Deletion variant in the ADRA2B gene increases coupling between emotional responses at encoding and later retrieval of emotional memories.

A deletion variant of the ADRA2B gene that codes for the α2b adrenoceptor has been linked to greater susceptibility to traumatic memory as well as attentional biases in perceptual encoding of negatively valenced stimuli. The goal of the present study was to examine whether emotional enhancements of memory associated with the ADRA2B deletion variant were predicted by encoding, as indexed by the subjectively perceived emotional salience (i.e., arousal) of events at the time of encoding. Genotyping was performed on 186 healthy young adults who rated positive, negative, and neutral scenes for level of emotional arousal and subsequently performed a surprise recognition memory task 1 week later. Experience of childhood trauma was also measured, as well as additional genetic variations associated with emotional biases and episodic memory. Results showed that subjective arousal was linked to memory accuracy and confidence for ADRA2B deletion carriers but not for non-carriers. Our results suggest that carrying the ADRA2B deletion variant enhances the relationship between arousal at encoding and subsequent memory for moderately arousing events.

Isolated nocturnal desaturation in COPD: prevalence and impact on quality of life and sleep.

BACKGROUND AND AIMS: The clinical impact of nocturnal desaturation on health related quality of life (HRQL) and sleep in chronic obstructive pulmonary disease (COPD) has been little studied. The aim of this study was to evaluate the prevalence and clinical impact of nocturnal desaturation in a typical outpatient population with COPD. PATIENTS AND METHODS: Between 2002 and 2005, consecutive patients with COPD attending outpatient services at the study centre underwent resting oximetry if they were not on domiciliary oxygen therapy. If their resting saturations were less than 95%, overnight pulse oximetry was performed. Significant nocturnal desaturation was defined as spending more than 30% of at least one of two nights with a saturation of less than 90%. The Chronic Respiratory Questionnaire (CRQ) and Short Form 36 (SF36) were used to assess HRQL, and the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Score (ESS) and Functional Outcomes of Sleep (FOSQ) questionnaires were used to assess sleep quality and daytime function. RESULTS: Of 1104 patients, 803 underwent resting oximetry and 79 had resting oxygen saturations of less than 95%. Of these, 59 agreed to undergo overnight oximetry (mean age 70 years, forced expiratory volume in 1 s 37.2% predicted, resting Po(2) on air 8.9 kPa). Significant nocturnal desaturation was seen in 29 (49.2%) of the 59 subjects. Assuming the less hypoxic patients do not have nocturnal desaturation, the prevalence of nocturnal desaturation in the whole clinic population could be estimated at 4.8%. There were no significant differences in CRQ, SF36, PSQI, ESS or FOSQ scores for desaturators compared with non-desaturators. CONCLUSION: Significant nocturnal desaturation was common in patients with COPD with resting saturations of less than 95%, but was estimated to have a prevalence of less than 5% in the whole outpatient population. Nocturnal desaturation was not associated with impairment of HRQL, sleep quality or daytime function.

Potential benefits of statins on morbidity and mortality in chronic obstructive pulmonary disease: a review of the evidence.

Studies show reduced forced expiratory volume in 1 s (FEV(1)) in patients with chronic obstructive pulmonary disease (COPD) is an important independent predictor of cardiovascular death and is characterised by both pulmonary and systemic inflammation. Evidence shows statins have important anti-inflammatory effects in both the lungs and arteries. Although randomised control trials are yet to be reported, non-randomised studies have consistently shown benefit in COPD patients taking statins compared with those not. These include reductions in both cardiovascular and respiratory morbidity/mortality. Other potential benefits include a reduced decline in FEV(1) and reduced risk of lung cancer. It is argued that confounding by a "healthy user effect" is unlikely to explain the observed benefit. Given the undisputed benefit of statins in high risk populations and the growing body of data suggesting statins may benefit patients with COPD, the question arises "Should statins be considered more often in patients with COPD?".

An arginine to histidine mutation in codon 311 of the C-erbA beta gene results in a mutant thyroid hormone receptor that does not mediate a dominant negative phenotype.

