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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 271 records · Page 15Linked to original sources
PubMed2000

Stereolithography: a potential new tool in forensic medicine.

Stereolithography is a computer-mediated method that can be used to quickly create anatomically correct three-dimensional epoxy and acrylic resin models from various types of medical data. Multiple imaging modalities can be exploited, including computed tomography and magnetic resonance imaging. The technology was first developed and used in 1986 to overcome limitations in previous computer-aided manufacturing/milling techniques. Stereolithography is presently used to accurately reproduce both the external and internal anatomy of body structures. Current medical uses of stereolithography include preoperative planning of orthopedic and maxillofacial surgeries, the fabrication of custom prosthetic devices; and the assessment of the degree of bony and soft-tissue injury caused by trauma. We propose that there is a useful, as yet untapped, potential for this technology in forensic medicine.

Forensic Anthropology↗
PubMed2000

Timing of perinatal human immunodeficiency virus type 1 infection and rate of neurodevelopment. The Women and Infant Transmission Study Group.

BACKGROUND: Identifying HIV-1-infected children who are at greatest risk for disease-related morbidities is critical for optimal therapeutic as well as preventive care. Several factors have been implicated in HIV-1 disease onset and severity, including maternal and infant host characteristics, viral phenotype and timing of HIV-1 infection. Early HIV-1 culture positivity, i.e. intrauterine infection, has been associated with poor immunologic, virologic and clinical outcomes in children of HIV-infected women. However, a direct effect of timing of infection on neurodevelopmental outcome in infancy has not yet been identified. METHODS: Serial neurodevelopmental assessments were performed with 114 infants vertically infected with HIV-1 in a multicenter natural history, longitudinal study. Median mental and motor scores were compared at three time points. Longitudinal regression analyses were used to evaluate the neurodevelopmental functioning of children with early positive cultures and those with late positive cultures. RESULTS: Early infected infants scored significantly lower than late infected infants by 24 months of age and beyond on both mental (P = 0.05) and motor (P = 0.03) measures. Early HIV-1 infection was associated with a decline in estimated motor scores of 1 standard score point per month compared with 0.28 point in the late infected group (P < 0.02). Estimated mental scores of the early infected group declined 0.72 point/ month, whereas the average decline of the late infected group was 0.30 point/month (P < 0.13). CONCLUSION: Early HIV-1 infection increases a child's risk for poor neurodevelopmental functioning within the first 30 months of life.

Child Development↗
PubMed2000

NMR structure of a concatemer of the first and second ligand-binding modules of the human low-density lipoprotein receptor.

The ligand-binding domain of the human low-density lipoprotein receptor consists of seven modules, each of 40-45 residues. In the presence of calcium, these modules adopt a common polypeptide fold with three conserved disulfide bonds. A concatemer of the first and second modules (LB(1-2)) folds efficiently in the presence of calcium ions, forming the same disulfide connectivities as in the isolated modules. The three-dimensional structure of LB(1-2) has now been solved using two-dimensional 1H NMR spectroscopy and restrained molecular dynamics calculations. No intermodule nuclear Overhauser effects were observed, indicating the absence of persistent interaction between them. The near random-coil NH and H alpha chemical shifts and the low phi and psi angle order parameters of the four-residue linker suggest that it has considerable flexibility. The family of LB(1-2) structures superimposed well over LB1 or LB2, but not over both modules simultaneously. LB1 and LB2 have a similar pattern of calcium ligands, but the orientations of the indole rings of the tryptophan residues W23 and W66 differ, with the latter limiting solvent access to the calcium ion. From these studies, it appears that although most of the modules in the ligand-binding region of the receptor are joined by short segments, these linkers may impart considerable flexibility on this region.

Amino Acid Sequence↗
PubMed2000

Specificity of perceptual learning in a frequency discrimination task.

On a variety of visual tasks, improvement in perceptual discrimination with practice (perceptual learning) has been found to be specific to features of the training stimulus, including retinal location. This specificity has been interpreted as evidence that the learning reflects changes in neuronal tuning at relatively early processing stages. The aim of the present study was to examine the frequency specificity of human auditory perceptual learning in a frequency discrimination task. Difference limens for frequency (DLFs) were determined at 5 and 8 kHz, using a three-alternative forced choice method, for two groups of eight subjects before and after extensive training at one or the other frequency. Both groups showed substantial improvement at the training frequency, and much of this improvement generalized to the nontrained frequency. However, a small but statistically significant component of the improvement was specific to the training frequency. Whether this specificity reflects changes in neural frequency tuning or attentional changes remains unclear.

