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R J Harrison

Publications and source records attributed to R J Harrison.

At least 19 recordsLinked to original sources
PubMed2002

A determination of healthcare worker exposure to Mycobacterium tuberculosis in two Californian hospitals.

The US Centers for Disease Control and Prevention (CDC) recommends the prompt and sustained placement of potentially infectious tuberculosis patients in to negative-pressure isolation rooms, to help prevent other patients and workers, who remain outside of the room, from exposure to potential aerosols of Mycobacterium tuberculosis. The purpose of this study was to assess the potential for healthcare worker exposure to such aerosols and, to study compliance with the CDC guidelines. All room locations of culture-positive pulmonary TB patients were identified retrospectively for a one-year period at two hospitals. Placement in a negative-pressure isolation room was delayed for >24h after admission in 30% of 54 patients at hospital 1, and for 56% of nine patients at hospital 2. The median delay in isolation was three days at hospital 1, and five days at hospital 2. At hospital 1, of the 16 patients with delayed or no isolation, 14 (88%) were AFB smear-positive, and 12 (75%) were admitted to the hospital during the winter months. At hospital 2, of five patients with delayed or no isolation, two (40%) were AFB smear-positive, and four (80%) were admitted to the hospital during the winter months. The main reason for non-isolation was failure to initiate and sustain isolation for all suspect tuberculosis patients during the winter. These delays may reflect an insufficient number of isolation rooms to accommodate an increased usage of isolation rooms during the winter months. Delays in suspecting tuberculosis also contributed to non isolation. For 33% of the non-isolated patients, recognition of the diagnosis was delayed for three or more days. Patients were hospitalized on most adult inpatient wards, and virtually every hospital location that had these patients also had, non-isolated sources of mycobacterial aerosol. All workers were at risk of exposure, although the risk varied by hospital location, and should be tuberculosis skin-tested, at least annually. Suspect and known tuberculosis patients should be isolated until they are demonstrated to be non-infectious.

Adult↗
PubMed2001

Inhibition of the Bloom's and Werner's syndrome helicases by G-quadruplex interacting ligands.

G-Quadruplex DNAs are folded, non-Watson-Crick structures that can form within guanine-rich DNA sequences such as telomeric repeats. Previous studies have identified a series of trisubstituted acridine derivatives that are potent and selective ligands for G-quadruplex DNA. These ligands have been shown previously to inhibit the activity of telomerase, the specialized reverse transcriptase that regulates telomere length. The RecQ family of DNA helicases, which includes the Bloom's (BLM) and Werner's (WRN) syndrome gene products, are apparently unique among cellular helicases in their ability to efficiently disrupt G-quadruplex DNA. This property may be relevant to telomere maintenance, since it is known that the sole budding yeast RecQ helicase, Sgs1p, is required for a telomerase-independent telomere lengthening pathway reminiscent of the "ALT" pathway in human cells. Here, we show that trisubstituted acridine ligands are potent inhibitors of the helicase activity of the BLM and WRN proteins on both G-quadruplex and B-form DNA substrates. Inhibition of helicase activity is associated with both a reduction in the level of binding of the helicase to G-quadruplex DNA and a reduction in the degree to which the G-quadruplex DNA can support DNA-dependent ATPase activity. We discuss these results in the context of the possible utility of trisubstituted acridines as antitumor agents for the disruption of both telomerase-dependent and telomerase-independent telomere maintenance.

Acridines↗
PubMed2001

Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors.

The telomerase enzyme is a potential therapeutic target in many human cancers. A series of potent inhibitors has been designed by computer modeling, which exploit the unique structural features of quadruplex DNA. These 3,6,9-trisubstituted acridine inhibitors are predicted to interact selectively with the human DNA quadruplex structure, as a means of specifically inhibiting the action of human telomerase in extending the length of single-stranded telomeric DNA. The anilino substituent at the 9-position of the acridine chromophore is predicted to lie in a third groove of the quadruplex. Calculated relative binding energies predict enhanced selectivity compared with earlier 3,6-disubstituted compounds, as a result of this substituent. The ranking order of energies is in accord with equilibrium binding constants for quadruplex measured by surface plasmon resonance techniques, which also show reduced duplex binding compared with the disubstituted compounds. The 3,6,9-trisubstututed acridines have potent in vitro inhibitory activity against human telomerase, with EC(50) values of up to 60 nM.

