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D Osborne

Publications and source records attributed to D Osborne.

At least 19 recordsLinked to original sources
PubMed2005

Elevated levels of WT1 transcripts in bone marrow harvests are associated with a high relapse risk in patients autografted for acute myeloid leukaemia.

Relapse postautograft in acute myeloid leukaemia (AML), may in part arise from leukaemia cells present in the bone marrow (BM) inoculum, and the level of minimal residual disease (MRD) in BM harvests used for autografting may therefore be clinically important. We have used the WT1 transcript as a marker of MRD, which was quantitated by RQ-PCR, in the BM harvests of 24 patients receiving an ABMT for AML. ABL was used as a control gene with WT1 level being normalised to 10(5) copies of ABL per sample. Median WT1 level was 651 copies (range=113-32 700) for the 13 patients with relapse-free survival (RFS) of less than 5 years, and 174 (range=0-1900) for patients with RFS of over 5 years postautograft (P<0.04). The RFS was 10.5 months for patients with WT1 level of >2000 copies (n=5), and has not yet been reached for patients with WT1 level<2000 (n=21), at a median follow-up of 92 months (P<0.05). We show that elevated levels of MRD in BM harvests are associated with a higher relapse risk in patients autografted for AML.

Acute Disease↗
PubMed2004

Longitudinal changes in cognition and behavior in asymptomatic carriers of the APOE e4 allele.

OBJECTIVE: To determine whether memory loss is detectable before the symptomatic presentation of mild cognitive impairment (MCI) in those at greater genetic risk for Alzheimer disease (AD) based upon presence or absence of the e4 allele of APOE. METHODS: Participants were age 50 years or older who responded to newspaper advertisements. A total of 212 cognitively normal individuals of known APOE genotype were initially enrolled in a match paradigm that included e4 homozygotes, e3/4 heterozygotes, and e4 noncarriers in a 1:1:2 ratio (53 sets). Of the original 212 individually matched participants, 180 completed at least two epochs of testing including 45 APOE e4/4 homozygotes, 42 APOE e3/4 heterozygotes, and 93 APOE e4 noncarriers, mean age 60 (+/-6.2) years. Of these, four developed MCI or AD during the follow-up period and were excluded from analysis. Longitudinal neuropsychological study included two verbal (Auditory Verbal Learning Test [AVLT], Selective Reminding Test [SRT]) and two visual (Complex Figure Test [CFT], Visual Retention Test) memory tests. RESULTS: Multiple measures on both verbal memory tests showed poorer performance over a mean interval of 33 months in e4 carriers than noncarriers: AVLT total learning, long term delayed recall; SRT free and cued recall. Among those age 50 to 59 years, AVLT long term delayed recall, SRT free and cued recall, and CFT recall declined more in APOE e4 carriers. No differences were found in the domains of language, spatial skills, or executive function. CONCLUSIONS: Memory declined in APOE e4 carriers before the symptomatic presentation of MCI in a cohort whose mean age was 60 years over a median period of 33 months. The decline began prior to age 60.

Aged↗
PubMed2002

Falls: a comparison of trends in community, hospital and mortality data in older Australians.

BACKGROUND AND AIMS: Falls are major contributors to disability, morbidity and death for older people. Frequently, falls-related data for each of these areas is viewed in isolation. The aim of this study was to establish trends in incidence of falls-related events including: community reporting of falls and falls-related injuries, hospitalizations as a result of accidental falls, and mortality related to accidental falls for older people in two states of Australia (Victoria and South Australia). METHODS: We analysed data sets for falls hospitalizations and mortality rates for the period 1988 to 1997, and from two longitudinal population-based proportional samples during the same time period. RESULTS: Age-standardised falls mortality rates have steadily declined in Victoria, and remained unchanged between 1988 and 1997 in South Australia. In both states, age-standardised falls hospitalization rates have increased significantly (in Victoria, RR=1.32, 95% CI: 1.30-1.34; and South Australia, RR=1.05, 95% CI: 1.03-1.06). In both states, there was a clear age-related effect, with those in the 85-year and older age group having a falls-related mortality rate approximately 40 times that of those aged 65-69 years, and a hospitalization rate 9 times that of those in the 65-69 age group. The community studies indicated that falls rates remain high among older Australians, and that injurious falls occurred in 10% in the first wave of data collection in each of these studies. CONCLUSIONS: The results highlight that various indicators related to falls trends taken in isolation may yield differing conclusions. For a true reflection of the effectiveness of falls prevention programs, falls-related mortality, hospitalization and community data need to be integrated. Increased focus on falls prevention activity in Australia during the 1990's has not reduced the magnitude of this major public health problem.

