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Biomedical subjects

L Finn

Publications and source records attributed to L Finn.

At least 19 recordsLinked to original sources

Epidemiology of restless legs symptoms in adults.

BACKGROUND: Restless legs syndrome (RLS) is a disorder characterized by sleep-disrupting unpleasant leg sensations, often accompanied by daytime behavioral problems. Treatment for this condition is available, but it is suspected that most instances of RLS remain undiagnosed. The goal of this investigation was to assess the prevalence and health status correlates of restless legs symptoms (hereinafter referred to as restless legs) in the general population. METHODS: A question reflecting the clinical features of RLS was added to the 1996 Kentucky Behavioral Risk Factor Surveillance Survey. Data on the frequency of experiencing restless legs, self-rated general and mental health status, demographics, and behavioral risk factors were collected by telephone interview from 1803 men and women, 18 years and older. RESULTS: Experiencing restless legs 5 or more nights per month was reported by 3% of participants aged 18 to 29 years, 10% of those aged 30 to 79 years, and 19% of those 80 years and older. The age-adjusted prevalence for Kentucky adults is 10.0%; prevalence did not vary significantly by sex. The adjusted odds ratios (95% confidence intervals) for restless legs and diminished general health and poor mental health status were 2.4 (1.4-4.0) and 3.1 (2.0-4.6), respectively. Restless legs were significantly associated with increased age and body mass index, lower income, smoking, lack of exercise, low alcohol consumption, and diabetes. CONCLUSIONS: The prevalence of restless legs in the general adult population is high. Restless legs may be associated with decreased well-being, emphasizing the need for further research and greater medical recognition of this condition.

Adolescent↗

The pattern of serum markers in patients with androgen-independent adenocarcinoma of the prostate.

In this exploratory study, our objectives were to correlate the serum and bone marrow concentrations of putative markers of prostate cancer progression in patients with advanced androgen-independent prostate cancer (AIPC), to assess the frequency and quantity of relative expression of these markers, and to correlate the expression of the markers with extent of disease (EOD) and overall survival. In a cohort of 50 patients with AIPC with bone metastases, we obtained serum and bone marrow samples and measured prostate specific antigen (PSA), serum interleukin-6 (sIL-6), bone marrow interleukin-6, serum chromogranin A (sCgA), bone marrow chromogranin A, and prostate specific membrane antigen (PSMA) by immunoassays. EOD was determined by quantifying identifiable bone lesions on radionuclide bone scans. Each variable was categorized into two groups (low and high) based on the median found in this cohort or on the cutoff based on normal limits when available. Analyses were performed in two subsets of patients with EOD either <20 or >/=20. Results showed that: (1) PSA is associated with EOD but not with outcome; (2) sIL-6 and sCgA may be intermediate markers of early progression in AIPC, because they are predictive of outcome only in patients with EOD <20; (3) elevated PSMA is associated with elevated sIL-6 but not with PSA, suggesting that PSMA may be a useful marker in AIPC; and (4) the ratio of PSA to putative markers of progression may reflect the complex clonal progression of prostate cancer. We conclude that patients with advanced AIPC exhibit one of two patterns of serologic marker expression: in some patients the disease status is reflected by PSA, and in others it is reflected by other markers. If these data are prospectively confirmed, this would help group patients with advanced AIPC into clinically relevant categories.

Journal Article↗

Neoadjuvant chemotherapy and hormonal therapy followed by radical prostatectomy: feasibility and preliminary results.

