Results of a self-absorption study on the Versapor 3000 47-mm filters for radioactive particulate air stack sampling.

Since the mid-1980's the Pacific Northwest National Laboratory (PNNL) has used a value of 0.85 as a correction factor for the self absorption of activity for particulate radioactive air samples collected from building exhaust for environmental monitoring. More recently, an effort was made to evaluate the current particulate radioactive air sample filters (Versapor 3000, 47-mm diameter) used at PNNL for self absorption effects. There were two methods used to characterize the samples. Sixty samples were selected from the archive for acid digestion to compare the radioactivity measured by direct gas-flow proportional counting of filters to the results obtained after acid digestion of the filter and counting again by gas-flow proportional detection. Thirty different sample filters were selected for visible light microscopy to evaluate filter loading and particulate characteristics. Mass-loading effects were also considered. Large error is associated with the sample filter analysis comparison and subsequently with the estimation of the absorption factor resulting in an inadequate method to estimate losses from self-absorption in the sample filter. The mass loading on the sample filter as determined after digestion and drying was approximately 0.08 mg cm; however, this value may not represent the total filter mass loading given that there may be undetermined losses associated with the digestion process. While it is difficult to determine how much material is imbedded in the filter, observations from the microscopy analysis indicate that the vast majority of the particles remain on the top of the filter. In comparing the results obtained, the continued use of 0.85 as a conservative correction factor is recommended.

Evaluation of sampling locations for two radionuclide air-sampling systems based on the requirements of ANSI/HPS N13.1-1999.

The Pacific Northwest National Laboratory characterized the performance of sampling locations for two radionuclide air-sampling systems that continuously monitor radioactive air emissions from research and development facilities. The testing was conducted to determine whether sampling system locations would meet the criteria for uniform air velocity and contaminant concentration in the American National Standard Institute standard, Sampling and Monitoring Releases of Airborne Radioactive Substances from the Stacks and Ducts of Nuclear Facilities (ANSI/HPS N13.1-1999). The standard is a revision of the 1969 version that the facilities have been required to meet. Whereas the 1969 standard provided prescriptive criteria for the selection of sampling locations, the 1999 standard is performance-based and requires well-mixed sampling locations that must be demonstrated through performance tests that are specified in the standard. Testing at the Life Sciences Laboratory I was performed on the existing stack at the current sampling location; a scale model was built and used in place of the Radiochemical Processing Laboratory. Although both facilities' sampling sites were compliant with the 1969 standard, only the Radiochemical Processing Laboratory met the criteria of the revised standard. In the future, the use of a computational fluid dynamics computer model may be useful in determining whether a sampling location is likely to test successfully.

Results of inspection and cleaning of two radionuclide air-sampling systems based on the requirements of ANSI/HPS N13.1-1999.

The Pacific Northwest National Laboratory inspected and cleaned two radionuclide air-sampling systems that continuously monitor radioactive air emissions from research and development facilities. The inspection and cleaning was performed to evaluate effective methods and potential cost impacts of maintenance requirements in the revised American National Standard Institute standard Sampling and Monitoring Releases of Airborne Radioactive Substances from the Stacks and Ducts of Nuclear Facilities. The standard requires at least annual inspections of sampling systems followed by cleaning if deposits are visible. During 2001 and 2002, inspections were performed leaving the sampling systems in place and inserting videoscope cables into different access points to allow viewing of the inside and outside of sampling manifolds and transport lines. Cleaning was performed on one of the systems by disconnecting and extracting the sampling manifold, then washing it with de-ionized water and scrub brushes. The wash water was analyzed for radioactivity and solids. Results of the inspection showed greater deposition in one of the systems than would be expected by a High Efficiency Particulate Air (HEPA) filtered exhaust stream, possibly due to accumulation of dust from a short period when unfiltered air was exhausted from construction areas. The second system was also downstream of HEPA filters and appeared much cleaner. The videoscope was a useful and cost-effective tool and provided a better view than could be obtained with the naked eye. However, because even small amounts of deposition were made visible with the videoscope, clarification is needed in defining when probe washing is merited, particularly in existing sampling systems whose design is not conducive to easy removal and cleaning.

Flunitrazepam used in a case of poisoning.

A male was found in a drowsy condition after being given a cup of tea and a tablet by a neighbour. An ambulance was called, he was taken to hospital and attended the police station on release. A blood sample taken 9h after the incident contained eight times the normal therapeutic level for Flunitrazepam. No motive could be proved and the neighbour was charged with Administering Poison under the Offences against the Person Act of 1861.

