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Radio-ecological and cytogenetic assessments were made in the vicinity of Totsk nuclear explosion in the Orenburg Region. Increased contents of radioactive isotopes Cs and Pu were detected in the soil. A comparative cytogenetic analysis indicated that the population continued to be exposed to radioactive agents.
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Genomic epidemiologic data, increasingly supported by clinical outcomes results, strongly suggest that overactivity of angiotensin I-converting enzyme (ACE) may underlie most age-related diseases. Angiotensin II, the main product of ACE, is a pleiotropic hormone, capable of serving as a neurotransmitter, growth factor, angiogenesis factor, vasoconstrictor, pro-thrombotic agent, and cytokine. So it is perhaps not surprising that the ACE D/D genotype is associated with several major psychiatric diseases, most cancers except prostate cancer (where the D/D genotype is actually protective), most cardiovascular diseases, most autoimmune diseases, and even infectious diseases like tuberculosis and HIV. In a preliminary study, angiotensin II blockade appeared to hasten recovery from West Nile virus encephalitis; it may be equally useful in SARS. The ACE gene underwent duplication at the origin of Chordata, just before the "Cambrian Explosion" in the number of species. The ancestral, unduplicated form of ACE is still expressed during the terminal differentiation of human spermatocytes, suggesting a critical role in reproduction. The crystal structure of testicular ACE (tACE) was recently published. Computer modeling suggests that tACE may be activated by both mechanical forces and reducing agents. The duplicated form of ACE (somatic ACE, sACE) is expressed in areas of high fluid flow. sACE may auto-dimerize via a novel protein motif, the "disulfide zipper." The sACE dimer is predicted to have higher catalytic efficiency and redox resistance than tACE.
OBJECTIVE: To report a patient with a rare clinical presentation of marginal keratitis and pyoderma gangrenosum (PG) that responded to the steroid-sparing agent azathioprine. DESIGN: Interventional case report. METHODS: Case report and MEDLINE review of the medical literature on PG-associated peripheral ulcerative keratitis (PUK) and its treatment. RESULTS: A patient with a biopsy-proven history of PG developed an explosive episode of PUK. The ocular inflammation was minimally responsive to topical therapy and required significant long-term oral steroids for control. The patient's active skin lesions and marginal keratitis responded dramatically to systemic oral azathioprine. Since the initiation of treatment with azathioprine, there have been no subsequent recurrences of PG or marginal keratitis. CONCLUSIONS: PUK may be associated with other inflammatory conditions, such as PG and arthritis. Systemic azathioprine may successfully control ocular and extraocular conditions and should be considered in the clinical setting of topical therapy failure and/or extraocular inflammatory conditions.
Over the past decade, there has been an explosion in data related to the treatment of patients with acute ischemic stroke. Thrombolytic therapy with intravenous tissue plasminogen activator has revolutionized the approach to stroke treatment. Intra-arterial administration of thrombolytic agents is also being investigated and is now being used on a compassionate basis. Medical management can have a large impact on stroke-related outcomes, even in patients who do not receive thrombolytic therapy.
Age-related deterioration in muscle performance is one of the major reasons for decreased functional capacity and disability in older people. In women, impaired muscle performance has already been observed during peri-menopause in concert with rapid and dramatic decrease in ovarian hormone production. This observation suggests that female sex steroids may have an important role among other agents in regulating muscle performance in middle-aged and older women. Previous experimental studies have shown that hormone replacement therapy (HRT) and intensive physical training have positive effects on muscle force and explosive power in healthy post-menopausal women. Hormone replacement therapy in combination with physical training may exert even greater gains in muscle performance than HRT and training alone. Despite the significant mean increase in muscle force and power by HRT and/or training, a considerable variability in the individual responses is observed. The mechanism, by which female sex steroids act on muscle performance, is still unclear. Therefore, more research is needed in order to explore all the pathways, by which these steroids could act on skeletal muscle in peri-menopausal and post-menopausal women.
