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Biomedical subjects

M Jeffrey

Publications and source records attributed to M Jeffrey.

At least 55 records · Page 3Linked to original sources
PubMed2000

Managed behavioral healthcare in the private sector.

Employers, in their search for cost containment and quality improvement, have driven the development of the behavioral health managed care vendor. More specifically, the behavioral health carve-out is an innovation that was developed to respond to employer and, more recently, health plan needs. Now that the product has matured, it is increasingly being asked to justify its existence. Costs have certainly been maintained, but improvements in quality have not always been evident. The issues the authors address include, as cost pressures continue, can the industry deliver on its promise to improve care? Will it need to evolve to yet another level, with new or different features?

Cost Control↗
PubMed2000

Synapse loss associated with abnormal PrP precedes neuronal degeneration in the scrapie-infected murine hippocampus.

Numbers of neurones, synapses and axon terminals were quantified in a murine scrapie model with severe hippocampal pyramidal cell loss, in which definite clinical scrapie is evident from 226 days post-infection (dpi) and death occurs around 250 dpi. Disease-specific PrP accumulations were first seen at 70 dpi (28% of the incubation period (IP)) in thalamus and as sparse foci within the stratum pyramidale of CA1. By 98 dpi (39% IP), PrP was seen in the stratum radiatum and was found at later stages throughout all levels of the hippocampus. At the ultrastructural level in the stratum radiatum of CA1, a decrease in the numbers of simple synapses from 84 dpi (34% IP) and in perforated synapses from 98 dpi (42% IP) was found using an unbiased stereological method, the disector analysis. Degeneration of axon terminals was found from 98 dpi (39% IP) onwards. Neuronal loss was detected in CA1 from 180 dpi (72% IP). The results suggest that the fundamental lesion in the hippocampus of ME7-infected mice is associated with PrP release from CA1 pyramidal neurones, which perturbs synaptic function and leads to degeneration of preterminal axons, and that subsequent pathological changes including neurone loss are sequelae to this initial insult.

Animals↗
PubMed2000

Dendritic and synaptic alterations of hippocampal pyramidal neurones in scrapie-infected mice.

Neurone damage and eventual loss may underlie the clinical signs of disease in the transmissible spongiform encephalopathies (TSEs). Although neurone death appears to be through apoptosis, the trigger for this form of cell death in the TSEs is not known. Using two different murine scrapie models, hippocampal pyramidal cells were studied through microinjection of fluorescent dye, and synaptic integrity, using p38-immunoreactivity (p38-IR), both visualized using confocal laser scanning microscopy. Intradendritic distensions and dendritic spine loss were found to co-localize to areas of vacuolar and prion protein pathology in the hippocampus of mice infected with ME7 or 87 V scrapie. A significant reduction in p38-IR was found concomitantly in the hippocampus in ME7 scrapie mice. These results indicate that both pre- and post-synaptic sites are altered by scrapie infection; this would disrupt neuronal circuitry and may initiate apoptotic cell death, giving rise to the neurological disturbances manifested in clinical TSE cases.

Animals↗
PubMed1999

In vitro isolation of Neospora caninum from a stillborn calf in the UK.

Neospora caninum was isolated in Vero cell culture from the brain of a stillborn calf. This isolate (designated NC-LivB1) is the first to be obtained from cattle in the United Kingdom and was confirmed as N. caninum by immunofluorescence with specific antibodies and by internal transcribed spacer 1 (ITS1) sequence analysis. Differences were found between NC-LivB1, other bovine isolates and canine isolates of N. caninum and closely related protozoal parasites, using random amplified polymorphic DNA polymerase chain reaction (RAPD - PCR) techniques.

Animals↗
PubMed1999

Effect of dietary conjugated linoleic acid on the quality characteristics of chicken eggs during refrigerated storage.

