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Biomedical subjects

J A Smith

Publications and source records attributed to J A Smith.

At least 91 records · Page 5Linked to original sources
PubMed2001

The feasibility of remote-controlled assistance as a search tool for patient education.

Patients often desire more information about their conditions than they receive during a physician office visit. To address the patient's information needs, a touchscreen information kiosk was implemented. Results from the first prototype identified interface, security, and technical issues. Misspelling of search terms was identified as the most observable cause of search failure. An experimental remote control assistance feature was added in the second prototype. The feature allowed a medical librarian to provide real-time remote help during searches by taking control of the patient's computer. Remote assistance improved patient satisfaction, increased ease of use, and raised document retrieval rate (86.7% vs. 56.7%). Both patients and librarians found the application useful. Reasons included its convenience and flexibility, opportunity for direct patient contact, ability to teach through direct demonstration, and complementing the librarian's role as an information gateway. The project demonstrated the feasibility of applying remote control technology to patient education.

Feasibility Studies↗
PubMed2000

To what extent are the needs of severely disabled people met by community rehabilitation services? A follow-up study.

PURPOSE: To evaluate which needs of disabled people would be met over a one year follow-up period and to examine which factors would be predictive of identifying those people who had more needs met from those who had fewer needs met. METHOD: A follow-up study of a cohort of community dwelling disabled people (aged 16-65) from two NHS Health Districts in Southern England with contrasting patterns of rehabilitation provision, who had participated in a cross-sectional interview study one year previously which had assessed their met and unmet needs. The Southampton Needs Assessment Questionnaire was used to examine needs. Disability was evaluated with the OPCS Disability and Severity Scales and perceived health status with the SF-36. RESULTS: Participation rate at follow-up was 92 %. Of the 300 baseline unmet needs reported by 69 of the 77 participants 33% had been met at follow-up. People whose disability had increased more and/or whose mental health status had improved more had greater percentages of their baseline needs met. There was a non-significant trend for smaller percentages of baseline needs to be met in Basingstoke than in Southampton. CONCLUSIONS: At ground level, disabled people's views were taken into account, to some extent, in the provision of rehabilitation services. This input should be made at a higher level, in the overall shaping of services.

Adolescent↗
PubMed2000

Randomized, cross-over, controlled comparison of two inactivated hepatitis A vaccines.

The immunogenicity, tolerability and interchangeability of two hepatitis A vaccines, Vaqta (Merck and Co.) and Havrix (SmithKline) were studied in a randomized, crossover, controlled clinical trial. Vaccine was administered to 201 volunteers at 0 and 26 weeks in one of four vaccine regimens: Havrix-Havrix; Havrix-Vaqta; Vaqta-Havrix or Vaqta-Vaqta. Seroconversion rates (>/=10 mIU/ml) for those whose first dose was Vaqta or Havrix, respectively, were: 41/96 (43%) versus 30/95 (32%) (P=0.15) at 2 weeks and 91/98 (93%) versus 84/97 (87%) (P=0.43) at 4 weeks, and 100% at 26 weeks. Geometric mean concentrations (GMC) of total antibody to hepatitis A virus (anti-HAV) for Vaqta and Havrix were 189 and 114 mIU/ml (P=0.011) at 4 weeks and 234 and 136 mIU/ml (P<0.001) at 26 weeks. At 30 weeks, the GMC after two doses of Havrix was 2612 mIU/ml compared with 5497 after two doses of Vaqta (P<0.001). The GMC in the Havrix-Vaqta group was 5672 mIU/ml compared with 3077 mIU/ml in the Vaqta-Havrix group (P<0.001). Less than half of vaccine recipients reported tenderness or pain. In this study, seroconversion rates of the two vaccines were similar. Vaqta produces significantly higher anti-HAV antibody than Havrix. Crossover immunization is well tolerated and results in high antibody concentrations, especially when Vaqta is the booster dose. The significance of higher anti-HAV antibody concentrations in terms of long-term protection is unknown.

Adult↗
PubMed2000

Depth-profiling and diffusion measurements in ice films using infrared laser resonant desorption.

