Search PubMed⌕ Search

Biomedical subjects

B Marks

Publications and source records attributed to B Marks.

At least 37 records · Page 2Linked to original sources

Environmental priming influences allergen-specific nasal reactivity.

BACKGROUND: Preceding mucosal response to one allergen leads to the priming of the nasal mucosal response to another allergen. This study aimed to determine whether environmental allergens, especially ubiquitous animal dander, can induce nasal priming. METHODS: We investigated 26 grass-pollen-allergic subjects with additional sensitization to other aeroallergens. We performed continuous allergen challenge for 2 h with 1500 Dactylis glomerata pollen/m3 in the Vienna challenge chamber. The nasal flow at 150 Pa was examined, and subjective scores were obtained every 15 min. Statistical analysis was calculated from the area under curve of nasal flow reduction by Student's t-test and the Mann-Whitney U-test. Alpha was 0.05. RESULTS: In subjects with positive cat-dander RAST (class of > or = 3), besides grass-pollen allergy, the specific nasal allergic reaction to Dactylis challenge was significantly pronounced (P < 0.01), and an earlier onset of reaction was evident. The same results were obtained with additional sensitization to dog dander (P < 0.05). Concomitant sensitization to mugwort also led to escalating symptoms (P < 0.05). CONCLUSIONS: These results indicate that a specific nasal allergic reaction is augmented by environmental priming caused by ubiquitous animal dander and possibly is influenced by the daily use of spices.

Adult↗

Efficacy and safety relative to placebo of an oral formulation of cetirizine and sustained-release pseudoephedrine in the management of nasal congestion.

BACKGROUND: The aim of this study was to assess the clinical efficacy of an oral formulation of cetirizine 5 mg with sustained-release pseudoephedrine (PSE) 120 mg relative to placebo in patients with nasal congestion. METHODS: Twenty-four patients with perennial rhinitis due to house-dust-mite (HDM) allergy were recruited in this crossover study. A treatment period of 1 week, in which cetirizine/PSE was administered twice daily, was followed by a washout period of at least 2 weeks and a further period of 1 week in which the alternative treatment was given to each patient. Immediately after the first dose of each medication (day 1), nasal congestion and related symptoms were assessed during a 7-h challenge with HDM feces, with the Vienna Challenge Chamber (VCC), to investigate onset of action of the preparation. A second challenge of 3-h duration, carried out at least 12 h after the final dose, was undertaken after 1 week (mean) of twice-daily treatment to assess residual effects of the formulation after achievement of steady state. RESULTS: The oral formulation of cetirizine/PSE was significantly (P<0.001) superior to placebo in improving nasal obstruction during both challenges. The improvement in nasal airflow and nasal patency was significantly greater with cetirizine/PSE than with placebo (P<0.02). In addition, subjective assessment of nasal symptoms showed that cetirizine/PSE was significantly superior to placebo in both challenges for the sum of nasal obstruction scores (P<0.01). Both medications were well tolerated, and no serious adverse events occurred during the study. CONCLUSIONS: In this study, cetirizine/PSE relieved nasal congestion and other objective and subjective symptoms to a significantly greater extent than placebo. No serious adverse events occurred, and both regimens were equally well tolerated.

Administration, Oral↗

Dose-dependent protection by azelastine eye drops against pollen-induced allergic conjunctivitis. A double-blind, placebo-controlled study.

