to diagenesis. The enamel prism arrangement is abnormal and there are deep vertical furrows lacking enamel on both buccal and lingual surfaces of all molars. The lesions differ from those characteristic of linear enamel hypoplasia that form discrete horizontal lesions or pits within otherwise normal enamel. We propose that the Garba IV child is the earliest example of AI and provides a link between palaeoanthropology and molecular biology in investigations of the evolutionary history of genetic disorders.

Amelogenesis Imperfecta↗

The policy analysis of 'values talk': lessons from Canadian health reform.

Despite widespread recognition of the importance of values, decision makers and stakeholders in health policy appear to disagree fundamentally over what 'values' essentially are. Hidden dissent about the nature of values can confuse policy deliberations. This study investigates empirically the following two questions: (1) what sorts of entities do Canadian health reformers typically call 'values'? and; (2) how do Canadian health reformers use the idea of values in health reform rhetoric? We conducted a qualitative, interpretive analysis of 36 Canadian health reform documents published during the period 1990-1999. The values raised in Canadian health reform rhetoric vary widely not only in topic (e.g. health states, health services, equity, economic viability, etc.) but also in substance (e.g. physical entities, goals, principles, attitudes, etc.). We review the diversity of concepts underlying 'values talk' in health policy, and discuss implications for policy analysis and future research.

Canada↗

Identification of proteins in human cytomegalovirus (HCMV) particles: the HCMV proteome.

Human cytomegalovirus (HCMV), a member of the herpesvirus family, is a large complex enveloped virus composed of both viral and cellular gene products. While the sequence of the HCMV genome has been known for over a decade, the full set of viral and cellular proteins that compose the HCMV virion are unknown. To approach this problem we have utilized gel-free two-dimensional capillary liquid chromatography-tandem mass spectrometry (MS/MS) and Fourier transform ion cyclotron resonance MS to identify and determine the relative abundances of viral and cellular proteins in purified HCMV AD169 virions and dense bodies. Analysis of the proteins from purified HCMV virion preparations has indicated that the particle contains significantly more viral proteins than previously known. In this study, we identified 71 HCMV-encoded proteins that included 12 proteins encoded by known viral open reading frames (ORFs) previously not associated with virions and 12 proteins from novel viral ORFs. Analysis of the relative abundance of HCMV proteins indicated that the predominant virion protein was the pp65 tegument protein and that gM rather than gB was the most abundant glycoprotein. We have also identified over 70 host cellular proteins in HCMV virions, which include cellular structural proteins, enzymes, and chaperones. In addition, analysis of HCMV dense bodies indicated that these viral particles are composed of 29 viral proteins with a reduced quantity of cellular proteins in comparison to HCMV virions. This study provides the first comprehensive quantitative analysis of the viral and cellular proteins that compose infectious particles of a large complex virus.

Cells, Cultured↗

Acute hemodynamic benefit of multisite ventricular pacing after congenital heart surgery.

BACKGROUND: Cardiac dysfunction after congenital heart surgery is a major cause of morbidity and mortality. Cardiac resynchronization through multisite ventricular pacing (MSVP) improves cardiac index and ventricular function, and lowers systemic vascular resistance (SVR) in adults with heart failure and interventricular conduction delay. METHODS: The acute hemodynamic effects of MSVP after congenital heart surgery were assessed. Twenty-nine patients (aged 1 week to 17 years) with prolonged QRS interval had atrial and ventricular unipolar epicardial temporary pacing leads placed at surgery. Group 1 consisted of patients with a single ventricle (n = 14); group 2 included patients with two-ventricle anatomy (tetralogy of Fallot, ventricular septal defect) undergoing ventricular surgery (n = 10); and group 3 included patients with two-ventricle anatomy undergoing other cardiac surgery (n = 5). At a mean postoperative day 1 (range, 0 to 6), blood pressure, systemic and mixed venous oxygen saturations, electrocardiograms, and echocardiograms were obtained before and after 20 minutes of MSVP. RESULTS: The QRS duration decreased with MSVP in all patients (mean, 23%, p < 0.005). Systolic blood pressure improved in all patients (mean, 9.7%, p < 0.005). Cardiac index improved in 19 of 21 patients tested, with no change in 2 patients (mean, 15.1%, p = 0.0001). In 2 patients, MSVP facilitated weaning from cardiopulmonary bypass. Echocardiographic mitral or tricuspid valve inflow was not significantly different with MSVP. CONCLUSIONS: Multisite ventricular pacing results in improved cardiac index and increased systolic blood pressure, and it can also facilitate weaning from cardiopulmonary bypass. Multisite ventricular pacing may be used as adjunct to standard postoperative treatment of cardiac dysfunction after congenital heart surgery.

Adolescent↗

Deliberations about deliberative methods: issues in the design and evaluation of public participation processes.