A new infrared laser resonant desorption (LRD) technique has been developed that permits depth-profiling and diffusion measurements in ice. This LRD technique utilizes an Er:YAG rotary Q-switched laser with an output wavelength of lambda = 2.94 microm and a pulse duration of approximately 100 ns. The Er:YAG laser light resonantly excites O-H stretching vibrations in the H2O molecules that form the ice. This laser resonant heating induces H2O desorption at the ice surface. Control experiments were conducted on pure and isotopically mixed laminated ice films to determine the optimum experimental parameters for the LRD depth-profiling and diffusion measurements. Depending on laser energy, the measured desorption depth was either less than, comparable to, or larger than the optical penetration depth of approximately 0.8 microm at lambda = 2.94 microm. LRD studies were used to analyze H2 18O/H2 16O stacked multilayers and laminate sandwich structures. These measurements revealed that the LRD technique can depth-profile into ice films with submicrometer spatial resolution and high sensitivity. Two types of experiments employing LRD depth-profiling were demonstrated to monitor diffusion in ice. HCl hydrate diffusion in ice was measured versus time after depositing ice/HCl/ice sandwich structures. Na diffusion into ice was studied after adsorbing Na using a continuous Na source for a given exposure time at the diffusion temperature.

Journal Article↗
PubMed2000

Met and unmet needs reported by severely disabled people in southern England.

PURPOSE: To examine the met and unmet needs for rehabilitation of disabled people living in the community in Southern England. METHOD: A cross sectional interview study of people with a primary physical disability, aged 1665. Disabled people were randomly selected from two existing disability registers, which comprised disabled people who had been identified by community rehabilitation services as being in need of regular surveillance by formal assessment of their care needs. A new semi-structured needs assessment questionnaire was developed and validated for the study (the Southampton Needs Assessment Questionnaire, SNAQ). Level of disability was examined with the OPCS Disability and Severity Scales. RESULTS: Ninety three disabled people participated. Their median (IQR) OPCS score was 8 (6-10). Participants reported a median (IQR) of three unmet needs (2-7). The most prevalent unmet needs were for adaptations, equipment, physiotherapy and wheelchairs, rather than unmet needs for intellectual and social fulfilment. CONCLUSIONS: Disabled people who were already in touch with community rehabilitation services continued to express unmet needs for further services. Meeting the more basic needs relating to people's housing, equipment, physiotherapy and wheelchairs may enable them to be more independent and fulfilled in other areas of their lives.

Activities of Daily Living↗
PubMed2000

Creation of a stress-activated p90 ribosomal S6 kinase. The carboxyl-terminal tail of the MAPK-activated protein kinases dictates the signal transduction pathway in which they function.

Mitogen-activated protein kinase-activated protein kinases (MAPKAPKs) lie immediately downstream of the mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK), and p38 MAPK. Although the family of MAPKAPKs shares sequence similarity, it demonstrates selectivity for the upstream activator. Here we demonstrate that each of the ERK- and p38 MAPK-regulated MAPKAPKs contains a MAPK docking site positioned distally to the residue(s) phosphorylated by MAPKs. The isolated MAPK docking sites show specificity for the upstream activator similar to that reported for the full-length proteins. Moreover, replacement of the ERK docking site of p90 ribosomal S6 kinase with the p38 MAPK docking site of MAPKAPK2 converts p90 ribosomal S6 kinase into a stress-activated kinase in vivo. It is apparent that mechanisms controlling events downstream of the proline-directed MAPKs involve specific MAPK docking sites within the carboxyl termini of the MAPKAPKs that determine the cascade in which the MAPKAPK functions.

Amino Acid Sequence↗
PubMed2000

Vacuolar chloride transport in Mesembryanthemum crystallinum L. measured using the fluorescent dye lucigenin.

To study vacuolar chloride (Cl(-)) transport in the halophilic plant Mesembryanthemum crystallinum L., Cl(-) uptake into isolated tonoplast vesicles was measured using the Cl(-)-sensitive fluorescent dye lucigenin (N,N'-dimethyl-9,9'-bisacridinium dinitrate). Lucigenin was used at excitation and emission wavelengths of 433 nm and 506 nm, respectively, and showed a high sensitivity towards Cl(-), with a Stern-Volmer constant of 173 m(-1) in standard assay buffer. While lucigenin fluorescence was strongly quenched by all halides, it was only weakly quenched, if at all, by other anions. However, the fluorescence intensity and Cl(-)-sensitivity of lucigenin was shown to be strongly affected by alkaline pH and was dependent on the conjugate base used as the buffering ion. Chloride transport into tonoplast vesicles of M. crystallinum loaded with 10 mm lucigenin showed saturation-type kinetics with an apparent K(m) of 17.2 mm and a V(max) of 4.8 mm min(-1). Vacuolar Cl(-) transport was not affected by sulfate, malate, or nitrate. In the presence of 250 microm p-chloromercuribenzene sulfonate, a known anion-transport inhibitor, vacuolar Cl(-) transport was actually significantly increased by 24%. To determine absolute fluxes of Cl(-) using this method, the average surface to volume ratio of the tonoplast vesicles was measured by electron microscopy to be 1.13 x 10(7) m(-1). After correcting for a 4.4-fold lower apparent Stern-Volmer constant for intravesicular lucigenin, a maximum rate of Cl(-) transport of 31 nmol m(-2) sec(-1) was calculated, in good agreement with values obtained for the plant vacuolar membrane using other techniques.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2000

