Search PubMed⌕ Search

Biomedical subjects

G Smith

Publications and source records attributed to G Smith.

At least 217 records · Page 12Linked to original sources
PubMed1999

Identification of human herpesvirus 8-specific cytotoxic T-cell responses.

Human herpesvirus 8 (HHV-8) (or Kaposi's sarcoma-associated herpesvirus) is implicated in the etiopathogenesis of Kaposi's sarcoma (KS) and certain lymphoproliferations. The introduction of more effective therapies to treat human immunodeficiency virus infection has led to a decline in the incidence of KS and also in the resolution of KS in those already affected. This suggests that cellular immune responses including cytotoxic T lymphocytes (CTLs) could play a vital role in the control of HHV-8 infection and in KS pathogenesis. Here we elucidate HLA class I-restricted, HHV-8-specific cellular immune responses that could be important in the control of HHV-8 infection and subsequent tumor development. We show the presence of CTLs against HHV-8 latent (K12), lytic (K8.1), and highly variable (K1) proteins in infected individuals.

AIDS-Related Opportunistic Infections↗
PubMed1999

Immunolocalisation of the VEGF receptors FLT-1, KDR, and FLT-4 in diabetic retinopathy.

AIM: To determine the spatial and temporal changes in the staining pattern of the VEGF receptors FLT-1, KDR, and the putative receptor FLT-4 during the pathogenesis of diabetic retinopathy. METHODS: Immunohistochemical localisation of VEGF receptors, using antibodies against FLT-1, FLT-4, and KDR, was carried out on specimens of normal human retina (n = 10), diabetic retinas (a) with no overt retinopathy (n = 12), (b) with intraretinal vascular abnormalities but no proliferative retinopathy (n = 5), (c) with active proliferative retinopathy (n = 6), and (d) with no residual proliferative retinopathy after scatter photocoagulation therapy (n = 14), and surgically excised diabetic fibrovascular membranes (n = 11). The degree and pattern of immunostaining was recorded. RESULTS: FLT-1 staining was apparent in the retinas from both non-diabetic and diabetic retinas; weak to moderate staining was generally confined to the inner nuclear layer, the ganglion cell layer, and the retinal vessels during all stages of the disease process. Staining of the retinal vessels was raised in diabetic tissue compared with non-diabetic tissue. The preretinal vessels of the diabetic subjects stained moderately to intensely for FLT-1. In contrast with FLT-1 staining minimal immunostaining for KDR was demonstrated in the non-diabetic eyes and the unlasered eyes; however, weak staining for KDR was observed in the inner nuclear layer and the ganglion cell layer of the unlasered eyes with diabetic changes. In those retinas with preretinal neovascularisation KDR immunoreactivity was moderate to intense in the intra- and preretinal vessels. However, in the excised membranes, where the vessels may have been in a quiescent state, the levels of KDR were weak to moderate. After apparently successful laser treatment KDR staining was reduced in the intraretinal vessels. Minimal FLT-4 staining was observed throughout normal eyes while weak to moderate FLT-4 staining was generally confined to the inner nuclear layer and the ganglion cell layer of the unlasered diabetic eyes. Weak to moderate levels of FLT-4 staining were observed in the intraretinal vessels except after apparently successful laser treatment where reduced levels of staining were observed. Weak to moderate staining was observed in the preretinal vessels. CONCLUSIONS: This study supports a role for FLT-1, KDR, and possibly FLT-4 in the pathogenesis of diabetic retinopathy; however, their specific roles in the progression of the disease may differ.

Aged↗
PubMed1999

Clearance of lower-pole stones following shock wave lithotripsy: effect of the infundibulopelvic angle.

OBJECTIVE: To assess the effect of anatomic factors, especially the angle of the lower-pole infundibulum, on stone clearance following shock wave lithotripsy (SWL) in order to determine selection criteria for percutaneous nephrolithotomy. METHODS: We retrospectively analyzed 116 patients with single lower-pole stones measuring 11-20 mm treated with SWL. Intravenous urograms were reviewed to measure the infundibulopelvic angle, the angle of the infundibulum to the vertical, and the anatomy of lower-pole calyces. RESULTS: The overall stone-free rate was 52%. Factors most closely associated with a stone-free status were obtuse infundibulopelvic angle, lack of calyceal distortion, and a large infundibular diameter. The infundibulopelvic angle was the only factor to attain significance in predicting stone-free status (p = 0.012). The size of the stone did not predict eventual stone-free status (p = 0.911), but larger stones were more likely to require intervention after SWL. CONCLUSION: For solitary lower-pole stones 11-20 mm in size, the angle of the lower-pole infundibulum as it relates to the pelvis plays a role in eventual stone clearance and should be taken into account before choosing a mode of treatment.

