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Biomedical subjects

D O'Leary

Publications and source records attributed to D O'Leary.

At least 19 recordsLinked to original sources
PubMed2002

Delivery of formoterol from a novel multi-dose inhaler Airmax.

Using a proprietary technology known as the X-ACT system--Active-metering, Cyclone-separator Technology, a novel multi-dose inhaler (Airmax) was developed to provide accurate and consistent dosing and a high-fine particle fraction ofthe drug. Formoterol, present as a blend with lactose monohydrate was delivered from Airmax to obtain a nominal formoterol dose of 6 or 12 microg. The devices were tested using a five-stage liquid impinger and a unit dose sampling apparatus, operated under conditions specified in European Pharmacopoeia (2000). Fine-particle dose (FPD) was defined as the dose of the aerosolized drug particles with an aerodynamic diameter < 5 microm and fine particle fraction (FPF) was the ratio of FPD to the total recovered dose. Dose per actuation was found to be 97.0+/-11.5% label claim (LC) or 5.8+/-0.7 microg (n = 140), and 100+/-9.4% LC or 12+/-1.1 microg (n=440), for the 6 and 12 microg strengths, respectively. The mass median aerodynamic diameter was 2.4+/-0.1 microm (n = 14), the geometric standard deviation 2.1+/-0.1 (n = 14), and FPF 44.4+/-24% (n= 14) for both strengths. Thus, the combination of active metering and cyclone separator produces highly consistent doses of formoterol that have a large respirable fraction.

Administration, Inhalation↗
PubMed2002

Delivery of salbutamol and of budesonide from a novel multi-dose inhaler Airmax.

A novel multi-dose inhaler has been developed to closely approach the characteristics of an "ideal" inhaler. The new device, Airmax, uses proprietary technologies known as the X-ACT system to provide accurate and consistent dosing and excellent lung deposition--even at low inspiratory flow rates--combined with ease of use by the patient. Dose delivery was close to label claim, with relative standard deviation of typically around 5% for through-life emitted mass and around 10% for dose per actuation. At a flow rate (60-70 l/min), which corresponds to 4 kPa pressure drop across the device, the mean fine particle (<5 microm) dose (FPD) from 100, 200 and 400 microg strength budesonide Airmax was around 46, 98 and 244 microg, respectively. The mean FPD from 100 microg strength salbutamol Airmax was approximately 50 microg at the same flow rate. At 30 l/min, the delivered dose from Airmax is over 85% label claim with fine particle fraction of over 35%. Performance was unaffected by shaking or orientation, provided the device was not used completely upside down, and priming was not required. There was no change in dose content uniformity and aerodynamic particle-size distribution after the devices have been stored unwrapped at 30 degrees C/60% RH up to 24 months. Airmax is robust, portable and intuitive to use.

Administration, Inhalation↗
PubMed2001

The outbreak of West Nile virus infection in the New York City area in 1999.

BACKGROUND: In late August 1999, an unusual cluster of cases of meningoencephalitis associated with muscle weakness was reported to the New York City Department of Health. The initial epidemiologic and environmental investigations suggested an arboviral cause. METHODS: Active surveillance was implemented to identify patients hospitalized with viral encephalitis and meningitis. Cerebrospinal fluid, serum, and tissue specimens from patients with suspected cases underwent serologic and viral testing for evidence of arboviral infection. RESULTS: Outbreak surveillance identified 59 patients who were hospitalized with West Nile virus infection in the New York City area during August and September of 1999. The median age of these patients was 71 years (range, 5 to 95). The overall attack rate of clinical West Nile virus infection was at least 6.5 cases per million population, and it increased sharply with age. Most of the patients (63 percent) had clinical signs of encephalitis; seven patients died (12 percent). Muscle weakness was documented in 27 percent of the patients and flaccid paralysis in 10 percent; in all of the latter, nerve conduction studies indicated an axonal polyneuropathy in 14 percent. An age of 75 years or older was an independent risk factor for death (relative risk adjusted for the presence or absence of diabetes mellitus, 8.5; 95 percent confidence interval, 1.2 to 59.1), as was the presence of diabetes mellitus (age-adjusted relative risk, 5.1; 95 percent confidence interval, 1.5 to 17.3). CONCLUSIONS: This outbreak of West Nile meningoencephalitis in the New York City metropolitan area represents the first time this virus has been detected in the Western Hemisphere. Given the subsequent rapid spread of the virus, physicians along the eastern seaboard of the United States should consider West Nile virus infection in the differential diagnosis of encephalitis and viral meningitis during the summer months, especially in older patients and in those with muscle weakness.