The efficacy and tolerability of azelastine (CAS 58581-89-8) eye drops at three different doses (0.025%, 0.05% and 0.1%) were investigated in a double-blind, randomized, placebo-controlled, crossover study in 24 subjects with a history of allergic conjunctivitis/rhinoconjunctivitis, who were challenged, out of season, by airbone allergen in the "Vienna Challenge Chamber" (VCC). Subjects received a single dose of azelastine eye drops 60 min before the start of a 4 h challenge in the VCC. Additional local challenge, mimicking a gust of wind, was administered 15 min before the end of the session. Each of the 4 study days was separated by a 2 week washout period. Azelastine eye drops showed a dose-dependent inhibition of the development of itching of the eyes. The effect was most pronounced 15 min after the additional local challenge. A maximal effect was achieved at a dose of 0.05%. Similar effects were observed on lacrimation. Azelastine eye drops also dose-dependently inhibited the degree of conjunctival redness, measured by digital imaging, and tended to reduce the low incidence of chemosis observed. Ranking of the results of all symptoms for each treatment group confirmed the optimal effect at a dose of 0.05%. Azelastine eye drops had no effect on nasal and bronchial symptoms or on measurements of airways function (FEV1). No adverse effects of the treatments were reported. The data support the use of 0.05% azelastine eye drops in the treatment of allergic conjunctivitis/rhinoconjunctivitis.

Adult↗

The structure of the prostaglandin EP4 receptor gene and related pseudogenes.

The EP4 prostaglandin receptor (EP4R) is a member of the seven transmembrane receptor superfamily. We have obtained the human EP4 receptor gene sequence and determined its structure relative to EP4R cDNA synthesized from peripheral blood lymphocytes. The EP4R gene spans approximately 22 kb and consists of three exons separated by two introns. The first exon (530 bp) is noncoding. After an intron of 472 bp, the second exon contains a short (43 bp) 5' sequence before a 289-amino-acid open reading frame (ORF). An 11.5-kb intron is found at the end of transmembrane 6, and the rest of the ORF is in exon 3. The gene structure is analogous to those of the thromboxane, PGI, and PGD receptors. The deduced initiation site does not contain a conventional TATA box but is 70% GC-rich and contains CCAAT boxes, SP1 and AP2 motifs, and motifs consistent with activation by proinflammatory cytokines. Southern blot analysis of human genomic DNA shows two genes with homology to the EP4R gene. Both appear to be pseudogenes with 70% amino acid identity to the EP4R up to the "ERY" sequence at the end of transmembrane 3, where an Alu-like repetitive sequence element was found. The ORF sequence is also interrupted by a stop codon. The pseudogenes differ in that one contains a second "repetitive element" (a line 1 repeat) in the 5' end of the ORF. Northern blot analysis of human mRNA using a pseudogene probe showed hybridization only to the EP4 receptor transcript. PCR also failed to detect expression of either pseudogene. This study defines the gene structure of EP4R and suggests the existence of two related pseudogenes.

Amino Acid Sequence↗

Vaginal wall sling for anatomical incontinence and intrinsic sphincter dysfunction: efficacy and outcome analysis.

PURPOSE: A prospective cohort study was done to determine the efficacy and clinical outcome of a new technique for anterior vaginal wall sling construction to treat urinary incontinence due to intrinsic sphincter dysfunction or anatomical incontinence. MATERIALS AND METHODS: Preoperative evaluation included lateral cystography, video urodynamics, cystoscopy and incontinence staging. Postoperative subjective and objective staging outcome measures were prospectively assigned at predetermined regular intervals by a third party. RESULTS: Of the patients 95 had intrinsic sphincter dysfunction and 65 had anatomical incontinence. The repair failed in 7% of the 160 patients who had recurrent incontinence during followup and 9% had de novo urgency incontinence. Time to failure comparing patients with intrinsic sphincter dysfunction and anatomical incontinence was modeled using Kaplan-Meier survival curves, and the log rank test showed no significant difference between the groups (p > 0.05). Logistic regression covariates revealed no significant predictive factors for postoperative failures. Preoperative patient age was the only predictive factor for de novo instability (logistic regression model p < 0.05). CONCLUSIONS: Our initial results indicate that the 2 groups are indistinguishable to date based on current clinical and experimental statistics except for time to full recovery of postoperative voiding and incidence of postoperative instability (regression model p < 0.05).