The structural basis for in situ activation of DNA alkylation by duocarmycin SA.

Duocarmycin SA is a member of a growing class of interesting lead compounds for chemotherapy, distinguished by the manner in which they bind to and react with DNA substrates. The first three-dimensional structure of a DNA adduct of an unnatural enantiomer from this family has been determined by (1)H NMR methods. Comparison to the previously determined structure of the natural enantiomer bound in the same DNA-binding site provides unique insights into the similarities and critical distinctions producing the respective alkylation products and site selectivities. The results also support the hypothesis that the duocarmycin SA alkylation reaction is catalyzed by the binding to DNA, and provide a deeper understanding of the structural basis for this unique mode of activation.

Alkylating Agents↗
PubMed2000

Differential expression of renal adenosine A(1) receptors induced by acute renal failure.

The distribution of renal adenosine A(1) receptors was investigated in rats with glycerol- or mercuric chloride (HgCl(2))-induced acute renal failure. Receptors were localised by autoradiography using [(3)H]8-cyclopentyl-1,3-dipropylxanthine ([(3)H]DPCPX), a selective A(1) adenosine receptor antagonist. In saline-injected control animals, significant labelling with [(3)H]DPCPX was detected in glomeruli, the inner stripe of outer medulla, and the inner medulla. Sixteen hours following induction of glycerol-induced acute renal failure (ARF), a 34% increase in labelling in glomeruli was noted compared to saline-injected controls, and by 48 hr, glomerular labelling had increased by 200%. In addition, 48 hr following glycerol injection, significant labelling was now detected in the cortical labyrinth and medullary rays whilst, in the inner medulla, labelling had decreased by 34%. By contrast to glycerol-induced ARF, the only significant change noted 48 hr following induction of HgCl(2)-induced ARF was a 39% decrease in labelling in the inner medulla. It is concluded that glycerol-induced ARF results in differential expression of renal adenosine A(1) receptors with increased expression in the cortex and reduced expression in the inner medulla. Increased density of A(1) receptors in glomeruli may account, at least in part, for the increased renal vasoconstrictor response to adenosine and depressed glomerular filtration rate noted previously in this type of acute renal failure.

Acute Kidney Injury↗
PubMed2000

Distinguishing the roles of the two different cGMP-binding sites for modulating phosphorylation of exogenous substrate (heterophosphorylation) and autophosphorylation of cGMP-dependent protein kinase.

The role of each of the two different cGMP-binding sites (referred to as slow and fast sites) of type I cGMP-dependent protein kinase (PKG) in altering the rate of catalysis of phosphorylation of exogenous substrates (heterophosphorylation) or the rate of autophosphorylation has not been resolved. In the present study, the cGMP concentration required for half-maximal activation (A(50)) of wild-type PKG type Ibeta (WT) was 5-fold higher for heterophosphorylation than for autophosphorylation. cGMP occupation of the slow site was associated with an increase in the autophosphorylation rate, whereas occupation of the fast and slow site together was associated with a decrease in the autophosphorylation rate compared with the rate observed with occupation of the slow site alone. The contributions of each cGMP-binding site were investigated using PKG mutants containing substitutions of an invariant threonine residue that is critical for high affinity cGMP-binding in each site. Site-directed mutagenesis of Thr-317 of the fast site (T317A) increased the cGMP A(50) for heterophosphorylation 4-fold at 30 degrees C, with nominal effect on cGMP A(50) for autophosphorylation compared with WT. The analogous slow site mutation (T193A) increased the cGMP A(50) for heterophosphorylation and autophosphorylation 32- and 64-fold, respectively. Compared with WT, the cGMP A(50) of the double mutant (T193A/T317A) for heterophosphorylation was increased 300-fold, whereas the cGMP A(50) for autophosphorylation was similar to that of T193A. Thus, occupation of both cGMP-binding sites of PKG is required for maximal stimulation of heterophosphorylation, whereas occupation of the slow site alone is sufficient for stimulation of the rate of autophosphorylation, and additional occupation of the fast site reduces this rate.