We have examined the c-erbA beta thyroid hormone receptor gene in a kindred, G.H., with a member, patient G.H., who had a severe form of selective pituitary resistance to thyroid hormones (PRTH). This patient manifested inappropriately normal thyrotropin-stimulating hormone, markedly elevated serum free thyroxine (T4) and total triiodothyronine (T3), and clinical hyperthyroidism. The complete c-erbA beta 1 coding sequence was examined by a combination of genomic and cDNA cloning for patient G.H. and her unaffected father. A single mutation, a guanine to adenine transition at nucleotide 1,232, was found in one allele of both these members, altering codon 311 from arginine to histidine. In addition, a half-sister of patient G.H. also harbored this mutant allele and, like the father, was clinically normal. The G.H. receptor, synthesized with reticulocyte lysate, had significantly defective T3-binding activity with a Ka of approximately 5 x 10(8) M-1. RNA phenotyping using leukocytes and fibroblasts demonstrated an equal level of expression of wild-type and mutant alleles in patient G.H. and her unaffected father. Finally, the G.H. receptor had no detectable dominant negative activity in a transfection assay. Thus, in contrast to the many other beta-receptor mutants responsible for the generalized form of thyroid hormone resistance, the G.H. receptor appeared unable to antagonize normal receptor function. These results suggest that the arginine at codon 311 in c-erbA beta is crucial for the structural integrity required for dominant negative function. The ARG-311-HIS mutation may contribute to PRTH in patient G.H. by inactivating a beta-receptor allele, but it cannot be the sole cause of the disease.

Criteria for the accurate interpretation of changes in left ventricular ejection fraction and cardiac volumes as assessed by rest and exercise gated radionuclide angiography.

Although serial left ventricular ejection fraction and volumetric measurements using gated radionuclide angiography are commonly used to evaluate clinical changes and therapeutic outcomes in individual patients, criteria are not available for accurately interpreting whether a change in any of these hemodynamic measurements is clinically meaningful. Accordingly, the magnitude of inherent variability among sequential measurements of hemodynamic variables assessed by gated radionuclide angiography was investigated in a double-blind placebo-controlled fashion in 39 patients during two placebo periods separated by 6 weeks. All patients analyzed had remained clinically stable during the study period. Although the mean values for all hemodynamic variables between the two placebo periods were minimally changed, the differences in individual patients were striking. Criteria were developed to allow meaningful interpretation of changes in hemodynamic variables by estimating the likelihood that an observed change is due to variability alone. On the basis of this analysis of placebo radionuclide angiographic data, variation due to chance alone is unlikely to account for all variability if a change observed between the two rest gated studies in a patient is greater than or equal to 7% units for left ventricular ejection fraction, greater than or equal to 45 ml/m2 for end-diastolic volume index, greater than or equal to 35 ml/m2 for end-systolic volume index, greater than or equal to 20 ml/m2 for stroke volume index and greater than or equal to 1.25 liters/min per m2 for cardiac index. An observed 4% unit change in left ventricular ejection fraction (increase or decrease) after a medical intervention in an individual patient occurs by random variation greater than 25% of the time.(ABSTRACT TRUNCATED AT 250 WORDS)

Geometries and conformational processes in phencyclidine and a rigid adamantyl analogue: variable-temperature NMR, X-ray crystallographic, and molecular mechanics studies.

The barriers to rotation of the aryl groups of m-nitrophenyladamantylpiperidine and m-nitrophenylcyclohexylpiperidine have been studied by variable-temperature NMR spectroscopy. NMR spectra of the free bases and salts of phenyladamantylpiperidine and phenylcyclohexylpiperidine (phencyclidine) and an X-ray crystal structure of the adamantane derivative verify the preferred conformations of these molecules in solution and the solid state. Force-field calculations provide additional information on the energetics of conformational processes in these molecules.

Photoelectron spectra of psychotropic drugs. 6. Relationships between the physical properties and pharmacological actions of amphetamine analogues.

