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Biomedical subjects

A Stokes

Publications and source records attributed to A Stokes.

At least 19 recordsLinked to original sources
PubMed2001

The efficacy and safety of oral desmopressin in children with primary nocturnal enuresis.

PURPOSE: We confirmed findings that oral desmopressin safely decreases the number of wet nights in children with enuresis and identified doses at which acceptable responses can be obtained. MATERIALS AND METHODS: We evaluated the safety and efficacy of oral desmopressin in a double-blind, placebo controlled, parallel group, randomized, multicenter trial of 193 children 6 to 16 years old with documented primary nocturnal enuresis. The study was conducted in 2 phases: 1) a 2-week dose ranging phase in which children received desmopressin (0.2, 0.4 or 0.6 mg.) or placebo at bedtime and 2) an 8-week dose titration phase that followed a 2-week placebo washout. Patients received 0.2 mg. desmopressin or placebo for the first 2 weeks and then the dose was increased in 0.2 mg. increments at 2-week intervals until the patient was completely dry or was receiving 0.6 mg. Patients were instructed to limit fluid intake. Mean decrease from baseline in the number of wet nights, percentage of responding patients and safety were assessed at 2-week intervals. RESULTS: There was a statistically significant linear response to oral desmopressin at doses from 0.2 to 0.6 mg. during the dose ranging phase (p < or =0.05). The decrease in wet nights after 2 weeks of treatment with desmopressin was 27%, 30% and 40% at 0.2, 0.4 and 0.6 mg. doses, respectively, compared to 10% with placebo. All doses were statistically significantly different from placebo (p < or =0.05). During the dose titration phase all placebo treated and 87% of desmopressin treated patients were receiving the maximum dose of 3 tablets nightly because they had not been completely dry in the previous 2 weeks. Nevertheless, 44% of desmopressin treated patients had achieved at least a 50% reduction from baseline in the number of wet nights per 2 weeks at the lower doses of 0.2 and 0.4 mg. Most adverse events (rhinitis, pharyngitis, headache and increased cough) were mild to moderate in severity, unrelated to treatment and resolved before the study was completed. CONCLUSIONS: Oral desmopressin administered at bedtime to children with primary nocturnal enuresis was significantly better than placebo for decreasing episodes of bed-wetting (p <0.05). A linear dose-response relationship was observed (p <0.05). An acceptable response to treatment (50% or greater reduction from baseline in wet nights per 2 weeks) was seen at all doses of desmopressin. Oral desmopressin, up to 0.6 mg. for 8 weeks, was well tolerated.

Administration, Oral↗
PubMed2000

Solid matrix-antibody-antigen complexes incorporating equine herpesvirus 1 glycoproteins C and D elicit anti-viral immune responses in BALB/c (H-2K(d)) and C3H (H-2K(k)) mice.

Glycoproteins C and D (gC and gD) derived from equine herpesvirus 1 (EHV-1)-infected cells were incorporated into individual solid matrix-antibody-antigen (SMAA) complexes and administered to BALB/c (H-2K(d)) and C3H (H-2K(k)) mice. Antibodies against each of the glycoproteins were produced that neutralised virus infectivity and mediated the lysis of EHV-1-infected target cells in the presence of complement. Immunoglobulin (Ig)G2b was the predominant antibody isotype produced in BALB/c mice against gC, while equal amounts of IgG2a/2b were found in the serum of C3H mice (indicative of a T-helper(1) response). Glycoprotein D immunisation elicited predominantly an IgG1 response in BALB/c mice (indicative of a T-helper(2) response) and an IgG2a/2b response in C3H mice. EHV-1-specific local and systemic T-cell proliferative responses were detected in vitro following administration of SMAA complexes. Suppression of the local T-cell response was seen following virus challenge of mice immunised with SMAA gC. SMAA gD provided some protection against intranasal EHV-1 challenge. These data show that the SMAA system is an effective way of presenting subviral components to the immune system and further emphasises the importance of including glycoprotein D as a component of a subunit EHV-1 vaccine.

Animals↗
PubMed1999

Making High-level Queries on Diverse Genome Data: A Structured Genome Document Database System Based on GXML and GQL.