Animals↗
PubMed2000

Analysis of topical cyclosporine treatment of patients with dry eye syndrome: effect on conjunctival lymphocytes.

OBJECTIVE: To study the effect of topical cyclosporine on lymphocyte activation within the conjunctiva of patients with moderate to severe dry eye syndrome (Sjögren and non-Sjögren). METHODS: Biopsy specimens were obtained at baseline and after 6 months of cyclosporine treatment from eyes of 32 patients with moderate to severe dry eye syndrome; 19 were cyclosporine treated (0.05% cyclosporine, n = 13; 0.1% cyclosporine, n = 6) and 13 were vehicle treated. Within this group there were 12 with Sjögren syndrome and 20 with non-Sjögren syndrome. Biopsy tissue was analyzed using immunohistochemical localization of binding of monoclonal antibodies to lymphocytic markers CD3, CD4, and CD8 as well as lymphocyte activation markers CD11a and HLA-DR. RESULTS: In cyclosporine-treated eyes, biopsy results of conjunctivae showed decreases in the number of cells positive for CD3, CD4, and CD8, while in vehicle-treated eyes, results showed increases in these markers, although these differences were not statistically significant. Following treatment with 0.05% cyclosporine, there was a significant decrease in the number of cells expressing the lymphocyte activation markers CD11a (P<.05) and HLA-DR (P<.05), indicating less activation of lymphocytes as compared with vehicle treatment. Within the Sjögren patient subgroup, those treated with 0.05% cyclosporine also showed a significant decrease in the number of cells positive for CD11a (P<.001) as well as CD3 (P<.03), indicating a reduction in number of activated lymphocytes. CONCLUSION: Treatment of dry eye syndrome with topical cyclosporine significantly reduced the numbers of activated lymphocytes within the conjunctiva. Arch Ophthalmol. 2000;118:1489-1496

Administration, Topical↗
PubMed2000

Short-term risedronate treatment in postmenopausal women: effects on biochemical markers of bone turnover.

The development of new biochemical markers has made it possible to assess the effects of therapeutic agents on bone turnover more rapidly and precisely. In this early phase II study, we analyzed the effects of short-term, high-dose treatment with risedronate, a potent pyridinyl bisphosphonate, on markers of bone resorption and formation. Resorption markers included urinary free deoxypyridinoline (D-Pyr) crosslinks, N-terminal telopeptide (NTx) and C-terminal telopeptide (CTx) type I collagen crosslinks. Bone formation markers included osteocalcin (OC), bone-specific alkaline phosphatase (BSAP) and the C-terminal peptide of type I procollagen (PICP). All three resorption markers showed rapid, significant (p<0.05) decreases from baseline following daily administration of 30 mg risedronate for 2 weeks. The mean decreases at 2 weeks were 28% for D-Pyr, 61% for NTx and 73% for CTx, respectively. Over the next 10 weeks after treatment, D-Pyr approached baseline while NTx and CTx remained well below baseline values. The markers of bone formation showed little change during therapy but decreased significantly at 4-10 weeks after therapy - an expected outcome of bisphosphonate therapy. Moreover, there was a significant correlation between the early effects on bone resorption markers and the delayed effects on formation markers. This study demonstrates that the approved dose of risedonate (30 mg/day) for Paget's disease is effective at decreasing bone turnover after 2 weeks of treatment, as observed by the sensitive response of bone turnover markers.

Alkaline Phosphatase↗
PubMed2000

Comparison of serum and urine assays for biochemical markers of bone resorption in postmenopausal women with and without hormone replacement therapy and in men.

Biochemical markers of bone resorption have been used to characterize metabolic bone disease and assess therapeutic response. Most studies have used the urinary measurement of collagen crosslinks, but serum assays have recently been developed that may have less analytic and biologic variability. In the present study, we measured urine and serum N- and C-terminal crosslinked telopeptides of type I collagen (NTX and CTX) and serum bone sialoprotein (BSP) in postmenopausal women with or without hormone replacement therapy (HRT) and in men of similar age. In these populations, the variability of serum and urine markers was similar, except that serum NTX showed somewhat lower variability in postmenopausal women. Urine and serum assays correlated well with one another and were significantly lower in postmenopausal women on HRT compared with untreated women. The difference in women on HRT was similar for sNTX, uNTX and BSP (35-40%) and greater for sCTX and uCTX (52-53%). There was an inverse correlation between markers and bone mineral density, largely attributable to the high correlation in women not on HRT. Fractional excretion of NTX and CTX were estimated at 0.20+/-0.07 and 0.44+/-0.11, respectively. These values were independent of the concentration of the marker or of creatinine in the urine. We conclude that serum markers are useful measures of bone resorption in these populations, in whom the use of such markers is likely to be helpful in the management of osteoporosis.