Adult↗

High-dose chemotherapy-induced platelet defect: inhibition of platelet signal transduction pathways.

Patients receiving high-dose chemotherapy and autologous bone marrow transplantation acquire a platelet secretion defect. The role of chemotherapeutic agents and their metabolites in mediating this platelet defect was investigated. 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU), but not cyclophosphamide or cis-platinum, was found to inhibit platelet aggregation in vitro in response to activation by either ADP, thrombin, or collagen. Inhibition by BCNU was dose dependent and required preincubation of platelets with BCNU. After a 60-min preincubation, 30 microM BCNU produced 50% inhibition of platelets in platelet-rich plasma. The cyclophosphamide metabolites acrolein and 4-hydroperoxycyclophosphamide also inhibited platelet aggregation in a dose-dependent manner, with a requirement for preincubation. Platelet inhibition occurred at clinically relevant concentrations of BCNU and metabolites of cyclophosphamide. The effects of acrolein were totally prevented by coincubation with the sulfhydryl-protecting agents N-acetylcysteine and 2-mercaptoethanesulfonic acid, whereas the effects of BCNU were incompletely prevented. The mechanism of platelet inhibition was investigated next by examining protein phosphorylation in response to platelet agonists. Acrolein inhibited thrombin- and phorbol ester-induced phosphorylation of a 40-kDa polypeptide and other substrates, indicating a cellular defect in protein kinase C signaling. BCNU did not interfere with protein phosphorylation, indicating preservation of initial signaling pathways. Thus, chemotherapeutic agents and their metabolites inhibit platelet function by inhibiting distinct components of the intracellular activation pathways.

Acrolein↗

The insertion of monoamine oxidase A into the outer membrane of rat liver mitochondria.

Human monoamine oxidase A that had been synthesized in a reticulocyte lysate translation system was capable of binding to and inserting into either rat liver mitochondria or isolated mitochondrial outer membranes. The inserted form was as resistant to proteinase K as endogenous mitochondrial monoamine oxidase A. The insertion, but not the binding, of monoamine oxidase A was prevented by depleting the reaction mixture of either ATP (with apyrase) or ubiquitin (with purified antibodies against this polypeptide). Addition of ATP or ubiquitin, respectively, to these depleted mixtures restored the insertion of the enzyme. In the absence of mitochondria, in vitro synthesized monoamine oxidase A did not catalyze its own alkylation by the mechanism-based inhibitor, [3H]clorgyline. However, both monoamine oxidase A that had been membrane-inserted in vitro and monoamine oxidase A that had been bound to the mitochondria under conditions of ATP depletion catalyzed adduct formation. Furthermore, reaction of either clorgyline or another mechanism-based inhibitor, pargyline, with the membrane-bound enzyme during ATP depletion inhibited the insertion of monoamine oxidase A when ATP was restored. These observations indicate that monoamine oxidase A acquired a catalytically active conformation on interaction with the mitochondrial outer membranes prior to its ATP and ubiquitin-dependent insertion into the membrane.

Adenosine Triphosphate↗

Empty sella syndrome associated with partial hypopituitarism (visualized on MRI scan).

The empty sella syndrome has become a rather frequent finding in magnetic resonance imaging (MRI) scanning. The usual presentation of empty sella syndrome involves an incidental finding on a computed tomography scan or an MRI scan. It is unusual to find empty sella syndrome associated with hypopituitarism. The authors describe such an unusual finding in a 54-year-old nulliparous woman.

Empty Sella Syndrome↗

Perception of eating and exercise in children as a function of child and parent weight status.