Adolescent↗
PubMed2001

Anatomic and functional variability: the effects of filter size in group fMRI data analysis.

In the analysis of group fMRI scans, an optimal spatial filter should be large enough to accurately blend functionally homologous anatomic regions, yet small enough not to blur the functionally distinct regions. Hanning filters varying from 0.0 to 18.0 mm were evaluated in a group analysis of six healthy controls performing a simple finger-tapping paradigm. Test-retest reliability and Talairach-based measurements of the sensorimotor region were used to explore the optimal filter size. Two distinct regions of functional activation were noted in the sensorimotor cortex in group images (n = 6) at both time 1 and time 2. These regions merge once the filter size exceeds approximately 6.0 mm. The original hypothesis that these represented a motor and sensory activation was rejected on the basis of structural and functional variability. A discussion of the inherent difficulties in choosing an appropriate filter size is presented.

Adult↗
PubMed2001

Personality and outcome in depression: an 18-month prospective follow-up study.

BACKGROUND: The relationship between personality and depressive illness is complex. The aim of this study was to assess whether the presence of a personality disorder or high neuroticism (N) scores predicted longer times to discharge or remission onset or higher risks of relapse for a cohort of depressed subjects admitted for the first time. METHODS: 100 consecutive subjects with ICD-10-defined depression were recruited on admission and followed up prospectively over an 18-month period. Personality function was rated using the informant-rated Standard Assessment of Personality in addition to the self-rated Maudsley Personality Inventory. Remission onset and relapse were defined operationally by scores on the Hamilton Rating Scale using recommended criteria. RESULTS: The presence of a personality disorder predicted longer times to remission onset. Personality trait accentuation did not. Higher end N-scores correlated with longer times to remission onset. Neither personality disorder nor high N-scores predicted relapse or discharge risk. Subjects with a personality disorder were treated as aggressively as those without but those with higher N-scores were not. LIMITATIONS: It is an in-patient sample. Fifteen subjects dropped out of follow-up and those who did so were more likely to have met criteria for two or more personality disorder categories or four or more traits from one personality disorder category. The analysis assumes that state and scar effects on N-scores were minimised. Treatment decisions were not controlled. CONCLUSIONS: These findings support the view that the presence of a personality disorder and high N-scores modify the short-term course to remission onset in depression.

Adult↗
PubMed2001

Suicide in primary affective disorders revisited: a systematic review by treatment era.

BACKGROUND: We reviewed suicide rates in affective disorder and their variation with electroconvulsive therapy (ECT) and antidepressant availability. METHOD: Suicide rates were calculated from 75 follow-up studies, identified by systematic literature searches and analyzed for differences over time eras characterized by the availability of specific treatments. DATA SOURCES AND STUDY SELECTION: MEDLINE, EMBASE, BIOSIS Previews, and Psychological Abstracts literature searches were conducted for the years 1966 to 1995. References from review articles identified from these sources from 1985 onward and textbook references were also included. Publications prior to 1966 were obtained from article references identified for the period 1966 to 1976 and reviews. Inclusion criteria were (1) articles written in English, French, or German; (2) sample size > 30; (3) age at recruitment between 18 and 64 years for each subject; (4) sample had to contain subjects hospitalized at time of recruitment; and (5) naturalistic follow-up of at least 6 months. RESULTS: Suicide rates decreased with longer follow-up periods. For follow-up periods over 20 years, the mean rate was 3.76/1,000 person-years (95% confidence interval [CI] = 2.35 to 5.17). Suicides accounted for 12.3% (95% CI = 8.52 to 16.04) of all deaths in samples in which 40% or more of patients had died. For studies with minimal overlap between eras, the mean suicide rate differed significantly between eras (pretreatment, before 1940: 6.3/1000; ECT treatment, 1940 to 1959: 5.7/1,000: antidepressant treatment, 1960 onward: 3.3/1,000; F = 31.4. df = 2,42; p < .001). CONCLUSION: The risk of suicide in follow-up studies of affective disorder has decreased compared to that reported in previous reviews. The availability of ECT and antidepressants may have contributed to this decrease, but prescription of these treatments cannot be assumed for all patients.

