Mobile Stroke Unit Reduces Time to Image Acquisition and Reporting.

Timely administration of thrombolytic therapy is critical to maximizing the likelihood of favorable outcomes in patients with acute ischemic stroke. Although emergency medical service activation overall improves the timeliness of acute stroke treatment, the time from emergency medical service dispatch to hospital arrival unavoidably decreases the timeliness of thrombolytic administration. Our mobile stroke unit, a new-generation ambulance with on-board CT scanning capability, reduces key imaging time metrics and facilitates in-the-field delivery of IV thrombolytic therapy.

Acquisition of dwarf male "harems" by recently settled females of Osedax roseus n. sp. (Siboglinidae; Annelida).

After the deployment of several whale carcasses in Monterey Bay, California, a time-series analysis revealed the presence of a new species of Osedax, a genus of bone-eating siboglinid annelids. That species is described here as Osedax roseus n. sp. It is the fifth species described since the erection of this genus and, like its congeners, uses a ramifying network of "roots" to house symbiotic bacteria. In less than 2 months, Osedax roseus n. sp. colonized the exposed bones of a whale carcass deposited at 1018-m depth, and many of the females were fecund in about 3 months post-deployment. As with other Osedax spp., the females have dwarf males in their tube lumens. The males accrue over time until the sex ratio is markedly male-biased. This pattern of initial female settlement followed by gradual male accumulation is consistent with the hypothesis that male sex may be environmentally determined in Osedax. Of the previously described species in this genus, Osedax roseus n. sp. is most similar to O. rubiplumus, but it has several anatomical differences, as well as much smaller females, dwarf males, and eggs. Osedax roseus n. sp. is markedly divergent (minimally 16.6%) for mitochondrial cytochrome oxidase subunit I (mtCOI) sequences from any other Osedax species.

N-glucuronidation of the platelet-derived growth factor receptor tyrosine kinase inhibitor 6,7-(dimethoxy-2,4-dihydroindeno[1,2-C]pyrazol-3-yl)-(3-fluoro-phenyl)-amine by human UDP-glucuronosyltransferases.

The potential cancer therapeutic agent, 6,7-(dimethoxy-2, 4-dihydroindeno[1,2-c]pyrazol-3-yl)-(3-fluoro-phenyl)-amine (JNJ-10198409), formed three N-glucuronides that were positively identified by liquid chromatography-tandem mass spectrometry and NMR as N-amine-glucuronide (Glu-A), 1-N-pyrazole-glucuronide (Glu-B), and 2-N-pyrazole-glucuronide (Glu-C). All three N-glucuronides were detected in rat liver microsomes, whereas only Glu-A and -B were found in monkey and human liver microsomes. In contrast to common glucuronides, Glu-B was completely resistant to beta-glucuronidase. Kinetic analyses revealed that glucuronidation of JNJ-10198409 in human liver microsomes exhibited atypical kinetics that may be described by a two-site binding model. For the high affinity binding, K(m) values were 1.2 and 5.0 microM, and V(max) values were 2002 and 2,403 nmol min(-1) mg(-1) for Glu-A and Glu-B, respectively. Kinetic constants of low affinity binding were not determined due to low solubility of the drug. Among the human UDP-glucuronosyltransferases (UGTs) tested, UGT1A9, 1A8, 1A7, and 1A4 were the most active isozymes to produce Glu-A; for the formation of Glu-B, UGT1A9 was the most active enzyme, followed by UGT1A3, 1A7, and 1A4. Glucuronidation of JNJ-10198409 by those UGT1A enzymes followed classic Michaelis-Menten kinetics. In contrast, no glucuronides were formed by all UGT2B isozymes tested, including UGT2B4, 2B7, 2B15, and 2B17. Collectively, these results suggested that glucuronidation of JNJ-10198409 in human liver microsomes is catalyzed by multiple UGT1A enzymes. Since UGT1A enzymes are widely expressed in various tissues, it is anticipated that both hepatic and extrahepatic glucuronidation will likely contribute to the elimination of the drug in humans. Additionally, conjugation at the nitrogens of the pyrazole ring represents a new structural moiety for UGT1A-mediated reactions.