The valence ionization potentials of seven additional members of a series of 2,4,5-trisubstituted amphetamines (1-phenyl-2-aminopropanes) were measured by UV photoelectron spectroscopy. These and previously published data provide experimental measures of the gross electron-donor ability of the aromatic rings of 23 amphetamines. Analogues bearing the 2,5-dimethoxy orientation were found to possess the lowest ionization potentials (IPs); for the analogously X-substituted compounds, the IPs increased in the order of 2,5-(OMe)2-4-X less than 2,4-(OMe)2-5-X less than 4,5-(OMe)2-2-X. Relationships between human psychotomimetic activity (MU), rabbit hyperthermia (SRU), serotonergic receptor affinity (pA2), and charge-transfer complex stabilities (KDNB) were evaluated statistically. A good correlation (r2 = 0.92) was established between the human and rabbit potencies, but poorer correlations were obtained between animal potencies and pA2's (r2 = 0.68-0.69) or KDNB's (r2 = 0.03!). Analysis of the regression relationships between these pharmacological measures and two physical properties, IP and lipid solubility (as modeled by log P), were explored. In general, greater potency is associated with decreasing IP and increasing log P. However, numerous exceptions to single parameter regressions are found. The unusually great potency of the 2,5-(OMe)2-4-X analogues, while qualitatively related to the physical properties, is quantitatively underestimated by these predictors. However, inclusion of a parameter (pi 4) which explicitly acknowledges the type of the 4-substituent leads to much improved correlations. These results support previous suggestions that 4-substituents interact directly with the receptor.

Does visual word identification involve a sub-phonemic level?

The phonological codes activated in visual word recognition can be thought of minimally as strings of discrete and unstructured phoneme-like units. We asked whether these codes might additionally express a letter string's phonological form at a featural or gestural level. Specifically, we asked whether the priming of a word (e.g. sea, film, basic) by a rhyming non-word would depend on the non-word's phonemic-feature similarity to the word. The question was asked within a mask--prime--target--mask sequence with both brief (57 ms in Experiments 1 and 2) and long (486 ms in Experiment 1) prime durations. Non-word primes that differed from their targets by a single phonemic feature (initial voicing as in ZEA, VILM, PASIC) led to faster target lexical decisions than non-word primes that differed by more than a single phonemic feature (e.g. VEA, JILM, SASIC). Visual word recognition seems to involve a sub-phonemic level of processing.

Allergic bronchopulmonary aspergillosis in the asthma clinic. A prospective evaluation of CT in the diagnostic algorithm.

OBJECTIVE: Allergic bronchopulmonary aspergillosis (ABPA) occurs in cases of atopic asthma and may result in important lung disease. Early diagnosis is essential as this disease is responsive to steroids. However, while asthma is common, ABPA is infrequently diagnosed. CT allows precision in the diagnosis of central bronchiectasis (which is virtually pathognomonic of ABPA) and may enable earlier diagnosis. DESIGN: A prospective evaluation of 255 patients with asthma for ABPA, using skin prick testing (SPT) for Aspergillus fumigatus (AF) as a screening tool and incorporating CT into the diagnostic algorithm. SETTING: Asthma clinic, Green Lane Hospital, Auckland, New Zealand. PARTICIPANTS: Patients with asthma. INTERVENTIONS: ABPA was diagnosed using "essential" criteria (ie, asthma, SPT positivity to AF, elevated serum total IgE, elevated serum AF-specific IgE, and pulmonary infiltrates seen on chest radiography or central bronchiectasis seen on CT scan) and "minimal essential" criteria (ie, asthma, SPT positivity, and central bronchiectasis). MEASUREMENTS AND RESULTS: Two hundred fifty-five consecutive patients with asthma who consented to SPT were studied: 218 of 255 patients (86.8%) were atopic; and 47 of 255 patients (21.6%) were AF-positive, of whom 35 accepted further evaluation including CT scanning. A secure diagnosis of ABPA, satisfying all essential criteria, was evident in 9 of 35 patients (25.7%), a proportion that increased to 13 of 35 patients (37.1%) by using the minimal essential diagnostic criteria. CONCLUSIONS: SPT positivity to AF was present in approximately 20% of patients in the asthma clinic. A diagnosis of ABPA is disclosed by CT in 25 to 40% of SPT-positive patients, depending on the selection of diagnostic criteria. These findings support the use of SPT as a screening tool in the asthma clinic and indicate that a routine CT scan is warranted in SPT-positive patients.

Spirometry in primary care practice: the importance of quality assurance and the impact of spirometry workshops.