Adolescent↗
PubMed1999

Home medical equipment receipt in a home care appropriate population.

OBJECTIVES: This study examines home medical equipment (HME) receipt for 1,040 veterans considered appropriate for home health services. METHODS: HME receipt was monitored for 12 months using the Department of Veterans Affairs' Prosthetics database. RESULTS: Eighty-three percent received at least one item; averaging 7.4 items (SD = 6.8). The most common items included commodes/bath benches (9%), canes/walkers (7%), safety equipment (7%), liquid oxygen (6%), and wheelchairs (6%). Two functional status variables, home care use and race, correctly classified 69% of HME recipients. Logistic regressions were run for specific equipment; c-indices ranged from .64 to .75. Age, race, income, functional status, risk of hospital readmission, and home care use were significant predictors. DISCUSSION: HME accounted for $4.5 billion in sales (16% of total) for medical products in 1996. As the HME market continues to expand, the characteristics of HME recipients are necessary to project future HME needs in a growing, elderly population.

Equipment and Supplies↗
PubMed1999

Statistical adequacy of the Abel Assessment for Interest in Paraphilias.

A review of the psychometric properties of the Abel Assessment for Interest in Paraphilias (AAIP) is presented. The data supporting the AAIP's history, purpose, data, reliability, validity, and norms are reported, with the conclusion that its use with adults is tenuous at best and its use with adolescents is as yet unsupported. Pragmatic concerns are noted, along with recommendations for further research.

Adolescent↗
PubMed1999

Assessment of juvenile sexual offenders: reliability and validity of the Abel Assessment for Interest in Paraphilias.

Empirical tests of the reliability and validity of the Abel Assessment for Interest in Paraphilias (AAIP) as used with juvenile sexual offenders were performed. Test-retest reliability, screening validity, and diagnostic validity were assessed using several analytical approaches. The temporal stability, sensitivity, and specificity of the AAIP as used with adolescents in residential and day treatment were not demonstrated. The results indicate the need for further refinement of the AAIP.

Adolescent↗
PubMed1999

Pharmacogenetics.

Inter-individual variability in drug response is a major clinical problem. Adverse drug reactions (ADRs) are common, are responsible for a number of debilitating side effects following drug therapy and are a significant cause of death. It is now clear that much of the observed variability in drug response has a genetic basis, arising as a result of genetically-determined differences in drug absorption, disposition, metabolism or excretion. The best characterised pharmacogenetic polymorphisms are those within the phase I cytochrome P450 family of drug metabolising enzymes. One of these enzymes, CYP2D6 (debrisoquine hydroxylase), metabolizes one-quarter of all prescribed drugs and is inactive in 6% of the Caucasian population. Individuals at risk of developing ADRs as a result of genetically-determined variation in genes such as CYP2D6 can now be identified using DNA-based tests. A detailed knowledge of the genetic basis of individual drug response is potentially of major clinical and economic importance and could provide the basis for a rational approach to drug prescription. This would have significant benefits for human health.

Cytochrome P-450 Enzyme System↗
PubMed1999

Fractures of the femoral shaft in children. Incidence, mechanisms, and sociodemographic risk factors.