BACKGROUND: The success rate of transplanted organs from brain-dead cadaver donors is consistently inferior to that of living sources. As cadaver and living unrelated donors are equally genetically disparate with a given recipient, the difference must lie within the donor himself and/or the effects of organ preservation and storage. We have hypothesized that irreversible central nervous system injury may up-regulate proinflammatory mediators and cell surface molecules in peripheral organs to be engrafted, making them more prone to host inflammatory and immunological responses. METHODS: Rats undergoing surgically induced acutely increased intracranial pressure (explosive brain death) were followed for 6 hr. Their peripheral tissues were examined by reverse transcriptase polymerase chain reaction and immunohistology, serum factors were assessed by enzyme-linked immunosorbent assay, and the influence of inflammatory molecules in the blood stream was determined by cross-circulation experiments with normal animals. RESULTS: mRNA expression of both lymphocyte- and macrophage-associated products increased dramatically in all tissues. Similar factors in serum were coincidentally increased; these were shown to be active in vivo by cross-circulation with normal animals. The organs of all control groups, including animals with important ischemic injury and with hemorrhagic shock, were negative. Up-regulation of MHC class I and II antigens and the co-stimulatory molecule B7 suggests increased immunogenicity of the peripheral organs. These changes could be inhibited by: (i) administration of a recombinant soluble P-selectin glycoprotein ligand-Ig, a P- and E-selectin antagonist; and (ii) a fusion protein, cytotoxic T lymphocyte antigen 4-Ig, which blocks B7-mediated T-cell co-stimulation. CONCLUSIONS: Activation of peripheral organs following explosive brain death may be caused by various interrelated events, including the effects of massive acute central injury, hypotension, and circulating factors. Almost complete suppression of these changes could be produced by biological agents. Such interventions, if reproducible in humans, could improve the quality of organs from "marginal" donors, broadening the criteria for donor acceptance.
The spectrum of infectious disease is changing rapidly in conjunction with dramatic societal and environmental changes. Worldwide, explosive population growth with expanding poverty and urban migration is occurring; international travel and commerce are increasing; and technology is rapidly changing-all of which affect the risk of exposure to infectious agents. Recent examples of important emerging infectious diseases include prolonged diarrheal illness due to waterborne cryptosporidium, hemorrhagic colitis and renal failure from foodborne Escherichia coli O157:H7, pneumonia and middle-ear infections caused by drug-resistant pneumococci, and rodentborne hantavirus pulmonary syndrome. These diseases as well as resurgent diseases (e.g., tuberculosis and cholera) illustrate human vulnerability to microorganisms in the environment. Three recent reports by the Institute of Medicine document the need to address emerging infectious disease threats. In partnership with representatives from health departments, other federal agencies, medical and public health professional associations, and international organizations, CDC has developed a strategic plan to address emerging infectious disease threats. The plain contains four goals that emphasize surveillance, applied research, prevention and control, and public health infrastructure. To ensure sustainability, plan implementation will be approached in stages, as a long-term endeavor with emphasis on extramural programs. As health-care reform proceeds, priority should be given to strengthening partnerships between health-care providers, microbiologists, and public health professionals to detect and control emerging infectious diseases.
At the present time, between 30% and 50% of individuals with epilepsy continue to have seizures and among those who are considered "controlled", a good many unpleasant side effects are endured. It is clear that we need more and better antiepileptic drugs. The virtual explosion in knowledge about the cellular and molecular mechanisms underlying both normal and pathological reactions of the brain provides encouragement that we are on the right path towards developing new, effective and safe agents. Whether we continue to use "model-based" screening or "mechanism-based screening", or both, we must not go another 14 years without the introduction of a new antiepileptic drug. The problem is too large, our patients are too impatient and our responsibilities are clear.
Bioregulators or modulators are biochemical compounds such as peptides, that occur naturally in organisms. Advances in biotechnology create the potential for the misuse of peptide bioregulators in offensive biological weapons programmes. Bioregulators are a new class of weapons that can damage the nervous system, alter mood, trigger psychological changes and kill. Over the last twenty years, neuroscience has produced an explosion of knowledge about receptor systems in the nerve cells that are of critical importance in receiving chemical transmitter substances released by other nerve cells. Bioregulators are closely related to substances normally found in the body that regulates normal biological processes. The potential military or terrorist use of bioregulators is similar to that of toxins. Together with increased research into toxins, the bioregulators have also been studied and synthesized. This paper presents a review of bioregulators that could be used in terrorist or other hostile activities.
From 1 January 1979 to 31 December 1993, 1109 patients were admitted to our burn unit located at Hacettepe University. Of the patients, 638 (57.5 per cent) were children (under the age of 16 years). The male to female ratio was 1.4:1 in children, and was approximately 2.6:1 for patients over 16 years of age. Of the 638 paediatric patients, 67 (10.5 per cent) sustained electrical burns. The causes of injury in the remaining 571 cases (89.5 per cent) were hot liquids in 379 (66.4 per cent of the non-electrical burns), flame in 190 (33.3 per cent) and contact burns in two (0.3 per cent). Of the scalds, 296 (78.1 per cent of the scalds), 52 (13.7 per cent), 22 (5.8 per cent) and nine (2.4 per cent) were caused by hot water, milk, meal and oil respectively. Of the flame burns, 21 (11.1 per cent) were due to LPG explosions. Of the 471 adult patients (over 16 years), 159 (33.8 per cent) were injured by electricity. The causes of non-electrical burn injuries were: hot liquid in 25, flame in 274, chemical agents in four, contact in four, and other causes in four. Although our centre is located in Central Anatolia, 41.8 per cent of all patients were referred from the other six regions of Turkey. Of the 1109 inpatients, 645 (58.2 per cent) were injured in Central Anatolia, 279 (25.2 per cent) in the Black Sea Region, 55 (5.0 per cent) in the Mediterranean Region, 18 (1.6 per cent) in the Marmara Region, 34 (3.1 per cent) in the Aegean Region, 52 (4.7 per cent) in Southeastern Anatolia and 26 (2.3 per cent) in Eastern Anatolia. Approximately two-thirds of the patients (419) required one or more surgical interventions, including debridement and grafting, as well as amputation. The most important early complications were acute renal failure (148 patients - 13.3 per cent), sepsis (660 patients - 59.5 per cent) and gastrointestinal haemorrhage (seven patients - 0.6 per cent). The overall mortality rate was 34.4 per cent. The epidemiological pattern of the burns showed that emergency measures should be taken to prevent scalding accidents to children throughout the country, and for electrical burns in adults, particularly those living in the Black Sea Region. In establishing, implementing and directing prevention programmes, regional differences should be taken into consideration.