Complete DNA sequences (genomes) and associated data are being made available worldwide at an astonishing rate. Through computer analysis of such data, molecular biologists hope to gain an overall understanding of the genome, such as by predicting large-scale gene networks. However, this is difficult because diverse genome data are scattered across many highly heterogeneous databases, and because existing database systems lack the facilities to expose and analyze functional relationships among the data. To address these problems, we propose a new type of genome database system. Since a genome can be thought of intuitively as a kind of 'document', our system uses a structured document language based on XML to effectively represent genomes and associated data. The information-rich structures of the genome documents help cope with data diversity and heterogeneity. A powerful query language is introduced that exposes important biological relationships among the genome data. We have obtained favorable results from several experiments, demonstrating the usefulness of our method in building a top-down view of genome functionality.

Journal Article↗
PubMed1998

The expression of receptor tyrosine phosphatases is responsive to sciatic nerve crush.

Given the importance of phosphotyrosine signaling in growth cone dynamics, we have examined the embryonic and adult expression of receptor-like protein tyrosine phosphatases in sensory neurons and studied their responsiveness to nerve lesions in young adult animals. The phosphatases LAR, PTPsigma, and PTPalpha are expressed in most neurons of E14 and E18 rat embryo dorsal root ganglia, while BEM-1 is expressed in a more restricted subset of these neurons. These phosphatases continue to be expressed in young adult animals, suggesting that they have roles in mature as well as in developing dorsal root ganglia neurons. After an experimental sciatic nerve crush, the expression of the phosphatase genes was significantly and differentially altered in these neurons. PTPsigma mRNA was increased by 50% after 3 days, while LAR and PTPalpha expression dropped by 50 and 20%, respectively. BEM-1 mRNA levels were unaltered. These data show that mRNA levels of specific tyrosine phosphatase genes are highly responsive to nerve damage and may be reset to a new and potentially optimal pattern of expression more conducive for nerve regeneration. We propose that tyrosine phosphatases are not only involved in primary axonogenesis but can also now be implicated in the molecular control of adult nerve repair.

Aging↗
PubMed1998

Membrane organization of bluetongue virus nonstructural glycoprotein NS3.

The smallest RNA segment (S10) of bluetongue virus (an orbivirus, family Reoviridae) encodes two closely related nonstructural proteins, the 229-amino-acid (aa) NS3 and the 216-aa NS3A. The proteins are found in glycosylated and nonglycosylated forms in infected cells (X. Wu, H. Iwata, S.-Y. Chen, R. W. Compans and P. Roy J. Virol. 66:7104-7112, 1992). The NS3/NS3A proteins have two hydrophobic domains (aa 118 to 141 and 162 to 182) and two potential asparagine-linked glycosylation sites (aa 63 and 150), one of which is located between the hydrophobic domains. To determine whether these features were used in the mature protein forms, we generated a series of mutants of the S10 gene and expressed them by using the vaccinia virus T7 polymerase transient-expression system. Our data indicate that both hydrophobic domains of NS3 span the cell membrane and that only the site at aa 150 is responsible for N-linked glycosylation of the NS3 proteins.

Amino Acid Sequence↗
PubMed1998

Peer relationship problems in children with Tourette's disorder or diabetes mellitus.

Peer relationships, social skills, self-esteem, parental psychopathology, and family functioning of children with Tourette's disorder and a chronic disease control group of children with diabetes mellitus were compared. Children with Tourette's disorder had poorer peer relationships than their classmates and were more likely to have extreme scores reflecting increased risk for peer relationship problems than children with diabetes mellitus, but did not report self-esteem problems or social skills deficits. Measures of peer relationships were not related to severity or duration of tics. Children with Tourette's disorder and Attention Deficit Hyperactivity Disorder were at increased risk for poor peer relationships. The psychosocial problems of children with Tourette's disorder do not appear to be the generic result of having a chronic disease.

Adolescent↗
PubMed1997

High level expression of equine herpesvirus 1 glycoproteins D and H and their role in protection against virus challenge in the C3H (H-2Kk) murine model.

N and C-terminal truncated forms of equine herpesvirus 1 (EHV 1) glycoproteins gD and gH were expressed in baculovirus resulting in the production of secreted recombinant proteins. A carboxy-terminal histidine tag was included on each of the genes for protein isolation by nickel affinity chromatography. Recombinant gD was recognized by three gD specific monoclonal antibodies, 20C4, 5H6 and F3132. F3132 is a conformationally dependent monoclonal antibody with virus neutralizing activity. Expression of gH was confirmed by reacting the protein with the gH peptide specific antiserum R319. The truncated gD gene was also expressed as a beta-galactosidase fusion protein which was purified from E. coli by nickel affinity chromatography. C3H mice were inoculated with purified recombinant gD or gH or insect cells which had been infected with recombinant baculoviruses. Mice were subsequently challenged with EHV 1. Purified recombinant baculovirus gD provided the most protection and produced high levels of virus neutralizing antibodies. The gD fusion protein was less effective at protecting mice and insect cells infected with either of the recombinant baculoviruses or purified recombinant gH were poor at conferring protection. The results emphasize the importance of using purified proteins in vaccine formulations and of including EHV 1 gD as a component of a subunit vaccine.