Adult↗
PubMed2000

Predictors of perioperative morbidity and mortality in lung volume reduction surgery.

BACKGROUND: Selection criteria for lung volume reduction surgery are still being refined. We sought to determine whether preoperative features could be used to predict early morbidity or mortality. METHODS: We reviewed preoperative characteristics of the first 89 patients who underwent lung volume reduction surgery at the Alfred Hospital. Data included arterial blood gases, prednisolone use, pulmonary function tests, 6-minute walk test, and anesthetic time. Length of stay and reintubation for respiratory failure were used as markers of morbidity. RESULTS: Findings included PaCO2 of 43 +/- 0.7 mm Hg, PaO2 70 +/- 1.1 mm Hg, percent predicted values for forced expiratory volume in 1 second 29.6% +/- 0.8%, TLCO% predicted 35.2 +/- 1.4%, and 6-minute walk test of 315 +/- 10.6 m (mean +/- SEM). Mean length of stay was 19 +/- 2 days, with 17 (19%) patients reintubated for respiratory failure. Mortality rate was 5.6% at 1 year post surgery, with no deaths in patients less than 65 years old. Multivariate analysis revealed that length of stay, reintubation and mortality were predicted by age and surgical time (p < 0.05), with no correlation with any other variables tested. Age greater than 70 years was associated with a significant risk of mortality (OR 9.0; p = 0.04). CONCLUSIONS: Age greater than 70 years and anesthetic time greater than 210 minutes predict both perioperative morbidity and mortality.

Adult↗
PubMed2000

Bilateral sequential single lung transplantation for pulmonary hypertension and Eisenmenger's syndrome.

BACKGROUND: Lung transplantation, with and without intracardiac repair for pulmonary hypertension (PH) and Eisenmenger's syndrome (EIS), has become an alternative transplant strategy to combined heart and lung transplantation (HLT). METHODS: Thirty-five patients with PH or EIS underwent either bilateral sequential single lung transplantation (BSSLT, group I, n = 13) or HLT (group II, n = 22). Another 74 patients, who underwent BSSLT for other indications, served as controls (group III). Immediate allograft function, early and medium-term outcomes, lung function, and 2-year survival were compared between the groups. RESULTS: Comparisons between groups I and II showed no significant difference in any variables except percent predicted forced vital capacity. Immediate allograft function was significantly inferior (p < 0.05) and the blood loss was greater (p < 0.01) in group I when compared with those in group III. However, this resulted in no significant difference in early and medium-term outcomes, and 2-year survival between the 2 groups. CONCLUSIONS: BSSLT for PH and EIS can be performed as an alternative procedure to HLT without an increase in early and medium-term morbidity and mortality. Results are comparable with BSSLT performed for other indications.

Adult↗
PubMed2000

Continent urinary reconstruction versus ileal conduit: a contemporary single-institution comparison of perioperative morbidity and mortality.

OBJECTIVES: To compare postoperative morbidity and mortality in a concurrent and contemporary series of patients who underwent radical cystectomy with ileal conduit versus orthotopic neobladder. METHODS: The data of 198 patients were reviewed, 117 with orthotopic reconstruction and 81 with ileal conduit during a 5-year time frame. Thirty-day morbidity, mortality, reoperative rates, and parameters associated with the surgical procedures were obtained from chart review. RESULTS: No perioperative or postoperative deaths occurred in either group. The median operative time for the ileal conduit was 201 minutes (range 140 to 373), and for the orthotopic neobladder, it was 270 minutes (range 230 to 425). The median blood loss was 389 and 474 mL, respectively. The median length of hospitalization was 8 days for the ileal conduit group and 7 days for the orthotopic neobladder group. Diversion-related complications recognized within 30 days that ultimately required a return to the operating room occurred in 3.4% of those with a neobladder and 1.2% of those with an ileal conduit. CONCLUSIONS: The orthotopic neobladder is a longer and technically more complex procedure than the ileal conduit procedure. However, no demonstrable difference in morbidity or perioperative complications were found between the two procedures in our review.

Adult↗