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Biomedical subjects

R Lockey

Publications and source records attributed to R Lockey.

15 recordsLinked to original sources
PubMed2006

Pharmacologic and anti-IgE treatment of allergic rhinitis ARIA update (in collaboration with GA2LEN).

The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evidence-based and step-wise approach based on the classification of the symptoms. The ARIA workshop, held in December 1999, published a report in 2001 and new information has subsequently been published. The initial ARIA document lacked some important information on several issues. This document updates the ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis. Literature published between January 2000 and December 2004 has been included. Only a few studies assessing nasal and non-nasal symptoms are presented as these will be discussed in a separate document.

Animals↗
PubMed2005

Tissue distribution of bovine spongiform encephalopathy infectivity in Romney sheep up to the onset of clinical disease after oral challenge.

Sixty Romney sheep of three prion protein genotypes were dosed orally at six months of age with an inoculum prepared from the brains of cattle clinically affected with BSE, and 15 sheep were left undosed as controls. They were randomly assigned within genotype to groups and were sequentially euthanased and examined postmortem at intervals of six or 12 months, depending on their predicted susceptibility. Tissue pools prepared from the three, four or five dosed animals in each group were inoculated into groups of 20 RIII mice as a bioassay for infectivity. Separate inocula were prepared from the matched control sheep killed at each time. In the ARQ/ARQ sheep killed four months after inoculation, infectivity was detected in the Peyer's patch tissue pool, and at 10 months it was detected in the spleen pool; from 16 months, infectivity was detected in a range of nervous and lymphoreticular tissues, including the spinal cord pool, distal ileum excluding Peyer's patches, liver, Peyer's patches, mesenteric and prescapular lymph nodes, spleen, tonsil and cervical thymus. No infectivity was detected in the tissue pools from the ARQ/ARR and ARR/ARR sheep killed 10 months or 22 months after infection.

Animals↗
PubMed2002

Inequalities in health care provision: the relationship between contemporary policy and contemporary practice in maternity services in England.

AIM: The project Addressing Inequalities in Health: new directions in midwifery education and practice (Hart et al. 2001) was commissioned by the English National Board for Nursing, Midwifery and Health Visiting (ENB). Here, we draw on those research findings to consider current midwifery policy and practice in England. BACKGROUND: Little guidance on providing equality of care exists for midwives. The Code of Conduct [United Kingdom Central Council for Nursing, Midwifery and Health Visiting (UKCC) 1992] makes no specific requirement for midwives to address issues of inequalities of health in their practice. Recent policy documents emphasize the need to work towards reducing inequalities and to target practice to 'disadvantaged clients' without giving guidelines on how to identify and care for target groups. METHODS: In-depth studies of midwifery education and service provision were conducted in three very different parts of England. Three months of fieldwork were undertaken at each site, comprising a series of interviews with midwifery educators, managers, students, midwives and service users. Focus groups were also held and observation of classroom sessions and midwifery practice undertaken. Findings. A lack of clear and specific strategies concerning inequalities in health was evident at managerial level. Patchy knowledge of current policy was also evident amongst practising midwives. Specific projects with disadvantaged clients usually resulted from a particular midwife's personal interest or evident local need. All midwives emphasized the importance of 'equality of care'. How this was operationalized varied, and 'individualized' or 'woman-centred' care was assumed to encompass the concept. In the few examples where care was systematically targeted in accordance with policy directives, the midwife's public health role was increased. CONCLUSION: In the absence of a co-ordinated strategic vision driven by managers, practitioners find difficulty in prioritizing care and targeting resources to disadvantaged clients in line with policy directives. Tensions between policy and practice in the care of 'disadvantaged' women clearly exist. Successful implementation of policy at practice level needs: commitment from managers; clarity of purpose in documentation; and provision of specific targets for practitioners. However, the latter should remain flexible enough for the delivery of care to be appropriate and sensitive to individual needs.

England↗
PubMed1998

Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper.

The World Health Organization and various allergy, asthma, and immunology societies throughout the world met on January 27 through 29, 1997, in Geneva, Switzerland to write guidelines for allergen immunotherapy. Over the ensuing year, the editors and panel members reached a consensus about the information to include in the WHO position paper "Allergen immunotherapy: Therapeutic vaccines for allergic diseases." The historical term allergen extract was changed to allergen vaccine to reflect the fact that allergen vaccines are used in medicine as immune modifiers. The document summarizes the scientific literature and rationale for the appropriate use of such therapy to treat allergic rhinoconjunctivitis, allergic asthma, and Hymenoptera hypersensitivity. It also includes recommendations to improve safety, discusses new techniques being developed that may result in better efficacy and less risk, and offers recommendations for areas of additional and necessary research.

