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Objectives: The aim of this study was to examine the contribution of Asian ethnicity to the variation in rates of practice prescribing for antidepressant and anxiolytic medication, taking into account other population and practice organizational factors., Methods: A practice-based cross-sectional survey was carried out of the prescribing of antidepressants and anxiolytics (daily defined dosages) in 164 general practices. The study was set in East London and the City Health Authority, which includes the multiethnic inner London boroughs of Hackney, Tower Hamlets, Newham and the City of London. The main outcome measures were the annual prescribing rates for each group of drugs, calculated as the total annual daily defined dosages divided by the practice population, and the ratio of antidepressant/ anxiolytic annual prescribing rates., Results: Prescribing rates for antidepressants showed a 25-fold variation between practices; this was greater for anxiolytics. The median annual prescribing rate for all antidepressants combined was 4.13 (interquartile range 2.50-5.88). For all anxiolytics and hypnotics combined the median annual prescribing rate was 3.55 (interquartile range 1.71-6.36). Univariate analysis showed that Asian ethnicity alone accounted for 28% of the variation in antidepressant prescribing and 20.5% of the variation in the anxiolytic prescribing. A backwards multiple regression model using 10 explanatory practice and population variables accounted for 47.7% of the variance in antidepressant prescribing and 34% of the variance in the anxiolytic prescribing., Conclusion: In practices where the proportion of Asian patients is high, both antidepressant and anxiolytic prescribing is low. This is important for understanding interpractice prescribing variation and for setting levels of drug budgets. This study confirms that the low rates of non-psychotic disorders presented by Asian populations is not a selective feature of access to secondary care, but is evident in the prescribing behaviour of GPs. Uncertainty remains as to how much this is due to a lower prevalence rate, "culture-bound syndromes" or practical difficulties in diagnosis and management within the general practice setting.

Current guidelines and recommendations for genotoxicity testing of pharmaceuticals are disparate, both in terms of the most appropriate tests to use and the protocols to follow. Recent attempts have been made to standardise genotoxicity testing procedures, coinciding with the current review of the OECD guidelines and the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). However, as with other aspects of non-clinical safety assessment of pharmaceuticals, guidelines have been prepared by evaluation of general chemical data due to the lack of specific information on pharmaceuticals. To address this, a project was undertaken to collect and collate information specifically pertaining to the genotoxicity testing of pharmaceuticals in order to obtain a clear understanding of international strategy and procedures in the pharmaceutical industry. It is clear that the practices and regional variations are strongly influenced by national guidelines and do not necessarily follow companies' preferences. However, there is a surprising amount of variation in approach between companies on some issues. This is evident in how companies define a genotoxin. This ranges from a positive result in an in vivo assay as indicative of a genotoxin (43%) to any positive result in vitro or in vivo (30%). Indeed many companies (particularly in Japan) will terminate development on the strength of a clear positive result in an Ames test. There is much debate within the ICH process concerning tests to detect gene mutations in mammalian cells as part of a primary test battery. This survey shows that in general, the pharmaceuticals industry has severe doubts about these assays. Thirty-seven (78%) of the 47 participating pharmaceutical companies include an in vitro test to detect gene mutation in mammalian cells as part of their routine test battery. The HPRT test using Chinese hamster cells has the most widespread use, although there is only limited use of such tests in Japan. Compound development has been affected by the results of such tests, but usually only in terms of clarification of equivocal results in other genotoxicity tests in the test battery. The majority (63%) of companies do not support its use as a primary regulatory requirement, and 83% do not consider the mouse lymphoma assay (L5178Y) an acceptable replacement for in vitro mammalian cytogenetics. In conclusion, this survey has provided valuable information on the current modus operandi of the international pharmaceutical industry for consideration in current harmonisation initiatives.

Rigors are not a recognized characteristic of miliary tuberculosis. We report two patients presenting with persistent rigors, thought to be suggestive of acute pyogenic infection, who were subsequently found to have miliary tuberculosis. In both cases, there was significant diagnostic delay. Miliary tuberculosis should therefore be included in the differential diagnosis of any patient presenting with unexplained rigors.

A synthetic DNA fragment of 19 residues was enlarged by the enzymatic addition of deoxyadenylate residues to its 3'-end with calf thymus terminal deoxynucleotidyl transferase. The 3'-terminus of this elongated DNA strand was blocked with 2', 3'-dideoxyadenylate to prevent hydrolysis by the 3'-exonuclease function of E. coli DNA polymerase I. This elongated and 3'-blocked fragment was annealed to an oligomeric primer and used as a template for the synthesis of a complementary copy of the synthetic 19-mer. The product of such a repair synthesis was separated by gel filtration and analyzed by nearest neighbor techniques. All template strands were copied with complete repair in over 90% of the chains. Facile recovery of the elongated template by virtue of its size permitted repetition of the copy process, thus allowing accumulation of the desired strand.

A component of Aspergillus fumigatus, Ag 7, previously identified as a major antigen for patients with allergic bronchopulmonary aspergillosis, has been isolated by gel filtration and further purified by affinity chromatography using monospecific antiserum. The antigen, which binds both specific IgG and IgE antibodies, was shown to be a high molecular weight, 150-200 kD, heat-stable glycoprotein, which binds to concanavalin A, suggesting the presence of alpha-D mannopyrannoside, or alpha-D glucopyrannoside end residues. On sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) it had a subunit of molecular weight 36 kD (with or without prior reduction), which retained antigenicity and allergenicity when tested with patients' sera.

A new method for determining the 3'-terminal nucleotide of a DNA strand is presented. Use is made of the fact that one (and only one) 2',3'-dideoxyribonucleotide can be added to the 3'-end of a DNA fragment with calf thymus terminal transferase. Addition of more than one nucleotide analog per strand is impossible due to the absence of a 3'-terminal hydroxyl group. If the terminatind dideoxyribonucleotide contains an (alpha 32p) label, the resulting 3'-blocked strand can be digested by "nearest neighbor" techniques and the original 3'-endgroup determined. Picomole quantities of DNA strands can be labeled and the 3'-end determined.

A second major antigen of Aspergillus fumigatus (Ag 13) has been identified and characterized as a 70 kD, heat-labile component which is able to bind to the lectin, concanavalin A. Ag 13 proved to be identical to the previously recognized C antigen, known to possess chymotryptic activity. A monospecific antiserum to Ag 13 has been affinity purified and used to develop a sandwich ELISA for measuring levels of Ag 13 specific IgG antibodies in patients' sera. Although all ABPA sera (25/25) had significantly raised levels, some aspergilloma sera (2/5) had only very low levels; of the control sera, 10/10 fungal atopics were negative, but 5/12 farmer's lung sera had low but positive values of Ag 13 specific IgG, i.e. sensitivity 100%, specificity 80%. Ag 13 is therefore a diagnostically important component of A. fumigatus and the antigen-specific ELISA may be of importance for the improved detection of disease-specific antibodies.