ST-246 is a low-molecular-weight compound (molecular weight‫؍‬Recent concerns over the use of variola (smallpox) virus as a biological weapon have prompted renewed interest in development of small molecule therapeutics that target variola virus replication. Currently, there is no U.S. Food and Drug Administration-approved drug for the prevention or treatment of smallpox infection. While a number of compounds have been shown to inhibit orthopoxvirus replication in vitro, these compounds often lack potency and/or are associated with significant adverse effects, due to their relative nonspecific mechanisms of virus inhibition (3).The cornerstone of the current national public health response plan to a smallpox bioterrorist attack calls for rapid mass immunization with vaccinia virus. However, concerns about vaccine-related adverse events have compromised implementation of a smallpox immunization program. Individuals with immunodeficiency disorders or certain common skin conditions are unusually susceptible to vaccine-related complications (6, 32). Moreover, the lag period for antibody formation from a vaccine leaves a window of vulnerability. Antiviral therapies can fill this void and provide an excellent complement to vaccination in that they reduce virus titers quickly, regardless of immune status, and lower transmission rates by diminishing the virus reservoir. A small-molecule antiviral drug designed to treat variola virus infection will be a critical component to a smallpox defense strategy.Currently, only cidofovir [CDV; (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine; Vistide], a drug approved for treatment of cytomegalovirus (CMV) retinitis in AIDS pa-* Corresponding author. Mailing address:

No abstract

Background: Heavy kava use in Aboriginal communities has been linked to various health effects, including anecdotes of sudden cardiac deaths. Aims: To examine associations between kava use and potential health effects. Methods: A cross-sectional study was carried out within a kava-using east Arnhem Land Aboriginal community in tropical northern Australia. One-hundred-and-one adults who were current, recent or non-users of kava were enrolled in March 2000. Main outcome measures were physical, anthropometric, biochemical, haematological, immunological and neurocognitive assessments. Results: Kava users more frequently showed a characteristic dermopathy (P < 0.001). They had increased levels of γ-glutamyl transferase and alkaline phosphatase (P < 0.001). Lymphocyte counts were significantly lower in kava users (P < 0.001). Fibrinogen, plasminogen activator inhibitor-1 and neurocognitive tests were not different between kava use categories. IgE and IgG antibodies were elevated across the whole group, as were C-reactive protein and homocysteine. Conclusions: Kava use was associated with dermopathy, liver function abnormalities and decreased lymphocytes. If kava continues to be used by Aboriginal populations, monitoring should focus on the health consequences of these findings, including a possible increase in serious infections. The interaction between kava, alcohol and other substances requires further study. Although markers of cardiovascular risk are increased across the population, these were not higher in kava users, and this increase may be linked to the large infectious pathogen burden reflective of the socioeconomic disadvantage seen in many remote Aboriginal communities. (Intern Med J 2003; 33: 336-340)

Objective: To assess use of free nicotine patches by Indigenous people when offered a brief intervention for smoking cessation, and to assess changes in smoking behaviour at six months. Methods:We conducted a pre and post study in three Indigenous communities in the Northern Territory.

Anecdotal observations suggest that neurological impairments associated with petrol (gasoline) sniffing resolve with abstinence, although these effects have not been proven empirically. Severe exposure to leaded petrol may induce a lead encephalopathy that extends beyond any acute intoxication and requires emergency hospital treatment. Previously, in chronic petrol sniffers, we showed neurological, saccadic, and cognitive abnormalities that were more severe in petrol sniffers with a history of hospitalization for lead encephalopathy, and that correlated with blood lead levels and the length of time of sniffing petrol. Ex-petrol sniffers showed a qualitatively similar but quantitatively less severe pattern of impairment. Petrol sniffing was stopped completely in one of the study communities by modifying social, occupational, and recreational opportunities. After 2 years, we obtained biochemical and neurobehavioral (neurological, saccade, and cognitive) data from all available participants of the earlier study including 10 nonsniffers and 29 chronic petrol sniffers, with six of these individuals previously receiving hospital treatment for lead encephalopathy. Here, we report that blood lead was reduced and that neurobehavioral impairments improved, and in many cases normalized completely. The most severe petrol-related neurobehavioral impairment was observed among individuals who had longer histories of abuse and higher blood lead levels, and among petrol sniffers with a history of lead encephalopathy. Those with the greatest extent of neurobehavioral impairment showed the greatest degree of improvement with abstinence, but were less likely to recover completely. This is the first direct evidence that neurological and cognitive impairment from chronic petrol sniffing ameliorates with abstinence and may recover completely.