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PubMed2003

Going for the green. As higher premiums and stable medical costs fuel health plans' profits, providers say time is right to win bigger reimbursement.

Thanks to higher premiums and a slowing of medical cost growth, the second quarter brought soaring profits at health plans across the nation. Hospitals plan to escalate their push for higher reimbursement while the iron is hot. Yet Oxford Health Plans President and CEO Charles Berg, left, says big profits don't paint the whole picture.

Data Collection↗
PubMed2003

Big physics, small doses: the use of AMS and PET in human microdosing of development drugs.

The process of early clinical drug development has changed little over the past 20 years despite an up to 40% failure rate associated with inappropriate drug metabolism and pharmacokinetics of candidate molecules. A new method of obtaining human metabolism data known as microdosing has been developed which will permit smarter candidate selection by taking investigational drugs into humans earlier. Microdosing depends on the availability of two ultrasensitive 'big-physics' techniques: positron emission tomography (PET) can provide pharmacodynamic information, whereas accelerator mass spectrometry (AMS) provides pharmacokinetic information. Microdosing allows safer human studies as well as reducing the use of animals in preclinical toxicology.

Animals↗
PubMed2006

Successful management of critical limb ischemia with intravenous sodium thiosulfate in a chronic hemodialysis patient.

Vascular calcification is common among hemodialysis (HD) patients and contributes to the development of peripheral arterial disease. A 57-year-old Japanese man who had been on HD for 30 years was referred to us for severe pain with multiple ulcers on his toes and fingers. He was an ex-smoker and had no diabetes mellitus. On admission, he had ulcers on his big toes bilaterally and right 2nd - 4th fingers. Peripheral pulses were strong and his ankle-brachial pressure index was above 1.3. Laboratory data were as follows: calcium 9.9 mg/dl, albumin 3.3 g/dl, phosphate 3.0 mg/dl, Ca x P product 30, and parathyroid hormone 98 pg/ml. He had a parathyroidectomy in 1998 and 1999. X-rays of his hands and legs showed diffuse subcutaneous arteriolar calcification. Angiography revealed no local stenotic lesions. Despite intensive therapies including hyperbaric oxygen therapy, painful gangrene developed on his right big toe and the pain was so intense that he could not go to sleep in a supine position. We infused intravenous sodium thiosulfate (20 g) 3 times weekly, based on previous reports. Within 4 - 5 days, he experienced rapid and dramatic symptom relief. The score of the visual analogue pain scale improved from 10/10 - 2/10. The signs of ischemia, measured by transcutaneous partial oxygen pressure and thermography, improved significantly. During the infusion of sodium thiosulfate, the patient complained of nausea, vomiting and hyperosmia. These adverse symptoms were resolved after discontinuation of the infusion. Pain relief was sustained and he could walk after 2 weeks of infusion. Our case supports the use of sodium thiosulfate as a novel therapeutic choice for critical limb ischemia with severe vascular calcification in chronic HD patients.

Calcinosis↗
PubMed2000

The new phylogeny of eukaryotes.

Molecular phylogeny has been regarded as the ultimate tool for the reconstruction of relationships among eukaryotes-especially the different protist groups-given the difficulty in interpreting morphological data from an evolutionary point of view. In fact, the use of ribosomal RNA as a marker has provided the first well resolved eukaryotic phylogenies, leading to several important evolutionary hypotheses. The most significant is that several early-emerging, amitochondriate lineages, are living relics from the early times of eukaryotic evolution. The use of alternative protein markers and the recognition of several molecular phylogeny reconstruction artefacts, however, have strongly challenged these ideas. The putative early emerging lineages have been demonstrated as late-emerging ones, artefactually misplaced to the base of the tree. The present state of eukaryotic evolution is best described by a multifurcation, in agreement with the 'big bang' hypothesis that assumes a rapid diversification of the major eukaryotic phyla. For further resolution, the analysis of genomic data through improved phylogenetic methods will be required.

Animals↗
PubMed1992

Release of endothelin in the oleic acid-induced respiratory distress syndrome in rats.

Rats injected intravenously with oleic acid developed pulmonary edema leading to hypoxia and hypercarbia. These changes were accompanied by an increase in immunoreactive endothelin (ir-ET) in plasma as early as 15 min after injection. At 45 min after injection plasma levels peaked at 114 +/- 19 pg/ml plasma (n = 8) and reached basal levels again after 240 min. In contrast, much larger amounts of ir-ET were found in the bronchoalveolar lavage fluid, with a peak at 120 min (2878 +/- 258 pg/lung, n = 7) preceding the maximum hypoxia observed at 180 min. In both plasma and bronchoalveolar lavage fluid samples ir-ET was characterized by reverse-phase HPLC as a mixture consisting mainly of ET-1 and smaller amounts of big ET-1, ET-2 and ET-3. In light of the biological effects of ET, the data suggest that these peptides might be of pathophysiological significance in this model of adult respiratory distress syndrome.