Antidepressive Agents↗
PubMed2000

Sexual dimorphism in the human brain: evaluation of tissue volume, tissue composition and surface anatomy using magnetic resonance imaging.

Magnetic resonance imaging (MRI) was used to evaluate sex differences in brain morphology by comparing measures of brain tissue volume, brain tissue composition (proportions of gray and white matter), and measures of cortical surface anatomy. A large and well-matched sample of healthy women (n=42) and healthy men (n=42) were evaluated. There was a significant gender effect on intracranial volume, males being larger. However, this increase in size was limited to the cerebrum as there was no sex difference in the volume of the cerebellum. The gender difference in size of the cerebral volume was evenly distributed, with all four lobes equally larger in males compared to females. Gray and white matter tissue proportions were similar between the sexes globally. Regional tissue composition analysis showed sex differences within the parietal lobes with females having proportionately more gray matter on the right side. There were no differences between the sexes in cortical surface anatomy measures. Overall, against the background of similarity in morphology, there are differences between the sexes with regard to general and regional brain measures. The functional significance of these sex differences is unclear, but may represent the differential effects of gonadal hormones during brain growth and development.

Adult↗
PubMed2000

Lack of mucin MUC5AC field change expression associated with tubulovillous and villous colorectal adenomas.

BACKGROUND: MUC5AC is a secreted mucin aberrantly expressed by polypoid colorectal adenomas. It has been hypothesised that the "normal" surrounding colorectal mucosa expresses MUC5AC as a field change phenomenon that can be used to predict adenoma recurrence following resection. AIM: To determine if there is a field change of de novo MUC5AC expression in histologically normal rectal mucosa adjacent to villous and tubulovillous adenomas, and thus whether MUC5AC expression can be used as a marker of early tumour recurrence. METHODS: In a prospective cohort study paired mucosal biopsies of adenomatous and macroscopically "normal" mucosa were obtained from 11 patients with villous and 11 patients with tubulovillous adenomas who underwent primary resection for purpose of cure. The tissues were studied to determine MUC5AC gene expression by immunohistochemistry and in situ hybridisation. Patients were followed up by flexible sigmoidoscopy to detect the presence of early local recurrence. RESULTS: 10 villous adenomas showed mature MUC5AC glycoprotein and all 11 expressed MUC5AC mRNA. Five tubulovillous adenomas showed mature MUC5AC glycoprotein and 10 expressed MUC5AC mRNA. Neoexpression of the MUC5AC mucin gene was not detected in any of the mucosal biopsies taken adjacent to either villous or tubulovillous adenomas, even in three patients with early, locally recurrent disease. CONCLUSIONS: Aberrant MUC5AC gene expression is not a "field change" in the colorectal mucosa in patients with rectal adenomas and therefore cannot be used to predict local recurrence of villous and tubulovillous adenomas.

Adenoma, Villous↗
PubMed1999

Generalized cognitive deficits in schizophrenia: a study of first-episode patients.

BACKGROUND: Cognitive impairment is recognized as a core characteristic of schizophrenia. There has always been a debate about the nature, selectivity, and time of onset of these deficits in relationship to the onset of illness and treatment factors. To our knowledge, the present study represents the largest sample of mostly neuroleptic-naive patients with first-episode schizophrenia that has been reported to date. METHODS: A group of 94 patients experiencing their first episode of schizophrenic illness and 305 normal comparison subjects were administered a comprehensive clinical and neuropsychological evaluation. Seventy-three patients were neuroleptic naive, 14 had received treatment for less than 1 week, and the remaining 7 had been medicated for less than 2 weeks. RESULTS: Patients performed significantly worse than the comparison subjects on every neuropsychological variable except those assessing savings scores (ie, forgetting over time). Twenty-five of 30 tests had an effect size (ES) greater than 0.75 when the 2 groups were compared. An ES analysis within the schizophrenia group revealed that the greatest relative impairments were on the Wechsler Adult Intelligence Scale-Revised digit symbol (ES, -0.52) and comprehension (ES, -0.42) subscales. CONCLUSIONS: Our findings are in concert with others demonstrating that significant cognitive impairment across multiple ability domains is a core characteristic of schizophrenia and is not caused by chronic illness, treatment, or institutionalization. The ES analysis emphasizes that patients with schizophrenia have a generalized deficit that is not easily explained by a single anatomical region or ability area.