PURPOSE: We assessed the feasibility and efficacy of integrating chemotherapy and androgen ablation with radical prostatectomy in patients with locally advanced prostate cancer. The neoadjuvant approach was adopted because it allows an in situ assessment of antitumoral activity. PATIENTS AND METHODS: Thirty-three patients were enrolled who met the clinical criteria of stage T1-2, Gleason score of >/= 8 or T2b-T2c, Gleason score of 7 and prostate-specific antigen (PSA) level greater than 10 ng/mL (n = 15), or clinical stage T3 (n = 18). Therapy consisted of 12 weeks of ketoconazole and doxorubicin alternating with vinblastine, estramustine, and androgen ablation followed by prostatectomy. The ability of neoadjuvant chemotherapy and hormonal therapy to induce a 20% rate of pT0 in the prostatectomy specimen as well as surgical feasibility were assessed. RESULTS: Chemotherapy complications were comparable to those reported with this regimen previously. No major intraoperative complications occurred. Postoperative complications occurred in 10 (33%) of 30 patients. One patient died at home after discharge (postoperative day 17; no autopsy was performed). Ten (33%) of the 30 patients had organ-confined disease, and 20 (70%) of 30 had extraprostatic extension; 11 (37%) of the 30 had positive lymph nodes. Only five (17%) of 30 exhibited positive surgical margins. All patients achieved an undetectable PSA level postoperatively, and 20 of the surviving 29 patients remain without disease recurrence with a median follow-up of 13 months (range, 9 to 18 months). CONCLUSION: Chemotherapy and androgen ablation followed by radical prostatectomy was feasible in patients with locally advanced prostate cancer. Although the goal of achieving a 20% rate for pT0 status was not achieved, we believe this type of integrated therapeutic strategy should be investigated further for its ability to alter the course of regionally advanced prostate cancer.

Adult↗

Nocturnal sleep and daytime sleepiness in normal subjects with HLA-DQB1*0602.

Narcolepsy, a neurological disorder characterized by excessive daytime sleepiness and abnormal REM sleep, is known to be tightly associated with the Human Leukocyte Antigen (HLA) DQ allele DQB1*0602. In this study, we have explored the possibility that normal subjects carrying this HLA allele (25% of the general population) could display subclinical REM sleep abnormalities and increased daytime sleepiness. Data from 525 middle-aged adults enrolled in the Wisconsin Sleep Cohort study were used for this analysis. Nocturnal polysomnography, sleep latency during the multiple sleep latency test (MSLT), and questionnaire items pertaining to excessive daytime sleepiness were compared between DQB1*0602 positive (n = 132) and negative (n = 393) participants. Results indicate shorter REM latency whether or not the latency was adjusted for wake after sleep onset (p = 0.003) and p = 0.02 respectively), increased sleep efficiency (p = 0.06) and decreased percent time spent in stage I sleep (p = 0.02) during nocturnal polysomnography in DQB1*0602 subjects. Data gathered using the Multiple Sleep Latency Test or the Epworth and Stanford sleepiness scales did not differentiate between DQB1*0602 positive and negative subjects. These results support the hypothesis that polymorphisms at the level of HLA DQ modulates sleep tendencies in humans.

Adult↗

Snoring and excessive daytime somnolence among Polish middle-aged adults.

There is considerable interest in the association of snoring and health consequences that have been linked to more severe sleep-disordered breathing, including obstructive sleep apnoea syndrome. The goal of this investigation was to assess the independent association of heavy, habitual snoring and daytime sleepiness. For this, a cross-sectional, population based study of snoring, sleepiness and other factors was conducted using the Warsaw sample of the Multinational Monitoring of Trends and Determinants of Cardiovascular Diseases (MONICA) study, a population-based multicentre study of cardiovascular disease. The well-defined MONICA sample of middle-aged males and females also allowed estimation of age- and sex-specific prevalences of habitual snoring in Polish adults. Data on self-reported snoring frequency and loudness, and daytime sleepiness using the Epworth Sleepiness Scale (ESS) and other questions, were collected with a postal questionnaire. Seventy-nine per cent of the MONICA sample completed the questionnaire, yielding a total of 1,186 participants. Of the total sample, 27% of the females and 48% of the males reported habitual snoring ("often" or "always"). There was an independent association of habitual snoring and excessive daytime sleepiness (EDS), sleepiness that interfered with work and with increasing ESS scores. Habitual snorers were 5.8 and 3.1 times more likely to report EDS in active and passive situations, respectively, compared to nonsnorers (all p<0.01). It is concluded that habitual snorers, most of whom are probably unlikely to have frank sleep apnoea syndrome, are at substantial risk for daytime sleepiness. These findings add support to the hypothesis that simple snoring is not benign and underscores the need for further research on health outcomes associated with this prevalent condition.

