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Biomedical subjects

S R Smith

Publications and source records attributed to S R Smith.

At least 55 records · Page 3Linked to original sources
PubMed2001

The AIDS drug assistance programs and coverage of HIV-related medications.

BACKGROUND: AIDS drug assistance programs (ADAPs) have been implemented in each state to facilitate access to medications for low-income, uninsured, and underinsured people with HIV disease. Policies for each ADAP differ, and these differences influence the access people with HIV have to medications. OBJECTIVE: To compare the coverage of medications and sources of program funding for the state ADAPs. DESIGN: A self-administered mailed survey, sent to administrators of the 50 state ADAPs and the District of Columbia ADAP in December 1998. RESULTS: Forty-nine of the 51 ADAPs (96%) responded to the survey. Title II of the Ryan White Comprehensive AIDS Resources Emergency Act provided a large majority of the funding for the ADAPs, with a number of states also using state funds and/or Title I funds for their programs. The formularies of all ADAPs were nearly identical with respect to coverage of antiretrovirals, but differed in the number and types of other medications included. Some states limited access to medications through waiting lists, enrollment caps, and other policies. Sixteen ADAPs reported that the coverage of protease inhibitors resulted in an appropriation of state government funds to their ADAP, while eight states reported an ADAP budget shortfall. In general, ADAPs in poorer and more rural states included a fewer number of medications on their formularies. CONCLUSIONS: Access to antiretrovirals and other medications is available through state ADAPs, but may be limited in some states due to waiting lists, controls on the enrollment of new beneficiaries, and policies on the number and types of medications beneficiaries may receive.

Acquired Immunodeficiency Syndrome↗
PubMed2001

The non-ischaemic blue finger.

Finger discoloration may result from recognized conditions affecting upper limb vasculature. We describe 11 patients who presented with acute pain, swelling and blue/purple discoloration in a finger. This benign condition mimicked digital ischaemia. There were 9 women and 2 men. The episode usually started with an ache/pain in the finger followed 2-3 h later by a blue/purple discoloration primarily on the volar aspect but always sparing the tip. This completely resolved after 4-7 days with no residual deficit. There was no history of trauma. Four patients had had previous episodes--2 had been started on warfarin. There was no family history and only one gave a history of spontaneous bruising of her legs. Examination of all patients--pulse rate, blood pressure, cardiac and subclavian artery auscultation and digital artery Doppler insonation--was normal. All patients had normal full blood counts, CRP, vasculitis screen and clotting (except those on warfarin). Six similar cases, all women, were reported in 1982. There was no common aetiological factor other than sex. Although of no prognostic significance, the condition is likely to concern patients and doctors in primary care. The discoloration is, however, clearly of a different distribution to that in an ischaemic finger where the tip of the digit is involved.

Acute Disease↗
PubMed2001

Anti-plaque efficacy of a chalk-based antimicrobial dentifrice.

A chalk-based antimicrobial dentifrice was developed and has undergone in vitro testing to determine antimicrobial efficacy by kill-time studies, and in vivo clinical studies to determine anti-plaque build-up properties. The antimicrobial efficacy of the formulation is attributable to the following components; sodium lauryl sulphate, sodium monofluorophosphate, flavouring oils, triclosan, and low water activity. In vitro kill-time testing showed the dentifrice to have good activity against organisms associated with plaque, showing at least 99% reductions in the numbers of each organism. In vivo clinical results showed the dentifrice to protect against the build-up of plaque when compared to water alone. These results demonstrate that this dentifrice is effective in controlling plaque, and can thus be expected to promote good oral hygiene.

Analysis of Variance↗
PubMed2001

Lisfranc injury--surgical fixation facilities an early return to work.