Twenty-four, 79-wk-old White Leghorn hens were assigned randomly to three diets containing 0, 2.5, or 5.0% conjugated linoleic acid (CLA). The diets were fed for 4 wk to determine the effect of dietary CLA on quality characteristics of eggs. Eggs were collected daily and stored at 4 C for 1, 7, 21, or 49 d. At the designated times, the eggs were processed to evaluate water content, fatty acid composition, color, proportions and pH of yolk and albumen. Firmness of yolk after the eggs were hard-cooked was also determined. The proportions of myristic, palmitic, stearic, CLA (9-cis, 11-trans CLA and 10-trans, 12-cis CLA isomers), and unidentified fatty acids in egg yolk lipids were increased as dietary CLA increased, but those of palmitoleic, oleic, linoleic, linolenic, arachidonic, and docosahexaenoic acid were decreased. Duration of refrigeration increased the proportion of egg yolk but decreased the contents of albumen and yolk lipids after 21 d or longer of storage. Egg yolk pH increased as refrigeration time increased, regardless of dietary treatment, but the increase was greater in the eggs produced by hens fed the CLA diets. Albumen pH increased significantly after 7 d of storage but remained unchanged until 21 d and then decreased by 49 d. Dietary CLA had no effect on the pH of albumen until 49 d of storage. After 49 d storage, egg albumen pH from hens fed CLA diets was lower than that of albumen from hens fed the control diet. Yolk color was not influenced by the dietary CLA and storage, but the egg yolk surface from hens fed CLA diets sometimes had relatively dark color with light spots. Dietary CLA and storage of CLA eggs increased the firmness of hard-cooked egg yolk. The texture of yolks from hard-cooked CLA eggs was rubbery and elastic, and the yolks were more difficult to break using an Instron. It was speculated that the quality changes of CLA eggs were related to the increase of yolk water content, the movement of ions between yolk and albumen through yolk membrane, and the changes of egg yolk pH during storage.

Animal Feed↗
PubMed1999

[Letrozole (Femara), a new aromatase inhibitor for advanced breast cancer].

The study compares letrozole (Femara and aminoglutethimide (AG), a standard therapy for postmenopausal women with advanced breast cancer, previously treated with anti-estrogens. 555 women were randomly assigned letrozole 2.5 mg once daily (n = 185), letrozole 0.5 mg once daily (n = 192) or aminoglutethimide 250 mg twice daily with corticosteroid support (n = 178) in an open-label, multicenter trial. The primary end-point was objective response rate (ORR), with time events as secondary. ORR was analysed nine months after enrollment of the last patient, while survival was analysed 15 months after the last patients was enrolled. We report the results of these analyses plus an extended period of observation (covering a total duration of approximately 45 months) to determine the duration of response and clinical benefit. Overall objective response rates (complete + partial) of 19.5%, 16.7% and 12.4% were seen for letrozole 2.5 mg, 0.5 mg and AG respectively. Median duration of response and stable disease was longest for letrozole 2.5 mg (21 months) compared with letrozole 0.5 mg (18 months) and AG (14 months). Letrozole 2.5 mg was superior to AG in time to progression, time to treatment failure and overall survival. Treatment-related adverse events occurred in fewer patients on letrozole (33%) than on AG (46%). Letrozole 2.5 mg offers longer disease control than aminoglutethimide and letrozole 0.5 mg in the treatment of postmenopausal women with advanced breast cancer, previously treated with anti-estrogens.

Aged↗
PubMed1998

Determination of the frequency and distribution of vascular and parenchymal amyloid with polyclonal and N-terminal-specific PrP antibodies in scrapie-affected sheep and mice.