Adolescent↗
PubMed2000

Geomapping of chlamydia and gonorrhoea in Birmingham.

OBJECTIVE: To investigate if the core population hypothesis is applicable to patients with genital chlamydia infections. DESIGN: Retrospective cross sectional study. SETTING: Two genitourinary medicine (GUM) clinics in the city of Birmingham and eight adjacent clinics. SUBJECTS: All patients with chlamydia (n = 665) or gonorrhoea (n = 584) attending between 1 October 1995 and 30 September 1996 with a postcode within the Birmingham health district. Controls were 727 patients seen in the same period with no infection. METHODS: Postcodes were used to calculate population prevalence rates per 100,000 aged 15-65 in the 39 wards of the city and to estimate the socioeconomic status using the Super Profile (SP). Ethnic specific rates were also calculated. Data were obtained on gonorrhoea and chlamydia isolation from all the major laboratories of the city over the same time period. RESULTS: GUM clinic attenders accounted for 67.6% and 82.5% of all chlamydia and gonorrhoea isolates reported by the laboratories and that were available for our epidemiological analysis. Both infections were more common in men and in black ethnic groups. However, patients with gonorrhoea only infection were more likely to be of black ethnicity than those with chlamydia only infection (p = 0.0001) and to have different SP distribution (p = 0.0001). On logistic regression age < 20 years, male sex, black ethnicity, and living in neighbourhoods with SP J ("have nots") were predictive of both infections compared with controls. Overall chlamydia and gonorrhoea prevalence rates were 129 and 98.4 per 10(5) respectively. Corresponding rates for whites was 64.7 and 37.2 and for black ethnic groups 1105 and 1183 per 10(5) of each ethnic group. Eight adjacent wards accounted for 41% of the chlamydia and 66.5% of the gonorrhoea. CONCLUSION: In a large urban setting patients attending GUM clinics with chlamydia belong to core population groups with similar, but not identical, sociodemographic characteristics to patients with gonorrhoea infection.

Adolescent↗
PubMed2000

Characterization of pharyngeal resistance during sleep in a spectrum of sleep-disordered breathing.

Aims of the study were 1) to compare Hudgel's hyperbolic with Rohrer's polynomial model in describing the pressure-flow relationship, 2) to use this pressure-flow relationship to describe these resistances and to evaluate the effects of sleep stages on pharyngeal resistances, and 3) to compare these resistances to the pressure-to-flow ratio (DeltaP/V). We studied 12 patients: three with upper airway resistance syndrome (UARS), four with obstructive sleep hypopnea syndrome (OSHS), three with obstructive sleep apnea syndrome (OSAS), and two with simple snoring (SS). Transpharyngeal pressures were calculated between choanae and epiglottis. Flow was measured by use of a pneumotachometer. The pressure-flow relationship was established by using nonlinear regression and was appreciated by the Pearson's square (r(2)). Mean resistance at peak pressure (Rmax) was calculated according to the hyperbolic model during stable respiration. In 78% of the cases, the value of r(2) was greater when the hyperbolic model was used. We demonstrated that Rmax was in excellent agreement with P/V. UARS patients exhibited higher awake mean Rmax than normal subjects and other subgroups and a larger increase from wakefulness to slow-wave sleep than subjects with OSAS, OSHS, and SS. Analysis of breath-by-breath changes in Rmax was also a sensitive method to detect episodes of high resistance during sleep.

Adult↗
PubMed2000

Orthostatic hypotension as a risk factor for stroke: the atherosclerosis risk in communities (ARIC) study, 1987-1996.

BACKGROUND AND PURPOSE: The association between orthostatic hypotension (OH) and stroke has rarely been investigated in longitudinal studies. The purpose of the present study was to determine whether OH predicts ischemic stroke in a middle-aged, biethnic population after adjustment for known stroke risk factors. Diastolic, systolic, and consensus OH were evaluated for baseline associations and for the ability to predict stroke. METHODS: In 11 707 persons from the Atherosclerosis Risk in Communities (ARIC) cohort who were free of stroke and overt heart disease at baseline, Cox proportional hazards analyses modeled the association between OH at baseline and incident ischemic stroke over 7.9 years of follow-up. OH was defined as a systolic blood pressure drop >/=20 mm Hg (systolic OH), a diastolic blood pressure drop >/=10 mm Hg (diastolic OH), or a drop in either (consensus OH) when a person changed from a supine to standing position. RESULTS: OH was predictive of ischemic stroke, even after adjustment for numerous stroke risk factors (consensus OH: hazard ratio, 2.0; 95% CI, 1.2 to 3.2). While the baseline characteristics associated with OH varied depending on the type of OH, all types of OH had a similar risk of stroke. CONCLUSIONS: OH is an easily obtained measurement that may help to identify middle-aged persons at risk for stroke.