Accidental Falls↗
PubMed2001

Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E-e4/4 homozygotes: a replication study.

In a previous cross-sectional study of 100 asymptomatic individuals aged 49-69, we reported age-related decline in immediate and delayed memory that was steeper in apolipoprotein E (apoE)-e4/4 homozygotes than in members of other genetic subgroups. These findings were preliminarily based upon the statistical problem of multiple comparisons. We therefore sought to replicate these findings in a new cohort. From 1998 to 2000, 80 asymptomatic residents of Maricopa County, AZ were recruited through newspaper ads. 20 apoE-e4/4 homozygotes, 20 e3/4 heterozygotes, and 40 e4 noncarriers were matched (1:1:2) by age, gender, and years of education. All had normal neurologic and psychiatric examinations, including Folstein minimental status exam (MMSE) and Hamilton depression scale, and underwent a battery of neuropsychological tests identical to those in our previous study. The groups were well-matched for age (55.9+/-5.9 years), gender (60% women), and education (15.9+/-2.2 years), and were demographically similar to our previous cohort. Complex figure test recall was lower in e3/4 heterozygotes than noncarriers, but there was no significant difference between e4/4 homozygotes and noncarriers. There were no other significant differences in mean test scores between groups, but Wechsler adult intelligence scale-revised (WAIS-R) digit span showed a significant negative correlation with age in the e4/4 homozygote group relative to e4 noncarriers (p=0.008) as we had found in our previous study. In conclusion, we found a significant negative correlation of WAIS-R digit span with age in apoE-e4/4 homozygotes relative to e4 noncarriers in two separate cohorts, possibly reflecting an age-related effect on frontal lobe function in this genetic subgroup.

Age of Onset↗
PubMed2001

Does increasing ovum donor compensation lead to differences in donor characteristics?

OBJECTIVE: To evaluate the effects of a compensation increase for anonymous ovum donors on demographic and social characteristics. DESIGN: Retrospective analysis. SETTING: The Mount Sinai Medical Center Ovum Donation Program. PATIENT(S): All program applicants for 2 years preceding (group I, n = 2,934) and 1 year following an increase in donor compensation (group II, n = 1,114; total N = 4,048). INTERVENTION(S): Compensation was increased from $2,500 to $5,000 per cycle. MAIN OUTCOME MEASURE(S): Demographic and social characteristics of applicants and donors. RESULT(S): More group II applicants (65.7%) than group I applicants (49.2%) returned an initial biographical questionnaire. Compensation level did not affect the percentage rejected at any stage in the application process or ultimately selected. There were no differences in donors in age, marital status, education, race, religion, or psychological profile. Group II donors had more previous pregnancies (group II mean = 1.2, group I mean = 0.6) and previous abortions (group II mean = 0.8, group I mean = 0.4). CONCLUSION(S): Increasing compensation may result in a higher percentage of potential donors completing an initial questionnaire but does not alter the demographic and social characteristics of selected donors. Adherence to a rigorous applicant screening ensures that donor characteristics remain independent from compensation.

Abortion, Induced↗
PubMed2000

Yohimbine ameliorates the effects of endotoxin on gastric emptying of the liquid marker acetaminophen in horses.

The effect of yohimbine pretreatment on gastric emptying of a liquid marker in horses was evaluated by measuring serum concentrations of acetaminophen. Gastric emptying was determined in normal, fasted horses, in horses given endotoxin (E. coli 055 B5; 0.2 microg/kg) intravenously, and in horses given yohimbine (0.25 mg/kg, IV, over 30 minutes) plus endotoxin. Acetaminophen (20 mg/kg) was given by stomach tube 15 minutes after the endotoxin infusion. Blood samples for acetaminophen analysis were collected, and time to reach the peak serum concentration (Tmax), the maximum serum concentration (Cmax) and the area under the acetaminophen serum concentration versus time curve (AUC) were determined for each treatment group. Endotoxin significantly increased Tmax, indicating a profound delay in gastric emptying and yohimbine pretreatment significantly (P < or = 0.05) prevented this effect.