Adult↗
PubMed1999

First admissions for depression: is the 'no-treatment interval' a critical predictor of time to remission?

BACKGROUND: This study aimed to replicate findings that length of episode prior to adequate antidepressant treatment (the 'no-treatment interval') and premorbid neuroticism predict time to remission from the institution of adequate treatment for depression. METHODS: Eighty-three inpatients meeting ICD-10 criteria for a depressive illness were entered into an 18-month prospective follow-up study of illness course. Subjects were assessed using the Schedules for Clinical Assessment in Neuropsychiatry, Maudsley Personality Inventory (MPI) and the Hamilton Rating Scale for Depression (HRSD). Remission was defined as an HRSD score of < 8 for 2 consecutive weeks. RESULTS: Twenty-two patients (27%) remained depressed 12 months after the onset of adequate treatment. Significantly longer times to remission were predicted by a longer no-treatment interval and higher premorbid neuroticism scores. LIMITATIONS: Adequate antidepressant treatment was commenced prior to admission in half the cases, requiring a retrospective assessment of illness course prior to study entry. Twenty-four patients (29%) had not remitted at the time of completion of the MPI. CONCLUSIONS: These results replicate previous findings identifying a longer time to treatment and higher neuroticism scores as predictors of chronicity in depression.

Adolescent↗
PubMed1998

Time to initial medical presentation in a first-admission group with depression.

This paper examines the interval between the onset of depressive illness and subsequent medical presentation in a group of patients undergoing their first psychiatric admission with moderate to severe depression. The average preconsultation interval was 76 days, compared with an average time from consultation to the commencement of adequate treatment of 40 days. The time to initial consultation was found to correlate significantly with neuroticism, but not with sociodemographic factors. This study suggests that neuroticism may act as a predictor of poor outcome in depressive illness through its impact on help-seeking behaviour.

Adolescent↗
PubMed1998

Proinsulin and insulin concentrations in relation to carotid wall thickness: Insulin Resistance Atherosclerosis Study.

BACKGROUND AND PURPOSE: Insulin resistance and hyperinsulinemia have been associated with atherosclerosis. Recent attention has focused on the possible role of proinsulin because most radioimmunoassays for insulin cross-react with proinsulin. Therefore, it is not known which of the two, insulin per se or proinsulin, is more strongly related to atherosclerosis. METHODS: We examined the relation between fasting proinsulin, fasting split proinsulin, fasting and 2-hour insulin (after oral glucose load), and intima-media wall thickness (IMT) in the common carotid artery (CCA) and internal carotid artery (ICA) in 985 nondiabetic subjects from the Insulin Resistance Atherosclerosis Study, a multiethnic study of insulin resistance and atherosclerosis. RESULTS: In the overall population, a weak but significant relation between proinsulin and CCA IMT was observed (r=0.07, P=0.029). However, the relation between proinsulin and IMT was stronger in Hispanics and non-Hispanic whites than in African Americans. In non-Hispanic whites and Hispanics, significant correlations between CCA and proinsulin (r=0.087) and between ICA and proinsulin (r=0.101), split proinsulin (r = 0.092), and fasting insulin (r = 0.087) were observed. The significant correlations became more attenuated (and nonsignificant) after adjustment for cardiovascular risk factors, especially plasminogen activator inhibitor-1 (PAI-1). CONCLUSIONS: The association between proinsulin and IMT, while weak, appears to be stronger than the association between insulin and IMT. Adjustment for PAI-1 markedly attenuated the association between proinsulin and IMT, suggesting a possible mediating role for PAI-1 in this association. It is possible that proinsulin may represent a marker of atherosclerosis rather than a causal factor for atherosclerosis. Studies of the insulin resistance syndrome and atherosclerosis that use insulin as a surrogate for insulin resistance should consider the use of specific insulin assays as well as determination of proinsulin concentrations.

Arteriosclerosis↗
PubMed1997

Cumulative effects of high cholesterol levels, high blood pressure, and cigarette smoking on carotid stenosis.