Animals↗
PubMed1997

Oral desmopressin: a randomized double-blind placebo controlled study of effectiveness in children with primary nocturnal enuresis.

PURPOSE: Desmopressin nasal spray has proved to be efficacious treatment of primary nocturnal enuresis. Oral desmopressin tablets would be a more easily used, convenient vehicle for our patients and their parents. We evaluated the effectiveness of oral desmopressin in decreasing the number of wet nights in patients with primary nocturnal enuresis. MATERIALS AND METHODS: We performed a double-blind, placebo controlled, parallel group trial of oral desmopressin in 141 children 5 to 17 years old with documented primary nocturnal enuresis at 14 sites. Patients were screened for number of wet nights for 2 weeks before study entry. A minimum of 3 wet nights weekly for 2 consecutive weeks was required for study entry. Patients were randomized to receive 200, 400 or 600 mcg. desmopressin or placebo before bedtime. Fluids were restricted 2 hours before bedtime based on body weight. The primary efficacy variable was mean decrease in the number of wet nights recorded during the last 2-week treatment period. The percentage of responding patients and mean decrease from baseline in number of wet nights at 2, 4 and 6 weeks were also assessed. RESULTS: The decrease in wet nights was 9, 20, 30 and 36% for placebo, and 200, 400, and 600 mcg. desmopressin orally per day, respectively. The 600 mcg. dose of oral desmopressin daily was statistically significantly different (p < 0.05) from placebo in decreasing wet nights. A complete or near complete response (0 to 2 wet nights) was noted in 3, 18, 33 and 24% of the patients who received placebo, and 200, 400 and 600 mcg. oral desmopressin daily, respectively. The 400 and 600 mcg. treatment groups were statistically significantly different (p < 0.05) from placebo. A less than 50% decrease in wet nights was noted in 83, 79, 64 and 61% of the patients who received placebo, and 200, 400 and 600 mcg. oral desmopressin daily, respectively. Oral desmopressin exhibited a dose response in the treatment of primary nocturnal enuresis. The linear trend for the decrease in wet nights was statistically significant (p < 0.05). CONCLUSIONS: A dose of 600 mcg. oral desmopressin daily significantly decreased the mean number of wet nights when administered for 6 weeks. A higher dose may be necessary for an improved response.

Administration, Oral↗
PubMed1996

The expression of the proteins of equine herpesvirus 1 which share homology with herpes simplex virus 1 glycoproteins H and L.

Several expression systems were used in studies aimed at characterizing the equine herpesvirus 1 (EHV-1) glycoprotein H and L homologues of HSV-1 (EHV-1 gH and gL) and the products were compared to the authentic proteins synthesized in virus infected cells. Using an in vitro transcription/translation system two gH species were detected (an unprocessed 89 kDa and a processed 116 kDa product). Three low molecular weight proteins were found in the case of gL (21.8 kDa, 22.9 kDa and 26.9 kDa) and these showed a slight reduction in mobility on the addition of microsomal membranes to the reactions. A gL fusion protein was produced in pGEX-2T, expression being confirmed by Western blotting using a gL-specific antiserum raised against a peptide incorporating the 13 carboxyl terminal amino acids of the protein. A gH specific peptide antiserum precipitated both gH and two smaller proteins from EHV-1 infected cells thought to be two forms of gL. Insect cells infected with gH or gL baculovirus recombinants were used to vaccinate C3H (H-2k) mice. Some protection against EHV-1 infection was conferred to the gH inoculated mice. The results will enable further studies on the importance of the gH and gL interaction in the pathogenesis of EHV-1 to be evaluated and their potential in contributing to a subunit vaccine to be assessed.

Animals↗
PubMed1996

The production of a truncated form of baculovirus expressed EHV-1 glycoprotein C and its role in protection of C3H (H-2Kk) mice against virus challenge.