BACKGROUND: Fractures of the femoral shaft in children are caused by major musculoskeletal trauma and result in high direct and indirect medical costs. To date, the American literature has focused on treatment options and outcomes, but the epidemiology of these injuries has been generalized from Scandinavian studies reported in the 1970s and early 1980s. The goals of the current study were (1) to determine the age, gender, and race-specific rates and mechanisms of fractures of the femoral shaft in children in a large United-States-based population and (2) to identify associations between the rates of these fractures and multiple sociodemographic indicators. Such information is vital for preventive efforts. METHODS: The Hospital Discharge Database of the Maryland Health Services Cost Review Commission for the years 1990 through 1996 was used to obtain demographic data on 1485 cases of acute fracture of the femoral shaft in patients who were less than eighteen years old, and data from the United States Bureau of the Census for the state of Maryland for the year 1990 were used to obtain denominator data. Reliable external-cause data were available from the 1995 and 1996 databases for 472 patients. Small-area analysis was performed at the zip-code level to determine associations between numerous sociodemographic indicators and the rate of femoral shaft fracture. RESULTS: The annual rate of femoral shaft fracture in children was 19.15 per 100,000. With regard to age, there was a bimodal distribution, with peaks at two and seventeen years. Boys had higher rates of fracture than did girls at all ages, and blacks had higher rates than did whites. The primary mechanisms of fracture were age-dependent and included falls, for children less than six years old; motor vehicle-pedestrian accidents, for those six to nine years old; and motor-vehicle accidents, for teenagers. Firearm-related injuries accounted for 15 percent of the fractures among black adolescents. Adverse socioeconomic conditions were significantly associated with higher rates of fracture. CONCLUSIONS: The rates and mechanisms of femoral shaft fractures in children depend on age, gender, and race. For children living in the United States today, the epidemiology of these fractures is different than that described in earlier, Scandinavian reports.

Adolescent↗
PubMed1999

Adaptive responses to environmental chemicals.

Adaption to chemical agents in the environment is a fundamental part of the evolutionary process and a large number of genes have evolved to specifically detoxify potentially harmful chemical agents. These genes can act at various levels within cells and determine circulating chemical or toxin concentrations, and uptake and efflux rates as well as intracellular detoxification enzymes, such as the cytochrome P-450-dependent mono-oxygenases and glutathione S-transferases. These multigene families of proteins play a central role in chemical and drug detoxification and their polymorphic expression may well be a factor in disease susceptibility.

Adaptation, Physiological↗
PubMed1999

Successful treatment of severe muscle necrosis with intravenous immunoglobulin.

Intravenous immunoglobulin (IVIG) is an effective treatment for a range of conditions believed to have an autoimmune basis, including inflammatory muscle disease. We describe a patient with muscle disease characterized by severe necrosis without clinical or biopsy evidence of inflammation or vasculitis, who responded to treatment with IVIG.

Biopsy↗
PubMed1999

Dopamine systems in human immunodeficiency virus-associated dementia.

OBJECTIVE: To provide an update of the neurobiologic basis of human immunodeficiency virus (HIV)-associated dementia (HAD), with emphasis on the relationship between dopamine (DA) system dysfunction and behavioral manifestations. BACKGROUND: HIV has a propensity to invade subcortical central nervous system areas, particularly the basal ganglia. Indeed, the core symptoms of HAD are similar to those seen in patients with frontal-striatal dysfunction, the "subcortical dementias" (e.g., Parkinson disease, Huntington disease, progressive supranuclear palsy). FINDINGS: Damage to DA neurons appears to occur in early stages of the disease. Patients with HIV have decreased levels of cerebrospinal fluid DA, and patients with HAD have a reduction of the DA metabolite homovanillic acid but a relative preservation of other neurotransmitters, suggesting a loss of DA neurons. Neuropathologic examinations have shown neuronal loss of the globus pallidus, which is less severe in the neocortex. Furthermore, extrapyramidal signs and marked hypersensitivity to DA antagonists (e.g., neuroleptics) have a propensity to develop in patients with acquired immunodeficiency syndrome. CONCLUSIONS: Neurobiologic investigations suggest that DA system dysfunction plays a critical role in the clinical manifestation of HIV infection, especially HAD. The causes of the vulnerability of this system to the infection are unknown. Understanding this mechanism is important to develop neuroprotective agents in the treatment of HAD and to design new therapies for HAD-related psychiatric symptoms.

AIDS Dementia Complex↗
PubMed1999

Cytochrome P450 CYP2D6.