BACKGROUND: Lisfranc injury is rare and the diagnosis maybe easily missed. This study reviews the experience of a single centre. METHODS: A prospective review of patients with Lisfranc injuries presenting to a single surgeon with a specialist interest in foot and ankle surgery over a one year period. RESULTS: Five patients were identified--four men and one woman with a median age of 31 years (range 22-50 years). Presentation was a mean of 25 days after injury (range 3-56 days). The left foot was affected in three cases and the right in two. There was joint diastasis in four patients and fracture-dislocation in one. Three patients presented early and were treated by internal fixation and two presented late and were managed conservatively. Mean follow-up was eight months (range 4.5-12 months). Surgery resulted in a return to work by 6 months with no symptoms. The two patients managed conservatively continued to experience pain at 12 months and were unable to return to their original occupations. CONCLUSION: Injury to the Lisfranc joint should be excluded in any foot injury. Early diagnosis and internal fixation appears to result in an earlier return to work when compared to non-operative management.

Adult↗
PubMed2000

Site-directed mutagenesis of 2,4-dichlorophenoxyacetic acid/alpha-ketoglutarate dioxygenase. Identification of residues involved in metallocenter formation and substrate binding.

2,4-dichlorophenoxyacetic acid (2,4-D)/alpha-ketoglutarate (alpha-KG) dioxygenase (TfdA) is an Fe(II)-dependent enzyme that catalyzes the first step in degradation of the herbicide 2,4-D. The active site structures of a small number of enzymes within the alpha-KG-dependent dioxygenase superfamily have been characterized and shown to have a similar HXDX(50-70)HX(10)RXS arrangement of residues that make up the binding sites for Fe(II) and alpha-KG. TfdA does not have obvious homology to the dioxygenases containing the above motif but is related in sequence to eight other enzymes in the superfamily that form a distinct consensus sequence (HX(D/E)X(138-207) HX(10)R/K). Variants of TfdA were created to examine the roles of putative metal-binding residues and the functions of the other seven histidines in this protein. The H167A, H200A, H213A, H245A, and H262A forms of TfdA formed inclusion bodies when overproduced in Escherichia coli DH5alpha; however, these proteins were soluble when fused to the maltose-binding protein (MBP). MBP-TfdA exhibited kinetic parameters similar to the native enzyme. The H8A and H235A variants were catalytically similar to wild-type TfdA. MBP-H213A and H216A TfdA have elevated K(m) values for 2,4-D, and the former showed a decreased k(cat), suggesting these residues may affect substrate binding or catalysis. The H113A, D115A, MBP-H167A, MBP-H200A, MBP-H245A and MBP-H262A variants of TfdA were inactive. Gel filtration analysis revealed that the latter two proteins were highly aggregated. The remaining four inactive variants were examined in their Cu(II)-substituted forms by EPR and electron spin-echo envelope modulation (ESEEM) spectroscopic methods. Changes in EPR spectra upon addition of substrates indicated that copper was present at the active site in the H113A and D115A variants. ESEEM analysis revealed that two histidines are bound equatorially to the copper in the D115A and MBP-H167A TfdA variants. The experimental data and sequence analysis lead us to conclude that His-113, Asp-115, and His-262 are likely metal ligands in TfdA and that His-213 may aid in catalysis or binding of 2,4-D.

Amino Acid Sequence↗
PubMed2000

Pyruvate formate-lyase-activating enzyme: strictly anaerobic isolation yields active enzyme containing a [3Fe-4S](+) cluster.

Pyruvate formate-lyase-activating enzyme (PFL-AE) from Escherichia coli (E. coli) catalyzes the stereospecific abstraction of a hydrogen atom from Gly734 of pyruvate formate-lyase (PFL) in a reaction that is strictly dependent on the cosubstrate S-adenosyl-l-methionine (AdoMet). Although PFL-AE is an iron-dependent enzyme, isolation of the enzyme with its metal center intact has proven difficult due to the oxygen sensitivity and lability of the metal center. We report here the first isolation of PFL-AE under nondenaturing, strictly anaerobic conditions. Iron and sulfide analysis as well as UV-visible, EPR, and resonance Raman data support the presence of a [3Fe-4S](+) cluster in the purified enzyme. The isolated native enzyme, but not apo-enzyme, exhibits a high specific activity (31 U/mg) in the absence of added iron, indicating that the native cluster is necessary and sufficient for enzymatic activity.