The present study assessed the effects of child body weight (obese/lean) and familial loading for obesity (two obese parents/two lean parents) on the psychophysics of sweetness, fatness and exercise workloads, as well as subjective ratings of foods varying in sugar and fat and activities varying in energy expenditure. Children were measured in a baseline state and at 6 months after the obese children had participated in a family-based behavioral weight control program. No differences between obese and lean children in perceptual ratings were observed. However, offspring of obese or lean parents differed on intensity rating, food palatability and activity enjoyment ratings. Intensity ratings for sweetness in offspring of obese parents was increased, with a similar trend for intensity ratings for fatness. Offspring of obese parents rated all foods and activities with lower palatability and enjoyment ratings than offspring of lean parents. After a 6 month family-based behavioral weight loss treatment, obese children had significant decreases in percent overweight while lean children remained stable. Changes in the pattern of food ratings were observed for the obese children, with a reduction in liking for foods high in fat and/or sugar, and an increase in ratings for food slower in fat and sugar. The effects of parental obesity on food and exercise intensity ratings and hedonic ratings were maintained. Overall, these results suggest parental weight influences behavioral factors related to obesity in children.

Body Weight↗

Resting metabolic rate in lean and obese children: relationship to child and parent weight and percent-overweight change.

Two studies were conducted to assess differences in metabolic rate as a function of child weight (study I); and the interaction of child and parent weight (study II). In both studies obese children had higher resting metabolic rates (RMRs) than lean children (p less than 0.05). Child weight accounted for 72 and 78% of the variance in RMR in studies 1 and 2, respectively. Including parental weight did not improve the prediction of RMR. After 6 mo of treatment, obese children decreased percent overweight, whereas lean children showed no change (p less than 0.01). RMR in both groups remained unchanged after 6 mo. These results indicate that the RMR is higher in obese than in lean children, that changes in percent overweight that result from increases in height and no change in weight do not decrease RMR over 6 mo, and parent weight does not improve the prediction of child RMR.

Basal Metabolism↗

Liaison psychiatry in general practice: a comparison of the liaison-attachment scheme and shifted outpatient clinic models.

Most psychiatrists who visit health centres use the shifted outpatient clinic model, the main aim of which is to improve secondary care by providing it in the primary care setting. For five years we have employed a liaison-attachment scheme in which support and advice from the psychiatrist enables general practitioners to improve their care of patients with psychiatric and psychological problems. One of the advantages of the latter model is that the psychiatrist can contribute to the care of patients not seen by the specialist psychiatric service and also to the development of the primary care team. The scheme is cost effective as psychiatrists can advise on the care of far more patients than they could see in formal referrals, fewer patients are taken on for a course of psychiatric treatment that could be provided by general practitioners and the skills of general practitioners and their trainees are enhanced. It is hoped that more general practitioners will adopt this pattern of working so that it can be fully developed and evaluated.

Consultants↗

Survey of patients' satisfaction with access to general practitioners.

The north west England faculty patients' liaison group, supported by community health councils and family practitioner committees, surveyed patients' perceptions of accessibility to general practitioners in seven districts in 1985 and 1986. Findings on appointment systems, telephone access and out-of-hours calls are compared with those from other surveys. The results show that patients' satisfaction with appointment systems is related to the efficiency of their own general practitioner's system. The results also show higher levels of dissatisfaction with waiting times for outof- hours visits than in studies 10 years ago and that a large proportion of patients would like direct telephone access to their general practitioner.

Consumer Behavior↗

Periodontal disease as a function of life events stress.

Studies relating stress and oral pathology have been limited to animal experiments or clinical studies of personality and psychological health that have ignored the role of specific life events. The present study related measurements of life events stress to measurements of periodontal disease. Subjects were fifty male volunteers recruited from a pool of dental patients from the Brooklyn VA Outpatient Dental Clinic. Oral examinations were given to determine the degree of periodontitis and gingivitis. Evidence of other somatic symptomatology was assessed by the somatization subscale of the Brief Symptom Inventory. The degree of life events stress was assessed with the Life Experience Survey. Measurements of life events stress were found to be significantly correlated with measures of periodontal disease. Periodontal disease was more severe and widespread as stressors increased. Subjects were found whose general physical health was unrelated to their life situation.

Adult↗