Brains from 17 histopathologically confirmed cases of scrapie, five of which had congophilic vascular amyloid, were stained immunohistochemically for prion protein (PrP) using a polyclonal antibody. Two clinically suspect but pathologically unconfirmed cases of natural sheep scrapie and the brains of four mice infected with the 111A murine scrapie strain were also examined. Selected sections containing amyloid were stained with each of two peptide antibodies which recognise the N-terminal amino acid residues which are lost following protease digestion of the disease-specific isoform of PrP. The mice infected with the 111A murine scrapie strain had large numbers of hypermature plaques. All the amyloid plaques from both natural sheep scrapie brains and experimental murine brains were heavily immunostained by the polyclonal and both peptide antibodies. In addition, disease-specific accumulations of PrP were detected in endothelial cells or in the intima of blood vessels of the cerebral cortex of sheep scrapie brains. The affected blood vessels were located in areas which otherwise lacked typical scrapie pathology. Vascular accumulations of PrP were also found in leptomeningeal and choroid plexus blood vessels. Vascular amyloid was found mainly in the neocortex. Vascular amyloid and disease-specific parenchymal accumulations of PrP were found in two sheep which showed clinical signs of scrapie but lacked its typical vacuolar pathology. These results show that the mature amyloid of scrapie is composed of, or contains a substantial proportion of, whole length PrP protein. Thus truncation of PrP is not essential for the aggregation of PrP into amyloid. The vascular amyloid of natural sheep scrapie originates from the accumulation and release of PrP from endothelial cells presumably following systemic scrapie infection. The topography of vascular amyloid distribution in Great Britain differs from that reported in the Netherlands. As amyloid deposition in mice is largely controlled by the strain of the infecting agent it is possible that the strain of the agent may influence vascular amyloid deposition.

Amyloid↗
PubMed1998

Alterations in potassium currents may trigger neurodegeneration in murine scrapie.

Conventional electrophysiological intracellular recording techniques were used to test the hypothesis that enhanced calcium entry via voltage-gated calcium channels or the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor-channel complex may be a primary pathological mechanism triggering neurodegeneration in scrapie and related diseases. This study was carried out at a time when cell loss is known to occur and when hippocampal pyramidal cells in area CA1 are rendered hyperexcitable following scrapie infection. There was no change to the NMDA receptor-mediated component of the Schäffer collateral evoked excitatory postsynaptic potential (EPSP) or the level of spontaneous firing activity of CA1 cells following addition of the specific NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (APV, 20 microM), to the perfusate in scrapie-infected mice, indicating that the NMDA receptor-channel complex is not compromised by scrapie. There was also no change seen in the non-NMDA mediated component of the EPSP. The calcium spike of CA1 pyramidal cells was not significantly altered by scrapie infection, indicating that high threshold voltage-gated Ca2+ channel function is not compromised by scrapie. By contrast, cells from scrapie-infected mice fired calcium spikes repetitively and the long, slow AHP, which in control cells inhibited repetitive firing, was absent. Cells from scrapie-infected mice showed more depolarized membrane potentials than controls but this difference in potential was no longer observed after exposure to TEA. These data indicate a loss of TEA-insensitive and TEA-sensitive potassium conductances. We suggest that altered potassium currents rather than increased calcium entry via voltage-sensitive calcium channels or the NMDA receptor complex may be the primary pathological mechanism triggering neurodegeneration in scrapie and related diseases.

2-Amino-5-phosphonovalerate↗
PubMed1998

Synaptic plasticity in the CA1 area of the hippocampus of scrapie-infected mice.

Using conventional in vitro extracellular field potential recordings we have investigated both short- and long-term synaptic plasticity in the hippocampal CA1 area of mice infected with ME7 scrapie. In agreement with earlier studies, no changes were seen in the properties of the Schäffer collateralevoked field excitatory postsynaptic potential during the early stages of the disease (up to 160 days, post inoculation, d.p.i) after which time the recorded potentials were seen to attenuate. Also, up to this time no changes were seen in either paired-pulse facilitation or post-tetanic potentiation, which are short-term phenomena associated with brief elevations in presynaptic calcium levels. However, there was a significant shift from the ability of slices to maintain long-term potentiation (LTP) from 100 d.p.i. onwards. In all of these experiments short-term potentiation (STP) was preserved, suggesting that from the time that abnormal PrP becomes detectable, or perhaps even earlier, the mechanisms responsible for stabilizing the maintenance phase of LTP are impaired. This result is discussed in terms of the relationship between STP and LTP and how this might be compromised by the conversion of cellular prion protein (PrPC) to the scrapie, protease resistant form of PrP (PrPSc).