Allergens↗
PubMed1996

Comparison of efficacy, safety, and skin test inhibition of cetirizine and astemizole.

BACKGROUND: Astemizole, an H1-histamine-receptor antagonist prescribed for seasonal allergic rhinitis, has a slow onset of action and a strong suppressive effect on the wheal and flare reaction, which interferes with skin testing results. The newer antihistamine cetirizine appears to have a rapid onset of action and a low potential to interfere with posttreatment skin testing results. OBJECTIVE: To compare the efficacy, safety, and skin test inhibition of astemizole and cetirizine in the treatment of seasonal allergic rhinitis. METHODS: In a double-blind, parallel-group study conducted at six sites during ragweed pollination season, 263 subjects were randomized to receive 10 mg of astemizole, 5 mg of cetirizine, or 10 mg of cetirizine daily for 2 weeks. The subjects rated seven allergic rhinitis symptoms daily, the subjects and investigators provided global assessments of the responses to the treatments, and the subjects rated their satisfaction with the treatments. Thirty-nine subjects at one study site underwent quantitative skin testing before and after treatment. RESULTS: As measured by reduction from baseline in total symptom severity score, which was the primary efficacy measure in the study, all three treatments significantly relieved the symptoms of allergic rhinitis (P less than .05). This finding was supported by the global ratings and the subject satisfaction ratings. There were no significant differences among the three treatments for reduction from baseline in total symptom severity score. The mean subject satisfaction score with 10 mg of cetirizine was significantly greater than that with astemizole (P less than .05). In the skin tests performed 3, 7, and 14 days after the end of antihistamine treatment, the subjects who had received the cetirizine doses had significantly greater mean sum of wheal and mean sum of erythema values than those who had received the astemizole dose (P less than .05). Sensitivity to ragweed pollen extract returned to 90% of baseline within three days of the end of cetirizine treatment. Both drugs were well tolerated and their adverse event profiles were similar. CONCLUSIONS: Astemizole and cetirizine are effective and well tolerated in alleviating the symptoms of ragweed-induced allergic rhinitis. Cetirizine inhibits skin test results to a much lesser extent than does astemizole. Physicians may wish to consider the potential for skin test inhibition when selecting an antihistamine for patients with allergic rhinitis.

Adolescent↗
PubMed1996

A comparative study of the clinical efficacy of nedocromil sodium and placebo. How does cromolyn sodium compare as an active control treatment?

Nedocromil sodium and cromolyn sodium are the only two currently available nonsteroid anti-inflammatory agents for treatment of asthma. Clinical differences between the two agents remain under continuous investigation with reports differentiating the two on the basis of atopy of the patient and reversibility of bronchoconstriction. This study investigated the efficacy of nedocromil sodium (4 mg, qid) for treatment of mild-to-moderate asthma in comparison to placebo using cromolyn sodium (2 mg, qid) as an active control treatment. Patients were primarily allergic asthmatics (with at least 15% reversibility) previously maintained on a regimen of regular bronchodilator therapy. During a 2-week run-in period, the patient's slow-release theophylline therapy was removed, and the patients were randomized to treatment after deterioration of asthma control (asthma symptom summary score of 3 for 7 of the 14 days). After 8 weeks of treatment, patients were returned to as occasion requires bronchodilator therapy, as per the 2-week baseline period. The results demonstrate that patients treated with nedocromil sodium showed statistically significant improvements during the primary time period (mean weeks 3 through 8) over placebo-treated patients as evidenced by all indexes of asthma symptoms, pulmonary function measures, and decreased bronchodilator reliance (p<0.05). Patients treated with cromolyn sodium demonstrated similar improvements over placebo-treated patients. Comparisons between nedocromil sodium and cromolyn sodium showed the two agents to be comparable in this group of primarily allergic patients with reversible disease. Between-group differences were noted for 3 of the 13 variables (nighttime asthma, FEV1, and forced expiratory flow rate between 25 % and 75% of the FVC) in favor of cromolyn sodium when the data were pooled during the primary time period. The number of patients missing 1 or more days from work/school/regular activity due to asthma was significantly fewer compared with placebo, and favoring nedocromil sodium over cromolyn sodium. No differences were observed among the three treatments for adverse events. This study demonstrated that in primarily allergic patients with reversible airways disease, nedocromil sodium and cromolyn sodium are both significantly more effective than placebo for treatment of mild-to-moderate asthma.

