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Biomedical subjects

E Hadley

Publications and source records attributed to E Hadley.

14 recordsLinked to original sources
PubMed2003

Clinical effects of air filters in homes of asthmatic adults sensitized and exposed to pet allergens.

BACKGROUND: Despite medical advice, many pet-allergic asthma sufferers refuse to remove the pet to which they are sensitized from their home. OBJECTIVE: We aimed to assess the clinical effects of air cleaners in the homes of adult asthma patients sensitized and exposed to cats and/or dogs. METHODS: We performed a randomized, parallel-group study of 30 asthmatic adults sensitized to and sharing a home with cats or dogs. The effects of placing air cleaners in the living room and bedroom for 12 months and using high efficiency particulate air filter vacuum cleaners (active group) were compared with using these vacuum cleaners alone (control group). Measures of airway responsiveness, treatment requirement, lung function, peak flow, reservoir and airborne allergen were recorded before, during and after the interventions. A beneficial clinical response was assessed in terms of a 'combined asthma outcome'. This was defined as a two or more doubling dose improvement in bronchial hyper-reactivity to histamine and/or a reduction in treatment requirement of at least one step change on the British Thoracic Society guidelines for asthma treatment. RESULTS: A beneficial clinical response was observed in 10/15 subjects in the active group compared with 3/15 in the control group after 12 months intervention (P = 0.01). No significant differences between the active and control groups were detected for changes in measures of lung function, reservoir pet allergen and airborne pet allergen during the study. CONCLUSION: Whilst the study design has not allowed complete exclusion of a placebo effect, we believe that this pragmatic study of adult asthmatic patients sensitized and exposed to pets resulted in a small, but significant improvement in combined asthma outcome.

Adult↗
PubMed1999

Dust mite allergens are carried on not only large particles.

The major obstacle for the successful measurement of airborne mite allergen is its very low concentration in the absence of vigorous disturbance. The aim of this study was to investigate the particle size distribution of group 2 dust mite allergen using an amplified ELISA system. Air sampling was performed using an Andersen sampler placed in the centre of the room, 1.2 m above floor level (airflow rate 28.7 l/min). This is a multistage, multiorifice cascade impactor that is comprised of six stages. Any particle greater that 4.7 microm should impact on stages 1 and 2, whilst stages 3-6 measure the predominantly respiratory range. The sampling was carried out for 30 min after 15 min of vigorous disturbance (vacuum cleaning without bag and filter). Der p 2 was measured using mAb-based ELISA with the AmpliQ amplification kit (Dako Ltd, Cambridgeshire, UK). The sensitivity was increased 15-fold as compared with standard assay, bringing the level of detection to 300 pg/ml. The majority of airborne Der p 2 (79.4%) was carried on large particles (> 4.7 microm). However, a small but important proportion of airborne Der p 2 (20.6%) was associated with small particles (1.1-4.7 microm). It is worth noting that all the levels measured were below the detection limit of standard assay. In conclusion, we have shown that using an amplification system, airborne mite allergen previously undetectable owing to its low concentration can be quantified. Group 2 dust mite allergen is carried not only on large particles. A small, but potentially significant proportion of this airborne allergen is associated with small particles which, when inhaled, may penetrate deep into the human respiratory tract.

Allergens↗
PubMed1996

Second-trimester pregnancy loss is associated with activated C resistance.

We have investigated whether activated protein C resistance (APCR) is associated with second-trimester miscarriage. The prevalence of APCR was significantly higher amongst women with a history of second-trimester miscarriage (10/50; 20%) compared with either women with a history of first-trimester miscarriages only (4/70; 5.7%) or a control group of parous women with no previous history of pregnancy losses (3/70; 4.3%) (P < 0.02). These results suggest that APCR may be an important mechanism of second-trimester pregnancy loss, possibly related to the increase in intravascular coagulation that occurs during pregnancy.

Abortion, Habitual↗
PubMed1995

Optimization of alkylating agent prodrugs derived from phenol and aniline mustards: a new clinical candidate prodrug (ZD2767) for antibody-directed enzyme prodrug therapy (ADEPT).