Animals↗
PubMed1998

Lymphadenopathy and non-suppurative meningo-encephalitis in calves experimentally infected with bovine immunodeficiency-like virus (FL112).

In an experiment on bovine immunodeficiency-like virus (BIV), the virological and serological aspects of which were reported in an earlier paper, three groups (A, B and C) of three calves were inoculated subcutaneously with a recently isolated strain (FL112). For group B and group C, the virus was suspended in milk, and for group C (controls) the viral suspension was subjected to pasteurization before inoculation. The calves were killed for necropsy 12 months later. Clinical assessment revealed subtle ataxia in two group A calves, which took the form of an intermittent "shifting" (from one leg to another) lameness, and palpable enlargement of the pre-scapular lymph nodes in one group B animal. At necropsy, haemal lymph nodes (0.1 to 0.5 cm in diameter), occurring singly, were observed in all animals. However, in groups A and B (but not C), enlarged haemal lymph nodes (< or = 2 cm in diameter) were also seen, occurring singly and in chains; and in one group A animal they occurred in grape-like clusters. In groups A and B (but not C), histopathological examination revealed generalized hyperplastic changes in lymph nodes, especially the haemal lymph nodes. This finding was particularly striking in the two clinically ataxic animals from group A, which also showed a non-suppurative meningo-encephalitis; the latter was possibly the cause of the subtle clinical signs. This study supports previous findings on lymphadenopathy resulting from experimental infection with BIV.

Animals↗
PubMed1998

Letrozole, a new oral aromatase inhibitor: randomised trial comparing 2.5 mg daily, 0.5 mg daily and aminoglutethimide in postmenopausal women with advanced breast cancer. Letrozole International Trial Group (AR/BC3).

BACKGROUND: The study compares letrozole and aminoglutethimide (AG), a standard therapy for postmenopausal women with advanced breast cancer, previously treated with antioestrogens. PATIENTS AND METHODS: 555 women were randomly assigned letrozole 2.5 mg once daily (n = 185), letrozole 0.5 mg once daily (n = 192) or aminoglutethimide 250 mg twice daily with corticosteroid support (n = 178) in an open-label, multicentre trial. The primary endpoint was objective response rate (ORR), with time events as secondary. ORR was analysed nine months after enrollment of the last patient, while survival was analysed 15 months after the last patient was enrolled. We report the results of these analyses plus an extended period of observation (covering a total duration of approximately 45 months) to determine the duration of response and clinical benefit. RESULTS: Overall objective response rates (complete + partial) of 19.5%, 16.7% and 12.4% were seen for letrozole 2.5 mg, 0.5 mg and AG respectively. Median duration of response and stable disease was longest for letrozole 2.5 mg (21 months) compared with letrozole 0.5 mg (18 months) and AG (14 months). Letrozole 2.5 mg was superior to AG in time to progression, time to treatment failure and overall survival. Treatment-related adverse events occurred in fewer patients on letrozole (33%) than on AG (46%). Transient nausea was the most frequent event with letrozole (7% on 0.5 mg, 10% on 2.5 mg, 10% on AG), rash with AG (11%, 1% on 0.5 mg, 3% on 2.5 mg letrozole). CONCLUSIONS: Letrozole 2.5 mg offers longer disease control than aminoglutethimide and letrozole 0.5 mg in the treatment of postmenopausal women with advanced breast cancer, previously treated with anti-oestrogens.

Administration, Oral↗
PubMed1997

Comparison of histology with maternal and fetal serology for the diagnosis of abortion due to bovine neosporosis.

