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Biomedical subjects

G Allen

Publications and source records attributed to G Allen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Mapping of a gene for severe pediatric gastroesophageal reflux to chromosome 13q14.

CONTEXT: Gastroesophageal reflux (GER) has not previously been widely regarded as a hereditary disease. A few reports have suggested, however, that a genetic component may contribute to the incidence of GER, especially in its severe or chronic forms. OBJECTIVE: To identify a genetic locus that cosegregates with a severe pediatric GER phenotype in families with multiple affected members. DESIGN: A genome-wide scan of families affected by severe pediatric GER using polymorphic microsatellite markers spaced at an average of 8 centimorgans (cM), followed by haplotyping and by pairwise and multipoint linkage analyses. SETTING: General US community, with research performed in a university tertiary care hospital. SUBJECTS: Affected and unaffected family members from 5 families having multiple individuals affected by severe pediatric GER, identified through a patient support group. MAIN OUTCOME MEASURES: Determination of inheritance patterns and linkage of a genetic locus with the severe pediatric GER phenotype by logarithm-of-odds (lod) score analysis, considering a lod score of 3 or greater as evidence of linkage. RESULTS: In these families, severe pediatric GER followed an autosomal dominant hereditary pattern with high penetrance. A gene for severe pediatric GER was mapped to a 13-cM region on chromosome 13q between microsatellite markers D13S171 and D13S263. A maximum multifamily 2-point lod score of 5.58 and a maximum multifamily multipoint lod score of 7.15 were obtained for marker D13S1253 at map position 35 cM when presumptively affected persons were modeled as unknown (a maximum multipoint score of 4.88 was obtained when presumptively affected persons were modeled as unaffected). CONCLUSION: These data suggest that a gene for severe pediatric GER maps to chromosome 13q14. JAMA. 2000;284:325-334

Child↗
PubMed2000

Role of brain-derived neurotrophic factor in the circadian regulation of the suprachiasmatic pacemaker by light.

The central pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus mediates the generation of mammalian circadian rhythms, including an oscillation in pacemaker sensitivity to photic signals conveyed by the retinohypothalamic tract. Because brain-derived neurotrophic factor (BDNF) has been implicated in the functional regulation of neural input to other targets of visual pathways, the present study examined whether changes in BDNF expression or blockade of its action in the SCN affect circadian pacemaker responses to light. In rats receiving infusion of exogenous BDNF into the SCN, the free-running rhythm of activity in constant darkness was characterized by large phase advances in response to light exposure during the midsubjective day, when the circadian pacemaker is normally insensitive to photic perturbation. In contrast, SCN infusion of BDNF did not potentiate either phase-delaying or phase-advancing effects of light on the rat activity rhythm during the subjective night. In heterozygous BDNF mutant mice, deficits and damped rhythmicity in SCN levels of this neurotrophin were accompanied by marked decreases in the amplitude of light-induced phase shifts during the subjective night. In agreement with the effects of decreased BDNF expression, SCN infusion of the tyrosine kinase inhibitor K252a blocked or strongly inhibited both the phase-delaying and -advancing effects of light during the subjective night. Collectively, these findings suggest that BDNF-mediated signaling may play an important role in the circadian regulation of SCN pacemaker sensitivity to light.

Animals↗
PubMed2000

Ambient pollution and heart rate variability.

BACKGROUND: We investigated associations between ambient pollution levels and cardiovascular function in a repeated measures study including 163 observations on twenty-one 53- to 87-year-old active Boston residents observed up to 12 times from June to September 1997. Particles with aerodynamic diameter </=2.5 microm (PM(2.5)) were measured continuously using a tapered element oscillating microbalance. METHODS AND RESULTS: The protocol involved 25 minutes per week of continuous Holter ECG monitoring, including 5 minutes of rest, 5 minutes of standing, 5 minutes of exercise outdoors, 5 minutes of recovery, and 20 cycles of slow breathing. Heart rate variability (HRV) was assessed through time domain variables: the standard deviation of normal RR intervals (SDNN) and the square root of the mean of the squared differences between adjacent normal RR intervals (r-MSSD). Mean 4-hour PM(2.5) levels ranged from 3 to 49 microg/m(3); 1-hour ozone levels ranged from 1 to 77 ppb. In multivariate analyses, significantly less HRV (SDNN and r-MSSD) was associated with elevated PM(2.5). During slow breathing, a reduction in r-MSSD of 6.1 ms was associated with an interquartile (14.3 microg/m(3)) increase in PM(2.5) during the hour of and the 3 hours previous to the Holter session (P=0.006). During slow breathing, a multiple pollution model was associated with a reduction in r-MSSD of 5.4 ms (P=0.02) and 5.5 ms (P=0.03) for interquartile changes in PM(2.5) and ozone, respectively, resulting in a combined effect equivalent to a 33% reduction in the mean r-MSSD. CONCLUSIONS: Particle and ozone exposure may decrease vagal tone, resulting in reduced HRV.

