CONTEXT On January 24, 2003, the US Department of Health and Human Services (DHHS) implemented a preparedness program in which smallpox (vaccinia) vaccine was administered to federal, state, and ...local volunteers who might be first responders during a bioterrorism event. OBJECTIVE To describe results from the comprehensive DHHS smallpox vaccine safety monitoring and response system. DESIGN, SETTING, AND PARTICIPANTS Descriptive study of adverse event reports from the DHHS smallpox vaccine safety monitoring and response system received between January 24 and October 31, 2003, through the Vaccine Adverse Event Reporting System (VAERS) and the Centers for Disease Control and Prevention. A total of 37 901 volunteers in 55 jurisdictions received at least 1 dose of smallpox vaccine. MAIN OUTCOME MEASURES Number of vaccinations administered and description of adverse events and reporting rates. RESULTS A total of 38 885 smallpox vaccinations were administered, with a take rate of 92%. VAERS received 822 reports of adverse events following smallpox vaccination (overall reporting rate, 217 per 10 000 vaccinees). A total of 590 adverse events (72%) were reported within 14 days of vaccination. Nonserious adverse events (n = 722) included multiple signs and symptoms of mild and self-limited local reactions. One hundred adverse events (12%) were designated as serious, resulting in 85 hospitalizations, 2 permanent disabilities, 10 life-threatening illnesses, and 3 deaths. Among the serious adverse events, 21 cases were classified as myocarditis and/or pericarditis and 10 as ischemic cardiac events that were not anticipated based on historical data. Two cases of generalized vaccinia and 1 case of postvaccinial encephalitis were detected. No preventable life-threatening adverse reactions, contact transmissions, or adverse reactions that required treatment with vaccinia immune globulin were identified. Serious adverse events were more common among older revaccinees than younger first-time vaccinees. CONCLUSIONS Rigorous smallpox vaccine safety screening, educational programs, and older vaccinees may have contributed to low rates of preventable life-threatening adverse reactions. Other rare, clinically significant, or unexpected cardiac adverse events were detected by timely review of VAERS data and intensive clinical case investigation.
A longitudinal study of malariometric indicators and their association with potential risk factors was conducted during August 1997-July 1998 at Padre Cocha, a village of 1,400 residents in the ...Peruvian Amazon. The incidence of Plasmodium falciparum infections during the study year was 166/1,000 persons; that of P. vivax was 826/1,000 persons. The mean duration of symptoms prior to diagnosis was 2 days; presenting geometric mean parasite densities were 3,976 parasites/microl for P. falciparum infections and 2,282 parasites/microl for P. vivax. There were no malaria-associated deaths. Consistent with the epidemic nature of malaria in the area, the incidence of both parasite species increased with age and there were no age-specific differences in mean parasite densities. No specific occupational risks for malaria were identified. Activities significantly associated with malaria risk reflected local vector behavior and included strolling outdoors after 6:00 PM and arising before 6:00 AM for adults, and attending evening church services for children.
Tetanus—Puerto Rico, 2002 Orengo, J C; Garcia, Y; Rodriguez, A ...
JAMA : the journal of the American Medical Association,
10/2002, Letnik:
288, Številka:
14
Journal Article
Recenzirano
Three Puerto Rico residents developed tetanus in 2002 and two died. During this time, there was a shortage of tetanus vaccine in the US and Puerto Rico, and none of the patients had a documented ...tetanus vaccination.
Combined hepatocellular injury and renal tubular necrosis developed in five alcoholic patients who were receiving acetaminophen therapeutically. Two patients were taking doses prescribed by a ...physician. The hepatitis was characterized by extremely high serum transaminase values that were maximal on admission. Two patients died, and autopsy disclosed hepatic centrizonal necrosis and acute renal tubular necrosis. The three who survived had clinical features typical of acute tubular necrosis. All five had measurable concentrations of acetaminophen in plasma, although measurements were requested on admission only in two patients. When an alcoholic presents with combined hepatic and renal insufficiency, acetaminophen should be considered as a possible inciting agent. This diagnosis should be considered when serum transaminase levels are markedly elevated and when renal failure is due to acute tubular necrosis.
Acetylcholine is a neurotransmitter that has a major role in the function of the insulin-secreting pancreatic beta cell. Parasympathetic innervation of the endocrine pancreas, the islets of ...Langerhans, has been shown to provide cholinergic input to the beta cell in several species, but the role of autonomic innervation in human beta cell function is at present unclear. Here we show that, in contrast to the case in mouse islets, cholinergic innervation of human islets is sparse. Instead, we find that the alpha cells of human islets provide paracrine cholinergic input to surrounding endocrine cells. Human alpha cells express the vesicular acetylcholine transporter and release acetylcholine when stimulated with kainate or a lowering in glucose concentration. Acetylcholine secretion by alpha cells in turn sensitizes the beta cell response to increases in glucose concentration. Our results demonstrate that in human islets acetylcholine is a paracrine signal that primes the beta cell to respond optimally to subsequent increases in glucose concentration. Cholinergic signaling within islets represents a potential therapeutic target in diabetes, highlighting the relevance of this advance to future drug development.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Intramolecular 1,3-dipolar cycloadditions of cinchona azides to the C10−C11 alkyne and C10−C11 olefin unit of the alkaloid have been designed via tandem strategy. A variety of fused triazoles and ...triazolines with a bis-azahomotwistane skeleton have been prepared. In trifluoroethanol, O-mesylcinchonidine 7-OMs and NaN3 furnish triazole 8 as well as cage-expanded 1,5-diazatricyclo4.4.1.03,8undecane derivative 10. Both fused triazoles 8 and 10 are formed with retention of configuration at C9 and C3, respectively. 1-Azabicyclo3.2.2cage expansion is shown to be reversible.
Stereochemistry, products, and driving forces of the “first and second Cinchona rearrangement” have been investigated and a unified theory is presented. The first cage expansion affords ...3.2.2azabicyclic α-amino ether and is formulated via a configurationally stable bridgehead iminium ion and quasiequatorial nucleophilic attack. The second cage expansion affords β-functionalized 3.2.2azabicycles. In this case a nonclassical nitrogen-bridged cation is postulated to account for retention of configuration and potential reversibility of the cage expansion. The second rearrangement is favored for the so-called cinch bases (6‘-R = H) in trifluoroethanol. Stereoelectronic factors, electron demand at C9, ground state conformation, and solvent type are crucial in all cases. A two-step protocol for preparing 9-epi-configured Cinchona alkaloids from 9-nat precursors is described.
Solvolysis of C9 mesylated cinchonidine 1-OMs and cinchonine 2-OMs in solvent MeOH, EtOH, and CF3CH2OH affords ring-expanded 1-azabicyclo3.2.2nonanes oxygenated at carbon C3 (“second Cinchona ...rearrangement”). The newly introduced substituents at C3 and the neighboring quinolyl group Q‘ at C2 adopt quasiequatorial positions. The derived 1-azabicyclo3.2.2nonan-3-ones 5 and 6 are easily equilibrated. On contact with MeOD uptake of deuterium takes place at room temperature.
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