Acetaminophen↗
PubMed1999

Preclinical memory decline in cognitively normal apolipoprotein E-epsilon4 homozygotes.

OBJECTIVE: To determine, in a cross-sectional evaluation of nondemented individuals, if age-related memory decline is influenced by apolipoprotein E (apoE) genotype. BACKGROUND: The apoE-4 allele is an important risk factor for AD. PET in cognitively normal apoE-4 carriers (mean age, 56 years) shows reduced cerebral metabolism suggestive of very early AD that precedes clinically evident memory loss or MRI-based hippocampal atrophy. METHODS: Tests of immediate and delayed recall (primary outcome measures) and other neuropsychological measures (secondary outcome measures) were given to three genetically defined groups of cognitively normal individuals (age, 49 to 69 years) including apoE-4 homozygotes (n = 25), apoE-4 heterozygotes (n = 25, all epsilon3/4), and apoE-4 noncarriers (n = 50). Groups were matched for age, gender, and educational background. Cross-sectional comparisons between the genetic subgroups of the relationship between age and test score were performed for each neuropsychological measure. RESULTS: There were no intergroup differences in mean scores on any neuropsychological measure, but tests sensitive to immediate and delayed recall showed a significant negative correlation with age in the apoE-4 homozygote group relative to the noncarrier group. CONCLUSION: Consistent with previous neuropsychological studies of early AD, this cross-sectional study suggests that age-related memory decline occurs earlier in cognitively healthy apoE-4 homozygotes than in apoE-4 heterozygotes and noncarriers, and precedes clinically detectable AD.

Age Factors↗
PubMed1999

Sulfation of chondroitin sulfate in human articular cartilage. The effect of age, topographical position, and zone of cartilage on tissue composition.

The chondroitin ABC lyase digestion products of normal human femoral condyle articular cartilage and of purified aggrecan were analyzed for their mono- and nonsulfated disaccharide composition. Changes in the total tissue chemistry were most pronounced during the period from birth to 20 years of age, when the -[GlcAbeta,3GalNAc6]- disaccharide content increased from approximately 50% to 85% of the total disaccharide content and there was a concomitant decrease in the content of the 4-sulfated disaccharide. In general, the disaccharide content of the deeper layers of immature cartilage were richer in the 4-sulfated residue than the upper regions of the tissue. As the tissue aged and decreased in thickness, the disaccharide composition became more evenly 6-sulfated. The newly synthesized chondroitin sulfate chains had a similar composition to the endogenous chains and also underwent the same age and zonal changes. The monoclonal antisera 3B3(+) and 2B6(+) were used to immunolocalize the unsaturated 6- and 4-sulfated residues generated at the reducing termini of the chondroitin sulfate chains by digestion with chondroitin ABC lyase, and these analyses indicated that the sulfation pattern at this position did not necessarily reflect the internal disaccharide composition of the chains. In summary, the sulfation pattern of chondroitin sulfate disaccharides from human normal articular cartilage varies with the age of the specimen, the position (topography) on the joint surface, and the zone of cartilage analyzed. Furthermore, these changes in composition are a consequence of both extracellular, post-translational processing of the core protein of aggrecan and changes in the sulfotransferase activity of the chondrocyte.

Adolescent↗
PubMed1999

Calcaneal ultrasound attenuation in an elderly population: measurement position and relationships with body size and past fractures.

