Intraocular adenosine levels in normal and ocular-hypertensive patients.

PURPOSE: Adenosine receptors modulate several ocular responses; however, our understanding of factors that influence ocular extracellular adenosine levels is limited. The objective of this study was to evaluate how changes in intraocular pressure (IOP) influence endogenous levels of the purines adenosine and inosine, in the aqueous humor of normal and ocular-hypertensive patients. PATIENTS AND METHODS: Informed consent was obtained from 51 individuals undergoing cataract extraction or glaucoma surgical procedures. IOP was measured immediately prior to surgery. At the start of the surgical procedure, an aqueous sample of 75-100 microL was obtained. Purine levels were determined by reverse-phase HPLC. RESULTS: In normotensive individuals, mean aqueous adenosine and inosine levels were 5.2 +/- 1.1 and 19.4 +/- 2.2 ng/100 microL, respectively. No significant correlation between IOP and purine concentration was measured in this group. In ocular hypertensive individuals, the mean aqueous adenosine and inosine concentration was significantly elevated when compared to normotensive individuals. In the ocular hypertensive individual, this elevation in adenosine level was significantly correlated with IOP (r(2) = 0.42). CONCLUSIONS: These results demonstrate that in ocular hypertensive individuals, aqueous adenosine concentration is correlated with IOP. As the activation of adenosine receptors can modulate IOP and retinal blood flow, adenosine release during periods of ocular hypertension may play an important role in the physiological responses to elevated IOP.     

Fungal infections of the bones and joints

Osteoarticular complications may occur with a variety of invasive fungal infections, and seem to be increasing with growing use of prosthetic joints and as the immunosuppressed patient population increases. Epidemiology, pathogenesis, presentation, and management strategies differ somewhat among the different fungal species. This review focuses on recent developments in diagnostic and management approaches for patients with osteoarticular mycoses, and outlines specific treatment strategies for the different species.     

Are there any successful men from criminogenic backgrounds?

In the Cambridge Study in Delinquent Development, a prospective longitudinal survey of 411 London males, a vulnerable group of 63 boys from criminogenic backgrounds was defined on the basis of the best nonbehavioral predictors of delinquency at age 8-10 (low family income, large family size, convicted parents, low intelligence, and poor parental child-rearing behavior). These males were followed up to age 32, and the more successful men were defined according to criteria such as the absence of convictions and of other deviant behavior, good relationships with wives and children, and good accommodation and employment histories. Hence, "success" here refers to satisfactory social adjustment. The more successful men were those who had been neurotic at age 10, those who had few or no friends at age 8, those without convicted parents or behavior problem siblings, those with mothers who had a high opinion of their sons, and those who did not spend their leisure time with their fathers. At age 8-10 they were already better behaved and less daring than those later judged as the unsuccessful men. There was some tendency for shyness to act as a protective factor against delinquency for non-aggressive boys but as an aggravating factor for aggressive boys.     

The effects of atrazine on microcosms developed from four natural plankton communities

Comparisons were made among Leffler microcosms developed from four different natural communities and exposed to 0, 20, 100, 200, 500, 1,000, and 5,000 g/L atrazine, a commonly used herbicide. Atrazine reduced net primary productivity, pH, and net productivity/respiration ratios in all four microcosm communities. In three of the four communities, the lowest observed (P < 0.05) effect concentration (LOEL) was 100 g/L. In the fourth community the LOEL was 200 g/L atrazine.The sensitivity and accuracy of bioassays with four different microcosm communities were evaluated by comparing results with values reported for acute and chronic single species bioassays, other types of microcosms, and experimental ponds exposed to similar concentrations of atrazine. The ranges of sensitivity noted in these experiments were less than the range reported for single species bioassays using common test organisms and similar to those reported for other microcosms. The similarity between Leffler microcosm results and the responses reported for the experimental ponds suggests that the Leffler microcosms accurately reflected concentrations causing ecosystem level changes in the experimental ponds.     

Adsorption of serum fetuin to hydroxylapatite does not contribute to osteoblast phenotype modifications