Acridines↗
PubMed2001

Physician reports of work-related asthma in California, 1993-1996.

BACKGROUND: Work-related asthma is a leading cause of occupational respiratory illness. METHODS: Work-related asthma was studied in California over a 36-month period, from March 1, 1993 to February 29, 1996. The surveillance system identified cases from Doctor's First Reports (DFRs), a mandated physician reporting system. Structured follow-up telephone interviews of DFR asthma cases were conducted to collect work history, exposure, and medical information. Statewide employment data was used to calculate disease rates among industry groups. RESULTS: Based on 945 cases of work-related asthma, the average annual reporting rate for work-related asthma in California was 25/million workers. We estimate that the actual rate is 78/million, adjusted for likely underreporting. Janitors and cleaners (625/million) and firefighters (300/million) had the highest reporting rates of work-related asthma. Half of all work-related asthma cases were associated with agents not known to be allergens. CONCLUSIONS: A greater proportion of work-related asthma associated with irritant exposures was identified than has previously been reported. The surveillance data provide a very conservative estimate of the incidence of work-related asthma.

Adult↗
PubMed2001

Repeated cocaine treatment activates flank marking in adolescent female hamsters.

Cocaine abuse during adolescence represents a significant health risk due to the potential for both acute and long-term negative physical and psychological sequelae, including increased aggressive behavior. This study examined the effect of adolescent cocaine treatment on flank marking (i.e., a stereotypic motor behavior that is part of the response pattern of offensive aggression) in female and male Syrian hamsters (Mesocricetus auratus). Adolescent cocaine treatment activated flank marking in female hamsters when animals were measured upon return to their home cage immediately following drug treatment. Sex differences were observed in cocaine-induced flank marking, as males failed to flank mark when returned to the home cage. In females, the behavioral response was most marked on Day 11 of cocaine treatment in all doses tested. Yet, animals treated with low-dose cocaine (0.5 mg/kg/day) showed the most significant increase in flank marking on and from Day 11 forward as compared to medium- and high-dose cocaine-treated animals and controls. In addition, the response of cocaine-treated animals was vigorous and nearly immediate, as >75% of the flank marks scored were performed within the first 2 min of the behavioral test in >85% of animals examined. Measures of locomotion showed that cocaine had stimulatory effects on motor activity in adolescent female hamsters at all doses tested. Cocaine-treated animals did not differ in body weight gain from controls, suggesting no dramatic physiological effects of adolescent cocaine exposure on body growth at the doses tested.

Aggression↗
PubMed2000

Chemicals and gases.

This article covers the major chemicals and gases that are considered to be of the most clinical relevance to the primary care provider. The reader is referred to other comprehensive textbooks of toxicology and occupational medicine for a complete discussion of the numerous additional products found in the workplace that may result in occupational exposure.

Gases↗
PubMed2000

Structure-activity relationships among guanine-quadruplex telomerase inhibitors.

The ribonucleoprotein telomerase is responsible for maintaining the length of telomeric ends of chromosomes in tumour cells. It is activated in over 85% of the tumour cells, and is emerging as a major target for cancer chemotherapy. A range of molecules containing tricyclic and tetracyclic aromatic chromophores has been shown to inhibit the telomerase enzyme system at the micromolar level. There is evidence that they do so via stabilisation of a guanine-quadruplex structure, which provides a stop signal for further telomere elongation. The known structure-activity relationships for these compounds are summarised, and pointers for the development of future molecules with enhanced selectivity are described.

Binding Sites↗
PubMed2000

Chronic anabolic-androgenic steroid treatment during adolescence increases anterior hypothalamic vasopressin and aggression in intact hamsters.