This study demonstrates, the relationship between past fracture, body size and broadband ultrasound attenuation (BUA) and investigates two sites of BUA measurement in a representative elderly population of men and women (n = 2106). We measured BUA at a fixed position and at a consistent anatomic position within the calcaneus. We found fixed BUA was less closely correlated with stature and age than anatomic BUA. Both correlations were substantially weaker in men than in women. Mean BUA was significantly lower in women with a past fracture compared with nonfracturers (fixed BUA 63.3 vs 69.4 dB/MHz, p = 0.0004; anatomic BUA 77.6 vs 81.7 dB/MHz, p = 0.013). However, in women, the fixed BUA was better than the anatomic BUA at discriminating between fracturers and nonfracturers (OR 1.38/SD (95% CI 1.12-1.68) and OR 1.22/SD (0.99-1.52), respectively) when adjusted for body size and age. There was no significant difference in either BUA in men with or without a past fracture. In conclusion, currently the fixed position for BUA measurement is preferable and, whilst we have demonstrated that it is possible to locate an anatomically consistent point in the calcaneus, the position chosen by this study did not provide a measurement with more discriminatory capability than the fixed position. In women, BUA behaves similarly to bone mineral density in relation to stature and in its strength of association with past fracture, while the lack of association in men may reflect differing contributions by bone strength to fracture risk in the sexes.

Age Factors↗
PubMed1999

Metoclopramide ameliorates the effects of endotoxin on gastric emptying of acetaminophen in horses.

The effect of metoclopramide on gastric emptying of a liquid marker in horses was evaluated by measuring serum concentrations of acetaminophen. Gastric emptying was determined in normal, fasted horses (n = 7), horses given endotoxin intravenously (n = 7), and horses given intravenous metoclopramide plus endotoxin (n = 6). The mean time to reach maximum serum acetaminophen concentration (Tmax), the maximum serum concentration (Cmax), and the area under the serum acetaminophen concentration vs time curve (AUC) were compared among treatment groups. Endotoxin caused a profound delay in gastric emptying, and pretreatment with metoclopramide significantly (P < 0.05) ameliorated this effect.

Acetaminophen↗
PubMed1998

Hippocampal volumes in cognitively normal persons at genetic risk for Alzheimer's disease.

Brain imaging techniques have the potential to characterize neurobiological changes that precede the onset of cognitive impairment in persons at risk for Alzheimer's disease. As previously described, positron emission tomography (PET) was used to compare 11 cognitively normal persons 50 to 62 years of age who were homozygous for the epsilon4 allele of apolipoprotein E and 22 persons without the epsilon4 allele with a reported family history of Alzheimer's dementia who were matched for sex, age, and level of education. The epsilon4 homozygotes had significantly reduced glucose metabolism in the same brain regions as patients with Alzheimer's dementia; the largest reduction was in the posterior cingulate cortex. As described here, magnetic resonance imaging (MRI) was used to compare hippocampal volumes in the same subject groups. The epsilon4 homozygotes showed nonsignificant trends for smaller left and right hippocampal volumes; overall, smaller hippocampal volumes were associated with reduced performance on a long-term memory test. Whereas PET measurements of cerebral glucose metabolism begin to decrease before the onset of memory decline, MRI measurements of hippocampal volume begin to decrease in conjunction with memory decline in cognitively normal persons at risk for Alzheimer's disease.

Aged↗
PubMed1998

From slowly progressive amnesic syndrome to rapidly progressive Alzheimer disease.

A 57-year-old woman had a neuropsychologically documented 5-year history of a slowly progressive amnesic syndrome followed by a 1-year history of rapidly progressive dementia. There was no family history of dementia. Magnetic resonance imaging failed to show a structural basis, electroencephalography failed to show changes of Creutzfeldt-Jakob disease, and cerebrospinal fluid examination was normal. A diagnosis of Alzheimer disease was confirmed by brain biopsy. The abrupt change in disease course was unique but suggested probable overlap between posited subtypes of Alzheimer disease.

Alzheimer Disease↗
PubMed1998

Burnout and issues of the work environment reported by general dental practitioners in the United Kingdom.

OBJECTIVE: To investigate causes of burnout among general dental practitioners. DESIGN: A cross-sectional investigation. SETTING: General dental practices in two areas of the UK and a group of continuing education sessions. SUBJECTS: 325 general dental practitioners, composed of two random samples recruited from two areas of the United Kingdom and an opportunistic sample, recruited from continuing education sessions. OUTCOME MEASURES: Levels of burnout, as measured by scores on one of the three burnout sub-scales--emotional exhaustion, depersonalisation and personal accomplishment. RESULTS: Respondents were more likely to report high levels of emotional exhaustion and low levels of personal accomplishment if they worked in practices with few other dentists. Those respondents reporting high levels of depersonalisation were more likely to provide a greater proportion of care through the National Health Service. CONCLUSIONS: Burnout in this sample of general dental practitioners was related to features of their work organisation structure rather than necessarily due to an involvement with patients or the respondents' personal characteristics. Levels of social support in the workplace, measured here by the number of dentists in a practice, appear to have a protective effect against some aspects of burnout.