Aged↗
PubMed2000

Maximizing nurses' advocacy role to improve patient outcomes.

Perioperative nurses are eminently situated, academically prepared, and professionally qualified to positively affect patient outcomes. Increasing efficiency and justifying the need for an RN in the perioperative milieu revolve around nurses' role as patient advocates. Perioperative nurses can take many measures to maximize this role, including reducing surgical site infections by enabling the timely administration of antimicrobial prophylaxis and by ensuring that surgical staff members realize the documented risks of removing hair from the surgical site.

Adult↗
PubMed2000

Echocardiographic texture analysis using the wavelet transform: differentiation of early heart muscle disease.

Echocardiographic quantitation of myocardial texture for diagnosis of early cardiomyopathy (CMP) remains problematic. Conventional statistical methods are limited, contributed by a small image region-of-interest (ROI) and difficulty in discrimination from noise. This study was performed to evaluate the 2-D Haar wavelet decomposition method as a tool to identify textural changes in a rat model of early CMP, focusing on changes that occur before development of M-mode structural abnormalities. Early diabetic CMP, ethanol CMP and diabetic-ethanol CMP rat models were evaluated. Echocardiography was performed on two groups of rats. Group I (5 week cohort, n = 4 per subgroup) included controls, rats on 12% ethanol, a diabetic subgroup, and diabetic rats on 4% ethanol. Group II (10 week cohort, n = 5 per subgroup) included the same categories as group I with an additional subgroup taking 4% ethanol was also studied. M-mode left ventricular measurements were comparable in all subgroups of group I. However, diabetic rats in group II had an increased left ventricular dimension (LVD) compared to all others and an increased septal dimension (IVSD) and posterior wall dimension (PWD) were noted in the 4% and 12% ethanol groups. End-diastolic digital images of all rats in the parasternal short axis view, at the papillary muscle level, were downloaded to a computer. A 16 x 16 (ROI) was selected from the anterior interventricular septum. Although standard statistical methods could not differentiate any of the groups, calculation of textural energy and normalized textural energy with the 2-D Haar wavelet decomposition method found at 5 weeks increased normalized texture energy in diabetics compared to all others. At 10 weeks increased texture energy was noted in diabetics. Diabetic-ethanol rats at both 5 and 10 weeks revealed a blunted textural energy compared to diabetic rats. In a rat model of diabetic cardiomyopathy, the 2-D wavelet decomposition method identified textural energy changes before development of echocardiographic structural changes. Ethanol-associated blunting of textural changes in diabetic rats was also noted. This method for quantitation of ventricular texture may be relevant for diagnosis of early cardiomyopathy.

Animals↗
PubMed2000

Method comparisons for particulate nitrate, elemental carbon, and PM2.5 mass in seven U.S. cities.