A truncated form of the equine herpesvirus 1 (EHV-1) glycoprotein C (gC) gene was expressed in baculovirus. The gC signal sequence was substituted with the honeybee melittin signal sequence and the transmembrane region was replaced with a histidine tag. The recombinant virus produced high levels of gC in both the cells and supernatants of infected cells. The protein was present by 24 h and maximal secretion occurred at 96 h post-infection. The recombinant protein was antigenically authentic as shown by its reaction with each of a panel of individual monoclonal antibodies specific for the five distinct antigenic sites on EHV-1 gC. Recombinant gC was purified from the supernatant of infected cells by immuno-affinity chromatography and used to immunize C3H (H-2Kk haplotype) mice. This incurred a gC specific antibody response against both the recombinant protein and EHV-1 gC. 'Pepscan' analysis showed that the gC specific antibodies in serum from these mice reacted with the same epitopes on gC as those recognized by antibodies in convalescent equine sera (i.e. antibodies were specific to antigenic sites one and five). A third previously unrecognized antibody binding site at the carboxyl terminus was also detected (Antibody binding domain I). A T-cell proliferative response against EHV-1 was detected in splenocyte populations taken from vaccinated mice. Further, the recovery of virus from the lungs and turbinates following challenge of mice with EHV-1 was significantly reduced. These findings indicate that baculovirus expressed gC may contribute significantly to a subunit vaccine preparation aimed at protecting horses from EHV-1 infection.

Animals↗
PubMed1996

Comparison of triamcinolone acetonide nasal inhaler with astemizole in the treatment of ragweed-induced allergic rhinitis.

BACKGROUND: Few clinical trials have directly compared the efficacy of antihistamines with topical nasal corticosteroids. OBJECTIVE: The study was performed to compare the efficacy and safety of triamcinolone acetonide nasal spray at a dose of 110 micro g in each nostril once daily with 10 mg of oral astemizole once daily for the treatment of seasonal allergic rhinitis. METHODS: A multicenter, double-blind, parallel-group study was conducted in 239 patients who were randomized to receive either triamcinolone acetonide or astemizole. A 5-day, drug-free, lead-in period was followed by 4 weeks of double-blind treatment. One hundred four patients treated with triamcinolone acetonide and 105 patients treated with astemizole could be evaluated. RESULTS: Overall, triamcinolone acetonide was more effective than astemizole in reducing total nasal symptoms, nasal stuffiness, nasal itching, and sneezing (p </= 0.01). Triamcinolone acetonide was superior to astemizole at weeks 1, 2, and 3 in reduction of the total nasal symptom score (p </= 0.0401) and in reduction of nasal stuffiness (p </= 0.05). Improvements in individual nasal symptoms (itching, postnasal drip, runny nose, and sneezing) were greater for triamcinolone acetonide at week 2 (p </= 0.01). Ocular symptoms improved from baseline in both groups. When pollen counts were correlated to mean nasal rhinitis scores, the triamcinolone acetonide group showed continued improvement from week 1 to week 2 in nasal symptoms when pollen counts were at their highest. During the same period, patients treated with astemizole failed to show improvement from week 1 to week 2. This study demonstrated that once daily administration of triamcinolone acetonide was more effective than astemizole for controlling nasal symptoms of seasonal allergic rhinitis, especially during the peak pollination period.

Administration, Intranasal↗
PubMed1995

Efficacious response with lower dose indapamide therapy in the treatment of elderly patients with mild to moderate hypertension.

A low dose (1.25 mg) of indapamide (Lozol, Rhône-Poulenc Rorer Pharmaceuticals, Collegeville, PA) was evaluated in 222 elderly patients (> or = 50 years) with mild to moderate essential hypertension in a multicenter, randomized, double-blind, parallel-group clinical trial. A 4-week single-blind placebo washout period was followed by an 8-week double-blind treatment period. Patients were randomized to receive indapamide 1.25 mg/day or to receive placebo. The primary efficacy variable was the mean change in sitting diastolic blood pressure from baseline to week 8. Eighty-one patients in the indapamide group (73%) and 87 patients in the placebo group (78%) completed the 8 weeks of double-blind therapy. Therapy with 1.25 mg of indapamide produced greater reductions compared with placebo in sitting diastolic blood pressure after 8 weeks of therapy, with statistical significance (P < or = 0.0015) seen after only 2 weeks of therapy and continuing throughout the 8 weeks. All secondary efficacy measures (sitting systolic blood pressure, standing systolic and diastolic blood pressures, and > or = 10 mm Hg decrease or final value of < or = 90 mm Hg in sitting diastolic blood pressure) also showed superior (P < or = 0.0014) improvement in the indapamide group compared with placebo after 8 weeks of double-blind treatment. During the 8-week double-blind treatment period, incidence rates for all adverse events and for drug-related adverse events were similar between the two treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Role of T-cells, virus neutralising antibodies and complement-mediated antibody lysis in the immune response against equine herpesvirus type-1 (EHV-1) infection of C3H (H-2k) and BALB/c (H-2d) mice.