Metabolism and excretion of the antiepileptic/antimigraine drug, Topiramate in animals and humans.

The metabolism and excretion of 2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate (TOPAMAX, topiramate, TPM) have been investigated in animals and humans. Radiolabeled [14C] TPM was orally administered to mice, rats, rabbits, dogs and humans. Plasma, urine and fecal samples were collected and analyzed. TPM and a total of 12 metabolites were isolated and identified in these samples. Metabolites were formed by hydroxylation at the 7- or 8-methyl of an isopropylidene of TPM followed by rearrangement, hydroxylation at the 10-methyl of the other isopropylidene, hydrolysis at the 2,3-O-isopropylidene, hydrolysis at the 4,5-O-isopropylidene, cleavage at the sulfamate group, glucuronide conjugation and sulfate conjugation. A large percentage of unchanged TPM was recovered in animal and human urine. The most dominant metabolite of TPM in mice, male rats, rabbits and dogs appeared to be formed by the hydrolysis of the 2,3-O-isopropylidene group.

Outcomes of newly referred neurology outpatients with depression and pain.

BACKGROUND: Although depression and pain are common in neurology outpatients, patient factors influencing chronicity are poorly understood. The authors sought to determine the predictors of persistent depression and pain symptoms at 3 and 12 months after an initial outpatient neurology clinic visit. METHODS: Consecutive new patients (n = 483) at three clinics completed the Patient Health Questionnaire nine-item depression scale and the Brief Pain Inventory at baseline and at 3- and 12-month follow-up. Multivariate analysis was used to model 3- and 12-month depression and pain severity. RESULTS: The prevalence of depression and pain at baseline/3/12 months was depression 33%/28%/27% and pain 66%/61%/62%. Independent predictors of depression severity at follow-up were more severe depression and pain at baseline and less improvement in pain (model r(2) = 0.53 to 0.56). Independent predictors of pain intensity at follow-up were more severe pain and depression at baseline and less improvement in depression (model r(2) = 0.44 to 0.46). Health care utilization and impairments in health status were greatest in patients with coexisting depression and pain and least in those with neither depression nor pain. CONCLUSIONS: Depression and pain symptoms in neurology outpatients often persist for at least 12 months and have long-term negative effects on patients' health status. Pain is more likely to persist in patients with depression, and depression is more likely to persist in those with coexistent pain.

Prevalence and impact of depression and pain in neurology outpatients.

BACKGROUND: We examined the prevalence and health related quality of life (HRQoL) of depression and/or pain in neurology outpatients. METHODS: Patients at outpatient clinics completed depression, pain, and HRQoL scales. Group comparisons between those with pain alone, depression alone, both conditions, and neither condition were done. RESULTS: Overall, pain was present in 2/3 and depression in 1/3 of patients. Pain with depression was present in 25%; 75% of depressed patients had pain. These conditions had significant negative impact on mental and physical health status scores. The odds ratio (OR) for having pain was significantly increased in women (OR 2.0), those with depression (OR 2.4), and those with neuropathy/neuromuscular (OR 3.8) or pain syndromes (OR 4.8). The odds of having depression were increased in those with pain (OR 2.4) and with cognitive (OR 4.8) or cerebrovascular (OR 3.3) diagnoses. Neurologists were more likely to recognise and treat pain than depression. CONCLUSIONS: Depression and pain are common in newly referred neurology outpatients and have substantial negative effects on patients' physical and mental health. Pain is more likely than depression to be recognised and treated by neurologists.

Analyses of nuclear ldhA gene and mtDNA control region sequences of Atlantic northern bluefin tuna populations.