The present study examines the hypothesis that exposure to anabolic-androgenic steroids (AAS) during adolescent development predisposes hamsters to heightened levels of aggressive behavior by influencing the anterior hypothalamic-arginine vasopressin (AH-AVP) neural system. To test this, adolescent male hamsters (Mesocricetus auratus) were treated with high doses of AAS, tested for offensive aggression in the absence or presence of AH-AVP receptor antagonists, and then examined for changes in AH-AVP expression and neural organization. AAS exposure during adolescence significantly increased aggression intensity (number of attacks and bites) and initiation (latency to the first bite). Yet, only increases in aggression intensity were inhibited by AH-AVP receptor antagonism. Adolescent AAS-treated hamsters showed significant increases in AH-AVP fiber density and peptide content. However, no alterations in AH-AVP neuronal organization or mRNA expression were found. Together, these data suggest that adolescent AAS exposure increase aggression intensity by altering AH-AVP expression and activity, providing direct evidence for a causal role of AH-AVP expression and function in early onset AAS-stimulated aggression.

Aggression↗
PubMed2000

Tuberculosis isolation: comparison of written procedures and actual practices in three California hospitals.

OBJECTIVE: To evaluate implementation of healthcare worker exposure control measures for tuberculosis (TB)-patient isolation, as specified by Centers for Disease Control and Prevention (CDC) guidelines and the hospital's TB-control policy. DESIGN: Prospective multihospital study comparing CDC guidelines and hospital policy for TB-patient isolation to once-weekly observations of TB-patient isolation practices over 14 consecutive weeks at each hospital. SETTING: Three urban hospitals (two county, one private community) in counties in California with a high incidence rate of TB. MEASUREMENTS: Work practices for TB-patient isolation were observed and ventilation performance of isolation rooms was assessed while patient rooms were in use for TB isolation. RESULTS: Of 170 TB-patient rooms observed, 119 (70%) involved a patient in a designated TB isolation room, the room was under negative pressure, the door was closed, and a "respiratory precautions" sign was on the door; 32 patient-room units (19%) were not under negative pressure or not designated as negative-pressure rooms. Of 151 patient-room units mechanically capable of negative pressure at a prior point in time, 16 (11%) were not under negative pressure at the time of use. Of 67 patient-room units equipped with continuous monitoring devices, 8 (12%) involved devices that did not accurately reflect the direction of airflow. Of the 62 healthcare workers observed using a respirator for TB, 40 (65%) did not don the respirator properly. CONCLUSIONS: Implementing CDC guidelines for TB-patient isolation was feasible but imperfect in the three hospitals. Day-to-day work practices deviated from hospital policy. Prospectively quantifying the implementation of a hospital TB isolation policy while the room is in use may lead to improved estimates of risk and may help to identify and thereby prevent avoidable healthcare worker exposures to Mycobacterium tuberculosis aerosol. Auditing practices and verifying equipment performance is likely to identify unexpected problems in implementation of the TB control program.

California↗
PubMed1999

Human telomerase inhibition by substituted acridine derivatives.

A series of 3,6-disubstituted acridine derivatives have been rationally designed as telomerase inhibitors. They have been designed on the basis that inhibition of telomerase occurs by stabilising G-quadruplex structures formed by the folding of telomeric DNA. The most potent inhibitors have IC50 values against telomerase of between 1.3 and 8 microM, comparable to their cytotoxicity in ovarian cancer cell lines.

Acridines↗
PubMed1998

Evaluating the control of tuberculosis among healthcare workers: adherence to CDC guidelines of three urban hospitals in California.

