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Biomedical subjects

J O'Brien

Publications and source records attributed to J O'Brien.

At least 289 records · Page 16Linked to original sources
PubMed1967

Metachromatic leukodystrophy (sulfatide lipidoses) cultured in vitro.

Cerebral white matter from a patient with metachromatic leukodystrophly was successfully cultured in vitro. A luxuriant growth in Rose chambers and in roller tubes was apparent by the 14th day. The outgrown cells contained large numbers of granules which stained dark brown with cresyl violetacetic acid. The growth and metachromasia were maintained up to 80 days in vitro.

Adolescent↗
PubMedDate not supplied

Percutaneous vertebroplasty--initial clinical experience in osteoporotic and myelomatous compression fractures.

BACKGROUND: To review the clinical impact of vertebroplasty in osteoporotic and myelomatous compression fractures METHODS: Eleven compression fractures in eight patients were treated by percutaneous cement vertebroplasty over a three-year period, May 2000 to May 2003. RESULTS: Successful percutaneous stabilisation and cement injection was performed in all compression fractures. In five of eight patients (eight of eleven compression fractures) injection of cement yielded dramatic reduction in pain within 24 hours of the procedure. CONCLUSION: Preliminary experience suggests that percutaneous cement vertebroplasty is an effective well tolerated method of stabilisation of spinal wedge compression fractures resulting in dramatic reduction in associated pain in most cases.

Administration, Cutaneous↗
PubMedDate not supplied

Antibiotic prophylaxis in patients with infectious risk factors undergoing gastrointestinal endoscopic procedures.

UNLABELLED: Consecutive patients undergoing gastrointestinal endoscopic procedures were prospectively evaluated for the presence of risk factors for the development of infectious complications that indicated a need for prophylactic antibiotics. Criteria for the evaluation of risk factors were based on (a) former American Heart Association guidelines, (b) current American Heart Association guidelines, and (c) American Society for Gastrointestinal Endoscopy guidelines. Four hundred eighty-six patients underwent 507 procedures. Risk factors for the development of endocarditis or other infectious complications were found in 74 (15%) of all patients during the study period. Cardiac conditions in 51 patients were the most frequently encountered risk factor (69% of risk factors, 10% of all patients), with mitral valve prolapse in 25 patients accounting for 49% of patients with cardiac risk factors and 5% of all patients. Of the patients with mitral valve prolapse, 7 (28%, 1.4% of all study patients) had associated valvular regurgitation. None of the patients with mitral valve prolapse knew whether or not they had associated valvular regurgitation, and if they had had a previous echocardiogram, they were unaware of the results. Only 0.8% of patients had a prosthetic heart valve. The most common non-cardiac risk factor was the presence of a prosthetic joint (9 of 486, 1.8%). Of the 486 patients, 14 required antibiotic prophylaxis according to the above-mentioned guidelines. Six of the 14 patients were given either a non-recommended antibiotic or the wrong dose of a recommended antibiotic. CONCLUSIONS: (1) A decision regarding whether to administer antibiotic prophylaxis had to be made in 15% of patients undergoing endoscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMedDate not supplied

Hazard characterisation of chemicals in food and diet. dose response, mechanisms and extrapolation issues.

Hazard characterisation of low molecular weight chemicals in food and diet generally use a no-observed-adverse-effect level (NOAEL) or a benchmark dose as the starting point. For hazards that are considered not to have thresholds for their mode of action, low-dose extrapolation and other modelling approaches may be applied. The default position is that rodents are good models for humans. However, some chemicals cause species-specific toxicity syndromes. Information on quantitative species differences is used to modify the default uncertainty factors applied to extrapolate from experimental animals to humans. A central theme for extrapolation is unravelling the mode of action for the critical effects observed. Food can be considered as an extremely complex and variable chemical mixture. Interactions among low molecular weight chemicals are expected to be rare given that the exposure levels generally are far below their NOAELs. Hazard characterisation of micronutrients must consider that adverse effects may arise from intakes that are too low (deficiency) as well as too high (toxicity). Interactions between different nutrients may complicate such hazard characterisations. The principle of substantial equivalence can be applied to guide the hazard identification and hazard characterisation of macronutrients and whole foods. Macronutrients and whole foods must be evaluated on a case-by-case basis and cannot follow a routine assessment protocol.

Animals↗
PubMedDate not supplied

Parallel synthesis of prostaglandin E1 analogues.

The first demonstration of the rapid parallel synthesis of diverse prostaglandin derivatives is reported. Upper (alpha-) side chain diversity was introduced to core 1 via the parallel Suzuki coupling of hydroborated alkenes. Conversion to the enones 3 and 9 was followed by the addition of the lower (omega-) side chains as higher-order cuprates 4. Upper side chains incorporating an N-acylsulfonamide protecting group were further transformed into prostaglandin amide analogues. Cleavage from support with HF/pyridine followed by scavenging provided 26 prostaglandin E1 analogues in high purity.

Alprostadil↗
PubMedDate not supplied

Short-range functional interaction between connexin35 and neighboring chemical synapses.