Osteoblasts exhibit enhanced differentiation and altered gene profiles when cultured on hydroxyapatite (HA) compared to plastic surfaces. To begin determining mechanisms for this response, we used proteomics to identify proteins predominantly found in osteoblasts on HA but not plastic surfaces. Two-dimensional gel electrophoresis and Western analyses indicate that fetuin is abundant in extracts from HA, but not plastic surfaces. Incubation of HA and plastic surfaces with cell culture medium (containing 10% serum) under cell-free conditions shows that fetuin is predominantly derived from the culture medium serum and readily adsorbs to the HA surface. However, we did detect low levels of fetuin B mRNA in osteoblasts. Serum albumin, actin-beta, apolipoprotein-AI, and vimentin also adsorbed to HA. To determine the role of fetuin in the HA-induced osteoblast phenotype changes, osteoblasts were seeded onto fetuin-coated or uncoated HA under serum-free conditions. Osteoblast morphology was similar on both HA surfaces, suggesting that HA alone (without adsorbed serum proteins) is sufficient for cell attachment and spreading. Similarly, genes previously reported to be modulated by HA (glvr-1, DMP-1, osteoglycin, and proliferin 3) were modulated even in the absence of fetuin or other serum proteins. These data show that HA surface can be enriched selectively with fetuin from serum; however, neither fetuin or other serum proteins are required to mediate HA-induced osteoblast attachment, spreading, or changes in expression of genes examined. This finding suggests that factors intrinsic to HA are required for the response.     

Two novel paradigms for the simultaneous assessment of conditioned taste aversion and food intake effects of anorexic agents

The conditioned taste aversion (CTA) is routinely used to assess the aversive consequences of anorexic agents, including potential pharmacological therapies for obesity. In a typical CTA paradigm, rats briefly sampling a novel tastant (e.g., saccharin) are acutely administered with toxin (e.g., lithium chloride, LiCl). After as few as one taste-toxin pairing, rats will reliably avoid the novel tastant. This paradigm is frequently used for the assessment of possible aversive consequences of drugs that are candidates for pharmacological therapies. The degree to which the drug supports development of a CTA is interpreted as an index of its aversive properties. Difficulties with previous work include the inability to assess affects on food intake and CTA simultaneously, particularly during chronic drug administration. We report here two novel CTA paradigms for the assessment of appetitive and aversive consequences of anorexic agents, simultaneously. In the first experiment, animals receive an intraoral infusion of a novel and highly palatable tastant immediately prior to administration of increasing doses of LiCl. In the second experiment, rats were implanted intraperitoneally with osmotic minipumps that chronically delivered a low dose of LiCl for 7 days. LiCl did not affect short or long term food intake in either experiment. However, LiCl did support the development of a CTA in both paradigms. These results suggest that both the appetitive and aversive consequences of anorexic agents can be assessed simultaneously during either acute or chronic drug administration.     

Care at the end of life: a novel curriculum module implemented by medical students.

End-of-life (EOL) and palliative care education in medical school curricula stand at a crossroads. Consensus has emerged that these topics merit systematic instruction throughout medical school training, yet curricula all too often consist of sporadic lectures focused on bioethics instead of clinical skills. The medical student authors identified a deficit in their curriculum, and designed and implemented an EOL curriculum module for their colleagues. In early 2000 the authors surveyed senior medical students about their experiences with EOL and palliative education, identifying deficits in clinical training and recommendations for interventions. They then designed a case-based educational module to teach EOL communication skills to medical students commencing clinical training. Faculty with national and local experience with EOL and palliative care reviewed the curriculum. Twelve of these faculty were oriented to the curriculum and then taught it in pairs to groups of 12 to 16 medical students in 2000 and 2001. The curriculum develops skills, attitudes, and knowledge relevant for communicating bad news and establishing treatment options in the EOL setting by utilizing trigger videos, group discussion, role plays, and case discussions. Approximately 75% of the 86 eligible students attended the module in 2000 and 2001. Feedback has guided the curriculum's refinement by the medical student authors. In addition, a standardized patient exercise, introduced in 2001, allowed students to reinforce the skills learned during the module.     

Opiate induced feeding is not dependent on the hippocampus

It has been shown that spreading depression of the hippocampus can elicit feeding, and that several opioid peptides elicit spreading depression when injected into the hippocampus. To determine whether such depression is the primary mechanism by which opiates induce feeding, we tested the feeding effects of naloxone, an opiate antagonist, and butorphanol tartrate, a kappa-sigma agonist, on feeding in rats with and without hippocampal lesions. Naloxone tended to reduce intake approximately equally in the two groups. Similarly, the doses of butorphanol that increased intake in sham rats were equally effective in lesioned rats. It was concluded that the hippocampus is not the major structure mediating opiate-induced feeding.     

The Turner syndrome research registry: Creating equipoise between investigators and participants

To address knowledge gaps about Turner syndrome (TS) associated disease mechanisms, the Turner Syndrome Society of the United States created the Turner Syndrome Research Registry (TSRR), a patient‐powered registry for girls and women with TS. More than 600 participants, parents or guardians completed a 33‐item foundational survey that included questions about demographics, medical conditions, psychological conditions, sexuality, hormonal therapy, patient and provider knowledge about TS, and patient satisfaction. The TSRR platform is engineered to allow individuals living with rare conditions and investigators to work side‐by‐side. The purpose of this article is to introduce the concept, architecture, and currently available content of the TSRR, in anticipation of inviting proposals to utilize registry resources.