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T Young

Publications and source records attributed to T Young.

At least 55 records · Page 3Linked to original sources
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

The interaction of thrombomodulin with Ca2+.

Thrombomodulin (TM) is a cofactor for protein C activation by thrombin and each residue of a consensus Ca2+ site in the sixth epidermal growth factor domain (EGF6) is essential for this cofactor activity [Nagashima, M., Lundh, E., Leonard, J.C., Morser, J. & Parkinson, J.F. (1993) J. Biol. Chem. 268, 2888-2892]. Three soluble analogs of the extracellular domain of TM, solulin (Glu4-Pro490), TME1-6 (Cys227-Cys462) and TMEi4-6 (Val345-Cys462) were prepared for equilibrium dialysis experiments by exhaustive dialysis against Ca2+-depleted buffer. However, all three analogs still contained one tightly bound Ca2+ (Kd approximately 2 microm), which could only be removed by EDTA. Epitope mapping with Ca2+-dependent monoclonal antibodies to EGF6 provided further localization of this tight Ca2+ site. Equilibrium dialysis of the soluble TM analogs in [45Ca2+] between 10 and 200 microm revealed a second Ca2+ site (Kd = 30 +/- 10 microm) in both solulin and TME1-6, but not in TMEi4-6. Ca2+ binding to this second site was unaffected by bound thrombin and we attribute it to the consensus Ca2+ site in EGF3. A 75-fold decrease in the binding affinity of thrombin to TM was observed with immobilized solulin treated with EDTA to remove the high affinity Ca2+ by measuring kassoc and kdiss rates in a BIAcoretrade mark instrument. Ca2+-dependent conformational transitions detected by CD spectroscopy in the far UV indicate a more ordered structure upon Ca2+ binding. Bound Ca2+ stabilized soluble TM against protease digestion at a trypsin-like protease-sensitive site between Arg456 and His457 in EGF6 compared with protease treatment in EDTA. Finally, TM containing EGF domains 4-6, but lacking the interdomain loop between EGF3 and 4 (TME4-6), has an identical Ca2+ dependence for the activation of protein C as found for TMEi4-6, indicating this interdomain loop is not involved in Ca2+ binding.

Animals↗
PubMed1999

Influence of ambulance crew's length of experience on the outcome of out-of-hospital cardiac arrest.

AIMS: To investigate whether an ambulance crew's length of experience affected the outcome of out-of-hospital cardiac arrest. METHODS AND RESULTS: This was a population-based, retrospective observational study of attempted resuscitations in 1547 consecutive arrests of cardiac aetiology by Nottinghamshire Emergency Ambulance Service crew. One thousand and seventy-one patients were managed by either a paramedic or a technician crew without assistance from other trained individuals at the scene of arrest. Overall, the chances of a patient surviving to be discharged from hospital alive did not appear to be affected by the paramedic's length of experience (among survivors, 18 months experience vs non-survivors 16 months experience, P = 0.347) but there appears to be a trend in the effect of a technician's length of experience on survival (among survivors, 60 months experience vs non-survivors 28 months experience, P = 0.075). However, when a technician had 4 years of experience or more and a paramedic 1 year's experience, survival rates did improve. Logistic regression analysis, adjusted for factors known to influence outcome, revealed that chances of survival increased once technicians had over 4 years of experience after qualification (odds ratio 2.71, 95% CI 1.17 to 6.32, P = 0.02) and paramedics after just 1 year of experience (odds ratio 2.68, 95% CI 1.05 to 6.82, P = 0.04). CONCLUSIONS: Survival from out-of-hospital cardiac arrest varies with the type of ambulance crew and length of experience after qualification. Experience in the field seems important as paramedics achieve better survival rates after just 1 year's experience, while technicians need to have more than 4 years' experience to improve survival.

Ambulances↗
PubMed1999

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↗
PubMed1999

Resuscitation from out-of-hospital cardiac arrest: is survival dependent on who is available at the scene?