Activities of Daily Living↗
PubMed1990

Report of the symposium on the use of intravenous gammaglobulin in adults infected with the human immunodeficiency virus.

On July 27, 1989, the International Conference on Molecular Aspects of Immune Response and Infectious Diseases devoted a symposium to the subject of the use of intravenous gamma globulin (IVIG) in acquired immunodeficiency syndrome (AIDS). The information presented confirmed that IVIG benefits human immunodeficiency virus (HIV)-infected children with recurrent infections and that much remains to be learned about the influence of IVIG in adult AIDS. The symposium participants recognized the urgent need to develop randomized clinical trials using a control group to assess the efficacy of a treatment with IVIG in PGL (persistent generalized lymphadenopathy), ARC (AIDS-related complex), and AIDS. To prepare this report, a committee was established, including individuals with expertise in immunology, immunopharmacology, microbiology, virology, infectious diseases, general medicine, and pediatrics and representing research experience in academia and hospitals. After an introduction to the report with a summary of immunotherapeutic agents under evaluation to treat HIV infection, section 1 lays out the present understanding of the disease pathogenesis. Section 2 then outlines the treatment of HIV-seropositive individuals, discussing the uncertainties that any treatment entails. Section 3 discusses the rationale for treating HIV-infected individuals with IVIG, and Section 4 examines the major differences between IVIG and hyperimmunoglobulins for the treatment of HIV infection. Section 5 looks at IVIG as a mean to delay the emergence of opportunistic infections and restore immunocompetence in AIDS and related illnesses, and Sections 6 and 7 suggest a pilot protocol on the use of IVIG in association with low-dose or standard-dose zidovudine (AZT).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

In vitro red tide toxin effects on human bronchial smooth muscle.

Airborne Ptychodiscus brevis toxin (PBTX), produced by Ptychodiscus brevis (Florida red tide), induces cough, rhinorrhea, watery eyes, and sneezing in normal individuals and wheezing in subjects with asthma. The mechanism of PBTX-induced contractile response has been investigated by the authors in vitro in dog and rat tissue. PBTX stimulates neuronal sodium channels, resulting in activation of autonomic cholinergic and adrenergic nerve endings in canine upper and lower airway smooth muscle and in rat vas deferens, respectively. This article concerns the investigation of the effect and mechanism of action of PBTX on human airways in order to determine the unique role of the toxin in the pathogenesis of asthma. PBTX elicited contractions of isolated human airway smooth muscle with a threshold concentration of 0.1 micrograms/ml, very similar to values obtained in canine lower airways. Pharmacologic analysis demonstrated that atropine (10(-6) mol/L) blocked the response to both PBTX and acetylcholine; tetrodotoxin (10(-7) mol/L) blocked PBTX but not acetylcholine; and verapamil (10(-5) mol/L) attenuated but neostigmine (10(-8) mol/L) potentiated the response to PBTX. Other selected blockers did not affect the PBTX response. These data indicate that PBTX produces contraction of human lower airway smooth muscle via stimulation of cholinergic nerve fiber sodium channels. The concept that PBTX triggers asthma through this mechanism is strengthened by these results.

Acetylcholine↗
PubMed1987

Comparison of inhaled albuterol powder and aerosol in asthma.

In this multicenter, randomized, double-blind study comparing the efficacy and safety of aerosolized albuterol with the dry powder formulation, 231 patients with chronic reversible obstructive airway disease were randomly allocated to receive either placebo albuterol aerosol followed immediately by active albuterol powder (200 micrograms) or active albuterol aerosol (two puffs, 180 micrograms) followed immediately by placebo lactose powder four times a day for a period of 12 weeks. No statistically significant differences were found between the powder and aerosol formulations with respect to pulmonary function, length of time mean FEV1 remained greater than or equal to 15% above baseline, physicians' assessments of patients' clinical response, or patients' subjective symptom scores. There were also no significant differences between treatment groups in cardiovascular effects, laboratory values, or adverse events. Among patients who expressed a preference for one of the delivery systems, half preferred using the powder. Results of this study demonstrate that 200 micrograms of albuterol powder is as safe and effective as 180 micrograms of albuterol aerosol.