Adult↗
PubMed1997

Transurethral microwave hyperthermia in the treatment of chronic nonbacterial prostatitis.

Chronic nonbacterial prostatitis is an ill-understood and difficult-to-diagnose disease. Symptoms of chronic nonbacterial prostatitis are similar to those of chronic prostatitis and include low back pain, frequency, dysuria, perineal discomfort, and painful ejaculation. In view of uncertainty about etiology, treatment of chronic nonbacterial prostatitis remains speculative. Most treatment is aimed at relieving symptoms and not at curing the disease. Because of the troublesome nature of chronic nonbacterial prostatitis and the poor results obtained from traditional treatment methods, a new modality of transurethral microwave hyperthermia was investigated. Six patients were treated from January 1994 through June 1995 by use of transurethral microwave hyperthermia. These men were treated four times during a 2-week period. Their average symptom score decrease was 74.9% and was associated with minimal morbidity. Based on this result, it is concluded that transurethral microwave hyperthermia is a safe and effective treatment modality for chronic nonbacterial prostatitis.

Adult↗
PubMed1996

Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E.

BACKGROUND: Variants of the apolipoprotein E allele appear to account for most cases of late-onset Alzheimer's disease, and persons with two copies of the epsilon 4 allele appear to have an especially high risk of dementia. Positron-emission tomography (PET) has identified specific regions of the brain in which the rate of glucose metabolism declines progressively in patients with probable Alzheimer's disease. We used PET to investigate whether these same regions of the brain are affected in subjects homozygous for the epsilon 4 allele before the onset of cognitive impairment. METHODS: Apolipoprotein E genotypes were established in 235 volunteers 50 to 65 years of age who reported a family history of probable Alzheimer's disease. Neurologic and psychiatric evaluations, a battery of neuropsychological tests, magnetic resonance imaging, and PET were performed in 11 epsilon 4 homozygotes and 22 controls without the epsilon 4 allele who were matched for sex, age, and level of education. An automated method was used to generate an aggregate surface-projection map that compared regional rates of glucose metabolism in the two groups. RESULTS: The epsilon 4 homozygotes were cognitively normal. They had significantly reduced rates of glucose metabolism in the same posterior cingulate, parietal, temporal, and prefrontal regions as in previously studied patients with probable Alzheimer's disease. They also had reduced rates of glucose metabolism in additional prefrontal regions, which may be preferentially affected during normal aging. CONCLUSIONS: In late middle age, cognitively normal subjects who are homozygous for the epsilon 4 allele for apolipoprotein E have reduced glucose metabolism in the same regions of the brain as in patients with probable Alzheimer's disease. These findings provide preclinical evidence that the presence of the epsilon 4 allele is a risk factor for Alzheimer's disease. PET may offer a relatively rapid way of testing future treatments to prevent Alzheimer's disease.

Aged↗
PubMed1995

Validated assays for the determination of gemcitabine in human plasma and urine using high-performance liquid chromatography with ultraviolet detection.

Procedures are described for the determination of gemcitabine, a new anti-tumor agent, and its uridine metabolite in human plasma and in human urine. The sample preparation for the plasma assay involves precipitation of plasma proteins with isopropanol and ethyl acetate. Following this, the solids are discarded and the supernatant is evaporated to dryness. For the urine assay, the sample is diluted with methanol and evaporated to dryness. For both procedures, the residue is reconstituted in mobile phase prior to injection into a normal-phase (amino column) liquid chromatographic system followed by UV detection at 272 nm. The limits of quantitation for both compounds are 50 ng/ml in plasma and 20 micrograms/ml in urine. The procedures were used to provide pharmacokinetic data for both compounds in man following the intravenous administration of a 1000 mg/m2 dose of gemcitabine.

Antimetabolites, Antineoplastic↗