OBJECTIVE: To determine whether survival from out-of-hospital cardiac arrest is influenced by the on-scene availability of different grades of ambulance personnel and other health professionals. DESIGN: Population based, retrospective, observational study. SETTING: County of Nottinghamshire with a population of one million. SUBJECTS: All 2094 patients who had resuscitation attempted by Nottinghamshire Ambulance Service crew from 1991 to 1994; study of 1547 patients whose arrest were of cardiac aetiology. MAIN OUTCOME MEASURES: Survival to hospital admission and survival to hospital discharge. RESULTS: Overall survival from out-of-hospital cardiac arrest remains poor: 221 patients (14.3%) survived to reach hospital alive and only 94 (6.1%) survived to be discharged from hospital. Multivariate logistic regression analysis showed that the chances of those resuscitated by technician crew reaching hospital alive were poor but were greater when paramedic crew were either called to assist technicians or dealt with the arrest themselves (odds ratio 6.9 (95% confidence interval 3.92 to 26.61)). Compared to technician crew, survival to hospital discharge was only significantly improved with paramedic crew (3.55 (1.62 to 7.79)) and further improved when paramedics were assisted by either a health professional (9.91 (3.12 to 26.61)) or a medical practitioner (20.88 (6.72 to 64.94)). CONCLUSIONS: Survival from out-of-hospital cardiac arrest remains poor despite attendance at the scene of the arrest by ambulance crew and other health professionals. Patients resuscitated by a paramedic from out-of-hospital cardiac arrest caused by cardiac disease were more likely to survive to hospital discharge than when resuscitation was provided by an ambulance technician. Resuscitation by a paramedic assisted by a medical practitioner offers a patient the best chances of surviving the event.

Aged↗
PubMed1999

Quality of life four years after acute myocardial infarction: short form 36 scores compared with a normal population.

OBJECTIVES: To assess the impact of myocardial infarction on quality of life in four year survivors compared to data from "community norms", and to determine factors associated with a poor quality of life. DESIGN: Cohort study based on the Nottingham heart attack register. SETTING: Two district general hospitals serving a defined urban/rural population. SUBJECTS: All patients admitted with acute myocardial infarction during 1992 and alive at a median of four years. MAIN OUTCOME MEASURES: Short form 36 (SF 36) domain and overall scores. RESULTS: Of 900 patients with an acute myocardial infarction in 1992, there were 476 patients alive and capable of responding to a questionnaire in 1997. The response rate was 424 (89. 1%). Compared to age and sex adjusted normative data, patients aged under 65 years exhibited impairment in all eight domains, the largest differences being in physical functioning (mean difference 20 points), role physical (mean difference 23 points), and general health (mean difference 19 points). In patients over 65 years mean domain scores were similar to community norms. Multiple regression analysis revealed that impaired quality of life was closely associated with inability to return to work through ill health, a need for coronary revascularisation, the use of anxiolytics, hypnotics or inhalers, the need for two or more angina drugs, a frequency of chest pain one or more times per week, and a Rose dyspnoea score of >/= 2. CONCLUSIONS: The SF 36 provides valuable additional information for the practising clinician. Compared to community norms the greatest impact on quality of life is seen in patients of working age. Impaired quality of life was reported by patients unfit for work, those with angina and dyspnoea, patients with coexistent lung disease, and those with anxiety and sleep disturbances. Improving quality of life after myocardial infarction remains a challenge for physicians.

Aged↗
PubMed1999

Relevance of clinical trial results in myocardial infarction to medical practice: comparison of four year outcome in participants of a thrombolytic trial, patients receiving routine thrombolysis, and those deemed ineligible for thrombolysis.