Age Distribution↗
PubMed2000

Antipsychotic drug use patterns and the cost of treating schizophrenia.

This study investigated the relationships between antipsychotic drug use patterns and direct costs for 3,321 Medi-Cal patients with schizophrenia. Ordinary least-squares regression models were used to estimate the impact on costs of receiving antipsychotic drug treatment, delays in treatment, changes in therapy, and continuous therapy. Average costs were $25,940 per year per patient. Having used an antipsychotic drug was correlated with lower psychiatric hospital costs ($2,846 less) but higher nursing home costs. Completing one year of uninterrupted drug therapy was correlated with higher nursing home costs. Delayed drug treatment and changes in therapy increased the cost by $9,418 and $9,719, respectively.

Adult↗
PubMed2000

Neurologic manifestations of Mycoplasma pneumoniae infections: diverse spectrum of diseases. A report of six cases and review of the literature.

Mycoplasma pneumoniae is a common cause of upper and lower respiratory tract infections of varying severity. It is also responsible for producing a wide spectrum of nonpulmonary manifestations including neurologic, hepatic, cardiac, and hematologic diseases. The neurologic manifestations are reported to be the most common nonpulmonary manifestations. We describe six patients demonstrating the protean neurologic manifestations of Mycoplasma pneumoniae infections. Four patients presented with the central nervous system manifestations of pyramidal and extrapyramidal tract dysfunction, seizures, cognitive abnormalities, and cerebellar dysfunction. Two patients presented with transverse myelitis. The outcome of this condition ranges from normal to severe residual deficits. Increased awareness of this disease entity may facilitate early diagnosis and thereby expedite starting appropriate therapy that may modify the outcome.

Adolescent↗
PubMed2000

Social support and physical and psychological recovery one year after myocardial infarction or coronary artery bypass surgery.

The aim of this study was to evaluate the role of different support factors supposed to explain physical and psychological recovery after myocardial infarction (MI) or coronary artery bypass surgery (CABS). The subjects comprised 147 MI patients and 159 CABS patients. Support factors included formal services, semi-formal assistance, and informal social support. The outcome measures used for analysis were functional activities level (Duke Activity Status Index, DASI), physical working capacity, anxiety, and depression one year after MI or CABS. In general, support factors had a limited role in this study. The patient's functional and psychological status at three months was the main determinant to recovery at one year. The outcome factors measured at three months explained 36-56% of their variance at one year, and the support factors increased the explanatory power by 0-10%. The support model employed in this study revealed that some single factors may have a positive or negative role in the recovery after MI or CABS.

Adult↗
PubMed2000

Corticotropin-releasing hormone gene expression in primary placental cells is modulated by cyclic adenosine 3',5'-monophosphate.

CRH, the principal neuropeptide regulator of pituitary ACTH secretion, is also expressed in placenta. Placental CRH has been linked to the process of human parturition. However, the mechanisms regulating transcription of the CRH gene in placenta remain unclear. cAMP signaling pathways play important roles in regulating the expression of a diverse range of endocrine genes in the placenta. Therefore, we have explored the effect of cAMP on CRH promoter activity in primary cultures of human placental cells. Both forskolin and 8-bromo-cAMP, activators of protein kinase A, can increase CRH promoter activity 5-fold in transiently transfected human primary placental cells, in a manner that parallels the increase in endogenous CRH peptide. Maximal stimulation of CRH promoter activity occurs at 500 micromol/L 8-bromo-cAMP and 10 micromol/L forskolin. Electrophoretic mobility shift assay and mutation analysis combined with transient transfection demonstrate that in placental cells cAMP stimulates CRH gene expression through a cAMP regulatory element in the proximal CRH promoter region and involves a placental nuclear protein interacting specifically with the cAMP regulatory element.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2000

Glucocorticoid stimulation of corticotropin-releasing hormone gene expression requires a cyclic adenosine 3',5'-monophosphate regulatory element in human primary placental cytotrophoblast cells.

