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Biomedical subjects

D Osborn

Publications and source records attributed to D Osborn.

At least 19 recordsLinked to original sources

The initial pathogenesis of cadmium induced renal toxicity.

The novel application of magic angle spinning 1H NMR spectroscopy, coupled with pattern recognition techniques, has identified biochemical changes in lipid and glutamate metabolism that precede classical nephrotoxicity. These changes occurred in the bank vole (Clethrionomys glareolus) after chronic dosing, at a low level of exposure and at a renal Cd(2+) concentration (8.4 microgram/g dry wt) that was nearly two orders of magnitude below the WHO critical organ concentration (200 microg/g wet wt). These early stage effects of Cd(2+) on the biochemistry of renal tissue may reflect adaptation mechanisms to the toxic insult or the preliminary stages of the toxicological cascade.

Acidosis, Renal Tubular↗

Chlorobenzenes in rivers draining industrial catchments

Eleven chlorobenzenes (out of a total of 12 in the congener series) were monitored weekly on four industrialized rivers (Aire, Calder, Don and Trent) of the Southern Humber Catchment in whole water samples. 1,2- and 1,4-dichlorobenzene were present at relatively high levels on both the Aire and Calder, having mean concentrations of approximately 30 ng/l. They were both at lower concentrations on the Don and Trent, although the 1,4-isomer dominated. All other chlorobenzenes monitored were routinely found on all the rivers, with the exception of hexachlorobenzene, which was only regularly detected on the Trent. Again, the rivers fell into two classes with respect to their total chlorobenzene concentrations, with the Aire and Calder being more polluted. The higher levels of chlorobenzenes (excluding hexachlorobenzene which was used widely as a agricultural pesticide) on the Aire and Calder, and the dominance of the 1,4-dichlorobenzene congener (accounting for 60-70% of sigma chlorobenzenes) on the Don and Trent, indicated that the Aire and Calder were predominately contaminated with chlorobenzenes through industrial sources, while the Don and Trent were mainly contaminated through domestic sources (1,4-dichlorobenzene is widely used as a toilet deodorant). 1,4-Dichlorobenzene dominated flux, with the Aire, Don and Trent exporting 52.5 kg/year into the Humber estuary, followed by the 1,2-dichlorobenzene at 38.8 kg/year. Sigma chlorobenzenes exported to the Humber was 133 kg/year. This is the first study to calculate chlorobenzene fluxes to the North Sea from a UK catchment.

Journal Article↗

Spatial and temporal regulation of the pesticide dieldrin within industrial catchments

The river catchments of south Yorkshire support a very high density of wool processing industries. Dieldrin was once used as a moth proofing agent, as a sheep dip, and as a pesticide to protect wool fleeces during storage and transport, all of which caused pollution of these catchments due to textile processing. Weekly sampling of four of these rivers revealed two classes of dieldrin contamination: the Aire and Calder (the rivers which support very high concentrations of wool processing industries) had higher concentrations (averaging approximately 3 ng/l) than the Don and Trent (approximately 1 ng/l). The average flux of dieldrin from these rivers into the Humber estuary was 9.8 g/day, with the Aire (of which the Calder is a tributary) and the Trent contributing almost equally, with a smaller contribution from the Don. The Trent has the highest average flow, explaining its large contribution to dieldrin flux. Less detailed sampling of rivers from the north Humber catchment which drain predominantly rural areas had dieldrin concentrations similar to the heavily industrialized southern catchment rivers. This suggests that dieldrin from agronomic and domestic usage may be more persistent than the pollution caused by textile processing industries. Evidence is presented to suggest that the principle dieldrin sources to the Humber catchments are sewage treatment plants, and that the dieldrin sources are in rapid equilibrium with the water column.

Journal Article↗

Intraocular involvement in multifocal fibrosclerosis.

OBJECTIVE: To report the clinical and histopathologic findings of intraocular involvement in a patient with multifocal fibrosclerosis and the response of the patient's choroidal masses to external beam radiotherapy. DESIGN: Case report with clinicopathologic correlation of enucleated eyes. METHODS: The patient was studied by clinical observation, contact B- and A-scan ultrasonography, orbital magnetic resonance imaging, fluorescein angiography, indocyanine green angiography, choroidal biopsy, and gross and histopathologic examination of the enucleated eyes. Tissue obtained at an earlier laparotomy was also reviewed. External beam radiotherapy was used when high-dose corticosteroid and low-dose methotrexate therapy failed to decrease the size of the choroidal masses or improve the patient's vision. MAIN OUTCOME MEASURES: Changes in the clinical and ultrasonographic size of the choroidal masses, the clinical appearance of these masses, and the patient's visual acuity in response to external beam radiotherapy were monitored premortem. Histopathologic findings in the enucleated eyes were compared with the changes in previous abdominal and choroidal biopsy specimens and with tissue alterations reported in multifocal fibrosclerosis. RESULTS: Biopsy of the choroidal mass revealed a fibrosclerosing process similar to that found in the abdomen. The patient received external beam radiotherapy with disappearance of the masses. Fibrosclerosing changes similar to those seen in the abdomen were observed replacing the choroid in the enucleated eyes. CONCLUSIONS: Multifocal fibrosclerosis may involve the choroid with histopathologic changes similar to those that have been described in other locations in the body. External beam radiotherapy may be an effective treatment for intraocular involvement by multifocal fibrosclerosis.