OBJECTIVE: To determine the quality of spirometry performed in primary care practice and to assess the impact of formal training. DESIGN: Randomized, controlled prospective interventional study. SETTING: Primary care practice, Auckland City, New Zealand. PARTICIPANTS: Thirty randomly selected primary care practices randomized to "trained" or "usual" groups. One doctor and one practice nurse were nominated to participate from each practice. INTERVENTIONS: "Trained" was defined as participation in an "initial" spirometry workshop at week 0 and a "maintenance of standards" workshop at week 12. "Usual" was defined as no formal training until week 12, when participants they attended the same "initial" workshop provided for the trained group. The study duration was 16 weeks. Each practice was provided with a spirometer to be used at their clinical discretion. MEASUREMENTS AND RESULTS: Spirometry data were uploaded weekly and analyzed using American Thoracic Society (ATS) criteria for acceptability and reproducibility. The workshops were assessed objectively with practical and written assessments, confirming a significant training effect. However, analysis of spirometry performed in clinical practice by the trained practitioners revealed three acceptable blows in only 18.9% of patient tests. In comparison, 5.1% of patient tests performed by the usual practitioners had three acceptable blows (p<0.0001). Only 13.5% of patient tests in the trained group and 3.4% in the usual group (p<0.0001) satisfied full acceptability and reproducibility criteria. However, 33.1% and 12.5% of patient tests in the trained and usual groups, respectively (p<0.0001), achieved at least two acceptable blows, the minimum requirement. Nonacceptability was largely ascribable to failure to satisfy end-of-test criteria; a blow of at least 6 s. Visual inspection of the results of these blows as registered on the spirometer for the presence of a plateau on the volume-time curve suggests that < 15% were acceptable. CONCLUSIONS: Although a significant training effect was demonstrated, the quality of the spirometry performed in clinical practice did not generally satisfy full ATS criteria for acceptability and reproducibility. Further study would be required to determine the clinical impact. However, the ATS guidelines allow for the use of data from unacceptable or nonreproducible maneuvers at the discretion of the interpreter. Since most of the failures were end-of-test related, the FEV1 levels are likely to be valid. Our results serve to emphasize the importance of effective training and quality assurance programs to the provision of successful spirometry in primary care practice.

An evaluation of short-term oxygen therapy: the prescription of oxygen to patients with chronic lung disease hypoxic at discharge from hospital.

The provision of domiciliary oxygen to patients hypoxic at hospital discharge has been termed short-term oxygen therapy (STOT). This practice appears widespread, although there is a paucity of literature and no evidence-based guidelines. We undertook this audit to examine the prescription of STOT and determine the proportion fulfilling for long-term oxygen therapy (LTOT) 2 months post-discharge. STOT was defined prospectively: resting PaO2 < or = 7.3 kPa (55 mmHg) or PaO2 between 7.3 and 8.0 kPa (60 mmHg) with any of the following: clinical evidence of cor pulmonale (pedal oedema or jugular venous distension), ECG evidence of pulmonale, echocardiogram evidence of pulmonary hypertension, haematocrit > 0.55 (adapted directly from LTOT criteria). Patients were evaluated for LTOT 2 months post-discharge when clinically stable on optimal medical management. All referrals to the Auckland Regional Oxygen Service between July 1998 and 1999 were systematically reviewed. The majority 289/405 (71%) of new referrals were for the prescription of STOT/LTOT in patients with chronic lung disease: 160/289 (55%) derived from hospitalized patients with the majority 130 (81%) fulfilling criteria for STOT, median age 73, range 24-96 years. Mean hospital stay was 10.2 days. Two months after discharge 22/127 (17%) of STOT patients had died, comparable with 4/22 (18%) not fulfilling criteria for STOT. A total of 123 patients were assessed for LTOT at 2 months; 76 (62%) fulfilled criteria for LTOT. The prescription of oxygen at hospital discharge represented a considerable proportion of our referral load. There was a high mortality in the 2-month follow-up period. A significant proportion of STOT patients did not subsequently fulfill criteria for LTOT. Further prospective studies are required in order to develop evidence-based guidelines.

The clinical utility of arterialized earlobe capillary blood in the assessment of patients for long-term oxygen therapy.