Auditory afferents terminating as mixed, electrical, and chemical, synapses on the goldfish Mauthner cells constitute an ideal experimental model to study the properties of gap junctions in the nervous system as well as to explore possible functional interactions with the other major form of interneuronal communication--chemically mediated synapses. By combining confocal microscopy and freeze-fracture replica immunogold labeling (FRIL), we found that gap junctions at these synapses contain connexin35 (Cx35), the fish ortholog of the neuron-specific human and mouse connexin36 (Cx36). Conductance of gap junction channels at these endings is known to be dynamically modulated by the activity of their co-localized chemically mediated glutamatergic synapses. By using simultaneous pre- and postsynaptic recordings at these single terminals, we demonstrate that such functional interaction takes place in the same ending, within a few micrometers. Accordingly, we also found evidence by confocal and FRIL double-immunogold labeling that the NR1 subunit of the NMDA glutamate receptor, proposed to be a key regulatory element, is present at postsynaptic densities closely associated with gap junction plaques containing Cx35. Given the widespread distribution of Cx35- and Cx36-mediated electrical synapses and glutamatergic synapses, our data suggest that the local functional interactions observed at these identifiable junctions may also apply to other electrical synapses, including those in mammalian brain.

Animals↗
PubMedDate not supplied

Simple standardised neuropsychological assessments aid in the differential diagnosis of dementia with Lewy bodies from Alzheimer's disease and vascular dementia.

Consecutive patients from a dementia case register received a standardised evaluation which incorporated a neuropsychological assessment with the Cambridge Assessment for disorders in the elderly (CAMCOG). Operationalised clinical diagnoses were made (consensus criteria for dementia with Lewy bodies, DLB; NINCDS- ADRDA for Alzheimer's disease, AD, NINCDS AIRENS for vascular dementia, VaD). Two-hundred and twenty-eight patients were studied (DLB 54, AD102, VaD 72). DLB patients had significantly better performance on recent memory than AD patients, but more impaired visuospatial praxis. DLB patients also had significantly better recent memory than those with VaD. Optimal cut-off points for the recent memory:praxis ratio achieved good discrimination between DLB and both other dementias.

Aged↗
PubMedDate not supplied

Neuropathological substrates of dementia and depression in vascular dementia, with a particular focus on cases with small infarct volumes.

The neuropathological substrates of dementia and depression were evaluated in 30 patients with cerebrovascular disease and significant cognitive impairment (VaD), with a particular focus on patients with small infarct volumes (<15 ml). VaD patients with small infarct volumes had a similar degree of cognitive impairment to those with larger infarct volumes (>15 ml) but were significantly more likely to be depressed and to have areas of microinfarction. A review of individual cases with small infarct volumes suggested that the combination of microinfarction, diffuse white matter disease and perivascular changes, or the overlap of neurodegenerative pathologies and microvascular changes were particularly important. Microinfarction was also significantly associated with major depression.

Aged↗
PubMedDate not supplied

One year follow-up of parkinsonism in dementia with Lewy bodies.

The progression of parkinsonism over 1 year was evaluated in a prospective cohort of patients (n = 338), suffering from dementia with Lewy bodies (DLB), Alzheimer's disease (AD) or vascular dementia (VaD). Parkinsonism was assessed using the modified Unified Parkinson's Disease Rating Scale. Significant parkinsonism was significantly commoner in DLB sufferers (71%) than amongst patients with AD (7%) or VaD (10%). DLB patients with established parkinsonism had an annual increase in severity of 9%, but progression was more rapid (49% in 1 year) in patients with early parkinsonism. Parkinsonism was frequent at all severities in DLB patients, but usually only present in other dementias when MMSE <10.

Aged↗
PubMedDate not supplied

Surfactant secretion by type II pneumocytes is inhibited by high glucose concentrations.

Delayed fetal lung maturation is observed in poorly controlled diabetic pregnancies. To investigate whether elevated glucose levels inhibit basal surfactant secretion and synthesis in type II cells and whether inhibitory effects on secretion can be reversed by secretagogues, type II cells isolated from 20-day fetal rat lung explants were initially cultured in [H3] choline containing media with glucose concentrations of 5.5, 10, 25, 50, and 100 mM, or in equiosmolar mannitol controls. Further incubation in nonradioactive media containing matched glucose levels with and without 1 x 10(-5) M terbutaline 1 x 10(-6) M and 1 x 10(-8) M 12-O-tetradecanoylphorbol 13-acetate (TPA) allowed assessment of incorporation of choline into phosphatidylcholine (PC) and its subsequent secretion. PC secretion was inhibited by culture in high glucose conditions, resulting in an approximately 30% reduction in secretion under 50 and 100 mM glucose conditions compared to culture at 5.5 or 10 mM glucose (p < .01); this decrease could not be explained by changes in osmolarity or in all viability after culture in high glucose. Insulin (1 unit/mL) had no significant impact on secretion (92 +/- 7% of control). Terbutaline-stimulated cells grown under 50 and 100 mM glucose conditions had significantly lower secretion rates than did terbutaline-stimulated cells cultured in 5.3 mM glucose (p < .05). Exposure to TPA resulted in significant increase in surfactant secretion by cells grown in both 5.5 and 100 mM glucose; however, the percentage increase (39.5 +/- 6.8% and 94.8 +/- 8.0% with 10(-8) M and 10(-6) MTPA, respectively) was significantly lower than in controls (87.8 +/- 8.0% and 152.1 +/- 18.8%, respectively) (p < .001). Choline incorporation into PG was also decreased by 100 mM glucose to 77 +/- 9% of control (p < .01). These data indicate that high glucose levels inhibit both surfactant synthesis and baseline and secretagogue-stimulated surfactant secretion by type II cells. This inhibitory effect on surfactant secretion may further exacerbate the decrease in surfactant synthesis and the pulmonary maturational delay seen in infants of diabetic pregnancies.

Animals↗