Acetyltransferases↗
PubMed2000

Anisotropy of Young's modulus of human tibial cortical bone.

The anisotropy of Young's modulus in human cortical bone was determined for all spatial directions by performing coordinate rotations of a 6 by 6 elastic stiffness matrix. The elastic stiffness coefficients were determined experimentally from ultrasonic velocity measurements on 96 samples of normal cortical bone removed from the right tibia of eight human cadavers. The following measured values were used for our analysis: c11 = 19.5 GPa, c22 = 20.1 GPa, c33 = 30.9 GPa, c44 = 5.72 GPa, c55 = 5.17 GPa, c66 = 4.05 GPa, c23 = 12.5 GPa. The remaining coefficients were determined by assuming that the specimens possessed at least an orthorhombic elastic symmetry, and further assuming that c13 = c23 c12 = c11 - 2c66. Our analysis revealed a substantial anisotropy in Young's modulus in the plane containing the long axis of the tibia, with maxima of 20.9 GPa parallel to the long axis, and minima of 11.8 GPa perpendicular to this axis. A less pronounced anisotropy was observed in the plane perpendicular to the long axis of the tibia. To display our results for the full three-dimensional anisotropy of cortical bone, a closed surface was used to represent Young's modulus in all spatial directions.

Aged↗
PubMed2000

The future of obesity research.

As endocrinologists, we view better treatment as the goal of obesity research. The ideal obesity treatment would reduce body fat substantially, with preferential loss from the visceral compartment, and preserve lean tissue with a minimum of side effects. Obesity has been recognized as a chronic disease since 1985. Chronic diseases recognized before obesity may predict the future of obesity research. Initial treatments of chronic diseases commonly arise from empirical observations. These observations often stimulate basic research into the physiologic mechanisms responsible. Such cross-fertilization between the clinic and basic science is desirable and expected. As more is learned about the physiology of obesity, treatments can be expected to use more downstream mechanisms with less unwanted side effects, the reliance on surgical treatments can be expected to decline, and molecular approaches are likely to play an increasingly important role. With a better physiologic understanding of obesity, advanced clinical endpoints will become more important and molecular approaches are likely to play a more important role in discovery and treatment. Due to the availability of molecular approaches, obesity treatment is expected to advance faster than chronic disease research of the past.

Chronic Disease↗
PubMed2000

CCR6 mediates dendritic cell localization, lymphocyte homeostasis, and immune responses in mucosal tissue.

Chemokine-directed migration of leukocyte subsets may contribute to the qualitative differences between systemic and mucosal immunity. Here, we demonstrate that in mice lacking the chemokine receptor CCR6, dendritic cells expressing CD11c and CD11b are absent from the subepithelial dome of Peyer's patches. These mice also have an impaired humoral immune response to orally administered antigen and to the enteropathic virus rotavirus. In addition, CCR6(-/-) mice have a 2-fold to 15-fold increase in cells of select T lymphocyte populations within the mucosa, including CD4+ and CD8+ alphabeta-TCR T cells. By contrast, systemic immune responses to subcutaneous antigens in CCR6(-/-) mice are normal. These findings demonstrate that CCR6 is a mucosa-specific regulator of humoral immunity and lymphocyte homeostasis in the intestinal mucosa.

Animals↗
PubMed2000

Systemic non-Hodgkin's lymphoma presenting as a serpiginous choroidopathy: report of a case and review of the literature.