Activities of Daily Living↗

A human period gene (HPER1) polymorphism is not associated with diurnal preference in normal adults.

Mammalian circadian rhythmicity has recently been shown to be regulated at the genetic level by transcription--translation feed-back loops. Key molecular components such as Clock, Bmal-1, Timeless and three Period proteins have been isolated in mammals. In this study, we hypothesized that polymorphisms at the level of one of these genes--HPER1--could be associated with differential morningness-eveningness tendencies. The sample comprised 463 middle-aged participants enrolled in the Wisconsin Sleep Cohort Study. Diurnal preferences were evaluated using the Horne-Ostberg questionnaire. An A to G synonymous substitution at position 2548 was identified in HPER1 c-DNA sequence by comparing available sequence data. This polymorphism was verified by sequencing and typed using established oligotyping techniques in all subjects, yielding allele frequencies of 0.85 and 0.15 for HPER1 2548G and HPER1 2548A, respectively. Morningness-eveningness scores were then compared between genotype groups. In contrast to data previously published using a Clock polymorphism, scores did not differ significantly across HPER1 groups. These results suggest that polymorphism at the level of HPER1 does not significantly modulate morningness-eveningness tendencies in the general population.

Adult↗

A district survey of vaccine cold chain protection in general practitioners' surgeries.

Failure to ensure that vaccines are kept within a prescribed temperature range at all times can reduce their potency and cause primary vaccine failure. A postal survey of 103 general practices in a health district to assess vaccine handling and storage yielded 75 responses (73%). Poor practice was identified in receipt and storage of vaccines, temperature monitoring and control, management of vaccines during immunisation sessions, and disposal of partly used vaccines. The data suggest that the vaccine cold chain is not maintained with the degree of care necessary for safe practice. National guidelines need to be implemented conscientiously by all those involved with immunisation programmes if the effectiveness of vaccines is to be guaranteed.

Drug Storage↗

A CLOCK polymorphism associated with human diurnal preference.

A single nucleotide polymorphism located in the 3' flanking region of the human CLOCK gene was investigated as a predictor of diurnal preference in a population-based random sample of 410 normal adults. Morningness-eveningness preferences were determined using the 19-item Home-Ostberg questionnaire. Subjects carrying one of the two CLOCK alleles, 3111C, had a significantly lower mean Horne-Ostberg score. The distribution of scores was clearly shifted toward eveningness for these subjects. The score difference was independent of age, sex and ethnic heritage, thus making population stratification effects unlikely to explain this difference. These subjects had a substantial 10- to 44-minute delay in preferred timing for activity or sleep episodes. We suggest that the identified polymorphism or another tightly linked polymorphism within the CLOCK gene or its regulatory elements may be responsible for the finding.

Adult↗

Minor surgery in general practice--setting the standards.

BACKGROUND: A self-assessment tool was trialled to set a baseline for control of infection in general practice and to assess the nature and adequacy of infection control precautions in primary care settings with particular reference to minor surgery. METHODS: A request for volunteers was included in a flier sent out periodically by the Communicable Disease Unit to all general practices in the county (n = 114). Eleven practices (9.6 per cent) volunteered to take part and an audit of infection control precautions was undertaken with the practice nurse and/or manager. RESULTS: Of the 11 general practices audited, nine did not have a written policy for control of infection, did not have a separate, dedicated room for minor surgery, did not use protective clothing appropriately, used terry towels for hand-drying and reprocessed single-use only items. Ten used inappropriate methods to decontaminate heat labile items, seven did not record sterilizer processing cycles and five did not comply with HTM 2010 with regard to sterilizer maintenance. Following the survey, minimum infection control requirements have been developed for future applications to provide extended minor surgery within general practice and these will be monitored at subsequent surgery inspection visits and through audit. CONCLUSIONS: Results suggest that there is little room for complacency with regard to standards of infection control in general practice. In view of the increasing shift towards primary care based minor surgery it would be helpful if minimum standards were to be agreed nationally.