Methods that measure PM2.5 mass, total particulate NO3-, and elemental carbon (EC) were evaluated in seven U.S. cities from 1997 to 1999. Sampling was performed in Bakersfield, CA; Boston, MA; Chicago, IL; Dallas, TX; Philadelphia, PA; Phoenix, AZ; and Riverside, CA. Evaluating and validating methods that measure the components of fine mass are important to the effort of establishing a speciation-monitoring network. The Harvard Impactor (HI), which measures fine particle mass, showed excellent agreement (r2 = 0.99) with the PM2.5 Federal Reference Method (FRM) for 81 24-hr samples in Riverside and Bakersfield. The HI also showed good precision (4.8%) for 243 24-hr collocated samples over eight studies. The Aethalometer was employed in six of the sampling locations to measure black carbon (BC). These values were compared to EC as measured from a quartz filter using thermal analysis. For the six cities combined, the two methods were highly correlated (r2 = 0.94; 187 24-hr samples); however, the BC values were approximately 24% less than the EC measurements consistently across all six cites. This compares well to results observed for EC/BC measurements observed in other semi-urban areas. Particulate NO3- was measured using the Harvard-EPA Annular Denuder System (HEADS). This was compared to the NO3- measured from the HI Teflon (DuPont) filter to assess NO3- artifacts. Significant NO3- losses (approximately 50% of total NO3-) were found in Riverside, Philadelphia, and Boston, while minimal artifacts were observed in the other sites. Two types of HEADS configurations were employed in five cities. One system used a Na2CO3-coated glass fiber filter, and the other type used a nylon filter to collect volatilized NO3- from the Teflon filter. The HEADS with the Na2CO3-coated filter consistently underestimated the total particulate NO3- by approximately 20% compared to the nylon HEADS.

Air Pollution↗
PubMed2000

Air pollution and incidence of cardiac arrhythmia.

Air pollution episodes have been associated with increased cardiovascular hospital admissions and mortality in time-series studies. We tested the hypothesis that patients with implanted cardioverter defibrillators experience potentially life-threatening arrhythmias after such air pollution episodes. We compared defibrillator discharge interventions among 100 patients with such devices in eastern Massachusetts, according to variations in concentrations of particulate matter, black carbon, and gaseous air pollutants that were measured daily for the years 1995 through 1997. A 26-ppb increase in nitrogen dioxide was associated with increased defibrillator interventions 2 days later (odds ratio = 1.8; 95% confidence interval = 1.1-2.9). Patients with ten or more interventions experienced increased arrhythmias in association with nitrogen dioxide, carbon monoxide, black carbon, and fine particle mass. These results suggest that elevated levels air pollutants are associated with potentially life-threatening arrhythmia leading to therapeutic interventions by an implanted cardioverter defibrillator.

Adult↗
PubMed2000

Characterization of indoor particle sources: A study conducted in the metropolitan Boston area.

An intensive particle monitoring study was conducted in homes in the Boston, Massachusetts, area during the winter and summer of 1996 in an effort to characterize sources of indoor particles. As part of this study, continuous particle size and mass concentration data were collected in four single-family homes, with each home monitored for one or two 6-day periods. Additionally, housing activity and air exchange rate data were collected. Cooking, cleaning, and the movement of people were identified as the most important indoor particle sources in these homes. These sources contributed significantly both to indoor concentrations (indoor-outdoor ratios varied between 2 and 33) and to altered indoor particle size distributions. Cooking, including broiling/baking, toasting, and barbecuing contributed primarily to particulate matter with physical diameters between 0.02 and 0.5 microm [PM((0.02-0.5))], with volume median diameters of between 0.13 and 0.25 microm. Sources of particulate matter with aerodynamic diameters between 0.7 and 10 microm [PM((0.7-10))] included sautéing, cleaning (vacuuming, dusting, and sweeping), and movement of people, with volume median diameters of between 3 and 4.3 microm. Frying was associated with particles from both PM((0.02-0.5)) and PM((0.7-10)). Air exchange rates ranged between 0.12 and 24.3 exchanges/hr and had significant impact on indoor particle levels and size distributions. Low air exchange rates (< 1 exchange/hr) resulted in longer air residence times and more time for particle concentrations from indoor sources to increase. When air exchange rates were higher (> 1 exchange/hr), the impact of indoor sources was less pronounced, as indoor particle concentrations tracked outdoor levels more closely.

Activities of Daily Living↗
PubMed2000

Feelings of knowing in the Ranschburg effect.

In two experiments, we assessed feelings of knowing (FOKs) for the Ranschburg effect to examine the types of retrieval ease that affect FOKs. In the Ranschburg effect, retrieval performance for repeated items differs from nonrepeated items in supramemory span tasks. We found that FOKs are affected by memory manipulations that affect recall processes, but not by manipulations that affect recognition. This suggests that processes that affect recognition, such as target familiarity, do not affect FOKs, whereas processes that affect recall, such as response suppression and guessing factors, affect FOKs. We propose that an integrated theory of FOKs must include mechanisms responsive to both encoding and retrieval factors (such as retrieval accessibility and cue familiarity), which are highly susceptible to output interference.

