Neoplasia in the rat induced by N-hydroxyphenacetin, a metabolite of phenacetin.

N-hydroxyphenacetin, a phenacetin metabolite, was fed to rats as a 0.05-0.5% dietary supplement. After 9 months, tumours of the liver were found in 36 of 64 animals. One animal also developed a renal tumour. No tumours were found in control animals. The findings implicate phenacetin as a carcinogen and suggest that N-hydroxyphenacetin may be the metabolite responsible.     

Intracellular T lymphocyte cytokine profiles in the aqueous humour of patients with uveitis and correlation with clinical phenotype

This study aimed to investigate whether T cells in aqueous humour are different in different types of uveitis and correlate with clinical phenotype. Patients with clinically different types of uveitis, but all displaying active anterior uveitis, were phenotyped and samples of aqueous humour (AH) and peripheral blood (PB) collected. Cells from AH and PB were separated by centrifugation and by density gradient centrifugation (to obtain mononuclear cells PBMC), respectively. Cells were activated with PMA and ionomycin in the presence of Brefeldin A, stained for surface markers and intracellular cytokines, and analysed by flow cytometry. The cytokine profile was correlated with the clinical phenotype. Increased percentages of interleukin (IL)-10+-, but not interferon (IFN)-gamma+ T lymphocytes were found in AH compared with PB in patients with acute anterior uveitis (AAU), FHC or chronic panuveitis (PU). There was a trend towards elevated levels of IL-10+ T cells in AH from patients with FHC compared with AH from acute uveitis and panuveitis patients. Increased levels of IL-10+ T cells in AH compared with PB were also found in samples from patients with isolated uveitis, but not those with associated systemic disease. Levels of cytokine-positive T cells were not associated with the use of topical steroids or to the severity of the anterior uveitis. While type I cytokine-producing T lymphocytes are present in AH during AU, the presence of increased proportions of IL-10+ T lymphocytes in AH from patients with uveitis may be indicative of an anti-inflammatory mechanism that may influence the type and course of ocular inflammation in these patients.     

The differentiation of O-2A progenitor cells into oligodendrocytes is associated with a loss of inducibility of Ia antigens

Current data suggest that some astrocytes, one of the 3 main types of macroglia in the central nervous system (CNS), can be induced by interferon-gamma (IFN-gamma) to express major histocompatibility complex class II antigens (immune-associated or Ia) and present antigen to T lymphocytes. In contrast, oligodendrocytes, another type of macroglia, cannot be induced to express Ia. The astrocytes which have been shown to express Ia are from a particular glial lineage and are called type-1 astrocytes. The oligodendrocyte-type-2 astrocyte (O-2A) lineage, which gives rise to oligodendrocytes, also gives rise to a second class of astrocytes called type-2 astrocytes and the ability of type-2 astrocytes or the common O-2A progenitor cell to express Ia is not known. We have now found that both type-2 astrocytes and O-2A progenitor cells can be induced to express Ia by IFN-gamma but Ia expression is not induced in oligodendrocytes in parallel cultures. Thus, it appears that differentiation of O-2A progenitor cells into oligodendrocytes is specifically associated with a loss of inducibility of Ia. This apparent loss of the capacity for Ia expression, and presumably antigen presentation, in oligodendrocytes (the cells which produce myelin in the CNS) is of particular interest in view of the ability of immunization of myelin components to produce autoimmune-mediated paralytic disease.     

Morphometric effects of use and disuse on peripheral nerve

Rat peripheral nerve was evaluated morphometrically following hemicordotomy, tenectomy, or both to assess the effects of disuse and hyperactivity on the peripheral nervous system. Hemicordotomy resulted in an increase in diameter of nerve fibers supplying both "fast" and "slow" skeletal muscles in hypoactive and hyperactive limbs. Nerve fiber atrophy occurred only in nerve to "fast" muscle following disuse induced by hemicordotomy and tenectomy. The possible role of "motor nerve growth factor" or altered axoplasmic flow in bringing about these morphologic changes in peripheral nerve is discussed.     

Development of an information system for a physiotherapy department

This paper outlines the rationale for the development of an information system and shows how much a system can become an effective management tool for physiotherapy department directors. The author points out the need to assess both costs and benefits before venturing into the world of computerized information systems, but also makes a case for the need to establish a useful system for the gathering and processing of data that will provide useful information, whether or not computers are used to store and analyze the data. A five-step approach to the development of an information system is presented. The steps include: system analysis, selection of design approach, systems design, implementation, and system maintenance. The author states that management information systems for the future--if they are to be efficient and effective---will require department heads to develop specific methodologies of approach.     