ATOMIC DETONATIONS ARE ESSENTIALLY OF TWO TYPES: contaminating and non-contaminating. The only non-contaminating burst is the high air burst, since it does not result in the contamination of the ground with radioactive bomb residue. This type of burst results in blast, thermal and ionizing radiation injury (often combined in the same patient). The only injurious agent peculiar to atomic warfare is ionizing radiation. With a high air burst these effects are due mainly to gamma rays, and they are no longer present after the first few seconds following the explosion. Although only about 15 per cent of the deaths resulting from this type of burst are likely to be due primarily to ionizing radiations, exposure to the latter may well complicate recovery from trauma. Since there is a latent period of a number of days between the initial and later symptoms and signs of whole body radiation exposure, it does not constitute an emergency and can be treated after the initial period of the disaster has passed. With the detonation of a contaminating burst (a surface, underwater or underground burst) the radii of damage from blast and thermal radiation are considerably less than with a high air burst. Two types of radiation may result from the radioactive fog (base surge) formed after an underwater burst-transit radiation and deposit or continuing radiation. The deposit radiation includes that resulting from inhaled or ingested radioactive material as well as that deposited on clothes or skin. Bomb residue contains material which would localize in bones if it entered the body, and much of it has a long radioactive and biological half-life. It would thus bombard the radiosensitive bone marrow for long periods.Fortunately, the materials which would localize in bone are poorly absorbed from the gastrointestinal tract and lungs. In general radiation injury to a person exposed to a contaminating burst should be reckoned primarily in terms of the penetrating gamma radiation to which he was exposed, rather than in terms of possible internal radiation from ingested or inhaled contaminants. The principles of broad planning, careful triage, decentralization of medical aid, intelligent stockpiling, and the greatest good to the greatest number are to be stressed in medical defense planning. The best appraisal of exposure and its degree of seriousness is, as it is with disease in general, an accurate clinical evaluation by the physician. The tempo of the disease is an important aid in evaluating severity of exposure. The use of the dosimeter in judging the fate of a given individual is, at least at present, of limited value.
The study of Streptococcus pneumoniae (the pneumococcus) had been a central issue in medicine for many decades until the use of antibiotics became generalized. Many fundamental contributions to the history of microbiology should credit this bacterium: the capsular precipitin reaction, the major role this reaction plays in the development of immunology through the identification of polysaccharides as antigens, and, mainly, the demonstration, by genetic transformation, that genes are composed of DNA-the finding from the study of bacteria that has had the greatest impact on biology. Currently, pneumococcus is the most common etiologic agent in acute otitis media, sinusitis, and pneumonia requiring the hospitalization of adults. Moreover, meningitis is the leading cause of death among children in developing countries. Here I discuss the contributions that led to the explosion of knowledge about pneumococcus and also report some of the contributions of our group to the understanding of the molecular basis of three important virulence factors: lytic enzymes, pneumococcal phages, and the genes coding for capsular polysaccharides.