Cognition↗
PubMed1999

Non-thiazolidinedione antihyperglycaemic agents. Part 3: The effects of stereochemistry on the potency of alpha-methoxy-beta-phenylpropanoic acids.

Rhizopus delemar lipase catalysed ester hydrolysis of the alpha-methoxy-beta-phenylpropanoate 1 affords the (R)-(+) and (S)-(-) isomers in > 84% enantiomeric excess. Absolute stereochemistry was determined by a single crystal X-ray analysis of a related synthetic analogue. The activity of these two enantiomers on glucose transport in vitro and as anti-diabetic agents in vivo is reported and their unexpected equivalence attributed to an enzyme-mediated stereospecific isomerisation of the (R)-(+) isomer. Binding studies using recombinant human PPARgamma (peroxisomal proliferator activated receptor gamma), now established as a molecular target for this compound class, indicate a 20-fold higher binding affinity for the (S) antipode relative to the (R) antipode.

Animals↗
PubMed1998

The impact of assertive community treatment on the social relationships of people who are homeless and mentally ill.

Two randomized experiments compared the effectiveness of the assertive community treatment (ACT) team against other treatments (outpatient therapy, drop-in center, and brokered case management) in improving the social relationships of individuals who were both homeless and suffered from severe and persistent mental illness. In both studies clients assigned to ACT teams reported having more professionals in their social networks than clients assigned to the other treatments. Clients did not report significant differences between treatment conditions on most of the other social relationship dimensions. Further attention to developing social skills and network interventions within ACT teams are recommended.

Adult↗
PubMed1998

Effect of rimantadine treatment on clinical manifestations and otologic complications in adults experimentally infected with influenza A (H1N1) virus.

Susceptible adults (n = 105) were enrolled into a randomized double-blind study of rimantadine treatment of experimental influenza A infection. Subjects were cloistered for 8 days and challenged with a rimantadine-sensitive strain of influenza A H1N1 virus at the end of the first day. Forty-eight hours after challenge and for 8 days, 54 subjects received placebo and 51 received rimantadine (100 mg orally, twice a day). Symptoms, signs, and pathophysiologies were monitored. Nine subjects were not infected. Seventeen subjects (38%) in the rimantadine and 26 (53%) in the placebo group became ill. A beneficial effect of rimantadine was documented for virus shedding, symptom load, and sinus pain. Rimantadine had no effect on nasal patency, mucociliary clearance, nasal signs, or on symptoms and signs of otologic complications. These results do not support a preventive effect of rimantadine on the development of otologic manifestations of influenza A infection in adults.

Adolescent↗
PubMed1998

Aggressive pituitary tumors.

Although almost all pituitary tumors are benign adenomas, a surprisingly large number of these tumors invade tissues outside of the pituitary gland. Such invasion, by itself, is not diagnostic of pituitary carcinomas, which are exceedingly rare (0.13% of 2,342 pituitary tumors in one series). Several different criteria are available to determine whether a tumor is invasive. Intraoperative biopsies demonstrate an 85% incidence of microscopic invasion of the dura. Evidence of gross invasion at surgery and radiologic evidence of invasion on magnetic resonance imaging (MRI) and computed tomographic (CT) scans occur at a much lower incidence but may be more predictive of surgical cure. Invasive adenomas also have higher proliferation rates than do noninvasive adenomas, as shown by immunohistochemical detection of proliferating cell nuclear antigen (PCNA), Ki-67, and MIB-1. The expression of p53, increased epidermal growth factor receptors, and protein kinase C activity also correlate with invasion and aggressive behavior. Clinically significant invasion is more frequent with macroadenomas. Macroadenomas of all pituitary tumor subtypes except gonadotroph macroadenomas have a greater than 50% incidence of gross invasion. Currently, there is no accepted means of predicting an adenoma's clinically significant invasiveness and long-term aggressiveness.

Adenoma↗