There has been considerable debate about whether the Atlantic northern bluefin tuna exist as a single panmictic unit. We have addressed this issue by examining both mitochondrial DNA control region nucleotide sequences and nuclear gene ldhA allele frequencies in replicate size or year class samples of northern bluefin tuna from the Mediterranean Sea and the northwestern Atlantic Ocean. Pairwise comparisons of multiple year class samples from the 2 regions provided no evidence for population subdivision. Similarly, analyses of molecular variance of both mitochondrial and ldhA data revealed no significant differences among or between samples from the 2 regions. These results demonstrate the importance of analyzing multiple year classes and large sample sizes to obtain accurate estimates when using allele frequencies to characterize a population. It is important to note that the absence of genetic evidence for population substructure does not unilaterally constitute evidence of a single panmictic population, as genetic differentiation can be prevented by large population sizes and by migration.

Genetics: year zero.

Ignorance, denial, and physician centric health care have prevented health systems from adopting new genetics technology into their practices.

PCR primers for an aldolase-B intron in acanthopterygian fishes.

BACKGROUND: Nuclear DNA sequences provide genetic information that complements studies using mitochondrial DNA. Some 'universal' primer sets have been developed that target introns within protein-coding loci, but many simultaneously amplify introns from paralogous loci. Refining existing primer sets to target a single locus could circumvent this problem. RESULTS: Aldolase intron 'G' was amplified from four fish species using previously described primer sets that target several loci indiscriminately. Phylogenetic analyses were used to group these fragments and other full-length aldolase proteins from teleost fishes into orthologous clades and a primer set was designed to target specifically an intron within the aldolase-B locus in acanthopterygian fishes. DNA amplifications were tried in a variety of acanthopterygian fishes and amplification products, identifiable as aldolase-B intron 'G', were observed in all atherinomorph and percomorph taxa examined. Sequence variation within this locus was found within and among several species examined. CONCLUSIONS: Using 'universal' primer sets coupled with phylogenetic analyses it was possible to develop a genetic assay to target a specific locus in a variety of fish taxa. Sequence variation was observed within and among species suggesting that this targeted assay might facilitate interspecific and intraspecific comparisons.

Validating the Questionnaire for Verifying Stroke-Free Status (QVSFS) by neurological history and examination.

BACKGROUND AND PURPOSE: The Questionnaire for Verifying Stroke-Free Status (QVSFS) is an 8-item structured interview designed to identify stroke-free individuals. Previously, the QVSFS was validated with medical record review in a cohort with a low prevalence (7.1%) of stroke or transient ischemic attack (TIA). The objective of this study was to evaluate the validity of the QVSFS by comparing it with stroke status as determined by neurological history and examination in a population with a higher prevalence of stroke. METHODS: A research assistant administered the QVSFS to outpatients from Veterans Administration stroke and general medicine clinics. Subjects were defined as QVSFS negative if responses to all 8 questions were negative. Questions requiring rephrasing or clarification were noted. Neurologists, blinded to QVSFS scores, interviewed and examined all subjects to determine stroke-free status, defined as no history or examination findings of previous stroke and/or TIA. RESULTS: One hundred fifty-five subjects were examined; mean age was 70 years; 98.1% were male. Seventy-eight subjects were determined to be stroke free by the neurologist. The negative predictive value of the QVSFS was 0.96, with positive predictive value of 0.71. No question required rephrasing or clarification >5 times. Twenty-two subjects (14.2%) required rephrasing or clarification of at least 1 question. CONCLUSIONS: The QVSFS can effectively identify stroke-free individuals with a high degree of accuracy, even in a population with a large proportion of patients with prior stroke or TIA. Accuracy for identifying subjects with stroke and/or TIA is lower, but the QVSFS may still be useful as a screening tool in that regard.

Metabolism of the analgesic drug, tramadol hydrochloride, in rat and dog.