Aged↗

Quantitative structure-toxicity relationships for halogenated substituted-benzenes to Vibrio fischeri, using atom-based semi-empirical molecular-orbital descriptors.

Quantitative structure-toxicity relationships (QSTR's) are derived for an extensive series of halogenated benzenes, anilines, phenols, nitrobenzenes, toluenes and other substituted benzenes against Vibrio fischeri using a wide range of whole molecule and atom-based descriptors derived from semi-empirical molecular-orbital calculations. In terms of direct statistical correlation with toxicity it was found that the molar refractivity was the most important parameter, closely followed by the solvent accessible surface area of the compound. The accuracy of these descriptors in fitting the numerous fluoro- and chloro-mono-aromatic compounds was compared with bromine and iodine analogues, where the 'best' descriptors for the former were found in general to be less accurate for the latter in the case of multi-halogen substitution. The equations obtained were also used to classify the compounds into narcosis-based mechanisms of toxicity and those with respiratory uncoupling potential. A combination of the molar refractivity and the nucleophilic susceptibility of one of the meta ring carbons predicted the toxicity of the halo-benzenes and toluenes, along with anisoles, benzonitriles, nitrobenzenes and most of the anilines. The relevance of these descriptors to developing coherent and more generally applicable models for QSTR's of mono-aromatic compounds to other species in environmental toxicology is discussed.

Benzene Derivatives↗

Quantitative structure-toxicity relationships for chlorophenols to bioluminescent lux-marked bacteria using atom-based semi-empirical molecular-orbital descriptors.

Literature data on the toxicity of chlorophenols for three luminescent bacteria (Vibrio fischeri, and the lux-marked Pseudomonas fluorescens 10586s pUCD607 and Burkholderia spp. RASC c2 (Tn4431)) have been analyzed in relation to a set of computed molecular physico-chemical properties. The quantitative structure-toxicity relationships of the compounds in each species showed marked differences when based upon semi-empirical molecular-orbital molecular and atom based properties. For mono-, di- and tri-chlorophenols multiple linear regression analysis of V. fischeri toxicity showed a good correlation with the solvent accessible surface area and the charge on the oxygen atom. This correlation successfully predicted the toxicity of the heavily chlorinated phenols, suggesting in V. fischeri only one overall mechanism is present for all chlorophenols. Good correlations were also found for RASC c2 with molecular properties, such as the surface area and the nucleophilic super-delocalizability of the oxygen. In contrast the best QSTR for P. fluorescens contained the 2nd order connectivity index and ELUMO suggesting a different, more reactive mechanism. Cross-species correlations were examined, and between V. fischeri and RASC c2 the inclusion of the minimum value of the nucleophilic susceptibility on the ring carbons produced good results. Poorer correlations were found with P. fluorescens highlighting the relative similarity of V. fischeri and RASC c2, in contrast to that of P. fluorescens.

Burkholderia↗

Proton spectroscopy in myotonic dystrophy: correlations with CTG repeats.

OBJECTIVES: To seek cerebral metabolite abnormalities in patients with myotonic dystrophy and to determine whether the degree of cerebral abnormalities (measured by proton magnetic resonance spectroscopy) correlates with severity of the genetic defect (measured by trinucleotide repeats). DESIGN: Fourteen patients with myotonic dystrophy were compared with 24 healthy control subjects. SETTING: A university-affiliated medical center. RESULTS: Compared with healthy subjects, patients with myotonic dystrophy had elevated levels of myoinositol (+19% in the occipital region and +12.9% in the temporoparietal region), total creatine (+7.6% and +6.8%), and choline-containing compounds (+21% and +7.7%). Furthermore, the creatine and myoinositol peak areas correlated with the number of trinucleotide cytosine-thymine-guanine(n) (CTG)n repeats from leukocytes, especially in the temporoparietal brain region (r=0.76; P=.004). CONCLUSIONS: Neurochemical alterations observed with proton magnetic resonance spectroscopy are proportional to the cytosine-thymine-guanine repeat size. Increases in myoinositol and creatine concentrations may be caused by increased glial content, while elevated levels of choline-containing compounds are most likely caused by increased glial content and cell membrane abnormalities. Proton magnetic resonance spectroscopy is a powerful noninvasive tool to study brain biochemistry, which may reflect the extent of neuropathological involvement in patients with myotonic dystrophy.