Altered expression of CYP2D6 (debrisoquine hydroxylase), resulting from genetic polymorphism at the CYP2D6 gene locus, is responsible for pronounced interindividual variation in the metabolism of many clinically important drugs. Although CYP2D6 substrates are structurally diverse, most are small molecules that interact with the protein via an electrostatic interaction between a basic nitrogen which is common to the majority of CYP2D6 substrates and an aspartic acid residue in the active site of the protein. As CYP2D6 substrates have a wide range of pharmacological functions, any variation in CYP2D6 expression can have profound clinical consequences. CYP2D6 activity can be determined both by phenotyping methods with a variety of probe drugs and by genotyping methods where PCR-based techniques are used to investigate the inheritance of individual CYP2D6 alleles. Allele frequencies have been shown to vary widely between populations of different racial origin. For example, the PM genotype is particularly rare in Orientals. The inheritance of certain CYP2D6 allelic variants has been associated with altered susceptibility to Parkinson's disease and several types of cancer.

Alleles↗
PubMed1998

Safety and immunogenicity of HIV recombinant envelope vaccines in HIV-infected infants and children. National Institutes of Health-sponsored Pediatric AIDS Clinical Trials Group (ACTG-218).

Study objectives were to evaluate the safety and immunogenicity of three HIV recombinant glycoproteins in HIV-infected infants and children between 1 month and 18 years of age with asymptomatic (P-1) infection. Using Chiron rgp 120 (SF-2) 15 or 50 microg; MicroGeneSys rgp 160 (IIIB) 40 or 320 microg; Genentech rgp120 (MN) 75 or 300 microg; or adjuvant control (Alum or MF-59), children were randomized to a double-blind, placebo-controlled, dose-escalating study of vaccine administered intramuscularly at entry and 1, 2, 3, 4, and 6 months later. No adverse events were attributed to study vaccines. Between 30% and 56% of volunteers exhibited a lymphoproliferative response as defined in terms of stimulation index (SI) to vaccine antigens; 65% of vaccinees but none of placebo recipients exhibited moderate or strong responses after enzyme immunoassay to HIV specific antigens. CD4 cell counts and quantitative HIV culture did not differ significantly among vaccine and control groups, nor were differences found among groups in HIV disease progression. The rgp160 and gp120 subunit vaccines were safe and immunogenic in this population.

AIDS Vaccines↗
PubMed1998

Brain function in spider phobia.

Measurements of regional cerebral blood flow (rCBF) were performed in 16 women suffering from spider phobia. The non-invasive 133Xe inhalation method, giving information about the blood flow of superficial areas, was used. The subjects were studied under three conditions: during resting, when exposed to a videotape showing nature scenery, and finally when watching a video with living spiders. During the rCBF measurements the subjects' behaviour was registered systematically and respiration, blood pressure, Pco2, and heart rate were monitored. Eight subjects who showed and reported severe panic during the spider exposure had marked rCBF decreases in frontal areas, especially in the right hemisphere. The remaining eight subjects displayed a more efficient control of their emotions and became frightened, but not panic-stricken, during the spider exposure. These showed a consistent rCBF increase in the right frontal area compared to neutral stimulation. Thus, results revealed significant functional changes in the frontal cortex in subjects with spider phobia during phobogenic exposure. It seems likely that these frontal changes are related to the experience and control of phobic anxiety.

Adult↗
PubMed1998

Reduced binding of [18F]altanserin to serotonin type 2A receptors in aging: persistence of effect after partial volume correction.

The serotonin (5-HT) neurotransmitter system, which has a widespread distribution in the central nervous system, has been implicated in regulating mood and many human behaviors. There is evidence from postmortem human studies and limited information from prior in vivo studies to support a decline in 5-HT2A receptor density with aging. We examined nine elderly (ages 61-76) and nine young (ages 18-29) healthy individuals with positron emission tomography (PET) and [18F]altanserin, a ligand with high affinity for the 5-HT2A binding site. The PET data were corrected for differences in brain tissue volume between the young and elderly subjects using a magnetic resonance (MR) imaging-based partial volume correction method. Highly significant and widespread cortical reductions in 5-HT2A specific binding were demonstrated in the elderly group relative to young controls. Regional losses averaged 61% before and 57% following correction for effects of cerebral atrophy. This finding, which is consistent with prior postmortem and in vivo studies, has both etiological and potential therapeutic implications for behavioral changes commonly observed in the elderly, including geriatric depression.

Adolescent↗