Sudden, unexpected death of a cannabis bodypacker, due to perforation of the rectum.

A forty year old cannabis bodypacker was found dead in his flat in November 2000, two days after arriving back from a trip to Northern India. On his return he had complained to his family of feeling unwell, although he had refused to let them in or accept medical help. At post-mortem he was found to have 55 packages of cannabis resin in the large intestine, wrapped in cellophane. Subsequent search of the flat by the police revealed the presence of a further 133 similar packages in the fridge, suggesting that he had concealed 188 packages in total. The cause of death was given as peritonitis due to perforation of the distal large intestine caused by swallowing the packages.

Zanamivir susceptibility monitoring and characterization of influenza virus clinical isolates obtained during phase II clinical efficacy studies.

Zanamivir is a highly selective neuraminidase (NA) inhibitor with demonstrated clinical efficacy against influenza A and B virus infections. In phase II clinical efficacy trials (NAIB2005 and NAIB2008), virological substudies showed mean reductions in virus shedding after 24 h of treatment of 1.5 to 2.0 log(10) 50% tissue culture infective doses compared to a placebo, with no reemergence of virus after the completion of therapy. Paired isolates (n = 41) obtained before and during therapy with zanamivir demonstrated no shifts in susceptibility to zanamivir when measured by NA assays, although for a few isolates NA activity was too low to evaluate. In plaque reduction assays in MDCK cells, the susceptibility of isolates to zanamivir was extremely variable even at baseline and did not correlate with the speed of resolution of virus shedding. Isolates with apparent limited susceptibility to zanamivir by plaque reduction proved highly susceptible in vivo in the ferret model. Further sequence analysis of paired isolates revealed no changes in the hemagglutinin and NA genes in the majority of isolates. The few changes observed were all natural variants. No amino acid changes that had previously been identified in vitro as being involved with reduced susceptibility to zanamivir were observed. These studies highlighted problems associated with monitoring susceptibility to NA inhibitors in the clinic, in that no reliable cell-based assay is available. At present the NA assay is the best available predictor of susceptibility to NA inhibitors in vivo, as measured in the validated ferret model of infection.

In vitro selection and characterisation of influenza B/Beijing/1/87 isolates with altered susceptibility to zanamivir.

We describe the in vitro selection and characterisation of virus derived from B/Beijing/1/87 passaged in the presence of zanamivir. During zanamivir passage, the phenotype of virus isolates was either drug dependent or drug resistant in plaque reduction assays. The susceptibility of the neuraminidase of the drug-dependent isolates was unchanged from that of the wild-type enzyme. The drug-dependent isolates contained two mutations in the viral haemagglutinin: V90A, close to the proposed secondary sialic acid-binding site, and L240Q, close to the primary sialic acid-binding site. Virus isolates that were drug resistant contained the same mutations in the haemagglutinin but also contained the mutation E116G in the neuraminidase. For the drug-dependent viruses, zanamivir susceptibility could not be measured because plaque numbers increased with increasing drug concentration. The in vitro zanamivir susceptibility of drug-resistant viruses was lower than that of the wild-type virus by a factor of 275- to >2532-fold. Neuraminidase containing the E116G mutation has a 33-fold lower affinity for zanamivir than the wild-type enzyme. The finding that the same haemagglutinin mutations are found in both drug-dependent and drug-resistant viruses confirms that the same changes to the receptor binding function can contribute to both phenotypes. This observation demonstrates the interplay between the influenza virus haemagglutinin and neuraminidase in escape from zanamivir inhibition in vitro.

Thick malignant melanoma is a long-term problem.

AIMS: To investigate changes in incidence of in-situ, 'thin' (< 0.76 mm) and 'thick' (> 0.76 mm) melanoma. To explore the relationship of melanoma depth with the patient's age at diagnosis. METHODS: A retrospective case series of melanoma was taken from pathology records in Palmerston North between 1983 and 1994. The denominator population was estimated, for each year, from published 1986 and 1991 census figures. RESULTS: Over the 12 years, the diagnostic rate of in-situ and invasive melanomas increased annually by 16% and 5%, respectively (Poisson regression, p < 0.0001). This analysis did not show a difference between the overall rate of increase in 'thin' and 'thick' invasive melanomas. After excluding Hutchinson's melanoma, the mean age at diagnosis for 'thin' and 'thick' melanomas was 49.0 and 55.4 years, respectively (p < 0.0001); the peak number of 'thin' and 'thick' melanomas were in the 30-39 and 60-69 age groups, respectively. CONCLUSIONS: There is evidence for progression from 'thin' to 'thick' melanoma over a 6-to 30-year period. Poor prognosis 'thick' melanomas are currently increasing. Providing removal of 'thin' melanomas is sustained, a decline in 'thick' melanomas is expected but may take decades.