Sixteen novel potential prodrugs derived from phenol or aniline mustards and their 16 corresponding drugs with ring substitution and/or different alkylating functionalities were designed. The [[[4-]bis(2-bromoethyl)-(1a), [[[4-[bis(2-iodoethyl)-(1b), and [[[4-[(2-chloroethyl)-[2-(mesyloxy)ethyl]amino]phenyl]oxy] carbonyl]-L-glutamic acids (1c), their [[[2- and 3-substituted-4-[bis(2-chloroethyl)amino]phenyl]oxy]carbonyl]-L- glutamic acids (1e-1), and the [[3-substituted-4-[bis(2-chloroethyl)amino]phenyl]carbamoyl]-L- glutamic acids (1o-r) were synthesized. They are bifunctional alkylating agents in which the activating effect of the phenolic hydroxyl or amino function is masked through an oxycarbonyl or a carbamoyl bond to a glutamic acid. These prodrugs were designed to be activated to their corresponding phenol and aniline nitrogen mustard drugs at a tumor site by prior administration of a monoclonal antibody conjugated to the bacterial enzyme carboxypeptidase G2 (CPG2) in antibody-directed enzyme prodrug therapy (ADEPT). The synthesis of the analogous novel parent drugs (2a-r) is also described. The viability of a colorectal cell line (LoVo) was monitored with the potential prodrugs and the parent drugs. The differential in the cytotoxicity between the potential prodrugs and their corresponding active drugs ranged between 12 and > 195 fold. Compounds 1b-d,f,o exhibited substantial prodrug activity, since a cytotoxicity differential of > 100 was achieved compared to 2b-d,f,o respectively. The ability of the potential prodrugs to act as substrates for CPG2 was determined (kinetic parameters KM and kcat), and the chemical stability was measured for all the compounds. The unsubstituted phenols with different alkylating functionalities (1a-c) proved to have the highest ratio of the substrates kcat:KM. From these studies [[[4-[bis(2-iodoethyl)amino]phenyl]oxy]carbonyl]-L-glutamic acid (1b) emerges as a new ADEPT clinical trial candidate due to its physicochemical and biological characteristics.

Antibodies, Monoclonal↗
PubMed1994

Impact of the treatment of isolated systolic hypertension on behavioral variables. Results from the systolic hypertension in the elderly program.

BACKGROUND: Little information has been published on the impact of antihypertensive medications on quality of life in older persons. Particular concern has existed that lowering systolic blood pressure in older persons might have adverse consequences on cognition, mood, or leisure activities. METHODS: A multicenter double-blind randomized controlled trial was conducted over an average of 5 years' followup involving 16 academic clinical trial clinics. Participants consisted of 4736 persons (1.06%) selected from 447,921 screenees aged 60 years and older. Systolic blood pressure at baseline ranged from 160 to 219 mm Hg, while diastolic blood pressure was less than 90 mm Hg. Participants were randomized to active antihypertensive drug therapy or matching placebo. Active treatment consisted of 12.5 to 25 mg of chlorthalidone for step 1, while step 2 consisted of 25 to 50 mg of atenolol. If atenolol was contraindicated, 0.05 to 0.10 mg of reserpine could be used for the second-step drug. The impact of drug treatment on measures of cognitive, emotional, and physical function and leisure activities was assessed. RESULTS: Our analyses demonstrate that active treatment of isolated systolic hypertension in the Systolic Hypertension in the Elderly Program cohort had no measured negative effects and, for some measures, a slight positive effect on cognitive, physical, and leisure function. The positive findings in favor of the treatment group were small. There was no effect on measures related to emotional state. Measures of cognitive and emotional function were stable in both groups for the duration of the study. Both treatment groups showed a modest trend toward deterioration of some measures of physical and leisure function over the study period. CONCLUSIONS: The overall study cohort exhibited decline over time in activities of daily living, particularly the more strenuous ones, and some decline in certain leisure activities. However, mood, cognitive function, basic self-care, and moderate leisure activity were remarkably stable for both the active and the placebo groups throughout the entire study. Results of this study support the inference that medical treatment of isolated systolic hypertension does not cause deterioration in measures of cognition, emotional state, physical function, or leisure activities.

Activities of Daily Living↗
PubMed1991

Working group recommendations: targeting criteria for geriatric evaluation and management research.