The prescription of long-term oxygen (LTOT) is underpinned by the measurement of arterial PO2, generally obtained by radial artery puncture. This test is commonly associated with patient discomfort and a test that is reliable, well-tolerated and non-invasive would be advantageous. Cutaneous oximetry has not proved sufficiently accurate. Arterialized earlobe capillary sampling has been proposed, with some authors stating that it is under-utilized. However, to date studies have yielded conflicting results and the clinical utility remains uncertain. Our regional oxygen service based at a specialist respiratory hospital undertook a prospective study of consecutive patients with chronic respiratory disease undergoing assessment for LTOT. Simultaneous radial artery and arterialized earlobe sampling was performed. Rigorous steps were taken to ensure optimal arterialization of the earlobe samples. Agreement between arterial and arterialized PO2 and PCO2 was compared using the Bland-Altman method. One hundred patients were studied. Procedural difficulties (insufficient sample or air in sample) were similar for both procedures, however clotting occurred more frequently in arterialized earlobe samples. Sixty-four sample pairs were available for comparison. The bias and limits of agreement between arterialized and arterial PO2 were wide, mean (+/- 2 SD), -048 (-2.05-1.09) kPa. The bias and limits of agreement for PCO2 were smaller. Using the absolute criterion (arterial PO2 < 7.3 kPa), 9/55 (16%) patients would receive oxygen inappropriately based on the arterialized earlobe sample. Conversely, no patients would have been denied LTOT. Radial artery puncture gave rise to significantly greater discomfort (P < 0.0001) and level of concern (P < 0.0001). Patient preference strongly favoured arterialized earlobe sampling. However, despite rigorous attention to arterialization earlobe sampling was insufficiently accurate to replace radial artery puncture in the prescription of LTOT.

Long-term oxygen therapy improves health-related quality of life.

Guidelines for the prescription of long-term oxygen therapy (LTOT) in hypoxemic COPD patients are based on two landmark studies in which survival was the primary outcome. Such patients are importantly symptomatic with poor health-related quality of life (HRQL) but the effect of LTOT on HRQL remains uncertain. We undertook a prospective longitudinal interventional study of consecutive COPD patients referred to our regional oxygen service; n = 43 fulfilling criteria and commenced on LTOT, n = 25 not fulfilling criteria and continued on standard care. HRQL was measured at baseline, 2 and 6 months. Both patient groups had severe COPD as defined by mean FEV1 < 35% predicted. At baseline the LTOT group demonstrated significantly worse HRQL as defined by the Chronic Respiratory Questionnaire (CRQ) (fatigue, emotional function, mastery and total scores), total generic Dartmouth COOP Charts and anxiety domain of the Hospital Anxiety and Depression scale. Significant improvements in HRQL were noted at 2 and 6 months in the LTOT group. Conversely the non-LTOT group demonstrated a progressive decline in HRQL. Using validated criteria for a minimal clinically significant improvement in CRQ, there were 28 (67%) and 26 (68%) 'responders' at 2 and 6 months respectively in the LTOT group. The introduction of LTOT to patients with severe COPD fulfilling standard criteria was associated with early significant improvements in HRQL with sustained or further response at 6 months.

Use of a real-time microbial air sampler for operational cleanroom monitoring.

A sampler that detects and counts viable particles in the air of cleanrooms in real-time was studied. It was found that when the sampler was used to monitor airborne particles dispersed from a number of materials used in cleanrooms, including garments, gloves, and skin, the number of viable particles dispersed from these materials was greater than anticipated. It was concluded that a substantial proportion of these viables were of a non-microbiological origin. When the sampler was used to monitor a non-unidirectional airflow cleanroom occupied by personnel wearing cleanroom garments, it was found that the airborne viable concentrations were unrealistically high and variable in comparison to microbe-carrying particles simultaneously measured with efficient microbial air samplers. These results confirmed previously reported ones obtained from a different real-time sampler. When the real-time sampler was used in a workstation within the same cleanroom, the recorded viables gave results that suggest that the sampler may provide an effective airborne monitoring method, but more investigations are required. LAY ABSTRACT: The airborne concentrations measured by a real-time microbial air sampler within an operational, non-unidirectional airflow cleanroom were found to be unrealistically high due to a substantial numbers of particles of non-microbiological origin. These particles, which resulted in false-positive microbial counts, were found to be associated with a number of materials used in cleanrooms. When the sampler was used within a cleanroom workstation, the counts appeared to be more realistic and suggest that this type of real-time airborne microbial counter may provide a useful monitoring method in such workstations, but further investigations are required.