Intraocular lymphoma is a rare tumour, the two main types being primary central nervous system non-Hodgkin's lymphoma (CNS-NHL) and, less commonly, systemic lymphoma that has spread to involve the eye. We present a case of a systemic NHL resulting in a serpiginous choroidopathy. To our knowledge, this presentation has not previously been reported. The diagnosis of this case was made based on the temporal relationship between the clinical activity of the choroidopathy and its response to chemotherapy. Diagnosis of intraocular lymphoma on vitreous biopsy is notoriously difficult, and this case is presented along with a review of the literature regarding vitreous biopsy and diagnostic techniques.

Aged↗
PubMed2000

Fat and carbohydrate balances during adaptation to a high-fat.

BACKGROUND: Dietary fat contents are highly variable. Failure to compensate for the positive fat balance that occurs during the shift to a high-fat, low-carbohydrate diet by increasing energy expenditure or by decreasing food intake may result in the gain of fat mass. OBJECTIVE: The objective of this study was to investigate the time course of fat oxidation during adaptation to an isoenergetic high-fat, low-carbohydrate diet. DESIGN: After a 5-d control diet, dietary fat was increased from 37% of energy to 50% of energy for 4 d in 6 healthy, young lean men. Respiratory quotient and substrate macronutrient oxidation and balance were measured in a respiratory chamber. Fasting concentrations of insulin, glucose, and triacylglycerol; maximal oxygen consumption (f1.gif" BORDER="0">O(2)max) during treadmill exercise; and free-living energy expenditure were determined. Body fat was measured by dual-energy X-ray absorptiometry and visceral adipose tissue by computerized tomography. RESULTS: Compared with the baseline diet, the high-fat, low-carbohydrate diet resulted in positive fat and protein balances and a negative carbohydrate balance. Insulin concentration and the postabsorptive respiratory quotient were positively correlated with the fat balance during the high-fat, low-carbohydrate diet, whereas f1.gif" BORDER="0">O(2)max during treadmill exercise was negatively related to fat balance. With use of stepwise regression, f1.gif" BORDER="0">O(2)max was the best predictor of fat balance. There was a negative correlation between fat balance and carbohydrate balance (r(2) = 0.88). CONCLUSION: Both baseline insulin concentration and f1.gif" BORDER="0">O(2)max during treadmill exercise predict fat balance during the shift to a high-fat diet under isoenergetic conditions.

Adipose Tissue↗
PubMed2000

Concurrent physical activity increases fat oxidation during the shift to a high-fat diet.

BACKGROUND: It takes several days to adapt to a high-fat diet. In an earlier study, we observed a large degree of interindividual variation in the capacity to adapt to a high-fat diet. We hypothesized that concurrent physical activity would accelerate fat oxidation during an isoenergetic high-fat diet. OBJECTIVE: The objective of this study was to determine the effect of increased physical activity on the ability of young healthy men to increase fat oxidation during the shift to a high-fat diet. DESIGN: Six young healthy men participated in a randomized, single-blind crossover study. The volunteers consumed a diet contributing 37% of energy as fat, 14% as protein, and 49% as carbohydrate for 4 d. Energy expenditure and macronutrient balance were then measured in a respiration chamber as the energy content of the isoenergetic diet was changed to 50% fat, 14% protein, and 36% carbohydrate. Treadmill walking, as the physical activity, was used to increase total daily energy expenditure to 1.8 times the resting metabolic rate during 1 of 2 stays in the metabolic chamber. Total daily energy expenditure was maintained at 1.4 times the resting metabolic rate for the other stay. RESULTS: Energy balance was not significantly different between the 2 conditions. The 24-h respiratory quotient decreased more rapidly and to a greater extent under conditions of increased energy expenditure. Further, there was a decrease in the interindividual variability in the response of the respiratory quotient to a high-fat diet with increased energy expenditure (physical activity). Cumulative carbohydrate and protein balances were greater under conditions of increased physical activity. Conversely, cumulative fat balance was greater under sedentary conditions. CONCLUSION: Concurrent physical activity increases fat oxidation during the shift to a high-fat diet.

Adaptation, Physiological↗