1. Metabolism of the analgesic agent, tramadol hydrochloride, was investigated after a single oral administration of 14C-tramadol to four rats (50)mgkg(-1) and two dogs (20)mg kg(-1). 2. Recovery of total radioactivity in rat and dog urine samples over 24 h was 73 and 65% of the radioactive dose, respectively. 3. Unchanged tramadol and a total of 24 metabolites, consisting of 16 Phase I metabolites and eight conjugates (seven glucuromides, one sulphate), were isolated and tentatively identified, which accounted for > 52% of the dose in urine of both species. 4. Of the metabolites, five (M1-5) were previously identified. 5. The metabolites were formed via the following six metabolic pathways: O-demethylation, N-demethylation, cyclohexyl oxidation, oxidative N-dealkylation, dehydration and conjugation. 6. Pathways 1-3 appear to be major steps, forming seven O-desmethyl/N-desmethyl and hydroxy-cyclohexyl metabolites in major quantities. 7. Pathways 1-3 in conjunction with pathway 6 produced four glucuronides along with four minor conjugates. 8. In addition, the in vitro metabolism of tramadol was conducted using rat hepatic S9 fraction in the presence of an NADPH-generating system. Unchanged tramadol (30% of the sample) plus nine metabolites, M1-7, tramadol-N-oxide (M31) and OH-cyclohexyl-M1 (M32), were profiled and tentatively identified based on MS and MS/MS data.

Host plant effects on activity of the mitosporic fungi Beauveria bassiana and Paecilomyces fumosoroseus against two populations of Bemisia whiteflies (Homoptera: Aleyrodidae).

Laboratory bioassays were conducted to determine the effect of host plant on mycosis in two geographically distinct populations of early 2nd-instar nymphs of Bemisia argentifolii Bellows & Perring from the entomopathogenic fungi Beauveria bassiana (Balsamo) Vuillemin and Paecilomyces fumosoroseus (Wize) Brown & Smith. Mycosis in B. argentifolii nymphs varied according to the host plant on which the nymphs were reared but not according to the population. Both populations of whiteflies reared on cotton were consistently significantly less susceptible to infection by either fungus than when reared on melon. We hypothesized that the cotton plant produced a fungal inhibitor that may confer protection on whiteflies feeding (and possibly sequestering) upon it. Germination of conidia of both fungi was strongly inhibited (below 12% germination) on the cuticle of nymphs reared on cotton but was over 95% on the cuticle of nymphs reared on melon. We further hypothesized that the terpenoid gossypol, produced by many cultivars of cotton, might have been involved in antibiosis. Gossypol mixed with Noble agar at five concentrations was tested for its effects on germination of conidia of both fungi. P. fumosoroseus was highly tolerant of gossypol, even at the relatively high concentration of 1000 ppm, while B. bassiana tolerated gossypol at concentrations up to 500 ppm and strong inhibition only occurred in presence of gossypol at 1000 ppm. Our in vivo findings on cotton and on the insect's cuticle pointed at a potential host plant-mediated antibiosis. The in vitro tolerance of P. fumosoroseus and partial tolerance of B. bassiana to gossypol disagreed with our in vivo data. Gossypol concentrations higher than 1000 ppm might have increased the sensitivity of the fungi in our in vitro tests. Sequestered gossypol (and/or other cotton plant allelochemicals) by B. argentifolii nymphs would explain, at least partially, the insect's defense against the pathogens.

Gene-gene concordance and the phylogenetic relationships among rare and widespread pygmy sunfishes (genus Elassoma).

Pygmy sunfishes (Elassoma) are primarily lowland species with an interesting biogeographic dichotomy: three species have broad geographic distributions, and three are narrowly distributed (and have been recommended for threatened or endangered status). To test phylogenetic predictions derived from the geographic distributions of pygmy sunfishes and possible historical factors contributing to the threatened/endangered status of the rare species, we reconstructed trees for two mitochondrial genes and introns of three nuclear genes. The pattern and rate of nuclear and mitochondrial sequence evolution were heterogeneous within Elassoma, but relationships were generally concordant across gene trees. Elassoma is monophyletic and, as predicted by geographic distributions, E. evergladei, E. okefenokee, and E. zonatum consistently branch from deeper nodes. Phylogeographic structure in mitochondrial and nuclear genes also supports an early origin of E. zonatum. Phylogenetic analyses of the five loci support widely divergent positions for the rare species E. alabamae. Two rare species, E. boehlkei and E. okatie, are sister taxa and are related to a widespread species, E. evergladei.