Animals↗
PubMed2003

Dispersion of odour: a case study with a municipal solid waste landfill site in North London, United Kingdom.

Municipal solid waste (MSW) landfills are a potential source of offensive odours that can create annoyance within communities. Dispersion modelling was used to quantify the potential odour strength causing an impact on the community around a particular MSW landfill site north of the London area in the United Kingdom. The case studies were completed with the short-term mode of COMPLEX-I, software developed by the US-EPA. The year 1998 was chosen as a source of baseline data. It was observed that by 2004, when the landfill will progress towards the west and a big band of the area towards the north would be partly/fully restored, the maximum contribution of the new sources giving higher odour concentrations would be in the southwesterly regions away from the landfill. Concentrations as high as 25.0 ou(E)/m(3) were observed with 3 min averaging time in the southwesterly areas as compared to concentrations of 20.0 ou(E)/m(3) at 10 min averaging times. However, the percentage frequency of such critical events occurring would be low. All other surrounding farms and small villages would be exposed to the concentration of 3.0 ou(E)/m(3) on certain occasions. In the year 2008, the majority of the filling fronts would be filled with wastes with no contributions from the active and operational cells. The maximum odour concentration around the landfill site for 1 h averaging time would be approximately 3 ou(E)/m(3) about 1.0 km north and 500 m west of the landfill site. For 3 min averaging time, the stretch of 5 ou(E)/m(3) band would be up to 2.5 km towards the north of the landfill site. It is argued that further analysis of the model calculations considering effects of wind direction, frequency of wind direction, stability of the atmosphere, selected odour threshold, integration time of the model, etc. would form a basis for calculating the separation distances of the landfill site from the surrounding community.

Air Movements↗
PubMed2003

Relationships between personality structure, structure of word meaning, and cognitive ability: a study of cultural mechanisms of personality.

Native-born Estonian men (N=912), 17-68 years old, participated in a study on relationships between personality characteristics, dominant structure of word meaning ("everyday concepts" thinking or "scientific concepts" thinking), and level of cognitive ability. Individuals who primarily used everyday concepts thinking or who possessed relatively low levels of cognitive ability did not reveal a coherent Big Five personality structure, whereas individuals who primarily used scientific concepts thinking or possessed high levels of cognitive ability did. Thus, personality may be shaped by a cultural factor--word meaning structure. Earlier studies, which seem to support the idea that Big Five personality structure is a biologically determined human universal, suffer from serious sampling problems and insufficient data analyses.

Adolescent↗
PubMed1995

Identification of two classes of prolactin-releasing factors in intermediate lobe tumors from transgenic mice.

Targeted tumorigenesis, using the POMC gene promoter ligated to the simian virus 40 large T antigen, generated transgenic mice with massive tumors of the intermediate lobe (IL) of the pituitary. Inoculation of nude mice with the IL tumor cells resulted in very large secondary tumors. As the IL from several species produces a potent PRL-releasing factor (PRF), it was of interest to determine whether IL tumors from these mice also contain PRF. The objectives were to 1) measure serum PRL levels in mice with IL tumors, 2) determine whether these tumors contain PRF and examine its chromatographic properties, and 3) analyze whether this PRF is related to POMC, its derivatives, or other PRL secretagogues. Serum PRL levels were 5- to 6-fold higher in transgenic than in control mice. Primary and secondary IL tumors were acid extracted and successively fractionated using Sephadex G-100 gel filtration and reverse phase and gel permeation HPLC. PRF activity was determined using short term incubation of tissue extracts or column fractions with GH3 cells. Crude tumor extracts exhibited a strong and dose-dependent PRF activity. Upon chromatography, the PRF activity from either primary or secondary tumors resolved into two classes of compounds: a big PRF with an estimated mol wt of 70-80 kilodaltons and two small, very hydrophobic peptides. The elution profiles of the three PRFs differed from those of beta-endorphin, alpha MSH, beta MSH, ACTH, TRH, oxytocin, angiotensin II, vasoactive intestinal polypeptide, or corticotropin-like intermediate peptide. In summary, we have identified an animal model with IL tumors that has hyperprolactinemia and overproduces PRF. Two classes of PRFs, big and small, were resolved which differ from POMC derivatives and known regulators of PRL release. These data suggest that PRF is produced by melanotrophs, but is not a product of the POMC gene. The IL tumors should provide an excellent source for the purification and structural elucidation of PRFs.