In the period 1970 through 1979, the Coxsackie B1, B2, B3, B4, and B5 viruses constituted 24 percent of more than 18,000 enteroviruses isolated and reported through national surveillance. Young children, especially males, were most frequently affected: 48 percent of the national surveillance population were less than 5 years of age, including 30 percent who were less than 1 year old. Among the most frequently reported clinical syndromes associated with B infection were meningitis (in 56 percent of patients with B1-B5 infections), encephalitis (in 15 percent), and respiratory tract disease (in 14 percent). Carditis, a well-known B syndrome, was reported with only 2 percent of B1-B5 infections. Like most enteroviral agents, Group B viruses were isolated primarily during the summer: 87 percent of all these isolations were made during the 5 months from June through October. Although B2, B3, and B4 viruses were isolated at relatively uniform levels each year, B1 and B5 viral illnesses occurred nationwide as explosive epidemics only in certain years. A separate population of B-infected patients, identified by the Nassau County Medical Center (NCMC) Virus Laboratory, East Meadow, N.Y., during the same 10-year period, was studied to compare epidemiologic characteristics and to evaluate in greater detail clinical and laboratory features of B infections. Because of more active solicitation of specimens for testing, ascertainment in the NCMC system was more complete. The most frequently reported clinical findings at NCMC included fever (97 percent of cases), which was biphasic in 27 percent; pharyngitis (85 percent); vomiting (56 percent); headache (49 percent); other respiratory signs and symptoms (44 percent); diarrhea (40 percent); abdominal pain (33 percent); rash (31 percent); and otitis (28 percent). Rash was more frequently associated with younger than with older age groups (P < .01) for all B agents. Overall, throat (T) and rectal (R) swabs had the highest B-positivity rates among known infected patients(83 percent for T and 78 percent for R). Only for T was the positivity rate correlated with the interval between onset of illness and obtaining the specimen (P < .05). B agents grew most quickly from T specimens, but most reliably from R specimens. On the basis of these data,the authors recommend that both T and R specimens be obtained from every patient for whom prompt and reliable laboratory diagnosis of B infection is sought.To the authors' knowledge, these results from 10 years of national surveillance represent the largest surveillance summary of Coxsackie B viruses to date in the literature. Comparison of these results with those reported over the same 10 years by NCMC reflects differences that arise mostly because of differences in ascertainment systems.
A wide variety of cancer therapy resistance mechanisms are available, with perhaps surprising overlap between causes of chemotherapy and radiation resistance. As previously discussed, most of the widely used chemotherapeutic agents and gamma-radiation utilize apoptosis as the common death pathway, thereby making apoptosis and the ability to manipulate apoptosis of integral importance to the future of cancer therapy. This is evidenced by the information explosion on this topic in the last 5 years. Obviously much remains to be learned. However, with the aforementioned cooperation of the oncology team and a greater understanding of the molecular mechanisms behind cancer and cancer therapy resistance, response rates, survival times, the quality of life of patients enduring antineoplastic therapies, and the importance of comparative oncology can only increase. We look forward to the findings in the coming years on this incredibly clinically relevant topic with great fondness and uncertainty.
Bartonella species have been recognized as important human pathogens only recently. Until the early 1990s, this genus was represented by one species, Bartonella bacilliformis. The recent identification of other Bartonella species as the agents of cat-scratch disease and bacillary angiomatosis has left little doubt of their emerging importance as opportunistic human pathogens. Over the last decade, extensive research has been performed on Bartonella species, resulting in an explosion in our knowledge of the genetic diversity of this genus. Unusual aspects of disease sequelae have fueled worldwide interest in defining the natural history, pathology, and molecular biology of Bartonella species. While much information about these interests has been presented, the advancement of immunological knowledge regarding Bartonella species has been slow. This review discusses immunological data on Bartonella species, focusing on the three primary human pathogens of this genus: B. bacilliformis, B. quintana, and B. henselae.
Methods are presented for the staining of blocks of tissue with trivalent indium so that good contrast and good specificity for nucleic acids is achieved for the electron microscope. The tissue is fixed in organic fixative, dehydrated, subjected to reduction by lithium borohydride, acetylated by acetic anhydride, stained with trivalent indium dissolved in organic solvent, and embedded. The embedding material may be either Vestopal or butyl methacrylate especially handled to eliminate the "explosion" phenomenon. Numerous new problems encountered are discussed and a brief description of the findings is included.
Several therapeutic agents have been tested for secondary prevention after acute myocardial infarction. Each patient presents a clinical challenge and gives the physician an opportunity to use the tests and therapy most likely to benefit the clinical course. The presence of other associated medical conditions, the type of myocardial infarction, the presence or absence of accompanying ischemia, left ventricular dysfunction, intracardiac thrombus, or ventricular arrhythmias dictate the choices that are to be made. It is apparent from this review that no single class of agents can be considered a cure, although beta-adrenergic blocking agents come the closest to this role. Analysis of these drugs helps individualize drug therapy and provides a physiologic probe to understanding the pathophysiologic processes that characterize the period after myocardial infarction. To address the impact of developing technology and drug availability on the practice and cost of medical care, the American College of Cardiology and the American Heart Association have developed guidelines for the management of patients with myocardial infarction. The clinical trial remains the best test for the assessment of therapeutic choices and can also expand our knowledge of the natural history of the disease process. Nevertheless, the issue of appropriate therapy is ever-changing, affected by the explosion of new technology and the continued investigation into the pathophysiology of coronary artery disease.