An indirect fluorescent antibody test was applied to sera from normally calving and aborting cows and to samples of pleural fluid from their aborted calves, and the antibody titres were compared with histology and immunocytochemistry for the diagnosis of Neospora-associated abortion. Two groups of aborting cows and a third group of cows which had calved normally were used; group A consisted of 36 cows which aborted calves showing characteristic non-suppurative inflammatory lesions in which Neospora was demonstrated by immunocytochemistry, group B consisted of 100 cows which aborted calves without histological evidence of neosporosis, and group C consisted of 128 normally calved cows which were sampled within one month of calving. Serology on the maternal sera and fetal fluids was highly specific and sensitive for Neospora infection although 5 per cent of the cows which aborted Neospora-negative calves and 4.7 per cent of the normally calved cows were also seropositive. Anti-Neospora antibodies were also detected in 7 per cent of the samples of fetal fluid from Neospora-negative abortions.

Abortion, Veterinary↗
PubMed1997

Scrapie-induced neuron loss is reduced by treatment with basic fibroblast growth factor.

Neuron loss can be a prominent feature of the pathology of transmissible spongiform encephalopathies (TSEs); recent evidence indicates that this loss occurs through apoptosis. Growth factor treatment of other neurodegenerative diseases has been shown to protect neurons destined for apoptosis, and several types of experimental retinopathy have been successfully treated with basic fibroblast growth factor (bFGF). In a murine scrapie model which develops a severe loss of photoreceptors, we administered a single intravitreal injection of bFGF four-fifths of the way through the disease process; this doubled the number of photoreceptors surviving for up to 5 weeks, i.e. to the terminal stages of the disease. This is the first time that a potential late-stage therapy for the TSEs has been demonstrated.

Animals↗
PubMed1997

Results of a survey to determine whether Neospora is a significant cause of ovine abortion in England and Wales.

Between January and April 1995, the brains and hearts of 281 aborted lambs derived from 209 submissions to veterinary investigation centres in England and Wales were examined histologically. One-hundred-and-seventy-nine samples of fetal pleural fluid from these lambs and 141 from lambs not examined histologically were examined for antibodies to Neospora by an indirect fluorescent antibody test. Non-suppurative myocarditis and encephalitis were present in nine lambs. Immunocytochemistry using antisera against Neospora caninum and Sarcocystis species resulted in no labelling but anti-sera to Toxoplasma gondii revealed labelled organisms in four lambs. No significant antibody titres against Neospora were detected in any of the samples of fetal pleural fluid. These results suggest that Neospora infection is not associated with significant numbers of abortions in sheep in England and Wales.

Abortion, Veterinary↗
PubMed1997

Tubulovesicular structures are not labeled using antibodies to prion protein (PrP) with the immunogold electron microscopy techniques.

Tubulovesicular structures (TVS) are disease-specific, intraneuronal particles found by thin-section electron microscopy in all of the transmissible spongiform encephalopathies. We used immunogold (both 10 nm immunogold and 1 nm immunogold silver enhanced) methods for ultrastructural localization of prion protein (PrP). In all scrapie models examined (263 K and 22CH in hamsters and 87V and ME7 in mice), TVS-containing processes were readily detected but neither these processes nor TVS themselves were decorated with gold particles. Even when amyloid plaques were observed in a close contact with TVS-containing neuronal processes, the processes remained unstained, while the plaques were decorated with gold particles. TVS located in areas adjacent to plaques in the 87V model and in areas of diffuse PrP immunolabelling in ME7 were also unlabelled with anti-PrP sera. Using immunogold techniques we were unable to label TVS with anti-PrP antibodies. As these technique proved to be sensitive enough to immunolabel not only amyloid plaques but also pre-amyloid accumulations of PrP, we strongly believe that the absence of staining reflects the structure of TVS and that they are not composed of PrP. That TVS are PrP negative may have several important implications for hypotheses about their nature. Principally, it does not support the suggestion that TVS are cross-sections of "thick tubules" visualized by touch-preparations of scrapie-affected mouse and hamster brains. If PrP is the infectious agent, as suggested by the prion hypothesis, the absence of stainable PrP in TVS would indicate that these are not the ultrastructural correlate of the agent. If however, TVS turn out to be more than merely a useful ultrastructural marker for the whole group of transmissible spongiform encephalopathies, it may suggest that PrP and the agent are two separate entities.