Animals↗
PubMed2004

Individual differences in the temporal variability of medically unexplained symptom reporting.

THEORY: Non-specific or medically unexplained symptoms account for up to 35% of outpatient referrals. In contrast to the literature on affect, little is known about how people frame daily symptoms and how these patterns are influenced by individual differences. METHOD: Three fixed occasion diary studies over an 8-day period (one on ill veterans of the Gulf War and two on healthy undergraduates) and a single cross-sectional survey (on ill Gulf War veterans) were conducted. The severity and frequency of daily symptoms were assessed in all daily diary samples, together with the Big 5 personality domains in one of the undergraduate samples and in the survey of veterans. The data were analysed using auto-correlations and hierarchical multivariate linear modelling. RESULTS: In all the chronically ill and healthy samples, the data suggested potential cyclical patterns for symptom severity reporting. With regard to the frequency of symptom reporting, the veterans showed a pattern of constant symptom reporting. Finally, the relationship between the reported severity of symptoms was attenuated by intellect and surgency. DISCUSSION: There is evidence that daily experiences of symptom severity are framed relative to each other and this relationship is influenced by personality. The practical implications of these findings are discussed.

Adult↗
PubMed2001

Plasma endothelin-1 and big endothelin-1 levels in superior and inferior vena cava during protracted antiorthostatic hypokinetic/hypodynamia in rats.

The plasma levels of endothelin-1 and big endothelin-1 were evaluated in blood of rats in the superior and inferior vena cava, in normal posture (synchronous controls), and after 12 days head-down suspension and 1 day recovery in normal posture. In synchronous controls, the mean plasma concentration of endothelin-1 in inferior vena cava or superior vena cava was almost the same (5.89+/-0.63 pmol/l and 5.67+/-0.64 pmol/l, respectively), whereas the mean plasma concentration of big endothelin-1 was higher (p<0.05) in superior vena cava compared to inferior vena cava (5.49+/-0.75 pmol/l and 1.39+/-0.15 pmol/l, respectively). In samples from superior vena cava of head-down suspended rats big endothelin-1 levels were significantly lower (p<0.05) up to day 9 of suspension, compared to non-suspended synchronous controls, whereas endothelin-1 values were higher (p<0.05). Big endothelin-1 concentration was higher (p<0.05) in inferior vena cava compared to non-suspended synchronous controls. The behaviour of endothelin-1 was more complex, endothelin-1 levels were lower (p<0.05) on day 1 of head-down suspension and higher (p<0.05) in samples taken on days 9 and 12. After 1 day recovery endothelin-1 and big endothelin-1 concentrations returned to normal in both superior vena cava and inferior vena cava. These data indicate that the endothelial system involvement for the two venous beds is different and suggest that local rather than systemic evaluation could better explain endothelial involvement and the contribution of different anatomic sites to the biosynthesis, conversion and clearance of the various involved molecules.

Animals↗
PubMedDate not supplied

The malarial impact on the nutritional status of Amazonian adult subjects.

The anthropometric (body weight, height, upper arm circumference, triceps and subescapular skinfolds; Quetelet index and arm muscle circumference) and blood biochemistry (proteins and lipids) parameters were evaluated in 93 males and 27 females, 17-72 years old voluntaries living in the malarial endemic area of Humaita city (southwest Amazon). According to their malarial history they were assembled in four different groups: G1--controls without malarial history (n:30); G2--controls with malarial history but without actual manifestation of the disease (n:40); G3--patients with Plasmodium vivax (n:19) and G4--patients with Plasmodium falciparum (n:31). The malarial status was stablished by clinical and laboratory findings. The overall data of anthropometry and blood biochemistry discriminated the groups differently. The anthropometric data were low sensitive and contrasted only the two extremes (G1 > G4) whereas the biochemistry differentiated two big groups, the healthy (G1 + G2) and the patients (G3 + G4). The nutritional status of the P. falciparum patients was highly depressed for most of the studied indices but none was sensitive enough to differentiate this group from the P. vivax group (G3). On the other hand the two healthy groups could be differentiated through the levels of ceruloplasmin (G1 < G2) and alpha nitrogen (G1 > G2). Thus it seems that the malaria-malnourishment state exists and the results could be framed either as a consequence of nutrient sink and/or the infection stress both motivated by the parasite.

Adolescent↗