To maximize the cost effectiveness of geriatric evaluation and management (GEM) programs, criteria need to be established for selecting patients most likely to benefit. A working group was convened to define appropriate patient selection (targeting) criteria for each type of GEM program and to consider research questions for future targeting studies. The group outlined targeting criteria for the spectrum of GEM program types and locations. GEM program types included: inpatient GEM units; hospital geriatric consultation service; GEM programs in nursing homes; outpatient GEM programs for functionally impaired persons; and geriatric community outreach/screening programs for functionally independent elders. For each program type, the group outlined targeting criteria based on current literature and experience. Because research has not yet established the effectiveness of many of these patient targeting strategies, the group drafted a set of research questions, pertinent to targeting, that require attention: (1) For each identifiable population of elderly people, who are most likely to benefit from GEM? (2) How should these people best be identified/targeted? (3) What criteria should be used for targeting? (4) How and how often should population screening be performed to identify persons in need of GEM?

Aged↗
PubMed1989

The prevalence of dysequilibrium and related disorders in older persons.

Dysequilibrium disorders such as dizziness, balance and gait changes, and falls are among the most common yet poorly understood medical problems for older persons. A recent analysis of data about people aged 65 and older indicates that dysequilibrium is one of most common diagnoses in short-stay hospitalizations, and it accounts for an average of 4.3 days of medical care. Older people without overt disease of any type tend to perform more poorly on balance tests than do younger people. Gait deficits in many older people are associated with considerable functional impairments. Deficits in postural control are associated with an increased risk of falling. Geriatric dysequilibrium disorders can be caused by one or more factors--vestibular, vascular, visual, neuromuscular, pharmacologic--each of which must be considered to understand and appropriately treat the dysequilibrium. The accurate identification of the cause of dysequilibrium must involve the testing of multiple, interacting systems. The literature suggests that often no clear cause for an older person's dysequilibrium can be found, and indicates the possible existence of presently unappreciated etiologic factors. Progress in understanding these problems probably has been stymied by the fact that only a small, select subgroup of older patients is referred to specialists in otolaryngology. Quite probably, considerable progress on the understanding of the cause, diagnosis, and treatment of geriatric dysequilibria would result from more extensive research collaboration between otorhinolaryngologists, geriatricians, epidemiologists, and other specialists.

Accidental Falls↗
PubMed1985

Conducting clinical research in geriatric populations.

Clinical research on geriatric populations requires adaptation of traditional methodologies, modification of expectations, and the development of new procedures. Some aspects of research methodology are unique to studies of geriatric populations. Experience in this relatively new area of geriatric research indicates that new partnerships between researchers and long-term care providers are needed. These new relationships require an understanding of the needs of geriatric populations and of the differences between providers of long-term care and of acute-care. Researchers must consider heterogeneity of the population, the probability of multiple diagnoses and treatments, subject attrition, and the possibility of invalid data. Such considerations require extra staff, more time, and increased funding as well as new thinking about study design and protocol implementation.

Aged↗
PubMed1983

Activation of polycyclic hydrocarbons in Reuber H4-II-E hepatoma cells. An in vitro system for the induction of SCEs.

Activation of polycyclic aromatic hydrocarbons (PAHs) was examined in the Reuber H4-II-E established cell line without the use of exogenous enzyme preparations. Metabolism of PAHs to genotoxic products was determined by the induction of sister-chromatid exchanges (SCEs). The induction of SCEs followed a dose-response pattern with plateaus at high doses of PAH. The effects of metabolic enzyme inducers (3-methylcholanthrene, phenobarbital, Aroclor 1254) and the epoxide hydrase inhibitor 1,1,1-trichloropropylene oxide were assessed as changes in SCE induction and enhanced production of water-soluble metabolites. Results indicate that Reuber H4-II-E cells can be employed in the testing of carcinogens activated by the P1-450 monooxygenase system and would be a useful in vitro system for the study of mechanisms of metabolic induction and their effect on genetic toxicity.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

Early experience with 'new federalism' in health insurance regulation.

The authors monitored the implementation of the Health Insurance Portability and Accountability Act (HIPAA) from 1997 to 1999. Regulators in all states and relevant federal agencies were interviewed and applicable laws and regulations studied. The authors found that HIPAA changed legal protections for consumers' health coverage in several ways. They examine how the process of regulating such coverage was affected at the state and federal levels and under an emerging partnership of the two. Despite some early implementation challenges, HIPAA's successes have been significant, although limited by the law's incremental nature.

Career Mobility↗