Compression versus sclerotherapy for patients with isolated refluxing reticular veins and telangiectasia: a randomized trial comparing quality-of-life outcomes.

OBJECTIVE: To prospectively study quality-of-life (QoL) benefits comparing compression stockings to sclerotherapy in subjects with symptomatic reticular veins and telangiectasia. METHODS: Fifty-eight consecutive female patients with normal saphenous and deep venous systems and venous dysfunction score (VDS) ≥ 4 were randomized to either sclerotherapy (N = 29) or thigh high 20-30 mmHg compression stockings (N = 29). Following a trial of compression, subjects in the compression arm were eligible to crossover to the sclerotherapy arm. Patient-reported QoL data were acquired using a modified Aberdeen Varicose Vein Questionnaire in five stages, initial severity (T0), following compression trial (T1), after reticular vein sclerotherapy (T2), approximately three months after sclerotherapy for telangiectasia (T3) and the 12-month mark (T4). RESULT: For patients in the compression arm, four key symptoms including aching, pain, leg cramps and restlessness were significantly reduced, while patients in the sclerotherapy arm of treatment reported broad symptom relief in all key symptoms assessed. CONCLUSION: Isolated refluxing reticular and telangiectatic vein disease may cause QoL impairment in select patients and represent far more than a cosmetic concern. Compression therapy offers relief of aching, pain, leg cramping and restlessness in patients with isolated refluxing reticular veins and telangiectasia. Sclerotherapy of reticular veins offers a statistically superior broad spectrum relief of symptoms, while additional sclerotherapy of residual telangiectasia in this cohort demonstrated additive relief of aching and pain. Symptom assessments at 12 months suggest ongoing symptom relief following sclerotherapy.

Age related decreases in thermoregulation and cardiovascular function in horses.

REASON FOR PERFORMING STUDY: Older horses have an increased risk of hyperthermia due to impaired cardiovascular function. While many studies have investigated thermoregulation in horses during exercise, none have investigated the effects of ageing. OBJECTIVE: To test the hypothesis that there is a difference in thermoregulation during exercise and plasma volume (PV) in young and old horses. METHODS: Study 1: 6 young (Y, 7.7 ± 0.5 years) and 5 old (O, 26.0 ± 0.8 years) unfit Standardbred mares (507 ± 11 kg, mean ± s.e.) ran on a treadmill (6% grade, velocity calculated to generate a work rate of 1625 watts) until core temperature reached 40 °C. Core (CT), skin (ST), rectal temperature (RT) and heart rate (HR) were measured every min until 10 min post exertion. Packed cell volume (HCT), lactate (LA) and plasma protein (TP) were measured in blood samples collected before, at 40 °C and every 5 min until 10 min post exercise. Sweat loss was estimated using bodyweight. Study 2: Plasma volume was measured in 26 young (8.2 ± 0.7 years) and 8 old (26.6 ± 0.7 years) Standardbred mares (515 ± 12 kg) using Evans Blue dye. Pre-exercise blood (rBV) and red cell (rRCV) volumes were calculated using PV and HCT. Data analysis utilised repeated measures ANOVA and t tests and data are expressed as mean ± s.e. RESULTS: Old horses reached 40 °C faster (998 ± 113 vs. 1925 ± 259 s; P < 0.05) with a greater HR at 40 °C (184 ± 6 vs. 140 ± 5 beats/min; P < 0.05) and greater sweat losses (P < 0.05). Heart rate did not differ (P > 0.05) post exercise. Age did not alter (P > 0.05) CT, ST, RT, LA, HCT or TP. Plasma volume was greater in Y vs. O horses (P < 0.05, 28.5 ± 1.4 vs. 24.1 ± 1.6 l) as was rBV (41.3 ± 2.0 vs. 35.3 ± 2.3 l) and rRCV (13.3 ± 0.6 vs. 11.1 ± 0.8 l). CONCLUSION: Ageing compromises the ability to handle the combined demand of exercise and thermoregulation in part due to decreased absolute pre-exercise PV.