Administration, Inhalation↗
PubMed1987

Lower airway smooth muscle contraction induced by Ptychodiscus brevis (red tide) toxin.

Ptychodiscus brevis toxin (PBTX) is produced by the organism Ptychodiscus brevis. This toxin causes a phenomenon that has come to be known as Florida red tide. It also stimulates neuronal sodium channels, resulting in activation of the cholinergic and adrenergic nerve endings of the autonomic nervous system in upper airway smooth muscle and rat vas deferens, respectively, as previously reported. It is the cholinergic stimulating action that has been implicated as a possible "triggering" event in bronchial asthma. This article concerns the investigation of whether PBTX may also affect lower airways and by what mechanism any contractile response to PBTX in lower airways may be induced. PBTX was found to elicit contractions in isolated canine lower airway smooth muscle. The threshold concentration was 0.15 microgram/ml, the peak response occurred at 6.0 micrograms/ml, and the concentration causing half-maximal response of the group was 0.57 microgram/ml. Pharmacologic analysis demonstrated that atropine (10(-6) mol/L) blocked the response to both PBTX and acetylcholine, tetrodotoxin (10(-7) mol/L) blocked the response to PBTX but not to acetylcholine, and verapamil (10(-5) mol/L) blocked the response to PBTX and reduced the response to acetylcholine. Four consecutive contractile responses to PBTX (3 micrograms/ml) produced rapid tachyphylaxis. The fourth contraction was 60% less than the initial response. A fifth response to PBTX after exposure to indomethacin (2.8 X 10(-6) mol/L) was increased and resulted in a contraction that was only 25% less than the initial response. The exogenous addition of prostaglandins (PG), PGE1 and PGE2, to indomethacin-treated lower airway strips selectively suppressed the contractile response to PBTX. Other PGs tested (PGA2, PGB2, PGD2, PGF2 alpha and PGI2) did not affect the PBTX response. These results indicate that PBTX produces spasm in lower airway smooth muscle and that it does this by stimulation of sodium channels in the cholinergic nerve fibers. The results also demonstrate a rapid reduction in the contractile response to PBTX. The results also demonstrate that the reduction is mediated by PGs of the E series.

Acetylcholine↗
PubMed1985

The mechanism of Ptychodiscus brevis toxin-induced rat vas deferens contraction.

Ptychodiscus brevis, which causes Florida red tide, produces Ptychodiscus brevis toxin (PBTX) known to contain neurotoxins and to induce rhinorrhea, tearing, and cough in normal humans and wheezing in asthmatic subjects. It was previously reported (J Allergy Clin Immunol 69:418, 1982; 73:824, 1984) that PBTX causes canine tracheal smooth muscle contraction via stimulation of sodium channels in the axons of parasympathetic postganglionic nerves and the release of acetylcholine from these nerve endings. This was postulated to be an asthma-triggering mechanism. In this article the toxins were evaluated to determine if they also stimulate sodium channels on adrenergic nerve endings and release norepinephrine. Rat vas deferens was selected as the experimental tissue. Both PBTX and norepinephrine contracted rat vas deferens. Prazosin 10(-6) mol/L blocked the response to PBTX (3 micrograms/ml) (88.3% to 27.3% contraction [n = 6; p less than 0.001]) and the response to norepinephrine (EC50 was shifted from 1.67 X 10(-6) mol/L to 1.25 X 10(-4) mol/L in the presence of prazosin 10(-6) mol/L [n = 6; p less than 0.001]). Phentolamine 10(-6) mol/L also blocked both PBTX and norepinephrine. Tetrodotoxin 10(-7) mol/L, a sodium channel blocker, completely blocked the response to PBTX but not to norepinephrine. The response to PBTX was significantly reduced from 1.53 gm of tension in controls to 0.29 gm of tension (n = 6; p = 0.002) in tissues obtained from rats pretreated with reserpine (2 mg/kg per day for 2 days, injected intraperitoneally). Verapamil 10(-5) mol/L blocked the PBTX response, and PBTX caused no contraction in calcium-free media.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