England↗

Epstein-Barr virus infections in children after transplantation of the small intestine.

Epstein-Barr virus (EBV) infection in association with immunosuppressive drugs used for solid organ transplantation can produce a spectrum of illnesses. Forty-one children who ranged in age from 6 months to 18.5 years received small intestinal transplants alone or in combination with other organs while undergoing primary tacrolimus (FK506) immunosuppression between July 1990 and June 1995. We reviewed hematoxylin and eosin-stained sections from all biopsy, surgical, and autopsy material from these children to determine the incidence and morphology of EBV-associated disease. Nuclear staining with in situ hybridization for EBV early RNA transcript (EBER) using the EBER-1 probe confirmed the presence of EBV. The EBV lymphoproliferations were graded as 1 to 4 according to histopathology and EBV quantitation determined in the area of greatest positivity. Twenty-one patients (51%) had EBV documented histologically on one or more occasions; only 8 (38%) are alive; 5 of these had the highest grade of 2. Posttransplant lymphoproliferative disease (PTLD) developed in 13 patients. Three of 10 patients (30%) with grade 3 lesions (polymorphous PTLD) are alive with intermittent evidence of EBV infection; 6 died with PTLD. Monomorphic PTLD (grade 4) was the cause of death in the three additional patients. Thirteen of 20 patients (65%) with no histologic evidence of EBV are alive. The incidence of EBV infection in pediatric small intestinal transplant recipients is higher than reported for any other solid organ cohort. With the aid of frequent EBER staining we were able to diagnose EBV infections in 51% of 41 patients; PTLD (grade 3 or 4) developed in 32% of these children. Low-grade EBV infections often preceded the development of PTLD and were identified in gastrointestinal biopsy samples from patients with concurrent PTLD; however, results of gastrointestinal biopsy samples may be negative for EBV in some patients with PTLD and, thus, underestimate systemic EBV-associated lymphoproliferations. Rejection and EBV infection can occur simultaneously, therefore, attention to low-grade infection may be useful to patient management.

Adolescent↗

Nasal obstruction as a risk factor for sleep-disordered breathing. The University of Wisconsin Sleep and Respiratory Research Group.

Nasal obstruction frequently has been associated with sleep-disordered breathing as a potential etiologic factor. Nasal obstruction results in pathologic changes in airflow velocity and resistance. Experimentally produced nasal obstruction increases resistance and leads to sleep-disordered breathing events, including apnea, hypopnea, and snoring. Clinical research examining the correlation between nasal obstruction and sleep-disordered breathing is limited, especially in regard to patients with conditions that increase nasal resistance, such as rhinitis and sinusitis. To further identify risk factors for sleep-disordered breathing, the role of chronic and acute nasal congestion was investigated in a population-based sample. Data on nasal congestion history and sleep problems were obtained by questionnaire (n = 4927) and by objective inlaboratory measurement (n = 911). Participants who often or almost always experienced nighttime symptoms of rhinitis (5 or more nights a month) were significantly (p < 0.0001) more likely to report habitual snoring (3 to 7 nights a week), chronic excessive daytime sleepiness, or chronic nonrestorative sleep than were those who rarely or never had symptoms. Habitual snorers had significantly (p < 0.02) lower air flow than nonsnorers, although a linear relation between decreased airflow and sleep-disordered breathing severity did not exist. Participants who reported nasal congestion due to allergy were 1.8 times more likely to have moderate to severe sleep-disordered breathing than were those without nasal congestion due to allergy. Men and women with nasal obstruction, especially chronic nighttime symptoms of rhinitis, are significantly more likely to be habitual snorers, and a proportion also may have frequent episodes of apnea and hypopnea, indicative of severe sleep-disordered breathing. Because allergic rhinitis is a common cause of nasal obstruction and it is a modifiable risk factor, further study of this association is warranted.