Adult↗

Effect of bovine serum albumin on passive transfer of immunoglobulin G1 to newborn calves.

The molecular mechanism in the intestine of newborn calves that results in transfer of intact colostral immunoglobulin from the lumen to the circulation also is capable of transferring a variety of non-immunoglobulin macromolecules. If the capacity of this mechanism is limited, transfer of a large amount of non-immunoglobulin protein may interfere with transfer of immunoglobulin. In this experiment, efficiency of IgG1 transfer in newborn calves was reduced from 59 to 36% by the addition of bovine serum albumin (37 mg ml-1) to colostral whey, while the addition of a similar mass of amino acids in the form of acid hydrolyzed casein (37 mg ml-1) did not detectably alter IgG1 transfer. Reduced IgG1 absorption efficiency in calves fed colostrum with added bovine serum albumin is consistent with a limited capacity for the macromolecular transport mechanism in the intestine of newborn calves.

Animals↗

Reliability of in vivo volume measures of hippocampus and other brain structures using MRI.

Volume reductions of the hippocampus are associated with Alzheimer's disease, schizophrenia, and epilepsy. We used clinically available MRI methods (2D acquisition; inversion recovery and calculated T2 images; 3 mm contiguous slices) that optimize image contrast, quality, and resolution and standardized positioning protocols to maximize the in vivo accuracy (test-retest reliability) of brain volume measurements in volunteers who were scanned two or three times. Volunteers were scanned in the same MRI instrument (intrascanner reliability) as well as in two different instruments (interscanner reliability). A single rater obtained brain volume measures of seven contiguous slices centered on the anterior commissure. The in vivo intrascanner reliability for measures of anterior hippocampus and ventricular volumes was very good, with reliability coefficients [intraclass r (rxx)] ranging between .855 and .997, and a median coefficient of variation (CV) of 6.4%. Reliability was good for amygdala (rxx of .740 and .764) and for total frontal and temporal lobe volumes and white matter volume measures (rxx ranging between .640 and .823, median coefficient of variation was 3.2%). Overall, interscanner reliability was also good. We discuss the implications of our results relative to the possible clinical utility of hippocampal quantification and the feasibility of prospective studies aimed at quantifying progressive neurodegeneration.

Adult↗

Polycarbonate intraocular lenses.

Bisphenol-A polycarbonate has been investigated as an improved polymer for ocular implants, especially for intraocular lenses (IOLs). Polycarbonate properties afford special opportunities for development of tougher, stronger, one-piece IOLs. Autoclave or gamma sterilizability and a higher refractive index may provide additional IOL advantages over polymethylmethacrylate. Implant studies in rabbits have shown polycarbonate IOLs to be well tolerated in the anterior chamber for 2.5 years. Polycarbonate appears promising for new IOLs and other ocular implant applications.

Animals↗

Relationships between tissue contaminant concentrations in a small sample of seabirds.

1. The metal and organochlorine contaminant concentrations were measured in a small sample of three seabird species collected from St Kilda, Scotland, UK, and the relationship between concentrations of different contaminants within and between tissues was compared. 2. There was little evidence that the concentration of a contaminant in one tissue was indicative of the concentration in any other tissue. 3. Generally, different contaminants had not co-accumulated in tissues; this was so even for the lipophilic compounds (DDE and PCBs), with the exception of puffin fat. 4. There was a tendency for the species containing the most fat to contain the highest concentrations of lipophilic contaminants and there was some suggestion that the fat in muscle could play a role in determining PCB concentrations.

Animals↗

Uterine rupture in Nigeria.

Uterine rupture in the developing world remains a significant problem. We treated 45 such cases. The predisposing factors included cephalopelvic disproportion (62%), grand multiparity (33%), previous cesarean section (24%), placental pathology (15%) and abnormal presentation (20%). The factors associated with maternal death included sepsis (71%), macerated stillborn infant (60%), vulvar edema (50%), hand presentation (50%), prolonged labor (42%) and hysterectomy (37.5%). Hemodynamic resuscitation and prompt surgical intervention remain the mainstays of therapy.

Adolescent↗

Comparative distributions of zinc, cadmium and mercury in the tissues of experimental mice.

Different groups of mice were injected with cadmium, zinc and mercury. Zinc injections had no effect on zinc tissue levels while both mercury and cadmium accumulated in various tissues. Cadmium persisted in the tissues much longer than mercury, and while the mercury concentrations began to decline as soon as dosing ceased, cadmium concentrations in kidney and intestine increased even after dosing ceased. There appeared to be an interrelationship between cadmium concentrations in spleen and intestine which warrants some further investigations. There was a linear, but discontinuous, effect of cadmium on zinc concentrations in liver, kidney and pancreas which may depend on metallothionein biochemistry. Mercury injections had no effect on zinc metabolism. It is proposed that differences in the rate of excretion of cadmium and mercury from the kidney could explain the differential accumulation of cadmium and mercury in animals.

Animals↗