The suitability of C3H (H-2k) and BALB/c (H-2d) mice for use as small animal models to study immunity to EHV-1 was assessed. An in vitro T cell response mediated by both CD4+ and CD8+ T cells was detected both during the acute phase of infection and after challenge with a second dose of EHV-1 at two months in lymphocyte populations taken from the spleens of both types of mouse. The responses were apparent until at least 61 days after the primary inoculation. After challenge, T cells from mice previously infected with EHV-1 responded by as early as day 3 after infection and higher levels of T cell proliferation were reached than in mice undergoing a primary infection. Immunological cross-reactivity with the closely related virus, EHV-4 was detected and some activity against herpes simplex virus type-1 (HSV-1) was observed during the acute phase of infection. T cell responses were detected in the draining cervical lymph nodes but not in the inguinal lymph nodes of the mice and these were the primary sites of T cell activation. Complement-dependent virus neutralising antibodies were present by day 8 after infection. These antibodies were also able to lyse EHV-1 infected target cells in vitro. Complement-independent virus neutralising antibodies were found before challenge only in C3H mice. The clinical signs and duration of virus shedding were reduced after challenge. The time course of the appearance of the different immune effector mechanisms is discussed in relation to the clearance of virus from the infected mice. The results suggest that C3H mice provide a better model in which to study potential vaccine candidates against EHV-1 infections of the horse than BALB/c mice.

Animals↗
PubMed1995

Conversion from 2.5 mg to 1.25 mg indapamide in patients with mild to moderate hypertension.

BACKGROUND: Indapamide is an effective antihypertensive drug with diuretic and vasodilating activities. The common starting dose has been 2.5 mg to 5 mg. A lower dose formulation (1.25 mg) is now available. The safety and efficacy of switching patients from indapamide 2.5 mg to indapamide 1.25 mg was evaluated in this randomized, double-blind, multicenter clinical trial. METHODS: Three hundred seventy-eight adult patients with mild to moderate essential hypertension were enrolled in a washout period, during which patients received single-blind placebo for 4 weeks. All 378 patients qualified for the study and received open-label treatment with indapamide 2.5 mg for 8 weeks. Of the 378 patients, 265 responded to indapamide 2.5 mg and were randomized to receive double-blind treatment with either indapamide 1.25 mg (n = 132) or 2.5 mg (n = 133) for 8 weeks. Overall, 245 of the 378 patients who were initially enrolled completed the study. The primary efficacy variable was the number of patients in each treatment group who maintained a supine diastolic blood pressure of < or = 90 mm Hg (treatment success) by the end of the double-blind period (week 16). RESULTS: Treatment with indapamide 1.25 mg once daily was as efficacious as the 2.5-mg once-daily dose. No significant difference was observed for the percentage of patients who achieved treatment success between the patients switched from indapamide 2.5 to 1.25 mg (74%) and the control group maintained on indapamide 2.5 mg (70%). The incidence of drug-related adverse events during the double-blind period was similar between the two treatment groups. The mean change from pretreatment baseline to endpoint in serum potassium was -0.2 mEq/L (-0.2 mmol/L) in the indapamide 1.25 mg treatment group, compared with -0.4 mEq/L (-0.4 mmol/L) in the indapamide 2.5 mg treatment group. CONCLUSIONS: Indapamide 1.25 mg given once daily for 8 weeks was as effective as 2.5 mg once daily in reducing systolic and diastolic blood pressure in patients with mild to moderate hypertension.

Adult↗
PubMed1994

Pseudo-tics in Tourette syndrome.

We describe two patients with Tourette syndrome who also had pseudo-tics. The psychogenic movements resolved in both children when the stressful issues in their lives were addressed. It is important to differentiate psychogenic symptoms from tics and compulsions in children with Tourette syndrome in order to avoid unnecessary medication and allow appropriate therapy.

Adolescent↗