The low potential for drug interactions with zanamivir.

OBJECTIVE: The objective of this study was to assess the potential of zanamivir, a specific inhibitor of influenza A and B virus neuraminidase, to interact with other coadministered therapies in the clinical setting. DESIGN: Potential interactions with zanamivir were examined in a series of in vitro and in vivo model systems. INTERVENTIONS: The expression of microsomal cytochrome P450 (CYP) isoenzymes was examined after daily treatment of rats with intravenous zanamivir. The ability of zanamivir to inhibit the metabolism of CYP probe substrates was studied in human liver microsomes. The binding of zanamivir to human and animal red blood cell fractions and plasma proteins was measured. Finally, the effect of commonly coadministered drugs on the ability of zanamivir to inhibit viral replication in vitro was tested. RESULTS: Zanamivir had no effect on the expression of microsomal CYP isoenzymes after daily intravenous treatment of rats with zanamivir 1, 9 or 90 mg/kg for 5 weeks. Zanamivir at concentrations up to 500 mumol/L (150 mg/L) had no effect on the metabolism of the CYP probe substrates bufuralol, chlorzoxazone, coumarin, ethoxyresorufin, mephenytoin, midazolam, phenacetin and tolbutamide by human liver microsomes. The binding of zanamivir 0.05 to 10 mg/L to human, dog and rat red blood cells and plasma proteins was low. The in vitro potency of zanamivir against influenza virus in Madin Darby canine kidney cells was not adversely affected by aspirin (acetylsalicylic acid) 1.2 mmol/L, paracetamol (acetaminophen) 6.6 mmol/L, ibuprofen 243 mumol/L, phenylephrine 6 mmol/L, oxymetazoline 380 mumol/L, promethazine 35 mumol/L and co-amoxiclav (amoxicillin-clavulanic acid) 1.66 mmol/L. CONCLUSIONS: These data suggest the following: (i) there is no theoretical basis for expecting metabolic interactions between zanamivir and other coadministered compounds; (ii) zanamivir is unlikely to interact with coadministered compounds that are protein bound; and (iii) commonly coadministered drugs will not interfere with the antiviral activity of zanamivir in vivo. Although none of these in vitro or in vivo studies were exhaustive, and although none were performed in humans, all the data are consistent with zanamivir having a very low potential for interactions with coadministered drugs in the clinical setting.

Role of neuraminidase in influenza virus-induced apoptosis.

The virulent influenza virus clone 7a produced a greater level of apoptosis in MDCK cells compared with the attenuated strain A/Fiji. In both cases, apoptosis could be partially blocked by treatment with three anti-neuraminidase compounds [4-amino-(GR121158A) and 4-guanidino- (GG167; Zanamivir) 2,3-dehydro-N-acetylneuraminic acid and 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA)] when they were given to cells during the virus attachment/entry phase, but not subsequent to this phase. In contrast, GG167, which does not enter cells, did not affect the numbers of infected cells and, in addition, acted late in the infection cycle to inhibit virus yields. Clone 7a neuraminidase was more active than A/Fiji neuraminidase when fetuin was used as the substrate. Similar differences in activity between the two viruses were seen when alpha-2,6 sialyl lactose was used as a substrate, but not with alpha-2,3 sialyl lactose. No sequence differences in the enzyme active site of the two neuraminidases were observed, indicating that differences in neuraminidase specificity and activity may be dictated by other residues. These results suggest that neuraminidase plays some role in the induction of apoptosis and that it acts prior to or during virus entry. However, apoptosis was considerably reduced when UV-irradiated virus, which retains >75% of its neuraminidase activity, was used. In addition, ammonium chloride, used to prevent virus entry, reduced virus-induced apoptosis. Amantadine, which inhibits virus uncoating, also inhibited apoptosis induced by the amantadine-sensitive strain A/Udorn/307/72 (H3N2), but not the amantadine-resistant clone 7a. Hence, one or more intracellular processes are also involved in influenza virus-induced apoptosis.

Can cirrus clouds produce glories?