OBJECTIVE: To assess the medium to long term outcome of patients ineligible for thrombolysis compared to those enrolled in a clinical trial of thrombolysis and patients receiving non-trial thrombolysis. DESIGN: Cohort study based on the Nottingham heart attack register. SETTING: Two district general hospitals serving a defined urban/rural population. SUBJECTS: All patients admitted with a confirmed acute myocardial infarction during 1992 categorised as either participants of a thrombolytic trial (group A, n = 140), receiving non-trial thrombolysis (group B, n = 329), or deemed ineligible for lytic treatment (group C, n = 431). MAIN OUTCOME MEASURES: Background characteristics, inhospital treatment, patterns of follow up, referrals to cardiologists, revascularisation rates, and short and long term survival. RESULTS: Clinical trial recruits were younger by almost 10 years, were less likely to have a previous history of myocardial infarction, and more likely to be in Killip class 1 on admission than those ineligible for thrombolysis. Cardiology follow up was mandatory for all surviving trial participants but 22% of patients in group B and 31% of patients in group C received no follow up, and during four years less than 50% ever saw a cardiologist. Revascularisation was performed in 17.2% of patients in group A, 13.6% of patients in group B, and 7.5% of patients in group C. Cumulative mortality at a median of four years was 24.3% in group A, 36.8% in B, and 59.6% in group C. Adjusting for age, sex, previous myocardial infarction, type of infarction, and Killip class in a logistic regression model the odds ratios (OR) of death at four years for groups B and C were 1.60 (95% confidence intervals (CI) 0.97 to 2.63, p = 0.065) and 2.64 (95% CI 1.61 to 4. 32, p < 0.001), respectively, when compared to group A (OR 1). CONCLUSIONS: Patients enrolled into thrombolytic trials are at low risk. Patients deemed ineligible for thrombolysis are high risk, receive less surveillance, are less likely to be revascularised or receive trial proven treatments, have a poor long term outcome not entirely explained by increased age or severity of infarction, and deserve further evaluation.

Aftercare↗
PubMed1998

Sleep-disordered breathing and self-reported general health status in the Wisconsin Sleep Cohort Study.

OBJECTIVE: To determine the relationship between sleep-disordered breathing and self-reported general health status. breathing status assessed by overnight in-laboratory polysomnography. SETTING: General Community. SUBJECTS: Employed men (n=421) and women (n=316), ages 30-60 years, enrolled in the Wisconsin Sleep Cohort Study. INTERVENTIONS: None. OUTCOME MEASURE: Self-reported general health profile and life satisfaction measured by the Medical Outcomes Survey Short Form-36 and obtained by interview. RESULTS: Sleep-disordered breathing was associated with lower general health status before and after adjustment for age, sex, body mass index, smoking status, alcohol usage, and a history of cardiovascular conditions. Even mild sleep-disordered breathing (apnea-hypopnea index = 5) was associated with decrements in the Medical Outcomes Short Form 36 Survey health constructs comparable to the magnitude of decrements linked to other chronic conditions such as arthritis, angina, hypertension, diabetes, and back problems. CONCLUSIONS: Sleep-disordered breathing is independently related to lower general health status, and this relationship is of clinical significance. Given the growing emphasis of the importance of patients' perceptions of health, these findings are relevant to estimating the overall impact of sleep-disordered breathing.

Adult↗
PubMed1998

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↗
PubMed1998

Ocular lens NAD kinase: partial purification and metabolic implications.

The ocular lens displays a significant amount of NADP(H) dependent metabolic traffic, but the origin of this cofactor has not been established. Size exclusion chromatography of bovine lens crude extract on a Sephacryl S300-HR column fitted with an eluate concentrator revealed two bands with NAD kinase activity, based on enzymatic cycling with signal amplification of the column fractions using a Cobas-Fara II centrifugal fast analyzer. Ve/Vo ratios from the chromatographic runs suggest that the relative molecular weight values lie within the ranges 8.91-3.98 x 10(5) and 2.04-1.26 x 10(5), respectively, for these two bands. An approximately 10-fold enhancement of enzyme activity over the crude fraction is realized from the chromatography step. Results point to NAD kinase as the source generator of this anchoring and linking cofactor for the oxidative stress and pentose phosphate enzyme systems, respectively.

Adenosine Triphosphate↗