Hydrogen concentrations in sulfate-reducing estuarine sediments during PCE dehalogenation.

Despite recent progress made evaluating the role of hydrogen (H2) as a key electron donor in the anaerobic remediation of chloroethenes, few studies have focused on the evaluation of hydrogen thresholds relative to reductive dehalogenation in sulfidogenic environments. Competition for hydrogen exists among microbial populations in anaerobic sediments, and direct evidence indicates that lower hydrogen thresholds are observed with more energetically favorable electron-accepting processes. This study examined aqueous hydrogen concentrations associated with sulfate reduction and perchloroethylene (PCE) dehalogenation in anoxic estuarine sediment slurry microcosms and evaluated the competition for H2-reducing equivalents within these systems. After an initial lag period of 13 days, PCE was reductively transformed to trichloroethylene (TCE). During the time of continuous PCE dehalogenation, a significantly (P < 0.05) lower hydrogen concentration (0.5 nM) was observed in the sediment slurries amended with PCE as compared to slurries without PCE (0.8 nM). Sulfate reduction to sulfide was observed in all sediment slurries, but in microcosms actively dechlorinating PCE, the amount of reducing equivalents directed to sulfate reduction was approximately half the amount in sediment slurries without PCE. These findings provide evidence that a lower hydrogen threshold exists in anoxic estuarine sediment slurries with PCE as a terminal electron acceptor as compared to sediment slurries in which sulfate reduction was the predominant electron-accepting process. Furthermore, our results utilizing the inhibitor molybdate indicated that H2-utilizing methanogens may have the potential to effectively compete with dechlorinators for hydrogen when sulfate reduction is initially inhibited.

Softgels: consumer perceptions and market impact relative to other oral dosage forms.

Softgels, which contain a liquid formulation of a drug, often provide clinical benefit over other solid oral dosage forms and may represent an attractive alternative to them. A consumer preference survey of softgels versus other solid forms investigated four areas: (1) identification of various dosage forms; (2) perception of therapeutic benefit (easiest to swallow, faster-acting, work longer); (3) impact of individual product characteristics on overall product selection; and (4) market impact in terms of premiums consumers would pay on the basis of dosage form. The 300 survey participants strongly preferred clear softgels over other dosage forms in virtually every area. Softgels were perceived as easy to swallow and fast-acting, with a duration of action second only to that of a two-piece capsule. Overall preference was driven by ease of swallowing, and softgels were rated first by the majority of respondents. Consumers would be interested in various products if these were available as softgels rather than in their current oral dosage forms and may be willing to pay a premium for softgel products. This survey confirms consumer preferences for particular dosage forms and for softgels over other solid forms. Pharmaceutical scientists and marketers should consider softgels as alternative dosage forms when developing new compounds or considering life-cycle management of existing products.

Public and private perspectives on hospital conversions: proposed MUSC-Columbia/HCA "partnership".

Conversion has been defined as "any type of transaction that results in the shift of all or a substantial portion of the assets of nonprofit health care organizations to for-profit use" (Claxton and Colleagues, 1997:10-11). Not surprisingly, efforts at such conversion create political conflict and opposition within communities with some groups supporting and others opposing the intended conversion. This study looks at a particular effort at conversion: the proposed "partnership" between three hospitals of the Medical University of South Carolina (MUSC) and Columbia/HCA, the largest for-profit health services network in the U.S. Beginning in 1995, the three-year effort (now at an impasse) has drawn local and state policy-markers into increasing controversy and acrimony. Beyond the details, the episode also raises fundamental issues about the nature of public health care and the extent to which we can convert public health facilities to private control while preserving their essential public missions.