Production of placental CRH, which is identical to the peptide synthesized and secreted in the hypothalamus, has been linked to human parturition. Glucocorticoids stimulate placental CRH secretion and messenger ribonucleic acid expression, in contrast to their inhibition of CRH synthesis in the hypothalamus. A positive feedforward loop involving glucocorticoid-CRH-ACTH-glucocorticoid is thought to drive the exponential increase in placental CRH leading to delivery. Tissue-specific effects of glucocorticoids on CRH expression are therefore of interest. Using human primary placental cells, we investigated the mechanism by which glucocorticoids stimulate placental CRH gene expression. Nuclear run-on transcription shows that in human placental cells glucocorticoids up-regulate transcription of human CRH (hCRH). Using transient transfection assays we demonstrate that dexamethasone up-regulates both basal and cAMP-stimulated hCRH promoter activity, correlating well with the increase in endogenous CRH peptide levels. Through mutagenesis and deletion analyses we show that dexamethasone stimulation of hCRH gene transcription requires a functional cAMP regulatory element (CRE); this CRE is adequate to confer dexamethasone stimulation upon a heterologous promoter, and electrophoretic mobility shift assay studies show that a placental nuclear protein specifically binds to the hCRH CRE.

Cell Nucleus↗
PubMed2000

Risedronate reverses bone loss in postmenopausal women with low bone mass: results from a multinational, double-blind, placebo-controlled trial. BMD-MN Study Group.

Our objective was to investigate the efficacy and tolerability of risedronate in postmenopausal women with low bone mass. Women with a mean lumbar spine T-score of -2 or less (n = 543) received 24 months of placebo or risedronate (2.5 or 5 mg/day). All received calcium (1 g/day). The principal outcome measures were bone mineral density (BMD) at the lumbar spine, femoral neck, and femoral trochanter. At 24 months, lumbar spine BMD increased from baseline by 4% with 5 mg risedronate and 1.4% in the 2.5-mg group, compared with no change with placebo. Efficacy was similar in women who were less than 5 yr and more than 5 yr postmenopausal. At 24 months, risedronate (5 mg) had also increased BMD at the femoral neck and trochanter, whereas BMD decreased in the placebo group. BMD increases were seen at all three sites with risedronate (5 mg) after only 6 months of therapy. Risedronate was well tolerated; upper gastrointestinal adverse events were similar to placebo. We conclude that risedronate (5 mg) increases BMD rapidly and effectively and is well tolerated in postmenopausal women with low bone mass, regardless of time since menopause.

Aged↗
PubMed2000

Expression of the heme oxygenase-carbon monoxide signalling system in human placenta.

Heme oxygenase (HO) catalyses the formation of endogenous carbon monoxide and bilirubin from heme. CO, a potent vasodilator, and bilirubin, an antioxidant may have local actions in the fetal-placental vasculature of the placenta. We sought evidence of expression of the two known isoforms of HO in normal human term placenta using reverse transcription polymerase chain reaction (RT-PCR), western blotting and immunohistochemistry. RT-PCR demonstrated the presence of messenger ribonucleic acid for HO-1 and HO-2. Immunoreactive proteins of appropriate size for each HO enzyme were identified in placental cell membrane preparations. Immunohistochemistry showed a wide distribution of HO immunoreactivity, including the syncytiotrophoblast layer of placental villi, the endothelium and smooth muscle cells of umbilical-placental blood vessels, and in all layers of the fetal membranes. These data demonstrate the expression of the two known isoforms of HO in human placenta and suggest that endogenous CO and bilirubin may have important roles in the control of placental vascular function.

Carbon Monoxide↗
PubMed2000

Early cognitive and motor development among infants born to women infected with human immunodeficiency virus. Women and Infants Transmission Study Group.

OBJECTIVE: To examine the frequency, timing, and factors associated with abnormal cognitive and motor development during the first 30 months of life in infants born to women infected with human immunodeficiency virus type 1 (HIV-1). METHODS: Serial neurodevelopmental assessment was performed with 595 infants born to women infected with HIV-1 in a multicenter, prospective, natural history cohort study. Survival analysis methods were used to evaluate 6 outcome events related to abnormal cognitive and motor growth (time to confirmed drop of 1 SD, time to first score <69, and time to confirmed drop of 2 SD) in Bayley Scales of Infant Development Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) scores among infected (n = 114) and uninfected (n = 481) infants. Proportional hazards modeling was used to evaluate the effects of HIV infection status, prematurity, prenatal exposure to illicit drugs, maternal educational attainment, and primary language. RESULTS: HIV-1 infection was significantly associated with increased risk for all outcome events related to abnormal mental and motor growth. Differences between infected and uninfected infants were apparent by 4 months of age. Prematurity was associated with increased risk for MDI <69 and PDI <69. Maternal education of <9 completed years was associated with increased risk for MDI <69. Neither prenatal exposure to illicit drugs nor primary language other than English was associated with abnormal development. CONCLUSION: A significant proportion of infants with HIV-1 infection show early and marked cognitive and motor delays or declines that may be important early indicators of HIV disease progression. These abnormalities are independent of other risk factors for developmental delay.

Adolescent↗