Children's blood lead levels in the lead smelting town of Port Pirie, South Australia

This survey included 1,239 children, representing 50% of the elementary school population of the lead smelting town of Port Pirie. Of these children, 7% had a capillary blood lead level equal to or greater than 30 micrograms/dl, which is the Australian National Health and Medical Research Council's "level of concern." There was a statistically significant difference in capillary lead levels by area of residence that was independent of age, sex, soil lead, rainwater tank lead, and school attended. A case-control study indicated that the following subset of factors was most predictive of an elevated blood lead level: household members who worked with lead in their occupations; living in a house with flaking paint on the outside walls; biting finger nails; eating lunch at home on school days; when at school, appearing to have relatively dirty clothing; when at school, appearing to have relatively dirty hands; and living on a household block with a large area of exposed dirt. A program to reduce the risk of elevated blood lead levels in Port Pirie children has been introduced.     

Low flow veno-venous ECMO: an experimental study

Clinical use of extracorporeal membrane oxygenation (ECMO) and carbon dioxide removal (ECCO 2R) have become well established techniques for the treatment of severe respiratory failure; however they require full cardiopulmonary bypass, representing major procedures with high morbidity. We theorized the possibility of an efficient low flow veno-venous extracorporeal membrane gas exchange method. Four mongrel 12 kg dogs were submitted to veno-venous extracorporeal membrane gas exchange via a jugular dialysis catheter using a low flow (10 ml/min) roller pump and a membrane oxygenator for a period of four hours. Respiratory rate was set at 4 breaths/min with a FiO 2 of 21% and ventilatory dead space was increased. Adequate gas exchange was obtained (pO 2139, pCO 224, Sat 99.4%), without major hemodynamic changes or hematuria. Our results demonstrate the feasibility of a low flow, less aggressive system. Further research should be considered.     

Differences in perceptions of hospital marketing orientation between administrators and marketing officers

Hospital administrators have been struggling for more than a decade to determine the role and proper position for marketing and marketers within their organizations. Results of a study now confirm the expected--administrators and their chief marketing officers do not see the same marketing actions being conducted for their hospitals. The consequence of such perceptual differences in marketing orientation for the role of marketers within the hospital are significant and are discussed in this article. Of particular importance is the finding that the marketing behaviors of the organization as identified by line managers correlate strongly with both revenues (r = .6r for inpatient revenue) and occupancy levels (r = .44). Additionally, it was found that as little as a 10 percent improvement in a hospital's marketing orientation is associated with a $25 million increase in total net patient revenues and an 8 percentage point increase in occupancy rate.     

The pharmacology of VA21B7: an atypical 5-HT3 receptor antagonist with anxiolytic-like properties in animal models

VA21B7 (3-[2-(4-piperonylpiperazinyl) indolyl] carboxaldehyde) was synthesized as a potential 5-HT₃ receptor antagonist. Even though VA21B7 showed a higher affinity towards 5-HT₃ receptors as compared to other receptors studied, it was not a potent 5-HT₃ receptor antagonist either in the periphery or in the brain. In a simple animal model of anxiety such as the two-compartment box in mice, a remarkable anxiolytic-like effect was found at doses of 2–500 µg/kg IP and also at low oral doses, in the microgram range. These drug doses did not produce any significant effect on spontaneous motor activity of mice. The anxiolytic profile of VA21B7 was further explored using other models of anxiety in rats such as the elevated plus-maze and punished-drinking. VA21B7 was compared with standard 5-HT₃ receptor antagonists such as ondansetron, tropisetron and granisetron, with the 5-HT_1A agent buspirone and with diazepam. In the plus-maze, VA21B7 showed an anxiolytic-like profile after doses of 0.25–0.5 mg/kg IP or 2–4 mg/kg PO which did not modify the number of total entries into the open and closed arms of the maze. Diazepam, granisetron and tropisetron were also effective in this test but not ondansetron and buspirone. VA21B7 was also able to release suppressed behaviour in the punished-drinking test. The dose-response curve was bell-shaped with a peak at 2–4 mg/kg. At variance with other studies, 5-HT₃ receptor antagonists also increased the number of shocks taken in this test and the dose-response curve was also bell-shaped. VA21B7 was not anticonvulsant like diazepam, its anxiolytic action in the light/dark test was not flumazenil-sensitive and there was no rebound anxiogenic effect on withdrawal from chronic VA21B7 treatment for 15 consecutive days. Moreover, VA21B7 was not amnesic like the benzodiazepines but low doses of 2–4 mg/kg reduced the memory deficits induced in rats by scopolamine. Much higher doses were necessary to decrease spontaneous motor activity in rats. Since VA21B7 appears to be well tolerated in rodents at high doses, we think that it is of potential interest as an anxiolytic in humans.