OBJECTIVE: To evaluate adherence to components of the Centers for Disease Control and Prevention (CDC) guidelines for preventing the transmission of Mycobacterium tuberculosis in healthcare facilities. DESIGN: Multihospital study using direct observation and a standardized questionnaire. SETTING: Three urban hospitals (two county hospitals and one private community hospital) in counties in California with a high number and incidence rate of tuberculosis (TB) cases. MEASUREMENTS: The ventilation performance of treatment and TB-patient isolation rooms was assessed. Questionnaire data regarding TB control policy and procedures were obtained through interviews with the person(s) responsible for each program component; review of written TB control plans, training, and educational materials; and attendance at hospital TB control meetings and trainings. RESULTS: Twenty-eight percent of isolation rooms tested (7/25) were under positive pressure; 83% of rooms tested (20/24) had six or more nominal air changes per hour (ACH), but supply air did not mix rapidly with room air. Therefore, the nominal ACH likely overestimated the effective ACH and the subsequent protection provided. In virtually all rooms tested (26/27), air potentially containing M tuberculosis aerosol moved toward, rather than away from, likely worker locations. None of the hospitals regularly checked the performance of engineering controls. Only one hospital adhered to the CDC minimum requirements for respiratory protection. Training of healthcare workers generally was underutilized as a TB prevention measure. Hospitals did not provide comprehensive counseling regarding the need for healthcare workers to know their immune status and the risks associated with M tuberculosis infection in an immunocompromised individual. Employee representatives did not have a voice in TB-related decision making. CONCLUSIONS: Important aspects of day-to-day TB control practice did not conform to the written TB control policy. Subsequent to the identification of TB patients, healthcare workers at all three hospitals were potentially exposed to M tuberculosis aerosol due to breaches in negative-pressure isolation, the limitations of dilution ventilation, and the failure to maintain engineering controls and to implement respiratory protection controls fully. These findings lend support to the Occupational Safety and Health Administration's policy presumption that, absent clear evidence to the contrary, newly acquired healthcare-worker M tuberculosis infections are work-related.

California↗
PubMed1998

Prevalence and patterns of psychotropic and anticonvulsant medication use in children and adolescents referred to residential treatment.

The prevalence and patterns of use of psychiatric and anticonvulsant medications were studied in 83 seriously emotionally disturbed children and adolescents at the time of their admission to a residential treatment facility. Youths (aged 5-19, mean = 13.6 years), consecutively admitted over 17 months, were assessed for the prevalence and patterns of use of psychotropic and anticonvulsant treatments. At admission, 76% of the youths were receiving psychiatric pharmacotherapy, 40% with more than one psychiatric agent, and 15% with a combination of psychotropic and anticonvulsant medications. Frequently prescribed medications were neuroleptics (35 % of the medicated youths), sedative-hypnotics (26 %), and anticonvulsants (15%). Psychostimulants (16%) and antidepressants (22%) were under-prescribed relative to their diagnostic indications. Over 50 different medication combinations were used. The neuroleptic + lithium combination was most common (25 % of the polypharmacological treatments). Neuroleptics were the most commonly prescribed medication and mostly used for nonpsychotic, nontic, and nonbipolar indications (55% of neuroleptic trials). Neuroleptics were used primarily for aggression regardless of diagnosis. Neuroleptics were used more in symptomatic treatments than in treatments for indicated diagnoses. The high prevalence of psychiatric and antiepileptic medication use in children and adolescents admitted to a residential treatment facility, and especially the pattern of their use, raises questions about prescribing practices for youths entering residential treatment and about pediatric psychopharmacotherapy in general.

Adolescent↗
PubMed1998

Overt categorical aggression in referred children and adolescents.

OBJECTIVE: To investigate descriptive and predictive correlates of aggression in children and adolescents who exhibit a high frequency of daily physical assault after admission to a structured residential treatment program and to examine correlations between subcategories of overt categorical aggression (OCA) in the same population. METHOD: Fifty-one admissions to a residential treatment program were assessed for frequency of physical assault after admission; analyses were corrected for length of stay. Patients with a high frequency of daily assault were compared with patients with a low frequency of daily assault on variables assessing demographics, history, family, concurrent behavior, treatment, and outcome. RESULTS: A high prevalence of OCA was found in this sample. Variables assessing history and concurrent behavior were significantly associated and predictive of subjects exhibiting a high frequency of daily physical assault after admission. Physical assault was significantly correlated with verbal aggression, property destruction, and self-injurious behavior. CONCLUSIONS: These findings support the distinctiveness of OCA as a separate subtype of aggression encompassing four subcategories. Further research on treatment, outcome, and associated comorbidity of OCA is warranted.

Adolescent↗
PubMed1997

Bilateral macular holes resulting from septic embolization.

PURPOSE: To report a previously undescribed cause of bilateral macular hole formation. METHOD: Case report. RESULTS: Septic emboli were noted at the center of the macula in both eyes of a 32-year-old man with acute bacterial endocarditis. Bilateral full-thickness macular holes later developed at the site of these retinal lesions. CONCLUSION: This case represents the first report of fundus lesions in septicemia resulting in full-thickness macular hole formation.

Adult↗