Adult↗

Phase I-II study of gamma interferon and 5-fluorouracil for patients with metastatic renal cell carcinoma

We have completed a phase I/II trial to evaluate the toxicity and efficacy of the combination of gamma interferon and 5-fluorouracil in metastatic renal cell carcinoma. Gamma interferon was administered at a weekly dose of 100 micrograms. 5-fluorouracil was given as a 5 day continuous infusion days 1-5 of each 21 day cycle. In the phase I portion of the trial, the gamma interferon dose was held constant, while the 5-fluorouracil was escalated from 500 to 800 mg/m2/day. Serum neopterin and beta 2 microglobulin were measured prior to and 48 hours after each dose of gamma interferon for the first six weeks of treatment. Dose limiting toxicity was not encountered in the phase I part of the trial; therefore the phase II study was initiated at the 800 mg/m2/day dose of 5-fluorouracil. No responses were seen among 34 patients treated on the phase II trial. Forty-six percent of patients experienced disease stabilization and the remainder progressed through treatment. In the phase I trial, increments in neopterin and beta 2 microglobulin levels differed significantly between patients treated with lower and higher doses of 5-fluorouracil. We conclude that the addition of 5-fluorouracil to gamma interferon does not appear to enhance the cytokines clinical activity. Incremental increases in macrophage activation markers with escalating 5-fluorouracil doses suggests a role for 5-fluorouracil beyond its usual proposed cytotoxic activity and warrants further investigation into potential immunologic effects of this drug.

Journal Article↗

Sleep-disordered breathing and motor vehicle accidents in a population-based sample of employed adults.

Studies have consistently shown that sleep apnea patients have high accident rates, but the generalizability of the association beyond clinic populations has been questioned. The goal of this investigation was to determine if unrecognized sleep-disordered breathing in the general population, ranging from mild to severe, is associated with motor vehicle accidents. The sample comprised 913 employed adults enrolled in an ongoing study of the natural history of sleep-disordered breathing. Sleep-disordered breathing status was determined by overnight in-laboratory polysomnography and motor vehicle accident (MVA) history was obtained from a statewide data base of all traffic violations and accidents from 1988 to 1993. Men with five or more apneas and hypopneas per hour of sleep [apnea-plus-hypopnea index (AHI) > 5], compared to those without sleep-disordered breathing, were significantly more likely to have at least one accident in 5 years (adjusted odds ratio = 3.4 for habitual snorers, 4.2 for AHI 5-15, and 3.4 for AHI > 15). Men and women combined with AHI > 15 (vs. no sleep-disordered breathing) were significantly more likely to have multiple accidents in 5 years (odds ratio = 7.3). These results, free of clinic selection bias, indicate that unrecognized sleep-disordered breathing in the general population is linked to motor vehicle accident occurrence. If the association is causal, unrecognized sleep-disordered breathing may account for a significant proportion of motor vehicle accidents.

Accidents, Traffic↗

Estimation of the clinically diagnosed proportion of sleep apnea syndrome in middle-aged men and women.

The proportion of sleep apnea syndrome (SAS) in the general adult population that goes undiagnosed was estimated from a sample of 4,925 employed adults. Questionnaire data on doctor-diagnosed sleep apnea were followed up to ascertain the prevalence of diagnosed sleep apnea. In-laboratory polysomnography on a subset of 1,090 participants was used to estimate screen-detected sleep apnea. In this population, without obvious barriers to health care for sleep disorders, we estimate that 93% of women and 82% of men with moderate to severe SAS have not been clinically diagnosed. These findings provide a baseline for assessing health care resource needs for sleep apnea.

Adult↗