A vague glory display was photographed over central Utah from an airplane beginning its descent through a cirrus cloud layer with an estimated cloud top temperature of -45 and -55 degrees C. Photographic analysis reveals a single reddish-brown ring of 2.5-3.0 degrees radius around the antisolar point, although a second ring appeared visually to have been present over the brief observation period. Mie and approximate nonspherical theory scattering simulations predict a population of particles with modal diameters between 9 and 15 mum. Although it is concluded that multiple-ringed glories can be accounted for only through the backscattering of light from particles that are strictly spherical in shape, the poor glory colorization in this case could imply the presence of slightly aspherical ice particles. The location of this display over mountainous terrain suggests that it was generated by an orographic wave cloud, which we speculate produced numerous frozen cloud droplets that only gradually took on crystalline characteristics during growth.

Six methods to assess potential radioactive air emissions from a stack.

In accordance with U.S. Title 40, Code of Federal Regulations, Part 61, "National Emission Standards for Hazardous Air Pollutants," Subpart H, U.S. Department of Energy stack emissions which have the potential to cause an exposure > or = 1 muSv y-1 to the offsite maximally exposed individual must meet the continuous monitoring requirements dictated therein. Since February 1993, all 125 stacks operated by the Westinghouse Hanford Company on the U.S. Department of Energy's Hanford Site have been assessed for their potential unabated radionuclide emissions using one of six methods approved for use by the U.S. Environmental Protection Agency, Region 10. These potential emissions combined with the CAP88 code were used to produce dose estimates to the maximally exposed individual. Results show there are 106 stacks in compliance and below the potential to emit greater than the EPA threshold. The 19 remaining stacks will be brought into full compliance under a Federal Facilities Compliance Agreement which was established in February, 1994. While each method maintains the safety and protection of the occupational worker, the public, and the environment, significant cost benefits may be derived by applying the best available technology. The CAP88 code and the methods for estimating potential emissions are presented, as well as the associated results.

A clinical and histologic mycosis fungoides simulant occurring as a T-cell infiltrate coexisting with B-cell leukemia cutis.

One year after the onset of chronic lymphocytic leukemia, an elderly man had scaly cutaneous plaques on the thighs that clinically and histologically resembled the mycosis fungoides type of cutaneous T-cell lymphoma. Two years later the patient had indurated, red dermal nodules on the face that clinically and histologically were characteristic of cutaneous chronic lymphocytic leukemia. Immunophenotyping results from a facial nodule confirmed the presence of a B-cell infiltrate (CD20+). Immunophenotyping of a lesion on the right thigh showed that half the cells were composed of a CD2+, CD45RO+ (UCHL-1+) upper dermal and focally epidermotropic population of T cells consistent with mycosis fungoides; however, these T cells coexisted with an equal number of CD20+ B cells arranged in distinct clusters. DNA from the thigh lesion exhibited a B-cell immunoglobulin gene rearrangement, but the T-cell receptor gene rearrangements were germline. In this case, the evidence favors a mycosis fungoides simulant occurring as a reactive T-cell infiltrate to an underlying B-cell chronic lymphocytic leukemia.

Lung dose estimates from 222Rn in Arizona groundwater based on liquid scintillation measurements.

Since August 1989, 222Rn groundwater samples from across the state of Arizona have been collected and analyzed using liquid scintillation. Of the 253 specimens acquired, 65% have 222Rn concentrations above 11 Bq L-1 (300 pCi L-1), while 16% have 222Rn activities over 37 Bq L-1 (1,000 pCi L-1). The geometric mean 222Rn concentration for all the wells tested is 13 Bq L-1 x divided by 4; the arithmetic mean is 37 +/- 122 Bq L-1. Using the geometric mean, it is estimated that an additional tracheobronchial lung dose equivalent of 0.19 mSv y-1 x divided by 13.9 is delivered to Arizona residents from the well water to home pathway.

Systematic underreporting of cutaneous malignant melanoma in Massachusetts. Possible implications for national incidence figures.

An independent tabulation of incidence of cutaneous malignant melanoma in Massachusetts indicates that 12% and perhaps as many as 19% of new cases of cutaneous malignant melanoma in Massachusetts are not recorded in the Massachusetts Cancer Registry, significantly more than the expected 5% (p = 0.0001). The increasing number of nonhospital medical settings in which melanomas can be diagnosed and/or treated appears to account for this discrepancy. We suspect that these findings in Massachusetts also apply to cancer reporting systems in other regions of the United States. We suggest that the true incidence of cutaneous malignant melanoma in Massachusetts, and perhaps in the United States, may be significantly higher than reported.

Nail cosmetics.

Disorders of the nails may be brought about by systemic disease or outside influences. Although many of the products available on the market may be of great benefit in offering palliation of abnormalities of the nail plate, they may also be a source of significant adverse effects. Treatment of nail disorders must be predicated on a well-focused history, physical examination, and proper tissue samples.