Animals↗
PubMed1997

Influence of supplementing corn-soybean meal diets with vitamin E on performance and selected physiological traits of male turkeys.

Three experiments were conducted to determine the effects of supplementing practical diets of male turkeys with dl-alpha-tocopheryl acetate (TA). In Experiment 1, a factorial arrangement of dietary treatments [0, 12, 50, 150, and 300 IU TA/kg with 0 or 300 mg ascorbic acid (AA)/kg] was used. These 10 treatments were fed to poults from 1 to 41 d of age. From 41 to 118 d of age, the AA treatments were discontinued, and the 300 IU TA treatment groups were changed to 12 IU TA/kg. Neither TA nor AA treatments affected 41-d BW, feed to gain ratio (FE), or livability. No effects of dietary TA concentrations on turkey performance were observed through 118 d of age alpha-Tocopherol (TOC) concentrations of plasmas and livers were increased by increments of dietary TA, with substantial liver storage when toms were fed 150 IU TA/kg from 1 to 118 d. Supplementing diets with 0, 25, 50, 75, or 100 IU TA/ kg in Experiments 2 and 3 had no effect on performance of toms through 119 and 105 d, respectively. alpha-Tocopherol concentrations of plasma and red blood cells (RBC) increased linearly with increments of dietary TA. The same was true for livers in Experiment 2. Susceptibility of RBC to hemolysis induced by 400 microM t-butyl hydroperoxide (TBH) in Experiment 2 decreased with increasing dietary TA, and these decreases corresponded to increases in TOC concentration of RBC. However, the relationships between hemolysis and dietary TA or RBC TOC were inconsistent in Experiment 3 and varied according to concentration of TBH (200, 300, or 400 microM) and age of the toms. At 105 d of age, RBC of toms fed no supplemental TA were resistant to hemolysis, irrespective of dietary TA and TBH concentration. In Experiment 3, there were no indications of dietary TA effects on plasma peroxide concentration or activity of plasma creatine kinase. A positive relationship between dietary TA and blastogenic responses of blood lymphocytes was observed with concanavalin A when toms were at 44 d but not at 23 or 86 d of age. The overall data indicate that corn-soybean meal diets containing from 6 to 20 IU TOC/kg, but no supplemental TA supported satisfactory performance and well-being of male turkeys from 1 d of age to market ages when the turkeys were free of disease, as was true in the research reported here.

Aging↗
PubMed1997

Immunodetection of PrPSc in spleens of some scrapie-infected sheep but not BSE-infected cows.

The development of diagnostic tools for transmissible spongiform encephalopathies (TSEs) would greatly assist their study and may provide assistance in controlling the disease. The detection of an abnormal form of the host protein PrP in noncentral nervous system tissues may form the basis for diagnosis of TSEs. Using a new antibody reagent to PrP produced in chickens, PrP can be readily detected in crude tissue extracts. PrP from uninfected spleen had a lower molecular mass range than PrP from brain, suggesting a lower degree of glycosylation. A simple method for detecting the abnormal form of the protein, PrPSc, in ruminant brain and spleen has been developed. PrPSc was detected in sheep spleen extracts from a flock affected by natural scrapie and was also found in spleens from some, but not all, experimental TSE cases. In spleens from cattle with bovine spongiform encephalopathy (BSE) no PrPSc was detected. It is therefore suggested that there is differential targeting of PrPSc deposition between organs in these different types of TSE infection which, with other factors, depends on strain of infecting agent.

Animals↗