A common thread weaving through the current public participation debate is the need for new approaches that emphasize two-way interaction between decision makers and the public as well as deliberation among participants. Increasingly complex decision making processes require a more informed citizenry that has weighed the evidence on the issue, discussed and debated potential decision options and arrived at a mutually agreed upon decision or at least one by which all parties can abide. We explore the recent fascination with deliberative methods for public involvement first by examining their origins within democratic theory, and then by focusing on the experiences with deliberative methods within the health sector. In doing so, we answer the following questions "What are deliberative methods and why have they become so popular? What are their potential contributions to the health sector?" We use this critical review of the literature as the basis for developing general principles that can be used to guide the design and evaluation of public involvement processes for the health-care sector in particular.

Community Participation↗

Graduate health professions education: an interdisciplinary university - community partnership model 1996 - 2001.

INTRODUCTION: In 1996, East Tennessee State University (ETSU) reinforced its historical commitment to multidisciplinary community engagement by developing a graduate level community partnerships program in the Division of Health Sciences. While the university's earlier health partnership efforts relied primarily on curricular innovation, the approach to graduate health professions education was to seed a series of curricular enhancements and interdisciplinary, community-based learning experiences and service into traditional curricula. This paper presents the experience of one school in crafting a regional network that became the basis of a division-wide graduate level teaching and learning initiative. INNOVATIONS AND EVALUATION: Carefully selected planning and implementation techniques enabled multidisciplinary practitioners and community members from across a 20-county region to participate with university faculty in training ETSU learners in community-based medical care. By year four of the project, curricular "enhancements" were institutionalized in over five departments across the Division and engaged 1160 medical residents and graduate learners in a give - get model of health education. Programme evaluation methodology was collaboratively defined and documentation of programme effort and outcomes regularly reported and strategically reviewed. CONCLUSIONS: Programme evaluation demonstrates mutual benefit to community and university. Faculty involvement in programme activity increased fourfold and community involvement in training of health professions graduate learners increased threefold by year four. Educational innovations were adopted into traditional curricula, thousands of hours of clinical services were provided to underserved communities and the university-community team forged by network links continues to promote multidisciplinary interests through joint public policy endeavors.

Appalachian Region↗

Serum leptin and IGF-I during growth hormone treatment in chronic renal failure.

Serum leptin decreases during growth hormone (hGH) treatment and pre-treatment values have been suggested as a predictor of the response to hGH in GH deficiency (GHD) but not in non-GHD syndromes. To investigate whether this holds true in children with chronic renal failure (CRF), we evaluated changes in serum leptin, insulin-like growth factor-I (IGF-I) and height before(b) and during the 1st year (3 months, 6 months, 9 months, 12 months) of hGH treatment (1 IU/kg per week) in 11 children (median age(b) 10.1 years, mean height(b) -2.9 SDS) with CRF. Serum leptin and IGF-I were compared with values from healthy children. Each patient also served as his/her own control, with values during treatment compared with those before treatment. Growth improved in all patients during treatment (mean change(12 m) +7.2 cm, change in height SDS(12 m) +0.5, P=0.001). Weight decreased (median decrease(12 m) 0.3 SDS, P=0.02) but body mass index (BMI) and serum leptin did not change during treatment. Serum IGF-I levels were low before (mean -1.1 SDS) but increased during hGH treatment, the increment being greatest at 10 days (mean increment +1.9 SDS, P<0.0001). Serum leptin(b) did not correlate with change in serum IGF-I(10d), height(12 m) or weight(12 m). Serum IGF-I SDS(b) correlated with height SDS at 12 months ( r=0.80, P=0.006) of hGH treatment. Serum leptin(b) correlated with BMI ( r(s)=0.75, P=0.01). Levels adjusted for BMI did not differ from values in healthy children and did not change during treatment. Despite an IGF-I and growth response during hGH treatment, serum leptin did not change and pre-treatment values did not predict the growth response in these children with CRF.

Adipose Tissue↗

Stories from frequent attenders: a qualitative study in primary care.

PURPOSE: Patients who make frequent office visits (frequent attenders) in primary care are often considered a major burden on resources, yet we know little about their perceptions and expectations. We wanted to explore how these patients viewed their rates of consultation, what they expected from the consultation, and how they perceived their relationship with the primary health care team. METHODS: Using a qualitative study design, we undertook in-depth semi-structured interviews with frequent attenders at 4 primary care practices of the Mersey Primary Care R&D Consortium in the North West of England. Participants were identified on the basis of office visits at least twice the mean standardized rate for 1 year and a medical assessment that these visits had no important clinical outcome. Interviews with 30 patients aged 24 to 81 years (18 men) were audiotaped and transcribed, and the text was methodically coded; data were analyzed by generating common themes. RESULTS: Participants were unable or unwilling to quantify their consultation rates. Despite the assertion by many participants that family doctors are caring, authority figures, there was an underlying tension between such perceptions and the apparent medical mismanagement of symptoms. Their expectations of the consultation were complex and included the presentation of old and new symptoms implicitly embedded within an illness framework. Gaining access to family doctors was generally perceived as problematic. CONCLUSION: The criteria held by family doctors and researchers regarding the appropriate rate of consultations in primary care may not be shared by patients who attend frequently. Such patients require family doctors to acknowledge their symptoms and to provide reassurance.

Adult↗