This paper presents selected results of the studies on emerging and reemerging infections caried out in D I Ivanovsky Research Institute of Virology with special reference to comprehensive ecological, virological, and molecular-genetic analysis of the following viruses: California encephalaitis serocomplex, West Nile fever, highly virulent avian influenza A virus (H5N 1), and new pandemic influenza A vires (HIN1). Special attention is given to the role of emerging and reemerging infections at the territory of Northern Eurasia in national and world-wide epidemiological cataclysms and their prognostication for minimizing their consequences based on monitoring pathogen evolution.

This study evaluated the pharmacokinetics of florfenicol in the white-spotted bamboo shark (Chiloscyllium plagiosum). In addition to the pharmacokinetics, the potential application for treatment of bacterial meningitis was explored. A pilot study was used to compare doses of 30, 40, and 50 mg/kg i.m. Following that study, 10 adult sharks were administered a single i.m. dose of florfenicol at 40 mg/kg. Plasma and cerebrospinal fluid were collected and analyzed for florfenicol by a sensitive and specific high-pressure liquid chromatographic method. Pharmacokinetic analysis was performed using both non-compartmental and compartmental techniques. The absorption produced an average peak at 54 (+/-19) hr from the i.m. site of administration, and the half-life was prolonged, averaging 269.79 hr (+/-135.87). Florfenicol plasma concentrations peaked at an average of 11.85 microg/ml (+/-1.45) and were maintained above our target minimum inhibitory concentration of 4-8 microg/ml for at least 120 hr. Cerebrospinal fluid concentrations peaked at an estimated 9 microg/ml around 48 hr, surpassing the target minimum inhibitory concentration for at least 72 hr.

When is a physician's act non-medical, and how might such non-medical acts be classified? One approach, analogous to the substantive due process inquiry employed by American courts weighing the constitutionality of legislative acts, would involve consideration of the following questions: 1) Is a legitimate medical goal being pursued? 2) Are the means being employed legitimately medical? 3) Are the goals and means appropriately related? Accordingly, a physician acts medically when employing legitimate and appropriate medical means in pursuit of a legitimate medical goal. In contrast, when the goals pursued or means employed are not legitimately medical, or when the two are not appropriately related, the act is medically ultra vires ("beyond the powers")--that is, an act beyond the physician's power or authority--and consequently non-medical. Medically ultra vires acts may be further sub-classified depending upon which prong of the above trident is defective. Where the goal of the act, though achievable, is not legitimately medical, the act is medically ultra vires because of goal illegitimacy, or medically ultra fines ("beyond the ends"). Where the means employed are not legitimately medical, the act is medically ultra vires because of means illegitimacy, or medically ultra modos ("beyond the means"). Where the means and goals are not appropriately related, the act is medically ultra vires because of means-goals disjunction, or medically ultra nexus ("beyond the connection"). Medical futility (where the medical goal in question, albeit legitimate, cannot be achieved by the act under consideration) represents the paradigmatic example of the latter.

In 1954, Papillon-Leage and Psaume were the first to describe the clinical characteristics of oral-facial-digital syndrome (OFDS). On the basis of their clinical features and the inheritance pattern, 2 variants were initially distinguished, namely OFDS type I (Papillon-Leage and Psaume) and OFDS type II, or Mohr syndrome. At present, 11 types of OFDS have been discovered. OFDS represents a heterogeneous group of disorders characterized by oral manifestations including oral frenula, cleft or lobulated tongue, high arched palate, cleft lip and/or palate, facial anomalies, and digital abnormalities such as syndactyly, polydactyly, brachydactyly, and clinodactyly. Depending on the type of OFDS, abnormalities may be present in other organs, such as the brain and heart. We report a patient with OFDS in whom multiple recurrent and de novo keratocysts were found. Although multiple keratocysts are commonly found in Gorlin-Goltz nevoid basal cell carcinoma syndrome, a relationship between OFDS and multiple keratocysts has not been described.

The controversy over the issues of carbon sinks and emissions trading nearly aborted the Kyoto Protocol. The lengthy and intense debate over the roles that each are to play under the Protocol and the consequent political compromises has resulted in a complex set of provisions and an arcane nomenclature. The distinction drawn between the use of carbon sinks in developed countries under Joint Implementation and their use in developing countries under the Clean Development Mechanism (CDM) is a particular source of intricacy. It is at least arguable that key elements of the compromises reached at COP-6 and COP-7 in this regard are inconsistent with the terms of the Protocol and are ultra vires the Convention on Climate Change. This is a source of both uncertainty and potential legal challenge. Not only do the recent decisions create needless complexity, they also clearly discriminate against developing nations. Among the recent political compromises is the creation of a third type of non-bankable but tradeable unit with respect to forest management, which is only available to Annex I countries. The result is an anomalous one in which a variety of otherwise equivalent carbon credits can be generated under three different regimes including one, the CDM, that is subject to an elaborate regulatory overlay that discriminates against carbon sequestration by developing countries. For example, complying developed countries can essentially self-certify sequestration projects. In contrast, projects in developing countries must obtain prior approval from a subsidiary body, the CDM Executive Board, mandated to require detailed information and impose substantive and procedural hurdles not required or imposed by its companion body, the Article 6 Supervisory Committee on Joint Implementation Projects. The parallel and related debate over the third 'flexibility' mechanism, emissions trading, compounded the complexity of an already asymmetric and bifurcated system. The new requirements devoted to 'environmental integrity' not only have raised the costs of compliance of developing country projects but also virtually ignore the fundamental principle of sustainable economic growth and development embodied in the Convention and related international agreements. The regulations for carbon sinks now being formulated at Conferences of the Parties will have a significant impact on their use worldwide. Of key importance, in addition to their successful integration of carbon sinks and emissions trading into other international treaties, is the development of practically achievable and objective standards and an efficient and transparent approval process consistent with the terms of the Convention and the Protocol. Most important of all is a rebalancing that restores the primacy of addressing climate change in the context of sustainable economic growth and development.