BACKGROUND: Single measurements of cardiovascular risk factors may not accurately reflect a person's past exposure to those risk factors. We therefore studied the long-term associations of cardiovascular risk factors such as high serum cholesterol levels, high blood pressure, and cigarette smoking with the prevalence of carotid stenosis. METHODS: We studied cross-sectional and longitudinal information from a sample of 429 men and 661 women in the Framingham Heart Study who underwent B-mode ultrasound measurements of the carotid artery. Their mean age was 75 years, and each had attended most of the biennial clinic examinations over the 34 years before the carotid ultrasound study. We used time-integrated measurements to assess the associations between various cardiovascular risk factors and the degree of carotid stenosis. RESULTS: Moderate carotid stenosis (> or =25 percent) was present in 189 men and 226 women. We assessed the odds ratios for this degree of stenosis as compared with minimal stenosis (<25 percent) according to increases in risk factors. In the men, the odds ratio for moderate carotid stenosis associated with an increase of 20 mm Hg in systolic blood pressure was 2.11 (95 percent confidence interval, 1.51 to 2.97). The odds ratio for an increase of 10 mg per deciliter (0.26 mmol per liter) in the cholesterol level was 1.10 (95 percent confidence interval, 1.03 to 1.16), and for an increase of five pack-years of smoking it was 1.08 (95 percent confidence interval, 1.03 to 1.13). The results were similar in the women. Time-integrated measurements of diastolic blood pressure showed significant associations with carotid stenosis in men and insignificant associations in women. CONCLUSIONS: Over the long term, high systolic blood pressure, high cholesterol levels, and smoking were associated with an increased risk of carotid stenosis in this elderly population.

Aged↗
PubMed1996

The endogenous subtype and naturalistic course in depression.

The naturalistic course of patients with endogenous subtype of depression is described. The subtype may predict shorter times to remission, and reduced relapse risk. In the longer term, the subtype predicts increased risk of readmission, though studies on recurrence are equivocal. Recurrence of endogenous episodes may be less dependent on life events and personality factors. The subtype does not predict a greater risk of suicide, and most studies show that it does not predict a poorer long-term global outcome. Further prospective studies including operational criteria for course and outcome are needed.

Depressive Disorder↗
PubMed1996

Landmark-based registration and measurement of magnetic resonance images: a reliability study.

We report a magnetic resonance imaging (MRI) study in a large number of subjects that examines various analytic techniques for anatomical landmark information. The initial issue involved interrater reliability in locating landmarks along the midsagittal plane. Another issue dealt with using landmarks to register (linear) individual scans for subsequent analyses or more sophisticated registration techniques. We next explore the use of interlandmark distances as indices of brain size. Twenty-seven landmarks were chosen from the midsagittal slice of 101 abnormal subjects. Interrater reliability estimates on a subset of the scans were excellent overall. Rotating to anterior-posterior commissure points was the best of the tested two-point registrations, although an average angular rotation was better. Reliability and validity for landmark-derived measures of size were excellent. Landmark-based analyses offer opportunities to explore shape and size questions, although they are not appropriate for addressing all questions. Under specific conditions, landmark data can be generated quickly and accurately.

Adolescent↗
PubMed1996

Normalizing counts and cerebral blood flow intensity in functional imaging studies of the human brain.

Image intensity normalization is frequently applied to eliminate or adjust for subject or injection global blood flow (gCBF) and other sources of nuisance variation. Normalization has several other positive effects on the analysis of PET images. However, the choice of an intensity normalization technique affects the statistical and psychometric properties of the image data. We compared three normalization procedures, the ratio approach (regional (r)CBF/gCBF), histogram equalization, and ANCOVA, on both PET count and flow data sets. The ratio method presents the proportional increase of regions, the histogram equalization method offers the relative ranking of intensities over the image, and the ANCOVA method provides statistical deviations from an expected linear model of regional values from the subject's gCBF. The original study used 33 normal subjects in a standard subtraction paradigm. The normalization methods were evaluated on their ability to remove extraneous error variation, induce homogeneity of intersubject variation, and remove unwanted dependencies. In general, the normalization modified the subtraction image more than the individual condition images. All three methods worked well at removing the dependency of rCBF on gCBF in count and flow images. For count data, the three methods also reduced the amount of error variation equally well, improving the signal to noise ratio. For flow data, the histogram equalization and ratio methods worked best at reducing statistical error. All three methods dramatically stabilized the variance over the image.

Analysis of Variance↗