In the class II region of the major histocompatibility complex (MHC(, four genes implicated in MHC class I-mediated antigen processing have been described. Two genes (TAP1 and TAP2) code for multimembrane-spanning ATP-binding transporter proteins and two genes (LMP2 and LMP7) code for subunits of the proteasome. While TAP1 and TAP2 have been shown to transport antigenic peptides from the cytosol into the endoplasmic reticulum, where the peptides associate with MHC class I molecules, the role of LMP2/7 in antigen presentation is less clear. Using antigen processing mutant T2 cells that lack TAP1/2 and LMP2/7 genes, it was recently shown that expression of TAP1/2 alone was sufficient for processing and presentation of the influenza matrix protein M1 as well as the minor histocompatibility antigen HA-2 by HLA-A2. To understand if presentation of a broader range of viral antigens occurs in the absence of LMP2/7, we transfected T2 cells with TAP1, TAP2 and either of the H-2Kb, Db or Kd genes and tested their ability to present vesicular stomatitis vires and influenza virus antigens to virus-specific cytotoxic T lymphocytes. We found that T2 cells, expressing TAP1/2 gene products, presented all tested viral antigens restricted through either the H-2Kb, Db or Kd class I molecules. We conclude that the proteasome subunits LMP2/7 as well as other gene products in the MHC class II region, except from TAP1/2, are not generally necessary for presentation of a broader panel of viral antigens to cytotoxic T cells. However, the present results do not exclude that LMP2/7 in a more subtle way may, or in rare cases completely, affect processing of antigen for presentation by MHC class I molecules.

The effects of aminophylline on diaphragmatic fatigue and recovery in the face of hypoxemia and hypercapnic acidosis were studied in anesthetized, spontaneously breathing, dogs. The phrenic nerves were stimulated supramaximally at 10, 20, 50, and 100 Hz during 2 s with electrodes placed around the fifth roots, and the resulting transdiaphragmatic pressure (Pdi) was measured with balloon catheters. The dogs were occluded before the stimulations at functional residual capacity. The latter was monitored by measuring the end-expiratory transpulmonary pressure, which remained constant throughout the experiment. Diaphragmatic fatigue was produced by resistive loaded breathing. At the end of the runs, which lasted 15 +/- 2 min, all the dogs were severely hypoxemic (30 +/- 5 mmHg), hypercapnic (65 +/- 4 mmHg), and acidotic (7.1 +/- 0.05). During the fatigue runs, phrenic stimulation resulted in a marked decrease in Pdi, which amounted at 20 Hz to 70 +/- 8% and 45 +/- 12% of the control values 5 min after the onset of the fatigue runs and at the end, respectively. After recovery (3 h), Pdi and arterial blood gas determinations returned to control values. Identical fatigue runs were repeated with aminophylline infusion (loading dose, 6 mg/kg in 10 min and maintenance dose, 1 mg/kg/h), leading to a plasmatic concentration of 16.4 +/- 2 mg/l. Aminophylline protected the diaphragm against fatigue, and despite the presence of hypoxemia and hypercapnic acidosis, the Pdi generated for a 20 Hz stimulation of the phrenic nerves at identical times of the preceding run amounting to 100 +/- 15% and 85 +/- 10% of control values, respectively.(

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For the early recognition of vitamin deficiencies, those methods are especially suitable in which changes in the biochemistry of blood or urine are measured. Here a low level of concentration of vitamins or their metabolites is seen, or a lowered activity of vitamin-dependent enzymes or hormones, and finally a disturbance of the actual metabolism. It is only when such metabolic disorders occur that there are functional disturbances or morphological changes. From the example of vitamin A, it is seen that in regions with endemic deficiency such functional disorders and morphological changes can be used to determine the degree of endemic deficiency, whereas in regions or population groups in which there are not manifest symptoms of deficiency, the certain criteria are lacking and there remain only indications. The same is true for the other vires of preventive medicine must be taken in the meanwhile. Certain arbitrary decisions as to the desirable level of blood and urine concentrations of vitamins and their metabolites, and the activity of vitamin-dependent enzymes and hormones, are indispensable. In the preparation of programs for prevention, the first consideration is whether it is for a region in which there is a general nutritional deficiency, or not. In the actual hunger regions, an improvement of the vitamin supply is vital where the vitamin deficiency is leading to irreversible damage, which represents a severe social burden. Such a situation is seen especially in the case of endemic vitamin A shortage. For the other vitamins, it can be assumed that an improvement in the supply of proteins and calories will include an improvement in the vitamin situation. Where this is not the case, the problems are similar to those of the industrial nations. ishort term measures should attempt the enrichment of the basic foodstuffs, on a legal basis, with certain essential food factors. How far nutritional habits can be changed by education is uncertain. In any case, this should be attempted as part of any longterm planning. Biochemical methods of early recognition of vitamin deficiency are suited for testing the success of such preventive actions. The duration of such actions which have been made on a world-wide scale, or are planned, and are tested by these methods is too short to allow any definite statement to be made as to their success.